Mucosal sensitization to German cockroach involves protease-activated receptor-2

<p>Abstract</p> <p>Background</p> <p>Allergic asthma is on the rise in developed countries. A common characteristic of allergens is that they contain intrinsic protease activity, and many have been shown to activate protease-activated receptor (PAR)-2 <it>in vitro</it>. The role for PAR-2 in mediating allergic airway inflammation has not been assessed using a real world allergen.</p> <p>Methods</p> <p>Mice (wild type or PAR-2-deficient) were sensitized to German cockroach (GC) feces (frass) or protease-depleted GC frass by either mucosal exposure or intraperitoneal injection and measurements of airway inflammation (IL-5, IL-13, IL-17A, and IFNγ levels in the lung, serum IgE levels, cellular infiltration, mucin production) and airway hyperresponsiveness were performed.</p> <p>Results</p> <p>Following systemic sensitization, GC frass increased airway hyperresponsiveness, Th2 cytokine release, serum IgE levels, cellular infiltration and mucin production in wild type mice. Interestingly, PAR-2-deficient mice had similar responses as wild type mice. Since these data were in direct contrast to our finding that mucosal sensitization with GC frass proteases regulated airway hyperresponsiveness and mucin production in BALB/c mice (Page et. al. 2007 Resp Res 8:91), we backcrossed the PAR-2-deficient mice into the BALB/c strain. Sensitization to GC frass could now occur via the more physiologically relevant method of intratracheal inhalation. PAR-2-deficient mice had significantly reduced airway hyperresponsiveness, Th2 and Th17 cytokine release, serum IgE levels, and cellular infiltration compared to wild type mice when sensitization to GC frass occurred through the mucosa. To confirm the importance of mucosal exposure, mice were systemically sensitized to GC frass or protease-depleted GC frass via intraperitoneal injection. We found that removal of proteases from GC frass had no effect on airway inflammation when administered systemically.</p> <p>Conclusions</p> <p>We showed for the first time that allergen-derived proteases in GC frass elicit allergic airway inflammation via PAR-2, but only when allergen was administered through the mucosa. Importantly, our data suggest the importance of resident airway cells in the initiation of allergic airway disease, and could make allergen-derived proteases attractive therapeutic targets.</p

Fast Control Systems: Nonlinear Approach

International audienceThis chapter treats the problem of fast control design for nonlinear systems. First, we discusses the question: which nonlinear system can be called fast? Next, we develop some tools for analysis and design of such control systems. The method generalized homogeneity is mainly utilized for these purposes. Finally, we survey possible research directions of the fast control systems

Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers

WOS: 000390900700001PubMed ID: 27903276Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.European CommissionEuropean Commission Joint Research Centre [658170]This work was funded by the European Commission H2020 Marie Sklodowska Curie Action Individual Fellowship (H2020-MSCA-IF, 658170) to CS and Breast Cancer Now to JMD and AHS

Global burden of peripheral artery disease and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures. Methods Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed. Findings In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2–128·4), with a global prevalence of 1·52% (95% UI 1·33–1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41–17·87] in those aged 80–84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2–74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles. Interpretation The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors. Funding Bill & Melinda Gates Foundation

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

An Efficient PWM Technique for Split Phase Induction Motor Operation Using Dual Voltage Source Inverters

Split phase induction motor operation from dual PWM voltage source inverters offers the advantage of reduced voltage rating for the inverter devices. In addition, a total of 49 different locations are possible for the resultant stator voltage space phasor. The outermost locations form a twelve sided polygon. By space phasor PWM generation based on the vertices of the twelve sided polygon, a higher range of fundamental motor voltage is possible in the modulation range, up to 0.643 $V_{DC}$, where $V_{DC}$ is the DC link voltage for an equivalent 3 phase inverter, as compared to 0.577 $V_{DC}$ for the three phase motor. This is brought about by the presence of 5th and 7th harmonics in the average poler voltage waveform. These harmonics get eliminated in the air gap mmf because of the winding disposition. However, they cause stator Currents to flow and these currents are limited Only by the stator leakage impedance. At low speeds, these currents can be very high. In this paper a PWM strategy is proposed for a split phase induction motor drive, wherein at low speeds each of the inverters is operated with conventional three and 7th harmonics in the motor voltage. At the higher end of the speed range a voltage space phasor modulation based on the twelve sided polygonal vertices is used, so that the benefit of a higher speed in the modulation range is retained. A technique for achieving the transition to that range without current transients is proposed. The scheme is verified through computer simulation, using a space phasor based model of the split phase motor. Details of a practical control circuit for voltage space phasor based PWM pulse generation are presented and the results from an experimental drive are highlighted

Vector Control of Induction Motor with Split Phase Stator Windings

A vector controlled scheme is described for induction motor with split phase windings. Such a motor is obtained by splitting the phase windings of a conventional three phase motor with an angular seperation of 30 electrical degrees between the axes of the two halves. In the proposed scheme the motor is run as a three phase machine by connecting the split phase windings in series. However the winding taps are utilized for making voltage measurements. Based on a space phasor model of the split phase machine, a method of acquiring the position of the rotor flux is developed. The scheme is based only on the voltage and current measurements, without the need for position encoders. It is also independent of machine resistance values. Results from computer simulation as well as from an experimental prototype drive are presented and discussed

Split-Phase Induction Motor Operation from PWM Voltage Source Inverter

The operation of split-phase induction motors from pulse-width modulated (PWM) voltage source inverters is examined. Splitting the phase windings leads to reduced voltage ratings for the inverter switches. As compared with seven positions for the space phasor of voltage in three-phase machines, 48 different locations bounded by a 12-sided polygon are possible in the split-phase machine. Based on space phasor modulation, a three-phase inverter can give a maximum peak fundamental of 0.577 $V_{DC}$. In comparison, the split-phase configuration can provide an equivalent three-phase maximum peak fundamental of 0.643 $V_{DC}$ with a DC bus voltage of 0.5 $V_{DC}$/cos 15

Vector control of induction motor with split phase windings

A vector controlled scheme is described for an induction motor with split phase windings. Such a motor is obtained by splitting the phase windings of a conventional three phase motor with an angular separation of 30 electrical degrees between the axes of the two halves. In the proposed scheme the motor is run as a three phase machine by connecting the split phase windings in series. An appropriate split phase induction motor model based on space phasor notations is proposed. From this space phasor model of the split phase machine, a simple technique for measuring the equivalent circuit parameters for the motor is presented. Based on the proposed model a method for acquiring the position of the rotor flux is developed. The scheme is based only on the voltage and current measurements, without the need for position encoders. It is also independent of machine resistance values. Results from computer simulation as well as from an experimental prototype drive are presented and discussed

An Efficient PWM Technique for Split Phase Induction Motor Operation Using Dual Voltage Source Inverters

Split phase induction motor operation from dual PWM voltage source inverters offers the advantage of reduced voltage rating for the inverter devices. In addition, a total of 49 different locations are possible for the resultant stator voltage space phasor. The outermost locations form a twelve sided polygon. By space phasor PWM generation based on the vertices of the twelve sided polygon, a higher range of fundamental motor voltage is possible in the modulation range, up to 0.643 $V_{DC}$, where $V_{DC}$ is the DC link voltage for an equivalent 3 phase inverter, as compared to 0.577 $V_{DC}$ for the three phase motor. This is brought about by the presence of 5th and 7th harmonics in the average poler voltage waveform. These harmonics get eliminated in the air gap mmf because of the winding disposition. However, they cause stator Currents to flow and these currents are limited Only by the stator leakage impedance. At low speeds, these currents can be very high. In this paper a PWM strategy is proposed for a split phase induction motor drive, wherein at low speeds each of the inverters is operated with conventional three and 7th harmonics in the motor voltage. At the higher end of the speed range a voltage space phasor modulation based on the twelve sided polygonal vertices is used, so that the benefit of a higher speed in the modulation range is retained. A technique for achieving the transition to that range without current transients is proposed. The scheme is verified through computer simulation, using a space phasor based model of the split phase motor. Details of a practical control circuit for voltage space phasor based PWM pulse generation are presented and the results from an experimental drive are highlighted