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The control system for energy-efficient train operation with the inclusion of a detailed train motion model and train traction system energy efficiency is presented in the paper. A piecewise affine train model is constructed with the parameters obtained for the electromotive train of an industrial manufacturer. The model encompasses intrinsic features of the train system such as linearized resistance force, a set of traction and braking force physical limitations and passengers comfort constraints. The resulting quadratic optimization problem is solved parametrically through dynamic programming giving the off-line precomputed optimal control law that is a function of train speed and traversed path. The on-line computed traction force profile is then tuned with respect to the traction system energy efficiency. The developed control system is evaluated on a detailed real case study scenario put together with a railway operator and the train manufacturer. The presented results show the possibility of significant energy consumption reductions achieved by energy-efficient train control. [ABSTRACT FROM AUTHOR]

Modular building energy management strategy based on a three-level hierarchical model predictive control is proposed in the paper. Building zones, central medium conditioning and microgrid subsystems are controlled independently by individual linear and nonlinear model predictive controllers, and further integrated together as levels of hierarchical coordination control structure based on price-consumption information exchange. The three-level coordination provides a holistic energy management strategy and enables significant demand response ancillary services for buildings as prosumers, while retaining the independence of required expertise in very different building subsystems. The approach is applied for daily operation scheduling of a full-scale building consisting of 248 offices. Models of building subsystems are obtained by identification procedures on measurement data. Compared to rule-based control, detailed realistic simulations show that the overall building operation cost for typical days in summer is reduced by 9-12% for level-by-level energy-optimal and by 15-24% for price-optimal, coordinated operation. The application of predictive control in the proposed way also improves the indoor comfort substantially. [ABSTRACT FROM AUTHOR]

The article elaborates on the mathematical modeling and control structure design of a grid-connected back-to-back voltage source inverter with a complex dc link and an LC filter for the current harmonics reduction. A cascaded, three-loop control structure is designed for controlling the converter current, the grid current, and the dc link voltage. The derived control structure, utilizing two sets of current sensors and a dc link voltage measurement, is based on proportional-integral controllers and a Truxal–Guillemin model-based controller for the dc link voltage control. The chosen control structure provides consistent results for great variations of the grid impedance. Robustness is tested for various scenarios of variations in grid filter parameters, controller parameters, chosen operating point for linearization, and grid impedance. Results are validated by simulations and experiments on a 7.5 kW converter and show highly robust performance for ± 20% parameter change and a large span of grid impedance variation. [ABSTRACT FROM AUTHOR]

Good vibrations: The lack of sensory feedback from the leg prosthesis in lower limb amputees is associated with risk of falls, low mobility, and perception of the prosthesis as external object. Here, Petrini et al. tested a leg neuroprosthesis, which provided real-time on-demand tactile sensory feedback through nerve stimulation in three transfemoral amputees. The stimulation improved mobility, decreased falling episodes, and increased the perception of the prosthesis as part of the body. Active complex tasks were accomplished with reduced effort when the nerve stimulation was turned on. The results suggest that real-time nerve stimulation could help restore natural sensation in lower leg amputees. Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability. [ABSTRACT FROM AUTHOR]

Background. Organized screening programs often rely on written materials to inform the public. In the United Kingdom, women invited for cervical cancer screening receive a leaflet from the National Health Service (NHS) to support screening decisions. However, information about screening may be too complex for people to understand, potentially hindering informed decision making. Objectives. We aimed to identify women's difficulties in interpreting the leaflet used in England and negative and positive responses to the leaflet. Methods. We used a sequential mixed-methods design involving 2 steps: cognitive think-aloud interviews (n = 20), followed by an England-wide survey (n = 602). Data were collected between June 2017 and December 2018, and participants included women aged 25 to 64 y with varying sociodemographics. Results. Interview results revealed misunderstandings concerning screening results, benefits, and additional tests and treatment, although participants tended to react positively to numerical information. Participants were often unfamiliar with the potential harms associated with screening (i.e., screening risks), key aspects of human papillomavirus, and complex terms (e.g., dyskaryosis). Survey results indicated that interpretation difficulties were common (M correct items = 12.5 of 23). Lower understanding was associated with lower educational level (β's >0.15, P 's <0.001), lower numeracy scores (β = 0.36, P < 0.001), and nonwhite ethnicity (β = 0.10, P = 0.007). The leaflet was evaluated positively overall. Conclusions. Despite previous user testing of the leaflet, key information may be too complex for some recipients. As a consequence, they may struggle to make informed decisions about screening participation based on the information provided. We discuss implications for the improvement of communications about screening and decision support. [ABSTRACT FROM AUTHOR]

The paper presents a railway energy management system based on hierarchical coordination of electric traction substation energy flows and on-route trains energy consumption. The railway system is divided into energy-efficient individual trains energy consumption management as lower level, and the price-efficient electric traction substation energy flows management as higher level. The levels are coordinated through parametric hierarchical model predictive control with the main goal of additionally increasing the energy efficiency and decreasing the operational costs of the overall system. Through interactions with the power grid on the higher level, the system is able to provide ancillary services and respond to various grid requests. At the same time, lower level trains driving profiles are adjusted to attain the minimal cost of system operation with timetables and on-route constraints respected. The developed algorithm is verified on a detailed real case study scenario put together with a railway operator and a trains manufacturer. The presented results show significant cost and energy consumption reductions achieved by simultaneous coordination of several trains supplied from the same traction substation. [ABSTRACT FROM AUTHOR]

The femoral fractures remain the great challenge for orthopedic surgeons regarding time of fixation and appropriate fixation techniques. There is a bimodal distribution of fractures occurring most frequently in young males after high-energy trauma (motor vehicle accidents) and in elderly females after falls from standing. Young patients with femoral fracture are under the great risk of multiple injuries. Hence, the great significance is optimal time of fixation. We present a case of unusual pattern of injury and fixation technique of bilateral proximal femur fracture associated with vascular injury, with very satisfied outcome. [ABSTRACT FROM AUTHOR]

The article examines the clinical course of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Topics discussed include the reasons behind the frequent delay in diagnosing DIPNECH, the data on pulmonary physiology and chest high-resolution computed tomography (HRCT) imaging for DIPNECH and the therapies ideal for DIPNECH.

The objective of this study is to describe severe road traffic injuries (RTIs) in the population under 18 years in Belgrade, the capital of Serbia. We analysed both severe non-fatal and fatal RTIs in children and adolescents under 18 years old in the Belgrade area, during the period 2008–2011. Data sources were the official statistics of the Public Health Institute in Belgrade and forensic-medical records from two paediatric university hospitals and five university hospitals for adults. Using descriptive statistical methods, demographic characteristics, mechanism, type and time of injuries, surgical treatment procedures, injury severity scores (ISS), length of stay and outcome were evaluated. The admission and mortality rates were calculated. Among the total of 379 injured, 256 (67.5%) were male; the average age was 13.0 ± 4.7 (range: 0–18 years). The annual hospital admission rate of RTIs for both sexes decreased in average by 12.6% (95% CI = 9.3%–15.9%). The mean percentage of annual changes of mortality rates was 2.0 %; 95% CI = 1.3%–5.3% (5.7 per 100,000 in 2008, 5.6 in 2009, 4.7 in 2010 and 5.9 in 2011). The highest admission rates and mortality rates were for pedestrians, followed by passengers and cyclists. Accidents occurred most commonly on Monday (18.7%). Among children hospitalised for traffic injuries, 57.8% had head and neck trauma, 30.6% extremity fractures, 5% abdominal injuries, 4.2% chest and 2.4% multiple injuries. The average ISS was 22.4 (SD = 20.4), ranging from 1 to 75. Alcohol in blood was confirmed in 7.4% males and 3.3% females (p> 0.05). The average time of hospital stay was 8.8 days (SD = 16.7), ranging from 1 to 14. The increased rates require implementation of a well-defined national strategy in our country. [ABSTRACT FROM PUBLISHER]

Amorphous silica plays an important role in heterogeneous catalysis as a support and is frequently presumed to be 'inert'. The structure of the supported catalyst is key to understanding the stability and reactivity of catalytic systems. To provide vital insights into the surface reactivity of silica, Polyhedral oligomeric silsesquioxanes (POSSs) can act as realistic homogeneous molecular models for silica surfaces. Here, we report novel reactivities associated with the silica surface, derived from our insights obtained by means of such model systems with potentially significant implications in catalysis when employing silica-supported catalysts. In this work, the gas-phase reactivities of two cyclohexyl-substituted POSSs, namely the completely condensed triganol prism [Si6cy6O9] ( a6 b0), and the incompletely-condensed partial cube [Si7cy7O9(OH)3] ( a7 b3), with cy= c-C6H11, were studied by using atmospheric pressure chemical ionisation (APCI) and collision-induced decomposition (CID) spectroscopies. Silsesquioxane a6b0, containing three-membered rings, was found to be much more reactive, undergoing novel CH2-insertion on reaction with gas phase molecules-a reaction not observed for a7b3, containing only four-membered rings. Both silsesquioxanes displayed the ability to trap ammonia formed in situ within the mass spectrometer from N2 in the instrument. This work also demonstrates the applicability of APCI and the role of CID in elucidating reactive POSS structures, highlighting novel gas-phase reactivities of POSS. [ABSTRACT FROM AUTHOR]

Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS) virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS) and structure-activity relationship (SAR) analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR); inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections. [ABSTRACT FROM AUTHOR]

Bony defects caused by trauma, tumors, infection or congenital anomalies can present a significant surgical challenge. Free vascularised fibular bone grafts (FVFGs) have proven to be extremely effective in managing larger defects (longer than 6 cm) where other conventional grafts have failed. FVFGs also have a role in the treatment of avascular necrosis (AVN) of the femoral head, failed spinal fusions and complex arthrodeses. Due to the fact that they have their own blood supply, FVFGs are effective even in cases where there is poor vascularity at the recipient site, such as in infection and following radiotherapy. This article discusses the versatility of the FVFG and its successful application to a variety of different pathologies. It also covers the applied anatomy, indications, operative techniques, complications and donor-site morbidity. Though technically challenging and demanding, the FVFG is an extremely useful salvage option and can facilitate limb reconstruction in the most complex of cases. [ABSTRACT FROM AUTHOR]

EXECUTIVE SUMMARY. *Radiology leaders met at the inaugural AHRA-GE Healthcare Annual Summit to discuss challenges facing the profession and opportunities to drive success in a fast changing care environment. * Changes in the healthcare environment mean unprecedented challenges for the radiology profession. The Affordable Care Act, declining reimbursement, an aging population, growing consumer choice, and other trends are forcing radiology leaders to reexamine their ways of doing business and even the basic role of radiologists in patient care. * Twelve members of AHRA shared their views on essential topics in a moderated roundtable discussion. That discussion is transcribed here. [ABSTRACT FROM AUTHOR]

Summary: Hip fracture incidence in the capital city of Serbia was assessed over a period of 10 years (2000-2009). Crude annual incidence rates increased significantly for all ages and both sexes ( p = 0.002). Age-adjusted rates also showed a steady increase. The mean rate of annual change for age-adjusted rates was 8.6 % (95 %CI 7.5-9.7) in males, 8.0 % (95 %CI 7.4-8.6) in females, and 8.2 % (95 %CI 7.7-8.7) in the total population. Introduction: The aim of this study was to estimate the incidence rate and trend of hip fractures in the population of Belgrade, the capital of Serbia. Methods: Data sources were the official statistics of the Public Health Institute in Belgrade. The patient's age, gender, residence, hospital admission, and diagnosis were registered for each hospital admission. Population estimates were based on census data from 2002 and on published estimates for the intercensus years. The annual incidence (crude) rates and age- and sex-specific incidence rates were calculated with 95 % confidence intervals (CI) and age-adjusted incidence rates for persons over the age of 50 years were computed. Results: A significantly increasing trend of crude incidence rates for all ages was observed in males ( p = 0.002), females ( p = 0.001), and overall ( p = 0.002). The proportion of trochanteric fractures rose significantly with age in women ( p < 0.0001), whereas it decreased nonsignificantly in men ≥70 years ( p = 0.44). The age-adjusted incidence rates (per 100,000 in subjects ≥50 years old) showed a steady increase. The mean rate of annual change for age-adjusted rates was 8.6 % (95 %CI 7.5-9.7) in males, 8.0 % (95 %CI 7.4-8.6) in females, and 8.2 % (95 %CI 7.7-8.7) in the total population. Conclusion: Hip fracture incidence continues to increase. In view of the rapid aging of the population, it is necessary to implement a comprehensive preventive policy in our community. [ABSTRACT FROM AUTHOR]

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Mangled describes an injury caused by cutting, tearing, or crushing, which leads to the limb becoming unrecognizable; in essence, there are two treatment options for mangled upper extremities, amputation and salvage reconstruction. With advances in our understanding of human physiology and basic science, and with the development of new fixation devices, modern microsurgical techniques and the possibility of different types of bony and soft tissue reconstruction, the clinical and functional outcomes are often good, and certainly preferable to those of contemporary prosthetics. Early or even immediate (emergency) complete upper extremity reconstruction appears to give better results than delayed or late reconstruction and should be the treatment of choice where possible. Before any reconstruction is attempted, injuries to other organs must be excluded. Each step in the assessment and treatment of a mangled extremity is of utmost importance. These include radical tissue debridement, prophylactic antibiotics, copious irrigation with a lavage system, stable bone fixation, revascularization, nerve repair, and soft tissue coverage. Well-planned and early rehabilitation leads to a better functional outcome. Despite the use of scoring systems to help guide decisions and predict outcomes, the decision to reconstruct or to amputate still ultimately lies with the surgical judgment and experience of the treating surgeon. [ABSTRACT FROM AUTHOR]

Purpose: Venous thromboembolism (VTE) is a common complication of orthopaedic surgery in the industrialised world; though there may be variability between population groups. This study aims to define the incidence and risk factors for symptomatic VTE following primary elective total hip and knee arthoplasty surgery in a single centre in Eastern Europe. Methods: This prospective study included 499 adult patients undergoing total hip and knee arthroplasty for symptomatic osteoarthritis over a two-year period at the Clinic of Orthopaedic Surgery and Traumatology, Belgrade. Results: The overall rate of confirmed symptomatic VTE during hospitalisation was 2.6%. According to the univariate logistic regression, an age greater than 75 years (OR = 3.08; 95%CI = 1.01-9.65), a family history of VTE (OR = 6.61; 95% CI = 1.33-32.90), varicose veins (OR = 3.13; 95% CI = 1.03-9.48), and ischemic heart disease (OR = 4.93; 95% CI = 1.61-15.09) were significant risk factors for in-hospital VTE. A family history of VTE and ischemic heart disease were independent risk factors according to multivariate regression analysis. Preoperative initiation of pharmacological thromboprophylaxis ( p = 0.03) and a longer duration of thromboprophylaxis ( p = 0.001) were protective for postoperative DVT. Though thromboprophylaxis was safe, with very few patients suffering major haemorrhage or heparin-induced thrombocytopenia, there was a general reluctance by our local surgeons to use prolonged thromboprophylaxis. Conclusion: VTE is common following hip and knee arthroplasty surgery. Orthopaedic patients with a family history of VTE, heart failure and coronary heart disease are at a considerable risk of thromboembolic complications in the postoperative period. There may be a role for preoperative thromboprophylaxis in addition to prolonged postoperative treatment. [ABSTRACT FROM AUTHOR]

The High Pathogenicity Island of Yersinia pseudotuberculosis IP32637 was previously shown to be horizontally transferable as part of a large chromosomal segment. We demonstrate here that at low temperature other chromosomal loci, as well as a non-mobilizable plasmid (pUC4K), are also transferable. This transfer, designated GDT4 (Generalized DNA Transfer at 4uC), required the presence of an IP32637 endogenous plasmid (pGDT4) that carries several mobile genetic elements and a conjugation machinery. We established that cure of this plasmid or inactivation of its sex pilus fully abrogates this process. Analysis of the mobilized pUC4K recovered from transconjugants revealed the insertion of one of the pGDT4--borne ISs, designated ISYps1, at different sites on the transferred plasmid molecules. This IS belongs to the IS6 family, which moves by replicative transposition, and thus could drive the formation of cointegrates between pGDT4 and the host chromosome and could mediate the transfer of chromosomal regions in an Hfr-like manner. In support of this model, we show that a suicide plasmid carrying ISYps1 is able to integrate itself, flanked by ISYps1 copies, at multiple locations into the Escherichia coli chromosome. Furthermore, we demonstrate the formation of RecA-independent cointegrates between the ISYps1-harboring plasmid and an ISYps1-free replicon, leading to the passive transfer of the non-conjugative plasmid. We thus demonstrate here a natural mechanism of horizontal gene exchange, which is less constrained and more powerful than the classical Hfr mechanism, as it only requires the presence of an IS6-type element on a conjugative replicon to drive the horizontal transfer of any large block of plasmid or chromosomal DNA. This natural mechanism of chromosome transfer, which occurs under conditions mimicking those found in the environment, may thus play a significant role in bacterial evolution, pathogenesis, and adaptation to new ecological niches. [ABSTRACT FROM AUTHOR]

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens. [ABSTRACT FROM AUTHOR]

Background: The Red recombinase system of bacteriophage lambda has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR) fragment that was obtained with a 1- or 3-step PCR protocol and that carries an antibiotic cassette flanked by a region homologous to the target locus into a strain that expresses the lambda Red recombination system. Results: This system has been modified for use in Pseudomonas aeruginosa. Chromosomal DNA deletions of single genes were generated using 3-step PCR products containing flanking regions 400-600 nucleotides (nt) in length that are homologous to the target sequence. A 1-step PCR product with a homologous extension flanking region of only 100 nt was in some cases sufficient to obtain the desired mutant. We further showed that the P. aeruginosa strain PA14 non-redundant transposon library can be used in conjunction with the lambda Red technique to rapidly generate large chromosomal deletions or transfer mutated genes into various PA14 isogenic mutants to create multi-locus knockout mutants. Conclusion: The lambda Red-based technique can be used efficiently to generate mutants in P. aeruginosa. The main advantage of this procedure is its rapidity as mutants can be easily obtained in less than a week if the 3-step PCR procedure is used, or in less than three days if the mutation needs to be transferred from one strain to another. [ABSTRACT FROM AUTHOR]

Long-term antibiotic use generates pan-resistant super pathogens. Anti-infective compounds that selectively disrupt virulence pathways without affecting cell viability may be used to efficiently combat infections caused by these pathogens. A candidate target pathway is quorum sensing (QS), which many bacterial pathogens use to coordinately regulate virulence determinants. The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). Here, we identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function. These compounds provide a starting point for the design and development of selective anti-infectives that restrict human P. aeruginosa pathogenesis, and possibly other clinically significant pathogens. [ABSTRACT FROM AUTHOR]

A new metabolite, 2,4-dihydroxyquinoline (DHQ), was identified in cultures of the bacteria Pseudomonas aeruginosa and Burkholderia thailandensis. We found that the biosynthesis of DHQ correlates with the presence of a functional PqsA, which is a product of the pqsABCDE operon responsible for the synthesis of 4-hydroxy-2-alkylquinolines (HAQs) in P. aeruginosa. However, DHQ is not a degradation product or precursor of HAQs. This finding sheds some light on the poorly understood biosynthesis pathway of HAQs, which includes important communication signals regulating the expression of virulence factors. [ABSTRACT FROM AUTHOR]

MvfR (PqsR), a Pseudomonas aeruginosa LysR-type transcriptional regulator, plays a critical role in the virulence of this pathogen. MvfR modulates the expression of multiple quorum sensing (QS)-regulated virulence factors; and the expression of the phnAB and pqsA-E genes that encode functions mediating 4-hydroxy-2-alkylquinolines (HAQs) signalling compounds biosynthesis, including 3,4-dihydroxy-2-heptylquinoline (PQS) and its precursor 4-hydroxy-2-heptylquinoline (HHQ). PQS enhances the in vitro DNA-binding affinity of MvfR to the pqsA-E promoter, to suggest it might function as the in vivo MvfR ligand. Here we identify a novel MvfR ligand, as we show that HHQ binds to the MvfR ligand-binding-domain and potentiates MvfR binding to the pqsA-E promoter leading to transcriptional activation of pqsA-E genes. We show that HHQ is highly produced in vivo, where it is not fully converted into PQS, and demonstrate that it is required for MvfR-dependent gene expression and pathogenicity; PQS is fully dispensable, as pqsH– mutant cells, which produce HHQ but completely lack PQS, display normal MvfR-dependent gene expression and virulence. Conversely, PQS is required for full production of pyocyanin. These results uncover a novel biological role for HHQ; and provide novel insights on MvfR activation that may aid in the development of therapies that prevent or treat P. aeruginosa infections in humans. [ABSTRACT FROM AUTHOR]

The article discusses intertextuality as one of the extremely useful and yet strangely vague theoretical concepts. In 1966 a young Bulgarian scholar named Julia Kristeva gave a demonstration on Mikhail Bakhtin's theory of the novel and the nature of the word/utterance/discourse in the novelistic genres in Roland Barthe's seminar. According to the author that if Bakhtin gave Kristeva some of his seductive terminology, he believed that the Formalists gave her most of the theories behind it.

The Yersinia high-pathogenicity island (HPI) encodes the siderophore yersiniabactin-mediated iron uptake system. The HPI of Yersinia pseudotuberculosis I has previously been shown to be able to excise precisely from the bacterial chromosome by recombination between the attB-R and attB-L sites flanking the island. However, the nature of the Y. pseudotuberculosis HPI excision machinery remained unknown. We show here that, upon excision, the HPI forms an episomal circular molecule. The island thus has the ability to excise from the chromosome, circularize and reintegrate itself, either in the same location or in another asn tRNA copy. We also demonstrate that the HPI-encoded bacteriophage P4-like integrase (Int) plays a critical role in HPI excision and that, like phage integrases, it acts as a site-specific recombinase that catalyses both excision and integration reactions. However, Int alone cannot efficiently promote recombination between the attB-R and attB-L sites, and we demonstrate that a newly identified HPI-borne factor, designated Hef (for HPI excision factor) is also required for this activity. Hef belongs to a family of recombination directionality factors. Like the other members of this family, Hef probably plays an architectural rather than a catalytic role and promotes HPI excision from the chromosome by driving the function of Int towards an excisionase activity. The fact that the HPI, and probably several other pathogenicity islands, carry a machinery of integration/excision highly similar to those of bacteriophages argues for a phage-mediated acquisition and transfer of these elements. [ABSTRACT FROM AUTHOR]

A polymerase chain reaction (PCR)-based procedure without any cloning step was developed for a rapid mutagenesis/deletion of chromosomal target genes in Yersinia. For this purpose, a PCR fragment carrying an antibiotic resistance gene flanked by regions homologous to the target locus is electroporated into a recipient strain expressing the highly proficient homologous recombination system encoded by plasmid pKOBEG-sacB. Two PCR procedures were tested to generate an amplification product formed of an antibiotic resistance gene flanked by short (55 bp) or long (500 bp) homology extensions. Using this method, three chromosomal loci were successfully disrupted in Yersinia pseudotuberculosis. The use of this technique allows rapid and efficient large-scale mutagenesis of Yersinia target chromosomal genes. [Copyright &y& Elsevier]

Measuring real-world impact is vital for demonstrating the success of a project and one of the most direct ways to justify taxpayers' contributions towards public funding. Impact reporting should identify and examine the potential positive and negative consequences of the continuing operations of a proposed project and suggest strategies to expand, further develop, mitigate, avoid or offset them. Designing a tool or methodology that will capture the impact of collaborative research and innovation projects related to sustainability requires input from technical experts but also from experts in the domains of survey design and communication. Without survey design insights and testing it can be very difficult to achieve unambiguous and accurate reporting of impacts. This paper proposes six key recommendations that should be considered for those monitoring projects when identifying metrics and designing a sustainability impact report. These recommendations stem from a series of in-depth interviews about sustainability and innovation impact reporting with research project co-ordinators in the process industries (e.g., cement, ceramics, chemicals, engineering, minerals and ores, non-ferrous metals, steel and water sectors). Our results show that factors such as ambiguous terminology, two-in-one questions, the stage of the project, over-hypothetical estimates, inadequate formats and alternatives and lack of guidelines can negatively influence the data collected in usual project monitoring activities and jeopardise the overall validity of the reporting. This work acts as a guideline for those monitoring to improve how they ask for impact data from projects, whether they are introducing new impact metrics or evaluating existing ones. [ABSTRACT FROM AUTHOR]