TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor.

Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many antipain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally innervated territories in mice. In addition, we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, and because we have recently defined TRPV4's role in response to airborne irritants and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion is supported by studies with Trpv4(-/-) mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca(2+). Using TRPA1-blocker and Trpa1(-/-) mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation of trigeminally innervated surface epithelia.

Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital.

Background: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. Methods: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients\' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. Results: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06–1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). Conclusion: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.

Traditions and contradictions of sexual function definitions for portuguese heterosexual men and women: medicalization and socially constructed gender effects

© 2015 College of Sexual and Relationship Therapists

Factor structure of the General Health Questionnaire-28 (GHQ-28) from infertile women attending the Yazd Research and Clinical Center for Infertility

Background: Nowadays, infertility problems have become a social concern, and are associated with multiple psychological and social problems. Also, it affects the interpersonal communication between the individual, familial, and social characteristics. Since women are exposed to stressors of physical, mental, social factors, and treatment of infertility, providing a psychometric screening tool is necessary for disorders of this group. Objective: The aim of this study was to determine the factor structure of the general health questionnaire-28 to discover mental disorders in infertile women. Materials and Methods: In this study, 220 infertile women undergoing treatment of infertility were selected from the Yazd Research and Clinical Center for Infertility with convenience sampling in 2011. After completing the general health questionnaire by the project manager, validity and, reliability of the questionnaire were calculated by confirmatory factor structure and Cronbach's alpha, respectively. Results: Four factors, including anxiety and insomnia, social dysfunction, depression, and physical symptoms were extracted from the factor structure. 50.12% of the total variance was explained by four factors. The reliability coefficient of the questionnaire was obtained 0.90. Conclusion: Analysis of the factor structure and reliability of General Health Questionnaire-28 showed that it is suitable as a screening instrument for assessing general health of infertile women.

Power spectrum model of visual masking: simulations and empirical data

In the study of the spatial characteristics of the visual channels, the power spectrum model of visual masking is one of the most widely used. When the task is to detect a signal masked by visual noise, this classical model assumes that the signal and the noise are previously processed by a bank of linear channels and that the power of the signal at threshold is proportional to the power of the noise passing through the visual channel that mediates detection. The model also assumes that this visual channel will have the highest ratio of signal power to noise power at its output. According to this, there are masking conditions where the highest signal-to-noise ratio (SNR) occurs in a channel centered in a spatial frequency different from the spatial frequency of the signal (off-frequency looking). Under these conditions the channel mediating detection could vary with the type of noise used in the masking experiment and this could affect the estimation of the shape and the bandwidth of the visual channels. It is generally believed that notched noise, white noise and double bandpass noise prevent off-frequency looking, and high-pass, low-pass and bandpass noises can promote it independently of the channel's shape. In this study, by means of a procedure that finds the channel that maximizes the SNR at its output, we performed numerical simulations using the power spectrum model to study the characteristics of masking caused by six types of one-dimensional noise (white, high-pass, low-pass, bandpass, notched, and double bandpass) for two types of channel's shape (symmetric and asymmetric). Our simulations confirm that (1) high-pass, low-pass, and bandpass noises do not prevent the off-frequency looking, (2) white noise satisfactorily prevents the off-frequency looking independently of the shape and bandwidth of the visual channel, and interestingly we proved for the first time that (3) notched and double bandpass noises prevent off-frequency looking only when the noise cutoffs around the spatial frequency of the signal match the shape of the visual channel (symmetric or asymmetric) involved in the detection. In order to test the explanatory power of the model with empirical data, we performed six visual masking experiments. We show that this model, with only two free parameters, fits the empirical masking data with high precision. Finally, we provide equations of the power spectrum model for six masking noises used in the simulations and in the experiments.

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Methods to improve gene signal: Application to cDNA microarrays

Microarrays are high throughput biological assays that allow the screening of thousands of genes for their expression. The main idea behind microarrays is to compute for each gene a unique signal that is directly proportional to the quantity of mRNA that was hybridized on the chip. A large number of steps and errors associated with each step make the generated expression signal noisy. As a result, microarray data need to be carefully pre-processed before their analysis can be assumed to lead to reliable and biologically relevant conclusions. This thesis focuses on developing methods for improving gene signal and further utilizing this improved signal for higher level analysis. To achieve this, first, approaches for designing microarray experiments using various optimality criteria, considering both biological and technical replicates, are described. A carefully designed experiment leads to signal with low noise, as the effect of unwanted variations is minimized and the precision of the estimates of the parameters of interest are maximized. Second, a system for improving the gene signal by using three scans at varying scanner sensitivities is developed. A novel Bayesian latent intensity model is then applied on these three sets of expression values, corresponding to the three scans, to estimate the suitably calibrated true signal of genes. Third, a novel image segmentation approach that segregates the fluorescent signal from the undesired noise is developed using an additional dye, SYBR green RNA II. This technique helped in identifying signal only with respect to the hybridized DNA, and signal corresponding to dust, scratch, spilling of dye, and other noises, are avoided. Fourth, an integrated statistical model is developed, where signal correction, systematic array effects, dye effects, and differential expression, are modelled jointly as opposed to a sequential application of several methods of analysis. The methods described in here have been tested only for cDNA microarrays, but can also, with some modifications, be applied to other high-throughput technologies. Keywords: High-throughput technology, microarray, cDNA, multiple scans, Bayesian hierarchical models, image analysis, experimental design, MCMC, WinBUGS.

Nonlinear Control Design for an Air-breathing Engine with State Estimation

A nonlinear control design approach is presented in this paper for a challenging application problem of ensuring robust performance of an air-breathing engine operating at supersonic speed. The primary objective of control design is to ensure that the engine produces the required thrust that tracks the commanded thrust as closely as possible by appropriate regulation of the fuel flow rate. However, since the engine operates in the supersonic range, an important secondary objective is to ensure an optimal location of the shock in the intake for maximum pressure recovery with a sufficient margin. This is manipulated by varying the throat area of the nozzle. The nonlinear dynamic inversion technique has been successfully used to achieve both of the above objectives. In this problem, since the process is faster than the actuators, independent control designs have also been carried out for the actuators as well to assure the satisfactory performance of the system. Moreover, an extended Kalman Filter based state estimation design has been carried out both to filter out the process and sensor noises as well as to make the control design operate based on output feedback. Promising simulation results indicate that the proposed control design approach is quite successful in obtaining robust performance of the air-breathing system.

Nonlinear Sliding Mode Control Design for an Air-breathing Engine with State Estimation

A modern system theory based nonlinear control design is discussed in this paper for successful operation of an air-breathing engine operating at supersonic speed. The primary objective of the control design of such an air-breathing engine is to ensure that the engine dynamically produces the thrust that tracks a commanded value of thrust as closely as possible by regulating the fuel flow to the combustion system. However, since the engine operates in the supersonic range, an important secondary objective is to manage the shock wave configuration in the intake section of the engine which is manipulated by varying the throat area of the nozzle. A nonlinear sliding mode control technique has been successfully used to achieve both of the above objectives. In this problem, since the process is faster than the actuators, independent control designs are also carried out for the actuators as well to assure the satisfactory performance of the system. Moreover, to filter out the sensor and process noises and to estimate the states for making the control design operate based on output feedback, an Extended Kalman Filter based state estimation design is also carried out. The promising simulation results suggest that the proposed control design approach is quite successful in obtaining robust performance of the air-breathing engine.

Nonlinear control of an air-breathing engine including its validation with vehicle guidance

An implementable nonlinear control design approach is presented for a supersonic air-breathing ramjet engine. The primary objective is to ensure that the thrust generated by the engine tracks the commanded thrust without violating the operational constraints. An important constraint is to manage the shock wave location in the intake so that it neither gets detached nor gets too much inside the intake. Both the objectives are achieved by regulating the fuel flow to the combustion chamber and by varying the throat area of the nozzle simultaneously. The design approach accounts for the nonlinear cross-coupling effects and nullifies those. Also, an extended Kalman filter has been used to filter out the sensor and process noises as well as to make the states available for feedback. Furthermore, independent control design has been carried out for the actuators. To test the performance of the engine for a realistic flight trajectory, a representative trajectory is generated through a trajectory optimization process, which is augmented with a newly-developed finite-time state dependent Riccati equation technique for nullifying the perturbations online. Satisfactory overall performance has been obtained during both climb and cruise phases. (C) 2015 Elsevier Masson SAS. All rights reserved.

一种新型结构的单纵模光纤激光器

单纵模掺铒光纤激光器在光通信和光传感等方面有着广泛的应用前景。设计了一种新型的光纤激光器，在光纤环形镜中嵌入未抽运的掺铒光纤作为可饱和吸收体以抑制多纵模，用光纤环谐振腔作为滤波器抑制拍频噪声，用光纤光栅作为波长选择器件，最终得到了单纵模输出并消除了拍频噪声。使用零拍法测量其线宽小于频谱仪的低频极限5kHz。实验结果证明了可饱和吸收体和光纤环的功能。

Efeito do treinamento físico intenso e da dose única de polifenóis sobre indicadores cardiometabólicos em militares fisicamente condicionados

O exercício físico pode promover o desequilíbrio oxidativo e na secreção e ação das adipocinas, leptina e adiponectina, que desempenham papel fundamental no desenvolvimento de doenças cardiometabólicas, incluindo a síndrome metabólica, disfunção endotelial, desordens inflamatórias e vasculares. Militares são submetidos a exercícios físicos intensos e podem apresentar maior risco de doenças cardiovasculares. A identificação de parâmetros capazes de detectar o risco cardiovascular precoce em grupos muito ativos fisicamente é complexa. A razão leptina/adiponectina (L/A) e a concentração de LDL eletronegativa (LDL (-)) vem sendo considerados bons indicadores de risco cardiovascular precoce porém não há estudos que investiguem a utilidade destes marcadores em militares. Os polifenóis, presentes na uva (Vitis vinífera), apresentam efeitos cardioprotetores como inibição da oxidação das lipoproteínas e controle glicêmico. Na presente tese objetivou-se identificar o risco cardiovascular em jovens militares altamente treinados, utilizando diferentes parâmetros, incluindo a razão L/A e investigar a influência do exercício militar e do uso de dose única de Vitis vinifera sobre parâmetros cardiometabólicos de militares fisicamente treinados. O primeiro estudo contou com a participação de 54 militares d gênero masculino, condicionados fisicamente, após descanso de 24h. No segundo estudo, participaram 54 militares do gênero masculino distribuídos aleatoriamente, de forma duplo-cego, para receber única dose contendo 200 mg de extrato seco de Vitis vinifera (GS, n = 27) ou 200 mg de placebo (amido) (GP, n = 27). Considerados em conjunto, os resultados sugerem que militares treinados poderiam ser classificados como limítrofes quanto ao risco cardiovascular, quando somente o perfil lipídico é empregado como marcador. As medidas de CC e CC/E são parâmetros de fácil obtenção e podem ser empregados na identificação do potencial risco cardiovascular, enquanto outros estudos não confirmam a eficácia da razão L/A para este fim. A comparação das concentrações plasmáticas de adiponectina e leptina apresentou diferença significativa apenas intragrupo para ambos os grupos. As concentrações plasmáticas das adipocinas foram influenciadas pelo treinamento. Os indicadores de homeostase glicêmica, glicemia de jejum e insulina plasmática, foram semelhantes entre os grupos, não sendo sendo influenciada pelo treinamento ou suplementação. A suplementação de polifenóis reduziu as concentrações de LDL(-) do GS em relação ao GP em T24h e T48h (p<0,05). Estes achados sugerem que o treinamento físico afeta a secreção das adipocinas independentemente do uso da Vitis vinífera. Entretanto, a dose única de polifenóis pode reduzir o risco cardiometabólico proveniente da oxidação da LDL (-)

Stochastic resonance in single-mode semiconductor lasers

Owing to the considerable virtues of semiconductor lasers for applications, they have become the main optical source for fiber communication systems recently. The behavior of stochastic resonance (SR) in direct-modulated semiconductor laser systems is investigated in this article. Considering the carrier and photon noises and the cross-correlation between the two noises, the power spectrum of the photon density and the signal-to-noise ratio (SNR) of the modulated laser system were calculated using the linear approximation method. We found that the SR always appears in the dependence of the SNR upon the bias current density, and is strongly affected by the cross-correlation coefficient of the carrier and photon noises, the frequency of modulation signal and the photon lifetime in the laser cavity. Hence, it is promising to use the SR mechanism to enhance the SNR of direct-modulated semiconductor laser systems and improve the quality of optical communication. (c) 2006 Elsevier B.V. All rights reserved.

Stochastic resonance in quantum-well semiconductor lasers

The quantum well (QW) semiconductor lasers have become main optical sources for optical fibre communication systems because of their higher modulation speed, broader modulation bandwidth and better temperature characteristics. In order to improve the quality of direct-modulation by means of the stochastic resonance (SR) mechanism in QW semiconductor lasers, we investigate the behaviour of the SR in direct-modulated QW semiconductor laser systems. Considering the cross-correlated carrier noise and photon noise, we calculate the power spectrum of the photon density and the signal-to-noise ratio (SNR) of the direct-modulated laser system by using the linear approximation method. The results indicate that the SR always appears in the dependence of the SNR on the bias current density, and is strongly affected by the cross-correlation coefficient of the carrier and photon noises, the frequency of modulation signal, and the photon lifetime in the laser cavity.

An algorithm for total variation inpainting based on nonlinear multi-grid methods

Image inpainting refers to restoring a damaged image with missing information. The total variation (TV) inpainting model is one such method that simultaneously fills in the regions with available information from their surroundings and eliminates noises. The method works well with small narrow inpainting domains. However there remains an urgent need to develop fast iterative solvers, as the underlying problem sizes are large. In addition one needs to tackle the imbalance of results between inpainting and denoising. When the inpainting regions are thick and large, the procedure of inpainting works quite slowly and usually requires a significant number of iterations and leads inevitably to oversmoothing in the outside of the inpainting domain. To overcome these difficulties, we propose a solution for TV inpainting method based on the nonlinear multi-grid algorithm.