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Inflammation plays an important role in the pathogenesis of diabetic retinopathy (DR). To precisely define the inflammatory mediators, we examined the transcriptomic profile of human retinal endothelial cells exposed to advanced glycation end products, which revealed the neutrophil chemoattractant chemokine CXCL1 as one of the top genes upregulated. The effect of neutrophils in the alteration of the blood-retinal barrier (BRB) was further assessed in wild-type C57BL/6J mice intravitreally injected with recombinant CXCL1 as well as in streptozotocin-induced diabetic mice. Both intravitreally CXCL1-injected and diabetic animals showed significantly increased retinal vascular permeability, with significant increase in infiltration of neutrophils and monocytes in retinas and increased expression of chemokines and their receptors, proteases, and adhesion molecules. Treatment with Ly6G antibody for neutrophil depletion in both diabetic mice as well as CXCL1-injected animals showed significantly decreased retinal vascular permeability accompanied by decreased infiltration of neutrophils and monocytes and decreased expression of cytokines and proteases. CXCL1 level was significantly increased in the serum samples of patients with DR compared with samples of those without diabetes. These data reveal a novel mechanism by which the chemokine CXCL1, through neutrophil recruitment, alters the BRB in DR and, thus, serves as a potential novel therapeutic target. Article Highlights Intravitreal CXCL1 injection and diabetes result in increased retinal vascular permeability with neutrophil and monocyte recruitment. Ly6G antibody treatment for neutrophil depletion in both animal models showed decreased retinal permeability and decreased cytokine expression. CXCL1 is produced by retinal endothelial cells, pericytes, and astrocytes. CXCL1 level is significantly increased in serum samples of patients with diabetic retinopathy. CXCL1, through neutrophil recruitment, alters the blood-retinal barrier in diabetic retinopathy and, thus, may be used as a therapeutic target.

The C-terminal stretch in SbGPRP1 (Sorghum glycine-rich proline-rich protein) acts as an antimicrobial peptide in the host innate defense mechanism. Cationic antimicrobial proteins or peptides can either bind to the bacterial membrane or target a specific protein on the bacterial membrane thus leading to membrane perturbation. The 197 amino acid polypeptide of SbGPRP1 showed disordered structure at the N-terminal end and ordered conformation at the C-terminal end. In the present study, the expression of N-SbGPRP1, C-SbGPRP1, and ∆SbGPRP1 followed by antimicrobial assays showed potential antimicrobial property of the C-terminal peptide against gram-positive bacteria Bacillus subtilis and phytopathogen Rhodococcus fascians. The SbGPRP1 protein loses its antimicrobial property when the 23 amino acid sequence (GHGGHGVFGGGYGHGGYGHGYGG) from position 136 to 158 is deleted from the protein. Thus, it can be concluded that the 23 amino acid sequence is vital for the said antimicrobial property. NPN assay, SEM analysis, and electrolyte leakage assays showed potent antimicrobial activity for C-SbGPRP1. Overexpression of the C-SbGPRP1 mutant protein in tobacco followed by infection with Rhodococcus fascians inhibited bacterial growth as shown by SEM analysis. To determine if C-SbGPRP1 might target any protein on the bacterial membrane we isolated the bacterial membrane protein from both Bacillus subtilis and Rhodococcus fascians. Bacterial membrane protein that interacted with the column-bound C-SbGPRP1 was eluted and subjected to LC-MS/MS. LC-MS/MS data analysis showed peptide hit with membrane protein YszA from Bacillus subtilis and a membrane protein from Rhodococcus fascians. Isolated bacterial membrane protein from Bacillus subtilis or Rhodococcus fascians was able to reduce the antimicrobial activity of C-SbGPRP1. Furthermore, BiFC experiments showed interactions between C-SbGPRP1 and YszA protein from Bacillus subtilis leading to the conclusion that bacterial membrane protein was targeted in such membrane perturbation leading to antimicrobial activity.

Nijmegen breakage syndrome 1 (NBS1) protein is a core member of the MRE11-RAD50-NBS1 (MRN) complex that plays a crucial role in DNA damage sensing and repair in plants. Here we report that NBS1 from moss Physcomitrium patens reduces oxidative damage by lowering the cellular ROS in addition to its known role in oxidative DNA damage recovery. Real-time transcript analysis showed up-regulation of the PpNBS1 transcript under different stress conditions. Bacterial cells showed better cell survivability upon over-expressing PpNBS1 protein as compared to untransformed cells. Likewise, overexpression of PpNBS1 in tobacco plants provides improved protection against oxidative damage and exhibited a lesser amount of ROS upon exposure to oxidative stress. Moreover, PpNBS1 contributes to the antioxidant defense mechanism by positively regulating the expression of the antioxidant genes under stress conditions in transgenic tobacco plants. PpNBS1 expressing transgenic tobacco plants resulted in lesser membrane damage, lower lipid peroxidation level, and higher chlorophyll content under stress conditions. Taken together, we conclude in addition to its known role as DNA damage sensor, PpNBS1 also plays a definite role in oxidative stress mitigation by minimizing ROS accumulation in the cell.

Red Serow Capricornis rubidus is an elusive herbivore native to the montane forests of the Himalaya. Currently it is categorized as ‘Vulnerable’ in the IUCN Red List and placed under Schedule I species of the Wildlife Protection Act, 1972. A serow was presented with complaints of mild inappetence, irritability, sporadic scratching of head over the enclosure barrier and serous ocular discharge from the left eye. Based on detail clinical examination, the animal was diagnosed with unilateral conjunctivitis, corneal oedema, and ulcerative keratitis. A combination of Xylazine @ 1.5mg/ kg body weight and Zolatile® (zolazepam and tiletamine) @ 2.5 mg/kg body weight was used to chemically restrain the animal, followed by auriculo-palpebral nerve block using 1 ml of 2 % lignocaine hydrochloride. The affected eye was adequately cleaned with isotonic sterile Normal Saline solution (NSS). Combination of 0.5 ml of ceftriaxone and 0.5 ml of flubiprofen was injected into upper and lower palpebral conjunctiva. The cornea and the third eyelid flap were carefully sutured using 5-0 and 3-0 Vicryl, respectively. Finally, tarsorrhaphy was done using 2-0 nylon. Post-operative care consisted of an antibiotic regimen of Cephalaxin @ 20 mg/ kg body weight b-i.d-twice in a day for seven days along with probiotic supplement (Vizylac®) and Vitamin A capsules (Aquasol A®) orally once daily for the next 30 days. The animal showed complete recovery within 30 days of proper treatment, monitoring, care and management.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Building resilient and sustainable cities in the face of rising climate change have captured the attention of the research community as well as decision-makers. Despite the sizable quantum of research on different aspects of urban resilience, the physical form of cities has received little attention from researchers. Another difficulty lies in generalizing these studies in varying settings and heterogeneous contexts. This study investigates different tools and frameworks proposed for assessing urban form resilience. The literature analysis has been done based on attribute selection, study context, methodology, and resilience perspective. Additionally, the applicability of these frameworks in the context of the Global South has been investigated. The result shows fragmentation in the selection of attributes, approaches, and perspectives in the literature assessing urban form resilience. Also, there are conflicting arguments regarding the influence of urban form attributes on urban resilience, i.e., density and city size. Apart from that, the study highlights the complications of imbibing these assessment frameworks in the distinct urban morphology of cities of the Global South, where informal development prevails. This study can help researchers and planners understand the relationship between resilience and urban morphology and utilize these concepts for assessing urban form resilience, particularly in the context of the Global South.

Though long-lived nanobubbles (NBs) have been reported by multiple researchers, the underlying reason behind their stability is still obscure. Some of the conjectured reasons include diffusive shielding, the presence of surface charges, and stability due to contamination. Still, the stability of NBs against coalescence and Ostwald ripening is not confirmed. Using molecular dynamics simulations, the present study aims to understand the stabilization effects due to diffusive shielding and the presence of an electrical double layer at the surface of NBs. Accumulation of charges on NBs for different concentrations of ions is discussed. Also, the collision of equal-sized NBs with different approach velocities and offset distances is simulated. A regime map is predicted on the basis of initial approach velocity and offset distance. The transition in regime obtained upon increasing the offset distance is discussed, which differs from the collision characteristics of macroscopic bubbles and drops. The merging of NBs is initiated through the bridge formation, for which the temporal evolution rate along with the scaling argument is presented. The stress terms involved and the corresponding regimes are predicted based on the fluid properties. For all the cases where merging is observed, the estimated probability is observed to be low, which suggests the stability of NBs against coalescence.

Objectives: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to five years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation or anti-VEGF injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. Methods: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of six months to four years. Early onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. Results: In unadjusted models, individuals with EDR (n=484) had an increased subsequent risk of PDR (hazard ratio HR=1.51, 95%CI [1.12,2.02], P=0.006), CSME (HR=1.44, [1.10,1.88], P=0.008) and diabetes-related retinal photocoagulation (HR=1.48, [1.12,1.96], P=0.006) compared to individuals without EDR (n=369). These associations remained significant adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and eGFR (HR=1.47, [1.04,2.06], P=0.028). Conclusions: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

The R2R3 type MYB transcription factors participate in controlling flavonoid production in plants, including anthocyanin and proanthocyanin. Black rice with high anthocyanin content is an important candidate for understanding R2R3-MYB-based regulation of the anthocyanin biosynthesis pathway (ABP). This study was undertaken to draw the functional relationship of an R2R3-MYB protein with anthocyanin biosynthesis and oxidative stress tolerance in plants. The expression levels of the late ABP genes in the panicle stage of black rice were in good agreement with the accumulation of anthocyanin, especially cyanidin 3-glucoside. Among all MYB genes present in rice, an R2R3 type (C1) regulates anthocyanin biosynthesis and was studied further. The positive correlation between the expression of ABP genes and OsC1 along with the nuclear localization of OsC1 are in line with its possible involvement as a transcriptional regulator of ABP genes. Interestingly, OsC1 overexpressed in white rice plants triggered anthocyanin production through augmentation of the transcript level of late ABP genes. Moreover, OsC1-transformed plants exhibited a lower amount of reactive oxygen species upon exposure to oxidative stress. The increased anthocyanin content in white rice seedlings resulted in higher photosynthetic efficiency, less membrane damage and consequently lower oxidative stress. The OsC1 transcriptional regulator helps to ameliorate oxidative stresses in plants owing to its anthocyanin modulating ability.

To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals.Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes.In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028).These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

Background: Congestive heart failure (CHF) is common disorder of dogs that occur most frequently as a result of Dilated Cardiomyopathy (DCM), Degenerative Mitral Valve Disease and pericardial diseases. An early diagnosis can be carried out through the use of specific diagnostic techniques such as x-rays, echocardiography etc. The goal of this study was to see if dogs with CHF go through any substantial alterations in their hematology or serum biochemistry. Methods: The current investigation was conducted during the period April, 2020 to April 2021 at Veterinary Clinical Complex, Khanapara, Assam. Thirty four (n=34) dogs with CHF confirmed by echocardiography and eight (n=8) healthy dogs were considered for the study. Blood samples from all selected dogs were subjected to routine hematological and serum biochemical examination. Result: The hematological assessment revealed no significant alterations. During the course of the study, there were significant alterations in the serum biochemical parameters viz. LDH, BUN, creatinine, AST, ALT, total serum protein, albumin and albumin: globulin ratio. Findings of the study revealed that hematology and biochemistry were more useful in ruling out CHF or in identifying concurrent diseases than diagnosing CHF itself.

Given India’s urbanization rate, economic growth, and population size, a rise in private vehicle ownership appears inevitable. Residential parking in particular remains a sizable by-product with fa...

Purpose To determine the relationship between refractive error and diabetic retinopathy (DR). Design Clinical trial. Participants Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. Methods Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤−0.5, >−0.5 and Main Outcome Measures For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. Results Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05–1.59), 3-step progression (HR, 1.35; 95% CI, 1.05–1.73), and PDR (HR, 1.40; 95% CI, 1.02–1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03–1.58; 3-step progression: HR, 1.30; 95% CI, 1.00–1.68; PDR: HR, 1.38; 95% CI, 1.00–1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00–1.24) in the adjusted models. Conclusions Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

The integration of renewable energy sources with active thermal power plants contributes to the green environment all over the globe. To achieve maximum reliability and sustainability of the renewable-thermal hybrid system, plentiful constraints need to be considered for minimizing the situation, which creates due to the unpredictable nature of renewable energy. In wind integrated deregulated system, wind farms need to submit the power generation scenario for future days to Independent System Operator (ISO) before the date of operation. Based on their submitted bid, ISO scheduled the power generation from different generating stations, including thermal and renewable. Due to the uncertain nature of the wind flow, there is always a chance of not fulfilling the scheduling amount of power from the wind farm. This violation in the market can impose an economic burden (i.e., imbalance cost) on the generating companies. The solar photovoltaic cell can be used to decrease the adverse economic effects of unpredicted wind saturation in the deregulated system. This paper presents consistent, competent, and effective operating schemes for the hybrid operation of solar PV and wind farms to maximize the economic profit by minimizing the imbalance cost, which occurs due to the mismatch between the actual and predicted wind speed. Modified IEEE 14-bus and modified IEEE 30-bus test systems have been used to check the usefulness of the proposed approach. Three optimization techniques (i.e., Sequential Quadratic Programming (SQP), Smart Flower Optimization Algorithm (SFOA), Honey Badger Algorithm (HBA)) have been used in this work for the comparative study. Bus Loading Factor (BLF) has been proposed here to identify the most sensitive bus in the system, used to place wind farms. The SFOA and HBA optimization technique has been used first time in this type of economic assessment problem, which is the novelty of this paper. The Bus Loading Factor (BLF) has been introduced here to identify the most sensitive bus in the system. After implementing the work, it has been seen that the operation of the solar PV system has reduced the adverse effect of imbalance cost on the renewable integrated deregulated power system.

Power system networks are becoming more complex and decentralized with the foreword of deregulation in the global power sector. In this scenario, an independent system operator (ISO) is responsible for determining the appropriate actions to deliver stable and quality power to the customers connected to the network at the lowest cost without violating the system security limits. Violations of any security limit may result in system risk. The unstable and non-reliable system always has some drawbacks and is not desirable from the consumer’s point of view. A deregulated power market always keeps the consumer on the advantage side by giving stable, reliable, and less costly power. By using risk assessment tools, we identify the fault conditions and we try to minimize the risk by various uses of sequential programming methods. In this paper, a novel power system risk analysis and congestion management approach are introduced with considering meta-heuristic algorithms i.e., Slime Mould Algorithm (SMA) and Artificial Bee Colony Algorithm (ABC) in renewable energy integrated electricity market. The proposed power system risk analysis is constructed with the help of two risk valuation tools named Conditional-Value-at-risk (CVaR) and Value-at-risk (VaR). The higher negative value of VaR and CVaR represents the higher risk system and lower negative value or towards a positive value of VaR and CVaR denotes the less risk or stable system. The projected method has been experienced on the IEEE 14-bus test system and IEEE 30-bus test system to examine the usefulness of the meta-heuristic algorithm in system risk analysis under the deregulated environment. The importance of renewable energy integration in system risk curtailment has also been depicted in this work: basically, to measure the system’s risk, hence enhancing the system’s reliability and societal welfare. As a result, it will benefit both supply and demand-side participants.

Plants are unavoidably exposed to a range of environmental stress factors throughout their life. In addition to the external environmental factors, the production of reactive oxygen species as a product of the cellular metabolic process often causes DNA damage and thus affects genome stability. Homologous recombination (HR) is an essential mechanism used for DNA damage repair that helps to maintain genome integrity. Here we report that the recombinase, PpRecA2, a bacterial RecA homolog from mossThe online version contains supplementary material available at 10.1007/s12298-022-01264-7.

Deregulation leads to a change of power system structure with the involvement of private market players and through strengthening the customer part in the pooled electrical market. It creates a competitive market platform, where the main trade product is electricity. This competitive market model is mainly classified as a single auction model and a double auction model. In a single auction model, the electricity market is cleared by conducting competition among the suppliers with single customers, and the customer does not know which generators succeeded to sell their power. But in the double auction model, it allows multiple suppliers and multiple buyers to clear the market, and market participants do not know which generators and customers succeeded to sell and buy the power. Suppliers optimally scheduled their generations under those market environments in order to maximize the profits. In this competitive environment, calculation of market clearing price (MCP) is one of the most significant approaches for both the suppliers and buyer in order to maximize their benefit. This paper presents the optimal market clearing strategy considering double auction competitive power market. For optimal scheduling of generators, artificial bee colony (ABC) and ant lion optimizer (ALO) algorithms are used over IEEE 30 bus system here.

Sorghum glycine rich proline rich protein (SbGPRP1) exhibit antimicrobial properties and play a crucial role during biotic stress condition. Several proteins in plants build up the innate immune response system in plants which get triggered during the occurrence of biotic stress. Here we report the functional characterization of a glycine-rich proline-rich protein (SbGPRP1) from Sorghum which was previously demonstrated to be involved in abiotic stresses. Expression studies carried out with SbGPRP1 showed induced expression upon application of phytohormones like salicylic acid which might be the key in fine-tuning the expression level. Upon challenging the Sorghum plants with a compatible pathogen the SbGprp1 transcript was found to be upregulated. SbGPRP1 encodes a 197 amino acid polypeptide which was bacterially-expressed and purified for in vitro assays. Gram-positive bacteria like Bacillus and phytopathogen Rhodococcus fascians showed inhibited growth in the presence of the protein. The NPN assay, electrolytic leakage and SEM analysis showed membrane damage in bacterial cells. Ectopic expression of SbGPRP1 in tobacco plants led to enhanced tolerance towards infection caused by R. fascians. Though the N-terminal part of the protein showed disorderness the C-terminal end was quite capable of forming several α-helices which was correlated with CD spectroscopic analysis. Here, we have tried to determine the structural model for the protein and predicted the association of antimicrobial activity with the C-terminal region of the protein.

OBJECTIVE The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy reduced the development and progression of retinopathy in type 1 diabetes (T1D) compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications (EDIC) study observational follow-up showed persistent benefits. In addition to glycemia, we now examine other potential retinopathy risk factors (modifiable and nonmodifiable) over more than 30 years of follow-up in DCCT/EDIC. RESEARCH DESIGN AND METHODS The retinopathy outcomes were proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and ocular surgery. The survival (event-free) probability was estimated using the Kaplan-Meier method. Cox proportional hazards models assessed the association between risk factors and subsequent risk of retinopathy. Both forward- and backward-selection approaches determined the multivariable models. RESULTS Rate of ocular events per 1,000 person-years was 12 for PDR, 14.5 for CSME, and 7.6 for ocular surgeries. Approximately 65%, 60%, and 70% of participants remained free of PDR, CSME, and ocular surgery, respectively. The greatest risk factors for PDR in descending order were higher mean HbA1c, longer duration of T1D, elevated albumin excretion rate (AER), and higher mean diastolic blood pressure (DBP). For CSME, risk factors, in descending order, were higher mean HbA1c, longer duration of T1D, and greater age and DBP and, for ocular surgeries, were higher mean HbA1c, older age, and longer duration of T1D. CONCLUSIONS Mean HbA1c was the strongest risk factor for the progression of retinopathy. Although glycemic control is important, elevated AER and DBP were other modifiable risk factors associated with the progression of retinopathy.

Electricity demand is sharply increasing with the growing population of human beings. Due to financial, social, and political barriers, there are lots of difficulties when building new thermal power plants and transmission lines. To solve this problem, renewable energy sources and flexible AC transmission systems (FACTS) can operate together in a power network. Renewable energy sources can provide additional power to the grid, whereas FACTS devices can increase the thermal limit of existing transmission lines. It is always desirable for an electrical network to operate under stable and secure conditions. The system runs at risk if any abnormality occurs in the generation, transmission, or distribution sections. This paper outlines a strategy for reducing system risks via the optimal operation of wind farms and FACTS devices. Here, a thyristor-controlled series compensator (TCSC) and a unified power flow controller (UPFC) have both been considered for differing the thermal limit of transmission lines. The impact of the wind farm, as well as the combined effect of the wind farm and FACTS devices on system economy, were investigated in this work. Both regulated and deregulated environments have been chosen to verify the proposed approach. Value at risk (VaR) and cumulative value at risk (CVaR) calculations were used to evaluate the system risk. The work was performed on modified IEEE 14 bus and modified IEEE 30-bus systems. A comparative study was carried out using different optimization techniques, i.e., Artificial Gorilla Troops Optimizer Algorithm (AGTO), Honey Badger Algorithm (HBA), and Sequential Quadratic Programming (SQP) to check the effect of renewable integration in the regulated and deregulated power systems in terms of system risk and operating cost.

Plants use a diverse set of proteins to mitigate various abiotic stresses. The intrinsically disordered protein dehydrin is an important member of this repertoire of proteins, characterized by a canonical amphipathic K-segment. It can also contain other stress-mitigating noncanonical segments—a likely reflection of the extremely diverse nature of abiotic stress encountered by plants. Among plants, the poikilohydric mosses have no inbuilt mechanism to prevent desiccation and therefore are likely to contain unique noncanonical stress-responsive motifs in their dehydrins. Here we report the recurring occurrence of a novel amphipathic helix-forming segment (D-segment: EGφφD(R/K)AKDAφ, where φ represents a hydrophobic residue) in Physcomitrella patens dehydrin (PpDHNA), a poikilohydric moss. NMR and CD spectroscopic experiments demonstrated the helix-forming tendency of the D-segment, with the shuffled D-segment as control. PpDHNA activity was shown to be size as well as D-segment dependent from in vitro, in vivo, and in planta studies using PpDHNA and various deletion mutants. Bimolecular fluorescence complementation studies showed that D-segment-mediated PpDHNA self-association is a requirement for stress abatement. The D-segment was also found to occur in two rehydrin proteins from Syntrichia ruralis, another poikilohydric plant like P. patens. Multiple occurrences of the D-segment in poikilohydric plant dehydrins/rehydrins, along with the experimental demonstration of the role of D-segment in stress abatement, implies that the D-segment mediates unique resurrection strategies, which may be employed by plant dehydrins that are capable of mitigating extreme stress.

Our world is developing very fast. This fast paced development needs a lot of energy. Our conventional, non-renewable sources are not enough to satisfy this huge demand. Extensive use of non-renewable sources is primarily responsible for environmental degradation. So we need to look for renewable resources like solar, wind etc. We should also explore applicability of renewable energy in different sectors like industrial, agricultural etc. Indian agricultural sector is gigantic. It comprises 26% of national GDP. So developing smart technologies to enhance crop production is extremely necessary for national prosperity. Solar radiation is primary source of energy for the plants. Plants generate energy from solar radiation through photo synthesis. Hence solar radiation plays a vital role in crop production cycle. So prediction of solar radiation data can be highly beneficial for farmers in optimizing crop production cycle. Our paper has the purpose of predicting solar radiation data and assisting farmers in enhancing crop production with the help of analyzed solar radiation data. This system is achieved using an IoT based approach followed by applying machine learning algorithm on the data obtained to predict the solar radiation and hence improve the crop production cycle based on this. The proposed system will offer great help towards agro-economic progress of a country.

An ever growing world population means an ever increasing energy demand. Our non-renewable energy sources are depleting fast. Excessive use of fossil fuels has led towards environmental problems like global warming, Greenhouse effect. Many Countries around the world are still dependent on fossil fuels because renewable sources cannot cater huge energy demand. The world is exploring renewable energy sources to develop technologies in order to enhance energy production capability of these sources. Solar energy is one of the most promising renewable sources that are currently being used worldwide to contribute for meeting rising demands of electric power. Solar power is a conversion of sunlight into electricity using photovoltaic devices. Solar Energy Measurement is very essential in harvesting energy in solar radiation. It is necessary for feasibility analysis of an solar power plant in order to know the suitable location for installing it. Internet of Things provides a smart platform to manage these alternative energy resources since remote monitoring can be done easily and the data can be accessed anywhere in the world over the internet. This paper incorporates a smart system which displays all the parameters of a solar panel by using multiple sensors connected to an Arduino. Using, IoT the data is monitored continuously and then this data is used for predicting feasibility of a site for generation of solar power to determine the suitable site location from which the data is fetched. The proposed system offers great portability and can be very beneficial to choose sites for generation of solar power.

Selective pericyte loss, the histological hallmark of early diabetic retinopathy (DR), enhances the breakdown of the blood-retinal barrier (BRB) in diabetes. However, the role of pericytes on BRB alteration in diabetes and the signaling pathways involved in their effects are currently unknown. To understand the role of diabetes-induced molecular alteration of pericytes, we performed transcriptomic analysis of sorted retinal pericytes from mice model of diabetes. Retinal tissue from non-diabetic and diabetic (duration 3 months) mouse eyes (n = 10 in each group) were used to isolate pericytes through fluorescent activated cell sorting (FACS) using pericyte specific fluorescent antibodies, PDGFRb-APC. For RNA sequencing and qPCR analysis, a cDNA library was generated using template switching oligo and the resulting libraries were sequenced using paired-end Illumina sequencing. Molecular functional pathways were analyzed using differentially expressed genes (DEGs). Differential expression analysis revealed 217 genes significantly upregulated and 495 genes downregulated, in pericytes isolated from diabetic animals. These analyses revealed a core set of differentially expressed genes that could potentially contribute to the pericyte dysfunction in diabetes and highlighted the pattern of functional connectivity between key candidate genes and blood retinal barrier alteration mechanisms. The top up-regulated gene list included: Ext2, B3gat3, Gpc6, Pip5k1c and Pten and down-regulated genes included: Notch3, Xbp1, Gpc4, Atp1a2 and AKT3. Out of these genes, we further validated one of the down regulated genes, Notch 3 and its role in BRB alteration in diabetic retinopathy. We confirmed the downregulation of Notch3 expression in human retinal pericytes exposed to Advanced Glycation End-products (AGEs) treatment mimicking the chronic hyperglycemia effect. Exploration of pericyte-conditioned media demonstrated that loss of NOTCH3 in pericyte led to increased permeability of endothelial cell monolayers. Collectively, we identify a role for NOTCH3 in pericyte dysfunction in diabetes. Further validation of other DEGs to identify cell specific molecular change through whole transcriptomic approach in diabetic retina will provide novel insight into the pathogenesis of DR and novel therapeutic targets.

OBJECTIVE: Determine relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial SUBJECTS: Myopia is a non-modifiable risk factor reportedly associated with less severe DR in small case series, but this association has not been confirmed in large prospective studies. With a large cohort of patients with type I diabetes followed over 30 years with serial refractive error and DR stage measurements, the Diabetes Control and Complications Trial and follow-up Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC) provide a unique opportunity to evaluate the association between refractive error and DR development and progression. METHODS: DR stage was measured every six months from standard fundus photographs and refractive error was measured annually during the 6.5 years of DCCT, then both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. DR outcomes were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME) or ocular surgery. Myopia, emmetropia and hyperopia were defined as a spherical equivalent of ≤ −0.5, > −0.5 and < 0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazards models assessed the association between refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with higher risk of 2-step progression (hazard ratio (HR)=1.29, 95%CI 1.05–1.59), 3-step progression (HR=1.35, 95%CI 1.05–1.73) and PDR (HR=1.40, 95%CI 1.02–1.92) compared to emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressure, pulse, LDL, HDL, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated HbA1c (2-step progression: HR=1.28, 95%CI 1.03–1.58; 3-step progression: HR=1.30, 95%CI 1.00–1.68; PDR: HR=1.38, 95%CI 1.00–1.90). Myopia was not associated with any of the five DR outcomes in the unadjusted models, and only marginally associated with 2-step progression (HR=1.11, 95%CI 1.00–1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Although there is strong clinical evidence that the control of blood glucose, blood pressure, and lipid level can prevent and slow down the progression of diabetic retinopathy (DR) as shown by landmark clinical trials, it has been shown that these factors only account for 10% of the risk for developing this disease. This suggests that other factors, such as genetics, may play a role in the development and progression of DR. Clinical evidence shows that some diabetics, despite the long duration of their diabetes (25 years or more) do not show any sign of DR or show minimal non-proliferative diabetic retinopathy (NPDR). Similarly, not all diabetics develop proliferative diabetic retinopathy (PDR). So far, linkage analysis, candidate gene studies, and genome-wide association studies (GWAS) have not produced any statistically significant results. We recently initiated a genomics study, the Diabetic Retinopathy Genetics (DRGen) Study, to examine the contribution of rare and common variants in the development of different phenotypes of DR, as well as their responsiveness to anti-VEGF treatment in diabetic macular edema (DME). Our preliminary findings reveal a novel set of genetic variants involved in the angiogenesis and inflammatory pathways that contribute to DR progression or protection. Further investigation of variants can help to develop novel biomarkers and lead to new therapeutic targets in DR.

PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P