Glaucoma is characterized by a slow and progressive degeneration of the optic nerve, including retinal ganglion cell (RGC) axons in the optic nerve head (ONH), leading to visual impairment. Despite its high prevalence, the biological basis of glaucoma pathogenesis still is not yet fully understood, and the factors contributing to its progression are currently not well characterized. Intraocular pressure (IOP) is the only modifiable risk factor, and reduction of IOP is the standard treatment for glaucoma. However, lowering IOP itself is not always effective for preserving visual function in patients with primary open-angle glaucoma. The second messenger cyclic adenosine 3',5'-monophosphate (cAMP) regulates numerous biological processes in the central nervous system including the retina and the optic nerve. Although recent studies revealed that cAMP generated by adenylyl cyclases (ACs) is important in regulating aqueous humor dynamics in ocular tissues, such as the ciliary body and trabecular meshwork, as well as cell death and growth in the retina and optic nerve, the functional role and significance of cAMP in glaucoma remain to be elucidated. In this review, we will discuss the functional role of cAMP in aqueous humor dynamics and IOP regulation, and review the current medications, which are related to the cAMP signaling pathway, for glaucoma treatment. Also, we will further focus on cAMP signaling in RGC growth and regeneration by soluble AC as well as ONH astrocytes by transmembrane ACs to understand its potential role in the pathogenesis of glaucoma neurodegeneration.
Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.
Damages to buildings affected by a near-fault strong ground motion are largely attributed to the vertical component of the earthquake resulting in column failures, which could lead to disproportionate building catastrophic collapse in a progressive fashion. Recently, considerable interests are awakening to study effects of earthquake vertical components on structural responses. In this study, detailed modeling and time-history analyses of a 12-story code-conforming reinforced concrete moment frame building carrying the gravity loads, and exposed to once only the horizontal component of, and second time simultaneously the horizontal and vertical components of an ensemble of far-field and near-field earthquakes are conducted. Structural responses inclusive of tension, compression and its fluctuations in columns, the ratio of shear demand to capacity in columns and peak mid-span moment demand in beams are compared with and without the presence of the vertical component of earthquake records. The influences of the existence of earthquake vertical component in both exterior and interior spans are separately studied. Thereafter, the correlation between the increase of demands induced by the vertical component of the earthquake and the ratio of a set of earthquake record characteristic parameters is investigated. It is shown that uplift initiation and the magnitude of tensile forces developed in corner columns are relatively more critical. Presence of vertical component of earthquake leads to a drop in minimum compressive force and initiation of tension in columns. The magnitude of this reduction in the most critical case is recorded on average 84% under near-fault ground motions. Besides, the presence of earthquake vertical components increases the shear capacity required in columns, which is at most 31%. In the best case, a direct correlation of 95% between the increase of the maximum compressive force and the ratio of vertical to horizontal 'effective peak acceleration (EPA)' is observed.
This investigation was undertaken in order to elicit the relationship between the extent of ultrafiltration processing of whey and its effect on composition and yield of resultant whey protein concentrate (WPC). Cheddar cheese whey was fractionated through ultrafiltration to an extent of 70, 80, 90, 95, 97.5% and 97.5% volume reduction followed by I stage and II stage diafiltration. After each level of ultrafiltration, the composition of WPC was monitored. Similarly, the initial whey was adjusted to 3.0, 6.2 and 7.0 pH levels and ultrafiltration was carried out to elicit the effect of pH of ultrafiltration on the composition. Further, initial whey was adjusted to different levels of whey protein content ranging from 0.5 to 1.0 per cent and subjected to ultrafiltration to different levels. The various range of retentate obtained were further condensed and spray dried in order to assess the yield of WPC per unit volume of whey used and the quantity of whey required to produce unit weight of product. With the progress of ultrafiltration, there was a progressive increase in protein content and decrease in lactose and ash content. The regression study led to good relationships with $R^2$ values of more than 0.95 between the extents of permeate removed and the resultant changes in composition of each of the constituents. Whey processed at pH 3.0 had significantly a very low ash content and high protein content as compared to processing at 6.2 and 7.0. The yield of WPC per unit volume of whey varied significantly with the initial protein content. Higher initial protein content led to higher yield of all ranges of WPC and the quantity of whey required per unit weight of spray dried WPC significantly reduced. Regression equations establishing the relationship between initial protein content of whey and the yield of various types of WPC have been derived with very high $R^2$ values of 0.99. This study revealed that, the yield and composition of whey can be monitored strictly by controlling the processing parameters and WPC can be produced depending on the food formulation requirement.
Bayraktar, Alemdar;Altunisik, Ahmet Can;Muvafik, Murat
Smart Structures and Systems
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제14권3호
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pp.479-499
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2014
This paper illustrates the damages of reinforced concrete and masonry minarets during October 23 (Erciş) and November 9 (Edremit), 2011 Van earthquakes in Turkey. Erciş and Edremit are townships located 90km and 18km from Van city center in Turkey, respectively. Ground accelerations and response spectrums for these earthquakes are given in this paper. A total of 63 reinforced concrete and masonry minarets are heavily damaged or collapsed in the city center and villages nearby after both earthquakes. Because of the fact that there is no Turkish standard and specification directly related to design of minarets, nearly all of the constructions are carried out by workers using only their own technical knowledge. So, all of the non-engineering reinforced concrete and masonry minarets completely collapsed or damaged heavily. From the study, it is seen that the damages are due to several reasons such as site effect, location, and length of the fault, reduction in cross section and formation of the discontinuity, use of plain reinforcement steel, use of concrete with insufficient strength, existence of short lap splices and incorrect end hook angle, larger mass and stiffness concentrations on some region, longitudinal reinforcements discontinuity, cracks at the cylindrical body, and damage of spire and end ornament. In addition to these reasons, the two earthquakes hit the minarets within seventeen days, causing progressive damage. So, the existing design and construction practices should be improved to provide sufficient earthquake performance. Also, it is recommended that there should be a safe distance between the minaret and surrounding structures to reduce the loose of life after earthquake.
Cervical pain is a rapid increase that is owing to a flexion-extension whiplash injury, unappropriated posture, chronical repetition injury from abdominal position of head and neck, excessive repeating work, chronical deficiency of excercise. Because of that is bring about muscle unbalance, tightness of cervical extensor muscle, weakness of cervical deep flexor muscles, instability of cervical region and reduction of proprioceptive sensor. Recent the role of muscle is more emphasized for preservation of sine stabilization. And cognition of integrated muscular system, importance for the operation and relation is increased to maintain stability of the motor system and pertinent function. Therefore we are going to introduce the sling exercise and stabilization exercise method for advanced efficient of cervical and upper limb and for the muscle strengthening to importance cervical stabilization through neurological program as control the reaction of cervical stabilization. Sling exercise therapy(SET) concept consists of a system of diagnosis and treatment. The system of diagnosis involves testing the muscle's tolerance through progressive loading in open and close kinetic chains. The SET system contains elements such as relaxation, increasing the range of movement, traction, training the stabilizing musculature, sensory-motor exercises, training in open and close kinetic chains, dynamic training of the mobilizing musculature, cardiovascular exercise, group exercise, personal exercise at home Sensory-motor training is an essential element of the SET concept. The emphasis is on closed kinetic chain exercise on an unstable surface, there by achieving optimum stimulation of the sensory-motor apparatus.
Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was long-acting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction ($FEV_1$, $FEV_1/FVC$). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.
Kwon, Soon-Chul;Piyush K. Dutta;Kim, Yun-Hae;Anido, Roberto-Lopez
Journal of Mechanical Science and Technology
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제17권1호
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pp.1-10
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2003
This paper summarizes the results of the fatigue test of four composite bridge decks in extreme temperatures (-30$^{\circ}C$ and 50$^{\circ}C$ ). The work was performed as part of a research program to evaluate and install multiple FRP bridge deck systems in Dayton, Ohio. A two-span continuous concrete deck was also built on three steel girders for the benchmark tests. Simulated wheel loads were applied simultaneously at two points by two servo-controlled hydraulic actuators specially designed and fabricated to perform under extreme temperatures. Each deck was initially subjected to one million wheel load cycles at low temperature and another one million cycles at high temperature. The results presented in this paper correspond to the fatigue response of each deck for four million load cycles at low temperature and another four million cycles at high temperature. Thus, the deck was subjected to a total of ten million cycles. Quasi-static load-deflection and load-strain responses were determined at predetermined fatigue cycle levels. Except for the progressive reduction in stiffness, no significant distress was observed in any of the composite deck prototypes during ten million load cycles. The effects of extreme temperatures and accumulated load cycles on the load-deflection and load-strain response of FRP composite and FRP-concrete hybrid bridge decks are discussed based on the experimental results.
Eid, Mohamed M.;El-Kowrany, Samy I.;Othman, Ahmad A.;El Gendy, Dina I.;Saied, Eman M.
Parasites, Hosts and Diseases
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제53권1호
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pp.51-58
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2015
Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.
In this work, Fe-Pd alloy films have been electrodeposited on different substrates using an electrolyte containing $[Pd(NH_3)_4]^{2+}$ (0.02 M) and $[Fe-Citrate]^{2+}$ (0.2 M). The influences of substrate and overpotential on chemical composition, nucleation and growth kinetics as well as the electrodeposited films morphology have been investigated using energy dispersive X-ray spectroscopy (EDS), current-time transients, scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD) patterns. In all substrates - brass, copper and sputtered fluorine doped tin oxide on glass (FTO/glass) - Fe content of the electrodeposited alloys increases by increasing the overpotential. Also the cathodic current efficiency is low due to high rate of $H_2$ co-reduction. Regarding the chronoamperometry current-time transients, it has been demonstrated that the nucleation mechanism is instantaneous with a typical three dimensional (3D) diffusion-controlled growth in the case of brass and copper substrates; while for FTO, the growth mode changes to 3D progressive. At a constant overpotential, the calculated number of active nucleation sites for metallic substrates is much higher than that of FTO/glass; however by increasing the overpotential, the number of active nucleation sites increases. The SEM micrographs as well as the XRD patterns reveal the formation of Fe-Pd alloy thin films with nanostructure arrangement and ultra-fine grains.
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