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The present study demonstrates the production and thrombolytic potential of a novel thermostable thiol-dependent fibrinolytic protease by Bacillus cereus RSA1. Statistical optimization of different parameters was accomplished with Plackett-Burman design and validated further by central composite design with 30.75 U/mL protease production. Precipitation and chromatographic approaches resulted in 33.11% recovery with 2.32-fold purification. The molecular weight of fibrinolytic protease was 40 KDa and it exhibited a broad temperature and pH stability range of 20-80 • C and pH 5-10 with utmost activity at 50 • C and pH 8, respectively. The protease retained its fibrinolytic activity in organic solvents and enhanced the activity in solutions with divalent cations (Mn 2+ , Zn 2+ , and Cu 2+ ). The enzyme kinetics revealed K m and V max values of 1.093 mg/mL and 52.39 µg/mL/min, respectively, indicating higher affinity of fibrinolytic activity towards fibrin. Also, complete inhibition of fibrinolytic activity with DFP and a 2-fold increase with DTT and β-mercaptoethanol indicates its thiol-dependent serine protease nature. MALDI-TOF analysis showed 56% amino acid sequence homology with Subtilisin NAT OS = Bacillus subtilis subsp. natto. The fibrinolysis activity was compared with a commercial thrombolytic agent for its therapeutic applicability, and fibrinolytic protease was found highly significant with absolute blood clot dissolution within 4 h in in vitro conditions. The isolated fibrinolytic protease of Bacillus cereus RSA1 is novel and different from other known fibrinolytic proteases with high stability and efficacy, which might have wide medicinal and industrial application as a thrombolytic agent and in blood stain removal, respectively.Biomolecules 2020, 10, 3 2 of 23 (active protease), converting soluble fibrinogen (glycoprotein) into fibrin polymer (insoluble blood clot) [5]. Fibrin clots are hydrolyzed by plasmin [12], which is stimulated from plasminogen by plasminogen activators (PAs) [13,14]. This natural dynamic equilibrium is disturbed when the process of natural fibrin clot hydrolysis undergoes pathophysiological shambles, leading to formation of fibrin clots. Such clots may cause hindrance in the circulation of blood, causing blockage in blood vessels, ultimately leading to cardiac disorders which are life-threatening [15,16].Approaches such as use of anti-coagulant agents, anti-platelet drugs, fibrinolytic enzymes, and surgical operations are employed for the treatment of thrombosis and to dissolve the blood clots [17]. Further, there are numerous side effects which may occur following the administration of the available anti-thrombotic strategies, as well as the high expense, which limit their scope. The effects of reperfusion, urticaria (allergic reaction), and hemorrhage are the major inimical consequences of such thrombolytic approaches on human health [18,19]. Other after effects include headache, dizziness, ulcers, increased clotting time, nausea and vomiting, etc. Management of thrombosis usin...

Collaboration has evolved as a key component of many modern supply chains, supporting the competitive advantages of companies in a range of operations from manufacturing to sales. With this viewpoint, the present paper develops an integrated inventory model in which manufacturing is carried out at the vendor's end so as to fulfill demand at the buyer's doorway. As the production process is presumed to be imperfect it shifts from an "in-control" state to "out-of-control" state at any random time and yields non-conforming items. The vendor uses regular preventive maintenance actions for the efficient operation of the production system and offers free minimal repair warranty on the products sold to the buyer. Along with preventive maintenance actions the vendor also uses the rework process and restoration process as effective steps towards minimizing the imperfections of the production system. The proposed model solves the non-linear cost minimization problem through a generalized reduced gradient method by using Lingo 15.0. The aim is to jointly optimize the order size, backorder size and the number of shipments in order to minimize the integrated cost of the vendor and the buyer. Numerical analysis and sensitivity analysis is performed on key parameters that render some important supervisory insights. MathematicsSubject Classification. 90B05. Article published by EDP Sciences c EDP Sciences, ROADEF, SMAI 2020 436 A. KHANNA ET AL.business and is widely implemented. Prompted to this, an integrated inventory model has been presented by considering rework of non-conforming items, restoration of the production system and use of regular preventive maintenance actions during the non-production time. Also, the vendor offers free minimal repair warranty to the buyer as a promotional tool. An integrated model is developed with the motive to serve the decision makers with some important inferences. Almost all the organizations these days consider quality and reliability as a genuine technique to achieve improved profitability and greater benefits for the organization. In the manufacturing sector occurrence of imperfect quality items due to the faulty production process is unavoidable. Some of the interesting work in this area is given by [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. In practical production systems, imperfect items can be reworked, which significantly reduces the overall costs of production and inventory [19][20][21][22][23][24][25][26].Since the production process is imperfect so it is essential to take proper maintenance actions to deliver breakdown-free operations. Preventive maintenance comes with a motto to ensure optimum life for the equipment and it also increases productivity by reducing the downtime of a production unit. The primary goal of maintenance actions is to safeguard the system against any breakdown and malfunction during run-time. Reference [29] investigated the effects of pull systems and level material shipping to derive formulas for the buffer in limited demand variab...

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The present paper develops a sustainable framework under a supply chain environment by considering a vendor and a buyer. The vendor governs the manufacturing process to serve the demand of the buyer. The manufacturing system is imperfect which ends up producing some fraction of defectives. For the sake of maintaining the goodwill of the organization, it is imperative to maintain the quality standards. Thus, the buyer employs the screening process to bifurcate the perfect items from the imperfect ones. The imperfect items secluded after screening are reverted back to the vendor, for which a warranty cost is incurred. Further, in an attempt to achieve sustainability the model considers the carbon-emissions costs during the transportation process. A one-time discrete investment is also considered for minimizing the setup cost of the vendor for subsequent cycles. The models are developed for the case of the individual decision and for the joint verdict of the players under consideration. Moreover, it has been proved that the integrated model performs proficiently over the individual model. The objective is to jointly optimize the costs sustained by the two players. Numerical analysis and sensitivity analysis is done for imparting the validity and robustness of the model.