RIS-assisted near-field localization using practical phase shift model.

Our research focuses on examining the problem of localizing user equipment (UE) in the uplink scenario using reconfigurable intelligent surfaces (RIS) based lens. We carry out a thorough analysis of the Fisher information matrix (FIM) and assess the influence of various RIS-based lens configurations using an actual RIS phase-dependent amplitude variations model. Furthermore, to reduce the complexity of the maximum likelihood (ML) estimator, a simple localization algorithm-based angular expansion is presented. Simulation results show superior localization performance when prior location information is available for directional and positional channel configurations. The position error bound (PEB) and the root mean square error (RMSE) are studied to evaluate the localization accuracy of the user utilizing the realistic RIS phase-dependent amplitude model in the near-field region. Furthermore, the achievable data rate is obtained in the same region using the realistic RIS phase-dependent amplitude model. It is noticed that adopting the actual RIS phase-dependent amplitude model under the near-field channel increases the localization error and degrades the data rate performance for amplitude value less than one so, the unity assumption of the RIS phase shift model used widely in the literature is inaccurate.

Configuring reconfigurable intelligent surfaces using a practical codebook approach.

It is proven that the scattering, reflection, and refraction properties of electromagnetic signals can be adapted and managed by using reconfigurable intelligent surfaces (RISs). In this paper, we have investigated the performance of a single-input-single-output (SISO) wideband system in terms of achievable data rate by optimizing the phases of RIS elements and performing a fair power allocation for each subcarrier over the entire bandwidth. A new beamforming codebook is developed from which the maximizing signal-to-noise (SNR) configuration is selected. The channel state information (CSI) along with the selected maximizing SNR configuration is then used by the proposed power algorithm to obtain the optimal configuration of the RIS. To validate our proposed method, it is compared with state-of-the-art semidefinite relaxation (SDR) scheme in terms of performance, complexity and run-time consumption. Our method shows dramatically lower computational complexity than the SDR method and achieves an order of 2.5 increase in the achievable data rate with an optimized RIS compared with an un-configured surface.

Plant reproduction: Stigma receptors regulate reactive oxygen species to establish pollination barriers.

Exciting new research highlights how stigmatic receptors purposed for recognizing self-incompatible pollen interact with the FERONIA pathway to regulate stigmatic reactive oxygen species production to enforce a barrier against self-, intra- and interspecific pollen.

Impact of Tree Cover Loss on Carbon Emission: A Learning-Based Analysis.

Describing the processes leading to deforestation is essential for the development and implementation of the forest policies. In this work, two different learning models were developed in order to identify the best possible model for the assessment of the deforestation causes and trends. We developed autoregressive integrated moving average (ARIMA) model and long short-term memory (LSTM) independently in order to see the trend between tree cover loss and carbon dioxide emission. This study includes the twenty-year data of Pakistan on tree cover loss and carbon emission from the Global Forest Watch (GFW) platform, a known platform to get numerical data. Minimum mean absolute error (MAE) for the prediction of tree cover loss and carbon emission obtained through ARIMA model is 0.89 and 0.95, respectively. The minimum MAE given by LSTM model is 0.33 and 0.43, respectively. There is no such kind of study conducted in order to identify the increase in carbon emission due to tree cover loss most specifically in Pakistan. The results endorsed that one of the main causes of increase in the pollution in the environment in terms of carbon emission is due to tree cover loss.

In Silico and In Vivo Evaluation of Synthesized SCP-2 Inhibiting Compounds on Life Table Parameters of Helicoverpa armigera (Hübner).

For environment-friendly, safe and nonpersistent chemical control of a significant polyphagous insect pest, Helicoverpa armigera, discovery of growth-regulating xenobiotics can offer a sustainable alternative to conventional insecticides. For this purpose, chemically synthesized compounds to inhibit sterol carrier protein (SCP-2) function using in silico and in vivo assays were evaluated to estimate their impact on the survivals and lifetable indices of H. armigera. From nine chemically synthesized compounds, OA-02, OA-06 and OA-09 were selected for this study based on binding poses mimicking cholesterol, a natural substrate of sterol carrier protein and molecular dynamics simulations. In vivo bioassays revealed that all compounds significantly reduced the larval and pupal weight accumulations and stadia lengths. Subsequently, the pupal periods were prolonged upon treatment with higher doses of the selected compounds. Moreover, OA-09 significantly reduced pupation and adult emergence rates as well as the fertility of female moths; however, fecundity remained unaffected, in general. The life table parameters of H. armigera were significantly reduced when treated with OA-09 at higher doses. The population treated with 450 µM of OA-09 had the least net reproductive rates (Ro) and gross reproductive rate (GRR) compared to the control population. The same compound resulted in a declining survival during the early stages of development coupled with reduced larval and pupal durations, and fertility. These results have a significant implication for developing an effective and sustainable chemical treatment against H. armigera infestation.

Supramolecular solvent-based liquid phase extraction of antimony prior to spectrophotometric quantification.

Antimony (Sb) is highly hazardous to human health even in minute concentration. Therefore, its accurate and precise determination in the real environmental samples is of immense importance. In this work for the first time, UV-Vis spectrophotometric method was developed for the quantification of Sb(III) from water samples using supramolecular solvent (undecanol-tetrahydrofuran)-based extraction. The maximum absorption wavelength for antomony-diathizone complex was found to be 590 nm having molar absorptivity of 3.1 × 104 L.mol.cm-1. Factors affecting extraction efficiency like solution sample volume, amount of chelating agent, pH, matrix effect, and type and volume of supramolecular solvent were determined and optimized. Analytical parameters like limit of detection (0.19 µg L-1), limit of quantification (0.62 µg L-1), pre-concentration factor (15), enhancement factor (15), and relative standard deviation for 8 successive analysis (0.8%) were calculated under optimized experimental conditions. The method was applied to real water samples like tap water of laboratory, waste water from Kohat hospitals, and dam water (Tanda dam Kohat) with quantitative addition recovery (94-100%).

Identification of Arabidopsis Protein Kinases That Harbor Functional Type 1 Peroxisomal Targeting Signals.

Peroxisomes are eukaryotic specific organelles that perform diverse metabolic functions including fatty acid ß-oxidation, reactive species metabolism, photorespiration, and responses to stress. However, the potential regulation of these functions by post-translational modifications, including protein phosphorylation, has had limited study. Recently, we identified and catalogued a large number of peroxisomal phosphorylated proteins, implicating the presence of protein kinases in this organelle. Here, we employed available prediction models coupled with sequence conservation analysis to identify 31 protein kinases from the Arabidopsis kinome (all protein kinases) that contain a putative, non-canonical peroxisomal targeting signal type 1 (PTS1). From this, twelve C-terminal domain-PTS1s were demonstrated to be functional in vivo, targeting enhanced yellow fluorescent protein to peroxisomes, increasing the list of presumptive peroxisomal protein kinases to nineteen. Of the twelve protein kinases with functional PTS1s, we obtained full length clones for eight and demonstrated that seven target to peroxisomes in vivo. Screening homozygous mutants of the presumptive nineteen protein kinases revealed one candidate (GPK1) that harbors a sugar-dependence phenotype, suggesting it is involved in regulating peroxisomal fatty acid ß-oxidation. These results present new opportunities for investigating the regulation of peroxisome functions.

Use of abbreviations in consent forms for orthopaedic surgery: A pilot study.

BACKGROUND: Consent is a process of communication and the consent form is an important legal document of the evidence of discussion between doctor and patients. We observed frequent use of abbreviations in the consent forms in our department that can result in misunderstanding and miscommunication when consenting patients for orthopaedic procedures. METHODS: We completed an audit cycle starting by reviewing a total of 350 consent forms retrospectively in level one trauma centres in October-November of 2019 for different orthopaedic trauma procedures. The standards for the project were guidelines published by the general medical council (GMC), The royal college of surgeons (RCS) Glasgow, and the British orthopaedic association (BOA).The results were presented at our mortality and morbidity meeting. Written Feedback was obtained from the attending members on how a change can be implemented to increase ccompliance in filling consent forms. A generic email was sent to all medical professionals to avoid the use of abbreviations on the document and encourage colleagues to point out errors if they spot them. The use of full medical terms and to avoid abbreviations in consent form was well advertised, The re-audit was performed for the period of January & February 2020 that included 400 consent forms. The results were analysed and compared with our original audit results. RESULTS: The use of abbreviations declined from 54% in first audit to 22% in the re-audit. DVT and PE were the most common abbreviations. CONCLUSION: This audit cycle has shown the importance of education and reminders to the health professionals in achieving better adherence to the guidelines and improves patient care.

Comparison of Medial Parapatellar and Transpatellar Tendon Approach in Intramedullary Interlocking Nailing for Tibial Fracture: A Retrospective Analysis.

Introduction Tibial fractures are one of the most common traumatic fractures, particularly in automobile accidents. Percutaneous reduction with conventional reduction forceps and un reamed intramedullary nailing, transpatellar, and medial parapatellar tendon approaches are all used, but tibial intramedullary nails are still primarily inserted through a transpatellar tendon splitting or medial parapatellar tendon approach. Objective The aim and objectives of this study are to assess the mean pain score after nailing for a tibial fracture using a medial parapatellar versus a transpatellar tendon method retrospectively in order to enhance operational planning. Materials and methods This is a retrospective study that took place in a UK level 1 trauma center. Data from 60 patients were included between February 2019 and February 2020. An equal number of patients were selected for both approaches to maintain accuracy. The advanced trauma life support (ATLS) protocol was used to handle all of the patients in both groups in order to rule out any other injuries or fractures, after which they were scheduled for surgery after stabilization. They were subsequently evaluated during a three-month follow-up in an outdoor clinic, where they were given a pain score using the visual analogue score (VAS) while moving their knee joints. The mean pain score was differentiated by age, gender, body mass index (BMI), injury side, and injury type. Results Patients were divided into groups based on their ages. Patients in the transpatellar tendon group were 32.83±5.13 years old, whereas those in the medial parapatellar tendon group were 31.4 ±5.42 years old. The gender distribution of the patients revealed that the majority of the patients in both groups were male. In both groups, the left side was the most usually affected. The difference between the two groups' mean pain scores at three months was substantially lower in the medial parapatellar approach (p=0.005). Conclusion For patients having intramedullary nailing for tibial fractures, the medial parapatellar route is associated with a lower mean pain score than the transpatellar route. As a result, we may use this method in these individuals regularly.

Ankle syndesmotic injury: Tightrope vs screw fixation, A clinical academic survey.

OBJECTIVE: The goal of the study is to find out the treatment of choice for ankle fractures involving syndesmotic injury based on level of experience of orthopaedic surgeons. METHODS: A survey was undertaken to analyse the management used for ankle fractures with syndesmotic injuries AO 44c in a 35-year-old patient. Surgeons attending an orthopaedic course were invited to take part in a survey sorted into groups: junior surgeons middle grades, and experienced. Pictures of an x ray were shown to the participants and treatment options were asked. RESULTS: 100 surgeons from 20 nations took part in the event. Juniors made up 39%, registrars made up 38%, and experienced doctors were 29%. Screws, were reported by 93% for syndesmosis fixation. 66% of surgeons who used screws for syndesmosis fixation favoured a single screw over two screws.3-4 cortices were virtually evenly divided in choice, with 54% preferring three and 46% preferring four cortices. Only 22% of the time did they utilise a washer with their screws. With 52% of patients, the most typical time for permitting them to weight bear was 4-6 weeks after surgery. At 1-2 months postoperatively, 34% preferred to remove the screw, and at 2-3 months postoperatively, 29% preferred to remove the screw. CONCLUSION: Data show that the majority of junior level doctors handle their patients according to AO principles. The majority prefer one 3.5 mm screw positioned between 2 and 4 cm above the ankle joint, with three cortices being somewhat preferred. Despite the lack of data to support one procedure, the majority of people remove their screws within 1-3 months.

A Study to See the Effect of Social Media Usage Among Healthcare Providers.

Purpose This study aimed to assess how healthcare professionals (HCPs) use social media to determine how it influences the quality of patient care. Materials and methods This is a cross-sectional study conducted over eight months, between August 2020 and March 2021 using a questionnaire and checked amongst investigators. Results One hundred fifty-eight participants had electronic devices and 145 (91.9%) used social media at work. 26.6% of these HCPs said they spent less than an hour on social media forums, 31% said they spent one to two hours, 28.5% said two to three hours, and 13.9% said they spent more than four hours. As compared to nurses (46%), consultants and pharmacists use social media at a much lower rate (1% for each group). Compared to junior doctors, a higher percentage of nurses (40%) said they were aware of a social media policy at their hospital (8%). A quarter of healthcare employees (20%) were unaware of their workplace policy, potentially exposing sensitive medical details to the public. More research is needed to assess the particular effects of these results on patient care quality and can help in providing literature informing applications encrypted and secure patient data. Conclusion According to our results, a large percentage of healthcare quality professionals used social media networks. A significant proportion of doctors and nurses use it to visit online medical forums for improving education. A large portion of surveyed sample was unaware of hospital policy on social media usage. Further education is required to improve the right use of social media in the hospital setting.

Total knee replacement: A comparison of the subvastus and medial parapatellar approaches.

OBJECTIVE: The goal of this study is to compare the subvastus method to the usual medial parapatellar technique for total knee replacement in patients with osteoarthritis who present to a tertiary care centre, based on quadriceps function recovery in days after surgery. MATERIALS AND METHODS: We retrospectively reviewed case notes of 76 patients with osteoarthritis who had total knee replacements in a tertiary care hospital over the course of a year from August 2019 to August 2020. We divided them into two groups: group A received TKR via the subvastus approach, and group B received TKR via the medial parapatellar approach. Preoperative quadriceps strength, BMI, and baseline demographics were all recorded from their initial pre-operative workup case notes. Starting on the first postoperative day, patients recorded first unassisted straight leg raise (SLR) was kept as the main determinant for muscle function. The data were evaluated to determine the quadriceps muscle function post TKR. RESULTS: When compared to the medial parapatellar approach, the quadriceps muscle function returns sooner with the subvastus technique. Patients in their sixties showed the highest improvement. Preoperative quadriceps strength has a major impact on muscle recovery after surgery. CONCLUSION: The subvastus method to total knee replacement is linked to a faster recovery of quadriceps muscle strength, resulting in a shorter hospital stay and postoperative therapy.

Cisplatin's potential for type 2 diabetes repositioning by inhibiting CDKN1A, FAS, and SESN1.

Cisplatin is a DNA-damaging chemotherapeutic agent used for treating cancer. Based on cDNA dataset analysis, we investigated how cisplatin modified gene expression and observed cisplatin-induced dysregulation and system-level variations relating to insulin resistance and type 2 diabetes mellitus (T2DM). T2DM is a multifactorial disease affecting 462 million people in the world, and drug-induced T2DM is a serious issue. To understand this etiology, we designed an integrative, system-level study to identify associations between cisplatin-induced differentially expressed genes (DEGs) and T2DM. From a list of differential expressed genes, cisplatin downregulated the cyclin-dependent kinase inhibitor 1 (CDKN1A), tumor necrosis factor (FAS), and sestrin-1 (SESN1) genes responsible for modifying signaling pathways, including the p53, JAK-STAT, FOXO, MAPK, mTOR, P13-AKT, Toll-like receptor (TLR), adipocytokine, and insulin signaling pathways. These enriched pathways were expressively associated with the disease. We observed significant gene signatures, including SMAD3, IRS, PDK1, PRKAA1, AKT, SOS, RAS, GRB2, MEK1/2, and ERK, interacting with source genes. This study revealed the value of system genetics for identifying the cisplatin-induced genetic variants responsible for the progression of T2DM. Also, by cross-validating gene expression data for T2DM islets, we found that downregulating IRS and PRK families is critical in insulin and T2DM signaling pathways. Cisplatin, by inhibiting CDKN1A, FAS, and SESN1, promotes IRS and PRK activity in a similar way to rosiglitazone (a popular drug used for T2DM treatment). Our integrative, network-based approach can help in understanding the drug-induced pathophysiological mechanisms of diabetes.

Genome-wide quantitative trait loci mapping on Verticillium wilt resistance in 300 chromosome segment substitution lines from Gossypium hirsutum × Gossypium barbadense.

Cotton Verticillium wilt (VW) is a devastating disease seriously affecting fiber yield and quality, and the most effective and economical prevention measure at present is selection and extension of Gossypium varieties harboring high resistance to VW. However, multiple attempts to improve the VW resistance of the most widely cultivated upland cottons have made little significant progress. The introduction of chromosome segment substitution lines (CSSLs) provide the practical solutions for merging the superior genes related with high yield and wide adaptation from Gossypium hirsutum and VW resistance and the excellent fiber quality from Gossypium barbadense. In this study, 300 CSSLs were chosen from the developed BC5F3:5 CSSLs constructed from CCRI36 (G. hirsutum) and Hai1 (G. barbadense) to conduct quantitative trait locus (QTL) mapping of VW resistance, and a total of 40 QTL relevant to VW disease index (DI) were identified. Phenotypic data were obtained from a 2-year investigation in two fields with two replications per year. All the QTL were distributed on 21 chromosomes, with phenotypic variation of 1.05%-10.52%, and 21 stable QTL were consistent in at least two environments. Based on a meta-analysis, 34 novel QTL were identified, while 6 loci were consistent with previously identified QTL. Meanwhile, 70 QTL hotspot regions were detected, including 44 novel regions. This study concentrates on QTL identification and screening for hotspot regions related with VW in the 300 CSSLs, and the results lay a solid foundation not only for revealing the genetic and molecular mechanisms of VW resistance but also for further fine mapping, gene cloning and molecular designing in breeding programs for resistant cotton varieties.

Dual Band and Dual Diversity Four-Element MIMO Dipole for 5G Handsets.

The increasing popularity of using wireless devices to handle routine tasks has increased the demand for incorporating multiple-input-multiple-output (MIMO) technology to utilize limited bandwidth efficiently. The presence of comparatively large space at the base station (BS) makes it straightforward to exploit the MIMO technology's useful properties. From a mobile handset point of view, and limited space at the mobile handset, complex procedures are required to increase the number of active antenna elements. In this paper, to address such type of issues, a four-element MIMO dual band, dual diversity, dipole antenna has been proposed for 5G-enabled handsets. The proposed antenna design relies on space diversity as well as pattern diversity to provide an acceptable MIMO performance. The proposed dipole antenna simultaneously operates at 3.6 and 4.7 sub-6 GHz bands. The usefulness of the proposed 4×4 MIMO dipole antenna has been verified by comparing the simulated and measured results using a fabricated version of the proposed antenna. A specific absorption rate (SAR) analysis has been carried out using CST Voxel (a heterogeneous biological human head) model, which shows maximum SAR value for 10 g of head tissue is well below the permitted value of 2.0 W/kg. The total efficiency of each antenna element in this structure is -2.88, -3.12, -1.92 and -2.45 dB at 3.6 GHz, while at 4.7 GHz are -1.61, -2.19, -1.72 and -1.18 dB respectively. The isolation, envelope correlation coefficient (ECC) between the adjacent ports and the loss in capacity is below the standard margin, making the structure appropriate for MIMO applications. The effect of handgrip and the housing box on the total antenna efficiency is analyzed, and only 5% variation is observed, which results from careful placement of antenna elements.

Stigma Receptivity Is Controlled by Functionally Redundant MAPK Pathway Components in Arabidopsis.

In angiosperms, the process of pollination relies on species-specific interaction and signaling between the male (pollen) and female (pistil) counterparts where the interplay between several pollen and stigma proteins decides the fate of the pollen. In Brassicaceae, the dry stigmatic papillary cells control pollen germination by releasing resources only to compatible pollen thereby allowing pollen to hydrate and germinate. Despite the identification of a number of stigmatic proteins that facilitate pollination responses, the signaling mechanisms that regulate functions of these proteins have remained unknown. Here, we show that, in Arabidopsis, an extremely functionally redundant mitogen-activated protein kinase (MAPK) cascade is required for maintaining stigma receptivity to accept compatible pollen. Our genetic analyses demonstrate that in stigmas, five MAPK kinases (MKKs), MKK1/2/3/7/9 are required to transmit upstream signals to two MPKs, MPK3/4, to mediate compatible pollination. Compromised functions of these five MKKs in the quintuple mutant (mkk1/2/3RNAi/mkk7/9) phenocopied pollination defects observed in the mpk4RNAi/mpk3 double mutant. We further show that this MAPK nexus converges on Exo70A1, a previously identified stigma receptivity factor essential for pollination. Given that pollination is the crucial initial step during plant reproduction, understanding the mechanisms that govern successful pollination could lead to development of strategies to improve crop yield.

Effects of zinc oxide nanoparticles on regulatory appetite and heat stress protein genes in broiler chickens subjected to heat stress.

This study was conducted to explore the effect of the zinc oxide nanoparticles (ZnONPs) supplement on the regulatory appetite and heat stress (HS) genes in broiler chickens raised under high or normal ambient temperatures. In this study, 240 one-day-old male broiler chicks (Cobb 500) were randomly assigned to 48 battery cages. From day 1, these 48 cages were randomly subjected to four different treatment strategies: Control (wherein, their basal diet included 60 mg/kg of ZnO), ZNONPs 40 (wherein basal diet included 40 mg/kg of ZnONPs), ZnONPs 60 (basal diet included 60 mg/kg of ZnONPs), and ZnONPs 100 (basal diet included 100 mg/kg of ZnONPs). Thereafter, from day 22 to 42, the chickens from each dietary treatment group were subjected to different temperature stresses either normal (23 ± 1 °C constant) or HS (34 ± 1 °C for 6 h/d), which divided them into eight different treatment groups. Our findings revealed that dietary ZnONPs altered the gene expression of cholecystokinin (ileum), heat stress proteins (HSP) 70 (jejunum and ileum), and HSP 90 (duodenum, jejunum, and ileum). The gene expression of ghrelin was affected by the interaction between the ZnONPs concentration and temperature in the duodenum and stomach. More studies are required to elucidate its complex physiological and biochemical functions of the regulation of gene expression within the intestine in heat-stressed broiler chickens.

Clinicopathological Characteristics and Short-Term Survival Analyses of Cutaneous Malignant Melanoma.

Objective Cutaneous malignant melanoma (CMM) arises from melanocytes, which are pigment-producing cells in the skin. CMM constitutes less than 5% of all cutaneous malignancies worldwide but is associated with the highest mortality rate among all skin cancers. The objective of this study was to examine the profile of clinicopathological factors, survival analyses, recurrence rate, metastatic rates, and the management of CMM at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan. Methodology All patients with a diagnosis of CMM treated at our institute from 2014 to 2017 were included in the study. Demographic variables and clinicopathological characteristics were collected and short-term oncological outcomes were recorded. All data were entered and analyzed in SPSS Statistics version 21 (IBM, Armonk, NY). Results A total of 28 patients were included in the study. The median age of the patients was 46.5 ±15.9 years. There were 16 male and 12 female patients. A family history of melanoma was present in 7.1% (n=2) of the patients. All patients had a mean survival of 13.43 ±9.09 months. The lower limb was the most common site of tumor among all patients, accounting for 46.4% (n=13) of the cases. On histopathological analyses, ulceration was seen in 53.6% (n=15) of the patients. Unclassified tumor type was present in 75% (n=21) of the patients, followed by nodular in 21.4% (n=6), and superficial spreading in 3.5% (n=1). Clark level IV was the most common presentation, constituting 46.4% (n=13) of the cases. Metastasis was seen in 50% (n=14) of the patients. Local recurrence was observed in 60.7% (n=17) of the patients; 64.3% (n=18) of the patients were alive after one year of treatment. Conclusion CMM is a disease with very high fatality rates. Although it is a disease commonly associated with fair-skinned populations, the incidence of CMM is rising in our part of the world as well. Early diagnosis and prompt management of the disease are crucial in its treatment. However, the mortality rate associated with this disease is still not favorable.

Identification and characterization of a female gametophyte defect in sdk1-7 +/- abi3-6 +/- heterozygotes of Arabidopsis thaliana.

Successful reproduction in angiosperms is dependent on the highly synchronous development of their male and female gametophytes and the ensuing fusion of the gametes from these reproductive tissue types. When crossing a T-DNA insertion line sdk1-7-/-(Salk_024564), one of the S-domain receptor kinases involved in ABA responses with a fast neutron deletion line abi3-6-/-, the F1 heterozygotes (sdk1-7+/-abi3-6 +/-) displayed 50% ovule abortion suggesting a likely gametophytic defects. We identified and characterized an early stage female gametophyte developmental defect in the heterozygous mutant ovules. Recombination frequency analysis of the F2 progenies from selfed heterozygotes revealed a possible pseudo-linkage of sdk1-7 and abi3-6 suggesting a reciprocal translocation event in the heterozygote. Our study emphasizes the importance of robust analysis to distinguish gametophytic defect phenotypes caused by genetic interactions and that resulting from possible chromosomal translocation events.

Polyvalent therapeutic vaccine for type 2 diabetes mellitus: Immunoinformatics approach to study co-stimulation of cytokines and GLUT1 receptors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide disease that have an impact on individuals of all ages causing micro and macro vascular impairments due to hyperglycemic internal environment. For ultimate treatment to cure T2DM, association of diabetes with immune components provides a strong basis for immunotherapies and vaccines developments that could stimulate the immune cells to minimize the insulin resistance and initiate gluconeogenesis through an insulin independent route. METHODOLOGY: Immunoinformatics based approach was used to design a polyvalent vaccine for T2DM that involved data accession, antigenicity analysis, T-cell epitopes prediction, conservation and proteasomal evaluation, functional annotation, interactomic and in silico binding affinity analysis. RESULTS: We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) Class-I molecules for immune activation to control T2DM. We found 13-epitopes of 9 amino acid residues for multiple alleles of MHC class-I bears significant binding affinity. The downstream signaling resulted by T-cell activation is directly regulated by the molecular weight, amino acid properties and affinity of these epitopes. Each epitope has important percentile rank with significant ANN IC50 values. These high score potential epitopes were linked using AAY, EAAAK linkers and HBHA adjuvant to generate T-cell polyvalent vaccine with a molecular weight of 35.6 kDa containing 322 amino acids residues. In silico analysis of polyvalent construct showed the significant binding affinity (- 15.34 Kcal/mol) with MHC Class-I. This interaction would help to understand our hypothesis, potential activation of T-cells and stimulatory factor of cytokines and GLUT1 receptors. CONCLUSION: Our system-level immunoinformatics approach is suitable for designing potential polyvalent therapeutic vaccine candidates for T2DM by reducing hyperglycemia and enhancing metabolic activities through the immune system.