A MINI REVIEW ON NON-ANTIBIOTIC THERAPIES TO TARGET EMERGING ANTIMICROBIAL RESISTANCE DURING POST COVID ERA

Antibiotics considered as miracle drugs and as one of the most demanding life-saving discoveries of the twentieth century have now imposed a threat to society due to its overuse and misuse. Antimicrobial resistance (AMR) is a growing global problem to which the current COVID-19 pandemic may fuel further. The high number of patients suffering from Covid-19 worldwide have been reported to suffer further from secondary microbial infections. This has become a challenge for the medical community. Hence, various non-antibiotic strategies have been sought after and their mechanisms have been evaluated to mitigate the rise of AMR. This review gives an overview of the success of the alternate methods to combat AMR

Botnet-based Distributed Denial of Service (DDoS) Attacks on Web Servers: Classification and Art

Botnets are prevailing mechanisms for the facilitation of the distributed denial of service (DDoS) attacks on computer networks or applications. Currently, Botnet-based DDoS attacks on the application layer are latest and most problematic trends in network security threats. Botnet-based DDoS attacks on the application layer limits resources, curtails revenue, and yields customer dissatisfaction, among others. DDoS attacks are among the most difficult problems to resolve online, especially, when the target is the Web server. In this paper, we present a comprehensive study to show the danger of Botnet-based DDoS attacks on application layer, especially on the Web server and the increased incidents of such attacks that has evidently increased recently. Botnet-based DDoS attacks incidents and revenue losses of famous companies and government websites are also described. This provides better understanding of the problem, current solution space, and future research scope to defend against such attacks efficiently

Role of powder metallurgical processing and TiB reinforcement on mechanical response of Ti-TiB composites

In this work, titanium–titanium boride (Ti–TiB) composites were synthesized by three different powder metallurgical techniques, namely, spark plasma sintering (SPS), hot iso-static pressing (HIP) and vacuum sintering (VS). The mechanical properties of the composites were determined using the nanoindentation technique. The role of the material processing route and TiB reinforcement employed on the mechanical properties of the composites was investigated. The results revealed that the composites processed by SPS possessed improved mechanical properties relative to those of the composites prepared by the HIP and VS techniques. Furthermore, reinforcement of the composites with TiB enhanced the hardness, elastic modulus and contact stiffness, whereas it reduced the fracture toughness and indentation creep

SPARE PARTS INVENTORY OPTIMIZATION FOR AUTO MOBILE SECTOR

In this paper the objective is to determine the optimal allocation of spares for replacement of defective parts on-board of a usage. The minimization of the total supply chain cost can only be achieved when optimization of the base stock level is carried out at each member of the supply chain. A serious issue in the implementation of the same is that the excess stock level and shortage level is not static for every period. This has been achieved by using some forecasting and optimization techniques. Optimal inventory control is one of the significant tasks in supply chain management. The optimal inventory control methodologies intend to reduce the supply chain cost by controlling the inventory in an effective manner, such that, the SC members will not be affected by surplus as well as shortage of inventory. In this paper, we propose an efficient approach that effectively utilizes the Genetic Algorithm for optimal inventory control. This paper reports a method based on genetic algorithm to optimize inventory in supply chain management. We focus specifically on determining the most probable excess stock level and shortage level required for inventory optimization in the supply chain so that the total supply chain cost is minimized . So, the overall aim of this paper is to find out the healthy stock level by means of that safety stock is maintained throughout the service period. Keywords: genetic algorithm, optimization, Inventor

Ethyl 7-oxo-3,5-diphenyl-1,4-diazepane-2-carboxyl­ate

The title compound, C20H22N2O3, crystallizes with two independent mol­ecules in the asymmetric unit. In both mol­ecules, the diazepane rings adopt chair conformations. The mean planes of the diazepane rings in the two molecules form dihedral angles of 71.6 (4)/40.3 (5) and 75.9 (5)/58.6 (7)° with the neighbouring benzene rings. The carbonyl-group O atoms deviate significantly from the diazepane rings, by 0.685 (14) and 0.498 (13) Å. The eth­oxy­carbonyl groups show conformational difference between two mol­ecules, as reflected in the orientation of the carbonyl O atoms and the C—C—O—C torsion angle of −179.0 (2)° in one mol­ecule and 73.2 (2)° in the other. In one molecule there is a short N—H⋯O contact that generates an S(5) ring motif. In the crystal, N—H⋯O inter­actions generate R 2 2(8) graph-set motifs and C—H⋯O inter­actions generate R 2 2(10) and R 2 2(14) graph-set motifs. C—H⋯π inter­actions also occur

Use of streptavidin magnetic beads in single strand conformation polymorphism profiles to detect mutations in rpoB gene of M.tuberculosis

Single strand conformation polymorphism (SSCP) is one of the promising techniques to identify mutations in short pieces of DNA (Orita et al. 1989). In this technique, DNA of interest is often amplified by the polymerase chain reaction (PCR) and then denatured by heat or alkali treatment before electrophoresis on a non denaturing polyacrylamide gel. Differences in mobility of either of the single strands compared to the control DNA indicate mutations which affect the secondary structure and alter the mobility of the DNA. We applied PCR-SSCP for the detection of mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis (Telenti et al. 1993a; 1993b). A nested PCR was used to amplify the RRDR. In the first PCR, 293-bp product was amplified and in the second PCR a 103- bp of the first PCR product was amplified. However, in our experience using denaturation by alkali or heating, the denatured PCR product most often reannealed to form a large proportion of double stranded DNA during the electrophoresis (Selvakumar et al. 1997a). After visualisation by staining with ethidium bromide or silver staining, most of the DNA was in the double stranded form, with very little or no single stranded DNA. The single strands that could be observed often ran close together, making analysis of any difference in mobility difficult. Therefore an attempt was made to generate biotinylated PCR product using a biotinylated forward primer and later the biotinylated strand was separated using sterptavidin magnetic beads. The separated strands eliminated the problem of strand reannealing during SSCP and were silver stained to detect the shift in the mobility. Since the nested PCR requires more time and is more expensive. a biotinylated PCR product was generated in a single PCR using a biotinylated forward primer and an unbiotinylated reverse primer. This simplified protocol was applied to clinical isolates in an attempt to detect rifampicin resistance

Is it worth treating category I failure patients with category II regimen?

Background: Very little information is available on the drug susceptibility profile among patients who are treated with standardized short-course chemotherapy regimens under programme conditions. Methods: Sputum samples were collected from new sputum smear-positive patients declared ‘failure’ after treatment with Category I regimen under tuberculosis control programme using DOTS strategy from a rural area of Tamil Nadu. Results: Of 1463 patients started on Category I regimen between May1999 and December 2002, 74 cases were declared as ‘failures’ (smear positive at 5/6 months of treatment). We collected sputum samples from 60 (81%) of 74 ‘failures’ and 27% (16 of 60) of them were culture-negative for M tuberculosis and 17% (10 of 60) had organisms resistant to Isoniazid and Rifampicin (MDR TB). Conclusion: Based on the drug susceptibility profile at the time of ‘failure’, treating Category I ‘failures’ with Category II regimen with close monitoring appears to be justified

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results: Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050- treated, compared to the untreated rabbits. Conclusions: Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment.We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment

Sensing cloud optimization to solve ED of units with valve-point effects and multi-fuels

In this paper a solution to an highly constrained and non-convex economical dispatch (ED) problem with a meta-heuristic technique named Sensing Cloud Optimization (SCO) is presented. The proposed meta-heuristic is based on a cloud of particles whose central point represents the objective function value and the remaining particles act as sensors "to fill" the search space and "guide" the central particle so it moves into the best direction. To demonstrate its performance, a case study with multi-fuel units and valve- point effects is presented

Ethyl 2-(7-oxo-3,5-diphenyl-1,4-diaze­pan-2-yl)acetate

In the title compound, C21H24N2O3, the diazepane ring adopts a chair conformation. The central diazepane ring forms dihedral angles 67.80 (7) and 72.29 (5)° with the two benzene rings. The eth­oxy­carbonyl group is disordered over two conformations with site-occupancy factors of 0.643 (5) and 0.357 (5). In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) loops