An Approach for Mitigating Denial of Service Attack

Distributed Denial of Service (DDoS) attacks are the most common types of cyber-attack on the internet and are rapidly increasing. Denial of service/distributed denial of service attack is an explicit attempt to make a machine or a network resource unavailable to its intended users. Attackers interrupt/suspend services of the host connected to internet temporarily or indefinitely.It involves saturating the target machine with external communication requests such that it cannot either respond to legitimate traffic or responds so slowly as to be rendered effectively unavailable. Two general form of Dos attacks are - those attacks that crashes services (computer attack) and those that flood services (network attack). Flooding DDoS attacks produce adverse effects for critical infrastructure availability, integrity and confidentiality. Current defense approaches cannot efficiently detect and filter out the attack traffic in real time. Based on the assumption that the attacker flows are very aggressive than the legitimate users the proposed work provides sufficient bandwidth to genuine users during flooding DDoS attack.The aim of the project is to implement an approach for mitigating DDoS based on “The Interface Based Rate Limiting (IBRL) algorithm”, used to mitigate the identified DDoS attacks. The implementation is carried out on a simulation tool Omnett++ installed on linux machine. The results are the plots that show that there is considerable increase in the two important and significant measures, response time and packet drop metrics for legitimate users even under DoS and DDoS attacks

Kapsule s asimetričnom membranom za osmotsku isporuku flurbiprofena

An asymmetric membrane capsule of cellulose acetate for osmotic delivery of flurbiprofen has been developed and influence of osmogents and solubilizing agent on in vitro drug release were evaluated. The capsule membrane was prepared by the phase inversion technique. To ensure the osmotic delivery of drug, two approaches were adopted: (i) the drug was encapsulated with osmogents like sodium chloride and mannitol to increase the osmotic pressure of the core, and (ii) the drug was encapsulated with sodium lauryl sulfate in the core of the formulation to increase the solubility and thus its osmotic pressure. Scanning electron microscopy of the membrane confirmed its porous, dense asymmetric nature. Dye test revealed in situ pore formation. The in vitro release study showed that as the proportion of osmogent and solubilizing agent was increased the release rate also increased. A good correlation was observed between the zero-order rate constant and the amount of the osmogent and solubilizing agent used.U radu je opisan razvoj kapsula s asimetričnom membranom od celuloznog acetata za osmotsku isporuku flurbiprofena. Proučavan je utjecaj osmotski-aktivnih tvari i tvari za povećanje topljivosti na oslobađanje ljekovite tvari in vitro. Membrane kapsula pripravljene su metodom inverzne faze. Osmotska isporuka je osigurana na dva načina. Ljekovita je tvar kapsulirana s: i) osmotski-aktivnim tvarima poput natrijeva klorida i manitola, koji su povećali osmotski tlak jezgre, ii) natrijevim lauril-sulfatom, koji je povećao topljivost te ujedno i osmotski tlak. Pretražna elektronska mikroskopija ukazuje na poroznu membranu asimetrične gustoće, a test boje na stvaranje pora in situ. In vitro pokusi su pokazali da oslobađanje ljekovite tvari iz kapsula raste s povećanjem količine osmotski-aktivnih tvari i tvari za povećanje topljivosti te da postoji dobra korelacija između upotrijebljene količine tih tvari i konstante oslobađanja nultog reda

Priprava i vrednovanje transdermalnih flastera karvedilola

Transdermal patches of carvedilol with a HPMC-drug reservoir were prepared by the solvent evaporation technique. In this investigation, the membranes of Eudragit RL100 and Eudragit RS100 were cast to achieve controlled release of the drug. The prepared patches possessed satisfactory physicochemical characteristics. Thickness, mass and drug content were uniform in prepared batches. Moisture vapour transmission through the patches followed zero-order kinetics. In vitro permeation studies were performed using a K-C diffusion cell across hairless guinea pig skin and followed super case II transport mechanism. The effects of non-ionic surfactants Tween 80 and Span 80 on drug permeation were studied. The non-ionic surfactants in the patches increased the permeation rate, Span 80 exhibiting better enhancement relative to Tween 80. The patches were seemingly free of potentially hazardous skin irritation.Metodom evaporacije otapala pripravljeni su transdermalni flasteri karvedilola s HPMC-lijek rezervoarom, s membranama od Eudragita RL100 i Eudragita RS100 koje kontroliraju oslobađanje. Flasteri su bili zadovoljavajućih fizičko-kemijskih svojstava, ujednačene debljine, mase i sadržaja ljekovite tvari. Prijelaz vlage i pare kroz flastere slijedio je kinetiku nultog reda. In vitro permeacija praćena je na koži zamorca pomoću K-C difuzijske ćelije, a slijedila je super II transportni mehanizam. Također je ispitivan učinak neionizacijskih površinski aktivnih tvari Tween 80 i Span 80 na permeaciju karvedilola. Rezultati su pokazali da su obje površinski aktivne tvari povećale permeaciju, ali Span 80 više. Flasteri nisu nimalo uzrokovali iritaciju kože

Pharmaceutical Considerations of Microemulsion as a Drug Delivery System

Microemulsions were recognized after the work of Hoar and Schulman in 1943, which revealed the use of strong surface-active agent leading to spontaneous emulsification; however, it was in 1959 when Schulman first used the term “microemulsion” for such emulsion system. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10–100 nm diameters that form spontaneously upon mixing of oil, water, and emulsifier. After its discovery in 1943 to till date, more than 1200 publications have been reported and development of O/W type of microemulsions has been the priority for the researchers, mostly using non-ionic surfactants. Although microemulsions seem to be one of the most promising candidates in pharmaceuticals because of relative ease in the formulation and distinct characteristics when compared to other dispersion systems, its commercial success as a drug delivery system has been very little. Much of the time after its discovery has been exhausted in failure to understand correct formulation requisites or confusing it with other similar systems. In the face of increasing the number of publication year after year, its formulation has been generally based on trial-and-error. Efficient strategies for excipient selection and detailed understanding of microstructures contributing to its formulation is still required which may serve as the foundation for attaining greater success in this field. Keywords: Microemulsion, Surfactants. Spontaneous emulsification, Solubilization

Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P. falciparum isolates by RT-PCR, and IgG/IgM against invasion ligands by Luminex(R), in 50 Mozambican adults, 25 children with severe malaria (SM) and 25 with uncomplicated malaria (UM). IRG expression differences among groups and associations between IRG expression and clinical/immunologic parameters were assessed. IRG expression diversity was higher in parasites infecting children than adults (p = 0.022). eba140 and ptramp expression decreased with age (p = 0.003 and 0.007, respectively) whereas p41 expression increased (p = 0.022). pfrh5 reduction in expression was abrupt early in life. Parasite density decreased with increasing pfrh5 expression (p < 0.001) and, only in children, parasite density increased with p41 expression (p = 0.007), and decreased with eba175 (p = 0.013). Antibody responses and IRG expression were not associated. In conclusion, IRG expression is associated with age and parasite density, but not with specific antibody responses in the acute phase of infection. Our results confirm the importance of multi-antigen vaccines development to avoid parasite immune escape when tested in malaria-exposed individuals

Plasmodium falciparum and helminth coinfections Increase IgE and parasite-specific IgG responses

Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We studied the effects of coinfections on the antibody profile in a cohort of 715 Mozambican children and adults using the Luminex technology with a panel of 16 antigens from P. falciparum and 11 antigens from helminths (Ascaris lumbricoides, hookworm, Trichuris trichiura, Strongyloides stercoralis, and Schistosoma spp.) and measured antigen-specific IgG and total IgE responses. We compared the antibody profile between groups defined by P. falciparum and helminth previous exposure (based on serology) and/or current infection (determined by microscopy and/or qPCR). In multivariable regression models adjusted by demographic, socioeconomic, water, and sanitation variables, individuals exposed/infected with P. falciparum and helminths had significantly higher total IgE and antigen-specific IgG levels, magnitude (sum of all levels) and breadth of response to both types of parasites compared to individuals exposed/infected with only one type of parasite (P ≤ 0.05). There was a positive association between exposure/infection with P. falciparum and exposure/infection with helminths or the number of helminth species, and vice versa (P ≤ 0.001). In addition, children coexposed/coinfected tended (P = 0.062) to have higher P. falciparum parasitemia than those single exposed/infected. Our results suggest that an increase in the antibody responses in coexposed/coinfected individuals may reflect higher exposure and be due to a more permissive immune environment to infection in the host. IMPORTANCE Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We compared the antibody profile between groups of Mozambican individuals defined by P. falciparum and helminth previous exposure and/or current infection. Our results show a significant increase in antibody responses in individuals coexposed/coinfected with P. falciparum and helminths in comparison with individuals exposed/infected with only one of these parasites, and suggest that this increase is due to a more permissive immune environment to infection in the host. Importantly, this study takes previous exposure into account, which is particularly relevant in endemic areas where continuous infections imprint and shape the immune system. Deciphering the implications of coinfections deserves attention because accounting for the real interactions that occur in nature could improve the design of integrated disease control strategies

Identifying Immune Correlates of Protection Against Plasmodium falciparum Through a Novel Approach to Account for Heterogeneity in Malaria Exposure

Background: A main criterion to identify malaria vaccine candidates is the proof that acquired immunity against them is associated with protection from disease. The age of the studied individuals, heterogeneous malaria exposure, and assumption of the maintenance of a baseline immune response can confound these associations. Methods: Immunoglobulin G/immunoglobulin M (IgG/ IgM) levels were measured by Luminex(R) in Mozambican children monitored for clinical malaria from birth until 3 years of age, together with functional antibodies. Studied candidates were pre-erythrocytic and erythrocytic antigens, including EBAs/PfRhs, MSPs, DBLs, and novel antigens merely or not previously studied in malaria-exposed populations. Cox regression models were estimated at 9 and 24 months of age, accounting for heterogeneous malaria exposure or limiting follow-up according to the antibody's decay. Results: Associations of antibody responses with higher clinical malaria risk were avoided when accounting for heterogeneous malaria exposure or when limiting the follow-up time in the analyses. Associations with reduced risk of clinical malaria were found only at 24 months old, but not younger children, for IgG breadth and levels of IgG targeting EBA140III-V, CyRPA, DBL5epsilon and DBL3x, together with C1q-fixation activity by antibodies targeting MSP119. Conclusions: Malaria protection correlates were identified, only in children aged 24 months old when accounting for heterogeneous malaria exposure. These results highlight the relevance of considering age and malaria exposure, as well as the importance of not assuming the maintenance of a baseline immune response throughout the follow-up. Results may be misleading if these factors are not considered

Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparum Infections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach

Epstein–Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005–2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein–Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P. falciparum antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL [high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81–15.64]. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02–1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1–22.2, P = 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against P. falciparum preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic P. falciparum antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to P. falciparum interact with EBV infection in the development of eBL