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To ensure the reliability and safety of bridges, one of the main important parameter in design and health assessment is normalized displacement in critical loading condition. It is important to ensure accuracy of determination of normalized displacement in different condition. The aim of this study is to explore the dynamic response of bridge subjected to two vehicles travelling in reverse direction. Moving masses (vehicles) are assumed to start at same time with same speed, then time is delayed for one of the moving mass and then speed of both moving masses is changed. Normalized mid-span response is lesser than that for single moving mass model and highest response for two ways traffic occurs for velocity ratio 0.6. The change of dynamic behavior is remarkable with change in highest normalized mid span response for change in traffic conditions like two way traffic, change in velocity and time of start of vehicles.

Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (gamma delta T) cells and NKT cells. Tear fluid collected using Schirmer's strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and gamma delta T cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1 beta, IL-6, LIF, IL-17A, TNF alpha, IFN alpha/beta/gamma, EPO, TGF beta 1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1 alpha and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.

The study of the dynamic effect of moving mass on structures such as vehicles moving on bridges or a crane trolley moving on girder beam has become an important research area in the recent past. The problems were originally modelled as moving force problems, but later on moving mass inertia effects have been also included and recently models are further modified considering vehicles as moving oscillators. Available literatures indicate that response characteristics are mostly obtained using numerical integration. This, however, does not give qualitative insight into the dependence of critical response behaviours on the variable parameters. The present work attempts to obtain an analytical expression for the response using a novel perturbation-based method, where moving mass-to-beam mass ratio is taken as the perturbation parameter. For a typical simply supported beam, expressions are derived in polynomial series form, up to second-order term. Analytical response, although truncated after the second-order polynomial term, is found to be in good agreement with numerically integrated response. Sensitivity studies are performed with respect to two parameters: mass ratios and velocity ratios. In addition, magnitude of deflection maxima and corresponding vehicle location are investigated for different velocity ratios and it is shown that low velocity ratio around 0.2 produces minimum deflection maxima than the velocities in the higher range. This is a significant observation as in case of a suspected degradation in a bridge, vehicular velocity can be monitored near a ratio of 0.2 to have minimum deflection and stresses on the bridge structure.

Investigation of the bridge and vehicle interaction problem received an extreme significance due to difficulty of solving the resulted equations, involvement of various parameters such as velocity, mass, traffic intensity, road roughness. The effect of velocity of vehicle on the dynamic response is a key issue in these problems. The objective of this study is to evaluate the theoretical results with the experimental results. The displacement and acceleration responses are compared for healthy as well as for damaged beam. A discontinuity present in the response provides the basis for continuous evaluation method for identifying the crack presence and its location. The problem of dynamic excitation caused by vehicles moving on a bridge is investigated by developing a small scale Lab-model. A beam simply supported is considered as bridge and vehicle is modeled by a moving mass. The mid-span displacement and acceleration response of the simply supported beam are recorded using the CDAQ-card of National Instruments and signal analysis is done with LABVIEW software. It is found that with velocity of mass increasing, vibration amplitude increases but transient fluctuation reduces. A slight shift in the maxima of the response towards right is also observed with increase in velocity. The response is also investigated in presence of crack and it is observed that the amplitude of maxima increases due to crack. The results of experiments are evaluated with simulated theoretical results and it is concluded that presence of crack and its location can be effectively identified using acceleration response. A close estimate is found in the response values of simulated and experimental for the damaged beam subjected to moving mass.

βA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as βA3 and βA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that βA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of βA3/A1-crystallin in metabolism of retinal astrocytes. We found that βA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but βA3-crystallin does not. Loss of βA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited βA1-knockdown (KD) mice, but not in βA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified βA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced βA1-crystallin and higher levels of PTP1B in the vitreous humor., Ghosh et al. show that a lens protein βA1-crystallin inhibits PTP1B activity, regulating the metabolism of retinal astrocytes. They find that knockdown of βA1-crystallin exacerbates the streptozotocin-induced diabetic retinopathy-like phenotype in mice, suggesting the possibility that the interaction between βA1-PTP1B may be targeted for diabetic retinopathy.

It is important to identify the presence of damage present in the structures like bridge which undergoes the excitation due to moving vehicles. In such type of problems, modal analysis and dynamic displacement response analysis are not sufficient to portray the crack presence. The presented work emphases on the analysis of acceleration response to investigate the crack presence. A mathematical model is developed by considering the two masses with fixed distance between them traversing on the Euler–Bernoulli beam having a crack. The acceleration response analysis can be effective to present the qualitative explanation of the fault present in the beam. A key features of the acceleration response of beam having a crack includes discontinuity at the crack location which vary with change in distance between the front and rear wheel and a greater response value compare to that for healthy in the last phase of travel from the time front wheel exits the beam. However, the effectiveness of the presentation of the crack through acceleration response depends upon the fixed distance between the front and rear wheel and the bridge length. The discontinuity will be higher for the higher ratio of distance between the front and rear wheel to the bridge length.

The study of dynamic response of bridges under the action of moving vehicles provides a tool for structural designing as well as damage identification. Bridge-vehicle interaction is generally modelled through single contact point for mathematical simplicity, although the interaction actually takes place through front and rear wheels. In the present work, dynamic deflection of the bridge modelled through two contact points is investigated for a range of vehicle velocity and wheel to wheel distance. It is observed that for wheelbase to bridge span ratio greater than a certain limit, two contact point model gives significantly different results particularly at higher velocity range. The results, presented in terms of non-dimensional parameters, can be used as a design monograph for any bridge-vehicle-velocity combination.

Age-related macular degeneration (AMD) is an expanding problem as longevity increases worldwide. While inflammation clearly contributes to vision loss in AMD, the mechanism remains controversial. Here we show that neutrophils are important in this inflammatory process. In the retinas of both early AMD patients and in a mouse model with an early AMD-like phenotype, we show neutrophil infiltration. Such infiltration was confirmed experimentally using ribbon-scanning confocal microscopy (RSCM) and IFNλ− activated dye labeled normal neutrophils. With neutrophils lacking lipocalin-2 (LCN-2), infiltration was greatly reduced. Further, increased levels of IFNλ in early AMD trigger neutrophil activation and LCN-2 upregulation. LCN-2 promotes inflammation by modulating integrin β1 levels to stimulate adhesion and transmigration of activated neutrophils into the retina. We show that in the mouse model, inhibiting AKT2 neutralizes IFNλ inflammatory signals, reduces LCN-2-mediated neutrophil infiltration, and reverses early AMD-like phenotype changes. Thus, AKT2 inhibitors may have therapeutic potential in early, dry AMD., Ghosh et al. find that in a mouse model, age-related macular degeneration (AMD) is associated with retinal infiltration of neutrophils, activation of interferon lambda and production of other cytokines. They also see increased interferon lambda production in the eyes of AMD patients.

Purpose Corneal dystrophies (CD) are classified as rare eye diseases that results in visual impairment and requires corneal transplant in advanced stages. Ocular surface inflammatory status in different types of CD remains underexplored. Hence, we studied the levels of tear soluble factors in the tears of patients with various types of corneal dystrophies. Methods 17 healthy subjects and 30 CD subjects (including epithelial, stromal and endothelial CD) were included in the study. Schirmer's strips were used to collect the tear fluid in all subjects. 27 soluble factors including cytokines, chemokines, soluble cell adhesion molecules and growth factors were measured in the eluted tears by multiplex ELISA or single analyte sandwich ELISA. Results Percentages of subjects with detectable levels of tear soluble factors were significantly higher in CD compared to controls. Significant higher level of IL-2 was observed in both epithelial and stromal CD. IL-4, TGFβ1 and IgE were significantly higher in stromal CD. VCAM, IL-13 and Fractalkine were significantly elevated in epithelial and macular CD. IL-1α, IL-8, IL-12, ANG, Eotaxin, MCP1, RANTES, ICAM1, L-selectin and P-selectin were significantly higher in epithelial CD. TGFBIp was significantly elevated in lattice CD and endothelial CD. Conclusion Distinct set of the tear soluble factors were dysregulated in various types of CD. Increase in tear inflammatory factors was observed in majority of the CD subjects depending on their sub-types. This suggests a plausible role of aberrant inflammation in CD pathobiology. Hence, modulating inflammation could be a potential strategy in improving the prognosis of CD.

PURPOSE. The purpose of this study was to study the status and association among tear-soluble factors, corneal dendritic cell density, vitamin D, and signs and symptoms in dry eye disease (DED).METHODS. A total of 33 control subjects and 47 evaporative dry eye patients were included in the study. DED diagnosis and classification was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II). DED workup, including tear film break-up time (TBUT), Schirmer's test I (STI), corneal and conjunctival staining, ocular surface disease index (OSDI) scoring, and in vivo confocal microscopy (to assess corneal dendritic cell density [cDCD] and subbasal nerve plexus [SBNP] features) was performed in the study subjects. Tear fluid using Schirmer's strip and serum were collected from the subjects. Multiplex ELISA or single analyte ELISA was performed to measure 34 tear-soluble factors levels including vitamin D.RESULTS. Significantly higher OSDI discomfort score, lower TBUT, and lower STI were observed in DED patients. cDCD was significantly higher in DED patients. No significant difference was observed in SBNP features. Tear fluid IL-1 beta, IL-17A, MMP9, MMP10, MMP9/TIMP ratio, and VEGF-B were significantly higher in DED patients. Significantly lower tear fluid IL-2, IP-10, NPY, VEGF-A, and vitamin D was observed in DED patients. These dysregulated tear factors showed significant associations with DED signs and symptoms.CONCLUSIONS. Altered tear fluid soluble factors with potential to modulate nociception exhibited a distinct association with ocular surface discomfort status, TBUT, STI, and cDCD. This implies a functional relationship between the various tear-soluble factors and dry eye pathogenesis, indicating new molecular targets for designing targeted therapies.

Aims S100A8 and S100A9 are myeloid-related damage-associated molecular patterns (DAMPs) primarily involved in the modulation of innate immune response to cellular injury. This study evaluated the correlation between circulating concentrations of S100A8 and S100A9 proteins with the severity of diabetic retinopathy (DR) in patients with type 2 diabetes (T2DM). Methods T2DM patients with HbA1c levels >7%, fasting blood glucose >126 mg/dl and history of diabetes were included in this study. DR severity was graded based on ETDRS and Gloucestershire classifications. Plasma samples were evaluated for S100A8 and S100A9 levels using ELISA. Results In this comparative study, DR patients (n = 89) had increased plasma S100A8 and S100A9 proteins compared to age-matched T2DM controls (n = 28), which was directly related to the severity of DR. Female DR subjects had increased S100A8 expression compared to their male counterparts. Substantial retention of S100A8 and S100A9 production was seen in DR patients above 50 years of age. Duration of T2DM was not found to affect protein levels, however T2DM onset at >50 years old significantly increased S100A8 and S100A9 concentrations. Conclusions Our findings suggest that systemic circulation levels of S100A8 and S100A9 are correlated with the progression of DR in T2DM patients, indicating their potential role in DR pathogenesis.

In the present study, acceleration response of cracked beam is analyzed by using the wavelet transform to detect the crack presence, its location and also to predict the crack severity. The equation of motion of beam under the moving mass is solved by using the fourth order Runge–Kutta method. A code is written by expanding the equation for first three vibration modes. Acceleration signal of the damaged beam under the moving mass contains the discontinuity at the crack location. This discontinuity contained in the acceleration signal is sufficiently visible but it is very small for some signals. Therefore, the acceleration signals are transformed using the wavelet analysis. A wavelet coefficient peak occurs at the location of discontinuity, so that we can identify the crack presence and its location. From the value of wavelet coefficient peak, we can also predict the crack effect with respect to the change in velocity of moving mass and change in crack depth. The main advantage of this method is that the wavelet coefficient peak is sufficiently higher even for the higher velocities and small size crack.