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The present study employs the S/N ratio and multiple regression analysis to evaluate the mechanical properties of laterized concrete with fly ash and steel fiber. The study considers compressive, split tensile, and flexural strengths as responses at 7 and 28 days. The Taguchi L16 (4 *4) orthogonal array experimental design is applied to optimize the performance of mechanical properties of concrete by using the design of experiments. The replacement of 25% of the granite aggregate with laterite aggregate resulted in a 12.44% increase in the strength of M30-grade concrete after 28 days. The composite's compressive strength decreases when the replacement level exceeds 25%. The split tensile and flexural strengths of the composite showed an increase of 14.54% and 16.93%, respectively, compared to the control mix. Furthermore, the test outcomes for durability factors like drying shrinkage and rapid chloride penetration in steel fiber reinforced fly ash-based lateritic concrete mixes with a 50% replacement rate adhere to the prescribed standards, verifying their designed performance over the designated structural lifespan. However, after multiple regression analysis, it is found that the error related to the correlation between experimental and analytical value strength is about 5%. Microstructural studies of the ideal mix were performed at 28 days to further understand the morphology of the laterized concrete containing fly ash and steel fiber.

Abstract Background Tubulins are highly conserved globular proteins involved in stabilization of cellular cytoskeletal microtubules during cell cycle. Different isoforms of tubulins are differentially expressed in various cell types, and their protein–protein interactions (PPIs) analysis will help in identifying the anti-microtubular drug targets for cancer and neurological disorders. Numerous web-based PPIs analysis methods are recently being used, and in this paper, I used Gene Ontology (GO) tools, e.g., Stringbase, ProteomeHD, GeneMANIA, and ShinyGO, to identify anti-microtubular target proteins by selecting strongly interacting proteins of tubulins. Results I used 6 different human tubulin isoforms (two from each of α-, β-, and γ-tubulin) and found several thousands of node-to-node protein interactions (highest 4956 in GeneMANIA) and selected top 10 strongly interacting node-to-node interactions with highest score, which included 7 tubulin family protein and 6 non-tubulin family proteins (total 13). Functional enrichment analysis indicated a significant role of these 13 proteins in nucleation, polymerization or depolymerization of microtubules, membrane tethering and docking, dorsal root ganglion development, mitotic cycle, and cytoskeletal organization. I found γ-tubulins (TUBG1, TUBGCP4, and TUBBGCP6) were known to contribute majorly for tubulin-associated functions followed by α-tubulin (TUBA1A) and β-tubulins (TUBB AND TUBB3). In PPI results, I found several non-tubular proteins interacting with tubulins, and six of them (HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41) were found closely associated with their functions. Conclusions Increasing number of regulatory proteins and subpopulation of tubulin proteins are being reported with poor understanding in their association with microtubule assembly and disassembly. The functional enrichment analysis of tubulin isoforms using recent GO tools resulted in identification of γ-tubulins playing a key role in microtubule functions and observed non-tubulin family of proteins HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41 strongly interacting functional proteins of tubulins. The present study yields a promising model system using GO tools to narrow down tubulin-associated proteins as a drug target in cancer, Alzheimer’s, neurological disorders, etc.

A sustainable method to reduce the use of natural resources and the negative effects of the concrete industry on the environment is to use waste lateritic aggregate in self-compacting concrete and evaluate its fresh, mechanical and durability characteristics. Using RSM's central composite design (CCD), Thirteen different SCC mixtures have been designed with varying input factor combinations (LA: 0–100%, PPF: 0–2%) and tested for eight responses (rheological properties, like slump flow, V-funnel time, and T500; mechanical properties, like compressive, split-tensile, and flexural strengths, and durability properties like drying shrinkage and rapid chloride penetration test). The analysis of variance (ANOVA) test was performed to determine the accuracy of the mathematical models developed following the experimental results. ANOVA was used to verify eight response models (seven quadratic and one linear). The inclusion of laterite aggregate has been found to linearly reduce the workability of fresh concrete. Self-compacting concrete will have a lower V-funnel value if any combination of components falls below these two limit values (31% LA and 1.12% PPF). The area bounded by the 760-mm contour line and the graph axes recorded the highest slump flow at (28% LA and 1.26% PPF). Similarly, SCC with a lower T500 value will be produced by any combination of components below these two limit values (25% LA and 1.11% PPF). By replacing 28.5% of the granite aggregate with laterite aggregate and adding 1.24% polypropylene fiber, the compressive strength of M30 grade self-compacting concrete increased by 12.33% after 28 days. A similar strength gain of 7.89% was seen in the splitting tensile by replacing 28% of the granite aggregate with laterite aggregate and adding 1.46% polypropylene fiber over the control mix, and a flexural strength gain of 14.46% was seen by replacing 31.4% of laterite aggregate and adding 1.2% polypropylene fiber, respectively. The low drying shrinkage values are related to a combination of LA concentration (34.4% replacement) and PPF (1.31%) and minimum chloride ingress is located in the region with a LA concentration (30.5% replacement) and a PPF content (1.26%), The projected optimal data were verified experimentally with an error rate of less than 5%. Thus, it is highly recommended that the created model be adequate and capable of optimizing both the experimental and analytical values. It is recommended that the utilization of 25% LA and 1% PPF in lateritic self-compacting concrete provides optimum outcomes for the construction industry in the field of civil engineering.

The ionosphere is a region of the upper atmosphere where free electrons and ions are created by solar radiation. An effort is made to study the solar radiation influence on the earth's ionosphere's total electron content (TEC) across the low latitude Indian subcontinent from January to October 2022. TEC readings were obtained using GNSS receivers over Bengaluru (13.021 °N, 77.570 °E) and Hyderabad (17.417 °N, 78.551 °E). Ionospheric TEC variations are studied by measuring the degree to which satellite-sent GPS signals are disrupted. The results were compared with geomagnetic measurements such as disturbed storm time (Dst) index and planetary K-index (Kp) and analyzed with TEC anomalies during geomagnetic storms, and the results may be used to estimate the magnetic field of the Earth. The study revealed that ionospheric storms had an advantageous impact in January, March, and April of 2022, but a negative effect in July 2022.

Inconel 718 is a hard-to-machine alloy with very poor machinability and low thermal conductivity. Machining of such alloy is a critical manufacturing issue that should be carefully controlled to obtain machined components with acceptable accuracy and surface integrity. In this paper, hybrid machine learning (ML) models are developed to predict the induced residual stresses (RSes) during turning of Inconel 718 alloy. The developed models are composed of a traditional artificial neural network (ANN) incorporated with bio-inspired optimizers, namely pigeon optimization algorithm (POA) and particle swarm optimization (PSO). These optimizers are used to fine-tune the ANN parameters to enhance its prediction accuracy. The models were trained using measured RSes at different cutting conditions. The effects of the cutting conditions, such as cutting speed, cutting depth, and feed rate on the induced RSes are also investigated. The predicted RSes obtained by the developed models were compared with the measured ones as well as with those predicted by traditional ANN. The prediction accuracy of the models was statistically evaluated using seven statistical measures. The ANN–POA and ANN–PSO outperformed the traditional ANN. The coefficient of determination of ANN–POA, ANN–PSO, and ANN was 0.991, 0.938, and 0.585, respectively, while root mean square error was 11.870, 31.487, and 119.437, respectively.

Non-laminated glass fiber-reinforced epoxy composites (GFREC) have shown promising applications in various engineering fields. In this study, an experimental investigation followed by artificial intelligent modeling is carried out on the drilling of GFREC under two cooling conditions, namely internal and external. The damage factor of the drilled holes and the temperature of the drill tip were considered as main process responses. The experiments were conducted under different combinations of feed, spindle speed and coolant pressure. All holes were drilled using fresh tungsten carbide twist drills coated by TiN/TiAlN layer. A fine-tuned random vector functional link network (RVFL) model incorporated with a new optimizer called parasitism-predation algorithm (PPA) was developed to model the drilling process. PPA acts as an advanced metaheuristic optimizer to obtain the best model variables of RVFL. The developed model was compared with the stand-alone RVFL as well as the fined-tuned RVFL using particle swarm optimizer (PSO). RVFL-PPA outperformed other models in terms of coefficient of determination, root mean square error and other measures. The coefficient of determination of RVFL-PPA for different responses and cooling conditions ranges between 0.995 and 1.

Wood-plastic composites (WPCs) have shown promising domestic and industrial applications. Both virgin and waste materials have been used as matrix and reinforcement materials in WPCs manufacturing which enhances the eco-efficiency of WPCs products. This study presents a comprehensive review on the WPCs manufacturing techniques including pre-processing of the composite ingredients and post-processing of the WPCs products. Three main types of pre-processing techniques have been discussed; chemical, mechanical, and thermal treatments. Conventional manufacturing techniques of WPCs such as extrusion molding, injection molding, compression molding, stir casting, and hot-press method have been presented. In addition, advanced manufacturing techniques such as selective laser sintering have been briefly discussed. The recycling of WPC is also discussed. Eco-friendly assessment of WPCs has been also introduced. Important conclusions and the future research trends have been mentioned in the end of the article.

Diets containing high proportions of fruits and vegetables reduce the risk of onset of chronic diseases. The role of herbal medicines in improving human health is gaining popularity over the years, which also increases the need for safety and efficiency of these products. Green leafy vegetables (GLVs) are the richest source of phenolic compounds with excellent antioxidant properties. Increased consumption of diets containing phenolic compounds may give positive and better results to human health and significantly improves the immune system. Highly selective, susceptible and versatile analytical techniques are necessary for extraction, identification, and quantification of phenolic compounds from plant extracts, which helps to utilize their important biological properties. Recent advances in the pre-treatment procedures, separation techniques and spectrometry methods are used for qualitative and quantitative analysis of phenolic compounds. The online coupling of liquid chromatography with mass spectrometry (LCâMS) has become a useful tool in the metabolic profiling of plant samples. In this review, the separation and identification of phenolic acids and flavonoids from GLVs by LCâMS have been discussed along with the general extraction procedures and other sources of mass spectrometer used. The review is devoted to the understanding of the structural configuration, nature and accumulation pattern of phenolic acids and flavonoids in plants and to highlighting the recent developments in the chemical investigation of these compounds by chromatographic and spectroscopic techniques. It concludes with the advantages of the combination of these two methods and prospects. Keywords: Green leafy vegetables, Phenolic acids, Flavonoids, HPLC, ESI-MS

Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LCâMS/MS, including (1) liquidâliquid extraction (LLE), (2) solid phase extraction (SPE) and (3) supported liquid extraction (SLE). Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring (MRM) in a positive ion mode with ESI. The transitions monitored were m/z 441.1â325.2 for simvastatin, 408.2â235.1 for sitagliptin and 278.1â260.1 for the IS. The lower limit of quantification (LLOQ) was 0.2Â ng/mL for sitagliptin and 0.1Â ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies. Keywords: Rat plasma, Simvastatin, Sitagliptin, Supported liquid extraction

In the present study, we have carried out the synthesis of novel dihydropyrimidinecarbonitrile (1a–c), its dimethylated adduct (2a–c), and hydrazine derivative (3a–c) of 2a–c and its triazole fused derivatives (4a–c, 5a–c and 6a–c). The structure of newly synthesized compounds was confirmed by IR, 1H NMR, mass spectral data and elemental analysis. Further the novel derivatives were investigated for their in vitro antioxidant and anti-inflammatory activity. The results revealed that some of the tested compounds showed potent antioxidant and anti-inflammatory activity. The mass spectral pattern of 6a has been investigated in order to elucidate the structure.

Objectives: To compare the efficacy of laparoscopic transabdominal cerclage (TAC) pre-pregnancy and laparoscopic TAC in pregnancy in treating cervical insufficiency., Method: A retrospective analytical study comparing outcomes of laparoscopic TAC pre-pregnancy with laparoscopic TAC in pregnancy. A total of 178 patients who underwent laparoscopic TAC at our hospital were enrolled in the study. In total, 122 patients underwent interval cerclage, and 56 patients underwent cerclage during pregnancy., Results: A total of 178 patients who met the inclusion criteria were included in the analysis. Second-trimester abortions decreased by 50%, with an overall increase in full-term live births (32.53%) in patients undergoing laparoscopic TAC pre-pregnancy. The fetal survival rate was around 90% and 85% with laparoscopic TAC pre-pregnancy and laparoscopic TAC in pregnancy, respectively. Although the obstetric outcomes of laparoscopic TAC pre-pregnancy and in pregnancy were comparable, laparoscopic TAC pre-pregnancy was safer than laparoscopic TAC in pregnancy due to the complications associated with the procedure during pregnancy., Conclusions: Laparoscopic TAC pre-pregnancy yielded better reproductive outcomes than laparoscopic TAC in pregnancy and was associated with fewer perioperative complications., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Satellite observations following flooding coupled with electronic health data collected through syndromic surveillance systems (SyS) may be useful in efficiently characterizing and responding to health risks associated with flooding., Results: There was a 10% (95% Confidence Interval (CI): 1%-19%) increase in asthma related ED visits and 22% (95% CI: 5%-41%) increase in insect bite related ED visits in the flooded ZCTAs compared to non-flooded ZCTAs during the flood period. One month following the floods, diarrhea related ED visits were increased by 15% (95% CI: 4%-27%) for flooded ZCTAs and children and adolescents from flooded ZCTAs had elevated risk for dehydration related ED visits. During the protracted period (2-3 months after the flood period), the risk for asthma, insect bite, and diarrhea related ED visits were elevated among the flooded ZCTAs. Effect modification by reported age, ethnicity and race was observed., Conclusion: Combining satellite observations with SyS data can be helpful in characterizing the location and timing of environmentally mediated adverse health outcomes, which may be useful for refining disaster resilience measures to mitigate health outcomes following flooding., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Wound and its treatment is one of the major health concerns throughout the globe. Various extrinsic and intrinsic factors can influence the dynamics of healing mechanism. One such extrinsic factor is moist environment in wound healing. The advantages of optimum hydration in wound healing are enhanced autolytic debridement, angiogenesis and accelerated cell proliferation and collagen formation. But hydrated wounds often end up with patient's uncomfortability, associated infection, and tissue lipid peroxidation. Healing process prefers antimicrobial, anti-inflammatory and optimum moist microenvironment. Here, we have synthesized fumaric acid incorporated agar-silver hydrogel (AA-Ag-FA); characterized by UV-Visible spectroscopy, FTIR spectroscopy and TEM. The surface morphology is evaluated through SEM. The size of the silver nanoparticles (Ag NPs) was found to be 10-15 nm. The hydrogel shows potential antibacterial effect against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa which are predominantly responsible for wound infection. The gel shows reasonable antioxidant property evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Topical application of the gel on the wound site heals the wound at much faster rate even compared to standard (Mega heal, Composition: Colloidal silver 32 ppm hydrogel) gel. Histological analysis reveals better tissue proliferation (i.e. epithelialization), more granulation tissue formation, neovascularisation, fibroblast and mature collagen bundles. The lipid peroxidation of wound tissue estimated through malondialdehyde (MDA) assay was found to be reasonably less when treated with AA-Ag-FA hydrogel compared to standard (Mega heal). Cytotoxicity of the samples tested through MTT assay and live-dead cell staining shows its nontoxic biocompatibility nature. In our hydrogel scaffold, the bio-degradable agar-agar provides the moist environment; the Ag NPs inside the gel acts as bactericidal agent and fumaric acid facilities the antioxidant and angiogenesis path implicitly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Esterases are one of the most important industrial enzymes. Here, a novel estA was cloned from Enterobacter sp. and characterized. The sequence alignment results showed that it was a novel esterase. The purified EstA had a molecular weight of 26 KDa with an optimum temperature and pH of 40 °C and 9.0. EstA retained >70% activity between 0 °C and 20 °C, indicating it was a low temperature active enzyme. EstA exhibited low activity after incubation at 45 °C for 120 min or 50 °C for 30 min. In the presence of organic solvents, detergents and different concentrations of NaCl, EstA retained high activity. In order to improve thermal stability, a mutant A92D with better thermal stability than EstA was obtained by random mutation. ESTA92D showed high activity at 45 °C for 120 min and maintained 85% of the original activity at 50 °C for 30 min, approximately a 3.4-fold increase over EstA. Homology modeling analysis showed that the improved thermostability of ESTA92D was attributed to hydrophilic Asp rather than hydrophobic Ala, leading to an increase of the interaction and solubility as well as the surrounding area. The improved thermostability of low-temperature-active EstA suggests its immense applications in industrial applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The occurrence of stent thrombosis (ST) in real world scenario is far different from that mentioned in the literature. Our study identifies the various parameters of ST., Methods: This is a prospective observational-cohort study where-in consecutive patients who received successful percutaneous transluminal angioplasty (PTCA) over the study period of 1-year was included and were followed for 1-year from the primary procedure., Results: The overall incidence of definite ST was 1.4% and 1.7% at 30 days and 1 year respectively. The most common mode of presentation of ST was ST-elevation myocardial infarction (82.6%). The history of prior PTCA, multi-vessel disease, emergent PTCA, acute coronary syndrome and type B2/C lesions were found to be the independent predictors for definite ST. The incidence of late ST was significantly higher with bare metal stent (BMS) than drug-eluting stent (DES) (OR-2.4, 95% CI:1.3-4.5). At mean follow-up of 13.9 months after ST, the overall mortality was 36.9%. The independent predictors of mortality after ST were post-PTCA thrombolysis in myocardial infarction (TIMI) flow grade < 3, and cardiogenic shock at the time of presentation., Conclusion: The overall incidence of definite ST is high in the real world scenario and the DES fared better than BMS. ST carries a bad prognosis especially so if the patients present in cardiogenic shock, or unable to achieve TIMI-3 flow after PTCA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Green synthesis of silver nanoparticles (AgNPs) using aqueous root extract of Delphinium denudatum (Dd) by reduction of Ag(+) ions from silver nitrate solution has been investigated. The synthesized DdAgNPs were characterized by using UV-Vis spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectroscopy (FTIR). The prepared DdAgNPs showed maximum absorbance at 416nm and particles were polydispersed in nature, spherical in shape and the size of the particle obtained was⩽85nm. The DdAgNPs exhibited antibacterial activity against Staphylococcus aureus ATCC 6538, Bacillus cereus NCIM 2106, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027. The DdAgNPs showed potent larvicidal activity against second instar larvae of dengue vector Aedes aegypti with a LC50 value of 9.6ppm., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: In the emergency management of patients with pelvic fractures, there is ongoing debate about the roles of angiography and open pelvic packing. It is agreed that some form of haemorrhage control is required for patients who are haemo-dynamically unstable despite resuscitation. We set out to determine whether on-call general and orthopaedic surgeons would feel able to perform emergency surgical procedures for these patients and whether vascular radiology was available to them., Methods: Surveys were sent to all 221 general and orthopaedic surgeons in Wales. Questions included: sub-speciality interest, geographical region, whether there is a pelvic binder in their hospital, availability of interventional radiology, and whether surgeons would perform a range of procedures to control haemorrhage in the emergency setting., Results: There were 141 responses to the survey, giving a 64% response rate. Only 18% reported that their unit had a formal rota for interventional radiology out of hours. 16% did not know. 96% of orthopaedic surgeons would perform external fixation, although only 49% would use a C-clamp. 90% of general surgeons would be able to pack the pelvis from within the abdominal compartment and 84% would be prepared to cross-clamp the aorta if the situation required. Despite being widely recommended in the literature as a method of haemorrhage control, our survey revealed only 45% would perform extra(pre)-peritoneal packing of the pelvis (58% of general surgeons; 34% of orthopaedic surgeons) and only 12% had received formal training in this procedure., Conclusions: With appropriately targeted training it is likely that the care of patients with pelvic fractures can be significantly improved., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Calcification currently represents a major cause of failure of biological tissue heart valves. It is a complex phenomenon influenced by a number of biochemical and mechanical factors. Recent advances in material science offer new polymers with improved properties, potentially suitable for synthetic leaflets heart valves manufacturing. In this study, the calcification-resistance efficacy and mechanical and surface properties of a new nanocomposite polymeric material (polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane; POSS-PCU) which has been developed by our group are assessed by means of in vitro testing. In particular, thin sheets of nanocomposite, glutaraldehyde-fixed bovine pericardium (BP) and polyurethane (PU) were exposed to a calcium solution into a specially designed in vitro accelerated physiological pulsatile pressure system for a period of 31days and a total of 4×10(7) cycles. The samples were investigated for signs of calcification after exposure to calcium solution by means of X-ray, microscopic and chemical inspections. Mechanical and surface properties were also studied using stress-strain behaviour and surface morphology and hydrophobicity. Comparison shows that, in the experimental conditions, the level of calcification for the nanocomposite is considerably lower than for the fixed BP (p=0.008) and PU samples (p=0.015). Also, mechanical properties were unchanged in POSS-PCU, while there was a significant deterioration in PU samples (p<0.05). Hydrophobicity was significantly reduced in both the POSS-PCU and PU samples (p<0.0001). However, the POSS-PCU nanocomposite remained more hydrophobic than the PU sample (p<0.0001). Less platelet adhered to the POSS-PCU compared to the PU (p<0.0001). These results indicate that the use of this nanocomposite in synthetic leaflets heart valves may lead to potential advantages in terms of long-term performances and durability., (Copyright © 2010. Published by Elsevier Ltd.)

The alpha v beta 6 integrin is a promising target for cancer therapy. Its expression is up-regulated de novo on many types of carcinoma where it may activate transforming growth factor-beta1 and transforming growth factor-beta 3, interact with the specific extracellular matrix proteins and promote migration and invasion of tumor cells. The viral protein 1 (VP1) coat protein of the O(1) British field strain serotype of foot-and-mouth disease virus is a high-affinity ligand for alpha v beta 6, and we recently reported that a peptide derived from VP1 exhibited alpha v beta 6-specific binding in vitro and in vivo. We hypothesized that this peptide could confer binding specificity of an antibody to alpha v beta 6. A 17-mer peptide of VP1 was inserted into the complementarity-determining region H3 loop of MFE-23, a murine single-chain Fv (scFv) antibody reactive with carcinoembryonic antigen (CEA). The resultant scFv (B6-1) bound to alpha v beta 6 but retained residual reactivity with CEA. This was eliminated by point mutation (Y100bP) in the variable heavy-chain domain to create an scFv (B6-2) that was as structurally stable as MFE-23 and reacted specifically with alpha v beta 6 but not with alpha 5 beta 1, alpha v beta 3, alpha v beta 5, alpha v beta 8 or CEA. B6-2 was internalized into alpha v beta 6-expressing cells and inhibited alpha v beta 6-dependent migration of carcinoma cells. B6-2 was subsequently humanized. The humanized form (B6-3) was obtained as a non-covalent dimer from secretion in Pichia pastoris (115 mg/l) and was a potent inhibitor of alpha v beta 6-mediated cell adhesion. Thus, we have used a rational stepwise approach to create a humanized scFv with therapeutic potential to block alpha v beta 6-mediated cancer cell invasion or to deliver and internalize toxins specifically to alpha v beta 6-expressing tumors.

Objective: The formation of an endothelial cell layer on the luminal surface of cardiovascular devices, especially bypass grafts, is an important attribute in order to improve their patency. Endothelial progenitor cells (EPCs) have a potential role in the endothelialisation of bypass grafts. We hypothesised that a novel approach to improve endothelialisation of bypass grafts by EPCs would be the creation on the graft lumen of a microenvironment that supports EPC adhesion and differentiation., Methods: A new generation of nanocomposite based on silsesquioxane in the form of polyhedral oligomeric silsesquioxane (POSS) nanocages which incorporate bioactive peptides (RGD) was made into sheets. Peripheral blood mononuclear cells (PBMCs) containing EPCs isolated from six consenting young, healthy, adult volunteers were then plated both on (1) sheets of the nanocomposite with the bioactive peptide, (2) sheets of the nanocomposite without the bioactive peptide, (3) culture dishes as control and then cultured in presence of vascular endothelial growth factor (VEGF). Confirmation of endothelial and EPCs markers was carried out using fluorescence-activated cell sorter (FACS) analysis, reverse transcription polymerase chain reaction (RT-PCR) and immunostaining., Results: One to two percent of PBMCs expressed CD34 as determined by FACS analysis. Cells were demonstrated to express mRNA for the EPC markers CD34, platelet-endothelial cell adhesion molecule-1 (CD31), CD133 and vascular endothelial growth factor receptor-2(FlK-1/KDR). Endothelial cell-colony forming units were formed between day 5 and day 7 after plating. Colonies were confirmed to be endothelial like cells by immunostaining. There were significantly greater numbers of EPC colonies on the bioactive nanocomposites as compared to the nanocomposite alone and the uncoated dishes., Conclusion: We report a new nanocomposite based biomaterial that has been demonstrated, in vitro, to promote endothelialisation from PBMCs containing EPCs.

The objective of the study was to investigate the role of Umbelliferone (UMB) on lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were induced diabetes by administration of STZ (40 mg/kg b.wt.) intraperitoneally. The normal and diabetic rats were treated with UMB (30 mg/kg b.wt.) dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had an elevation in the levels of lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD)), and a reduction in nonenzymic antioxidants (vitamin C and reduced glutathione (GSH) except vitamin E in the plasma and liver, and enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the liver. Decreased level of beta-carotene and increased level of ceruloplasmin (Cp) were observed in the plasma of diabetic rats. Treatment with UMB and glibenclamide brought back lipid peroxidation markers, nonenzymic and enzymic antioxidants to near normalcy. Since UMB treatment decreases lipid peroxidation markers and enhances antioxidants' status it can be considered as a potent antioxidant.

Background: The host inflammatory response and innate immunity play a complex role in respiratory diseases., Methods: We evaluated the levels of inflammatory mediators and antibacterial proteins in children who required bronchoscopy and bronchoalveolar lavage fluid (BALF) for clinical indications such as chronic tracheostomy (n=15) and chronic suppurative lung disease (n=8)., Results: Our results suggested the presence of interleukin-1beta (IL-1beta) and IL-8 as major inflammatory mediators in BALF samples. The level of the antibacterial protein sIgA was higher than lactoferrin and lysozyme. BALF IL-8 levels significantly correlated with the presence of IL-1beta, IL-6, IL-10, IL-16, sIgA and lysozyme. BALF IL-8 levels did not correlate with the levels of immunomodulatory and anti-inflammatory clara cell 10 kDa protein (CC10) or lactoferrin., Conclusion: This study suggests that patients with high levels of BALF IL-8 could potentially have high levels of IL-6, IL-10, IL-16, lysozyme and sIgA. Evaluating the inflammatory mediators (IL-8) in relation to other BALF protein components provides insight into understanding the role of inflammatory mediators in the regulation of host defense and the response to lung inflammation and injury.

Cardiac varix is a rare entity. It is generally small and is in relation to the interatrial septum, often mistaken as cardiac myxoma. A 19-year-old girl, on evaluation of respiratory infection, was found to have a mass compressing the right atrium. Computed tomographic scan and magnetic resonance imaging suggested a differential diagnosis of pericardial cyst or hydatid cyst. Peroperatively, a large (8 x 6.5 x 5.5 cm) cystic lesion in relation to the right atrial free wall was found. The histopathology of the resected mass revealed it to be a cardiac varix. The case is notable for its large size and its location in relation to the right atrial free wall.

We investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells. This was accompanied by a decrease in both the protein and the mRNA expression of the iron-response element containing variant of the divalent metal transporter (DMT1[+IRE]). In contrast, iron efflux and iron-regulated gene1 (IREG1) expression were unaffected by hepcidin. Hepcidin interacts directly with a model intestinal epithelium. The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet.

Background: Analysis of the protein components of airway secretions is a potential means of detecting and characterizing biochemical alterations associated with airway diseases., Methods: We evaluated airway protein secretions using the airway epithelial cell line Calu-3 grown at an air-liquid interface. To observe changes in apically secreted proteins, we analyzed the protein content of apical surface fluid (ASF) washings of Calu-3 monolayers treated with ion transport mediators., Results: Immunoassay screening for antibacterial and inflammatory proteins indicated the presence of measurable levels of lysozyme and IL-8 in Calu-3 ASF. RT-PCR and immunoassay studies indicated that Calu-3 cells do not produce clara cell 10 kDa protein (CC10). The total protein secretion of Calu-3 was not altered by bradykinin, but amiloride and adenosine significantly increased Calu-3 protein secretion. Lysozyme secretion was not altered by bradykinin, but amiloride and adenosine significantly reduced lysozyme secretion. IL-8 secretion was not altered by bradykinin or adenosine, but amiloride significantly decreased IL-8 secretion., Conclusion: Our results demonstrate the presence of antibacterial protein lysozyme and the pro-inflammatory cytokine IL-8 in Calu-3 ASF and that ion transport mediators such as bradykinin, amiloride and adenosine influence the secretion of Calu-3 ASF proteins.

The effect of the putative iron regulatory peptide hepcidin on iron absorption was investigated in mice. Hepcidin peptide was synthesized and injected into mice for up to 3 days, and in vivo iron absorption was measured with tied-off segments of duodenum. Liver hepcidin expression was measured by reverse transcriptase-polymerase chain reaction. Hepcidin significantly reduced mucosal iron uptake and transfer to the carcass at doses of at least 10 microg/mouse per day, the reduction in transfer to the carcass being proportional to the reduction in iron uptake. Synthetic hepcidin injections down-regulated endogenous liver hepcidin expression excluding the possibility that synthetic hepcidin was functioning by a secondary induction of endogenous hepcidin. The effect of hepcidin was significant at least 24 hours after injection of hepcidin. Liver iron stores and hemoglobin levels were unaffected by hepcidin injection. Similar effects of hepcidin on iron absorption were seen in iron-deficient and Hfe knockout mice. Hepcidin inhibited the uptake step of duodenal iron absorption but did not affect the proportion of iron transferred to the circulation. The effect was independent of iron status of mice and did not require Hfe gene product. The data support a key role for hepcidin in the regulation of intestinal iron uptake.

Complement inhibition is to a large extent achieved by proteolytic degradation of activated complement factors C3b and C4b by factor I (FI). This reaction requires a cofactor protein that binds C3b/C4b. We found that the cofactor activity of C4b-binding protein towards C4b/C3b and factor H towards C3b increase at micromolar concentrations of Zn(2+) and are abolished at 2 mM Zn(2+) and above. 65Zn(2+) bound to C3b and C4b molecules but not the cofactors or FI when they were immobilized in a native form on a nitrocellulose membrane. Zn(2+) binding constants for C3met (0.2 microM) and C4met (0.1 microM) were determined using fluorescent chelator. It appears that higher cofactor activity at low zinc concentrations is due to an increase of affinity between C4b/C3b and cofactor proteins as assessed by surface plasmon resonance. Inhibition of the reaction seen at higher concentrations is due to aggregation of C4b/C3b.