Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.

PurposeTo redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD).MethodsWe present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1).ResultsThe sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD.ConclusionsWe have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD

Factors which influence the cardiac surgeon's decision not to operate on patients referred for consideration of surgery

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to document what proportion of patients referred for consideration of cardiac surgery are turned down, the reasons given for not operating and also to evaluate what happens to those patients who do not undergo surgery.</p> <p>Methods</p> <p>382 elective patients referred for consideration of cardiac surgery to one of six consultant cardiac surgeons at Wythenshawe Hospital during a one year period from were included in the study. Data for those patients who underwent an operation were collected prospectively in a cardiac surgery database. The case notes of those patients who did not undergo an operation were reviewed to establish reasons given by surgeons for not operating. Patients were followed up to determine vital status at the end of the study period.</p> <p>Results</p> <p>333 (87.2%) patients underwent an operation and 49 (12.8%) did not. 68% of patients turned down were thought to be too high-risk. 14% of patients did not fulfill symptomatic or prognostic criteria for surgery and in 8% of patients coronary artery surgery was thought ineffective due to poor distal vessels. 6% of patients declined an operation and 4% were thought to be more suitable for coronary angioplasty. Patients turned down for surgery had more renal dysfunction (p = 0.017), respiratory disease (p < 0.001) and peripheral vascular disease (p < 0.001), were more likely to have undergone prior heart surgery (p < 0.001) and to have poor left ventricular function (p = 0.003). Patients turned down for surgery had significantly higher EuroSCORE values compared to patients who underwent an operation: 5 versus 4 (p = 0.006). Freedom from death in the patients turned down for surgery at 1-, 6-, 12- and 24-months was 95.9%, 91.8%, 83.7% and 71.4% respectively, compared with 97.9%, 96.7%, 96.4% and 94.5% for the patients who underwent an operation (p < 0.001 [log-rank]). 14 of the 15 deaths that occurred in the turned down group occurred in the category considered too high-risk for surgery.</p> <p>Conclusion</p> <p>12.8% of patients referred for consideration of cardiac surgery did not undergo an operation. Two thirds of patients not accepted for surgery were thought too high risk. Those patients who did not undergo an operation had a significantly worse mortality.</p

Transfer Learning based Automated Essay Summarization

The human evaluation of essays has become a very time-consuming process as the number of schools and universities has grown. The available software entities are unable to assess the sentiment associated with essays. Thus, we propose a model using Natural Language Processing to assess the essay based on both grammar and sentiment associated with the essay by using linear regression and ULMFiT (Universal Language Model Fine-tuning for Text Classification) models.&nbsp; Evaluation of essay is done in two parts. Part one is on essay grading with respect to grammar with maximum 12 and minimum 0 grade points and in part two score of 0/1 for sentiment analysis with 0 being negative and 1 being positive. The model can be used to score the essay and discard any essay with a score less than a specified value or specified sentiment score

GENERATING OF POWER THROUGH WHEELS AND SOLAR WITH SMART LIGHTING SYSTEM

My concept is about an innovative idea on wheel power which is a useful source of energy and can be stored and used. Lacks of vehicles like Motorcycles and Trains, cars all run on wheels daily. Whenever a vehicle moves its wheels rotates and generate some energy unless until we stop the vehicle. Since now nobody has thought to use this idle energy to produce energy. This idea is developed to generated energy from the moving wheels of the vehicle &amp; stores it in a battery. So dynamos are installed to the  front wheels of the vehicle to generate the energy from the moving wheels which is turn rotates the motor that generates power and stored in battery and used for automatic lighting system. In addition to this wheel power, solar panel is also placed to generate power for sun and is used for moment of vehicle and wheel power is used for smart lighting system to the vehicle. The concept mentioned is aimed to design and implement generate power from moving wheels and automatic lighting system for automobiles by which the vehicle can be protected by avoiding collision with other vehicl

Efficiency Improvement of a Plant Layout

Abstract: Facilities layout is a systematic and functional arrangement of different departments, machines, equipments and services in a manufacturing industry. It is essential to have a well developed plant layout for all the available resources in an optimum manner and get the maximum out of the capacity of the facilities. The efficiency of production depends on how well the various machines, services production facilities and employee&apos;s amenities are located in a plant. This research paper aims to study and improve the current plant layout and are analysed &amp; designed by using string diagram. An Attempt is made to simulate the current and proposed factory layout by using ARENA software. Efficiency of the current &amp; proposed plant layout are calculated

Genetic diversity and evolution of human metapneumovirus fusion protein over twenty years

<p>Abstract</p> <p>Background</p> <p>Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in children. We examined the diversity and molecular evolution of HMPV using 85 full-length F (fusion) gene sequences collected over a 20-year period.</p> <p>Results</p> <p>The F gene sequences fell into two major groups, each with two subgroups, which exhibited a mean of 96% identity by predicted amino acid sequences. Amino acid identity within and between subgroups was higher than nucleotide identity, suggesting structural or functional constraints on F protein diversity. There was minimal progressive drift over time, and the genetic lineages were stable over the 20-year period. Several canonical amino acid differences discriminated between major subgroups, and polymorphic variations tended to cluster in discrete regions. The estimated rate of mutation was 7.12 × 10^-4substitutions/site/year and the estimated time to most recent common HMPV ancestor was 97 years (95% likelihood range 66-194 years). Analysis suggested that HMPV diverged from avian metapneumovirus type C (AMPV-C) 269 years ago (95% likelihood range 106-382 years).</p> <p>Conclusion</p> <p>HMPV F protein remains conserved over decades. HMPV appears to have diverged from AMPV-C fairly recently.</p

Manual on Edible Oyster and Green Mussel Farming कालवं आणि काकई संवर्धन तंत्र प्रशिक्षण पुस्तिका

Manual on Edible Oyster and Green Mussel Farming कालवं आणि काकई संवर्धन तंत्र प्रशिक्षण पुस्तिका (Marathi Version

Plasma glial fibrillary acidic protein is associated with 18F-SMBT-1 PET: Two putative astrocyte reactivity biomarkers for Alzheimer\u27s disease

Background: Astrocyte reactivity is an early event along the Alzheimer\u27s disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD. Objective: The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers. Methods: Plasma GFAP and Aβ were measured using the Simoa® platform in participants who underwent brain 18F-SMBT-1 and Aβ-PET imaging, comprising 54 healthy control (13 Aβ-PET+ and 41 Aβ-PET-), 11 mild cognitively impaired (3 Aβ-PET+ and 8 Aβ-PET-) and 6 probable AD (5 Aβ-PET+ and 1 Aβ-PET-) individuals. Linear regressions were used to assess associations of interest. Results: Plasma GFAP was associated with 18F-SMBT-1 signal in brain regions prone to early Aβ deposition in AD, such as the supramarginal gyrus (SG), posterior cingulate (PC), lateral temporal (LT) and lateral occipital cortex (LO). After adjusting for age, sex, APOE ɛ4 genotype, and soluble Aβ (plasma Aβ42/40 ratio), plasma GFAP was associated with 18F-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE ɛ4 genotype and insoluble Aβ (Aβ-PET), plasma GFAP was associated with 18F-SMBT-1 signal in the SG. Conclusion: There is an association between plasma GFAP and regional 18F-SMBT-1 PET, and this association appears to be dependent on brain Aβ load