The study of glial scar formation after brain ischemia using in-vitro strategies

Reactive gliosis is a generic response to Central Nervous System (CNS) injury mediated by astrocytes and microglia. Following ischemic damage to the CNS parenchyma, the injured area becomes surrounded by a dense astroglial cell layer known as glial scar. Glial scar formation has been recognized for many decades as a major impediment for neuronal reconnection and a serious obstacle for functional recovery. However, more recent studies have shown that scar limits the area of damage, preventing the diffusion of blood-derived activated immune cells into the CNS that could cause a generalized proinflammatory-neurodegenerative response.\nIn spite that it has been morphologically recognized for many years since Ramon y Cajal times, to study the biochemical signaling cascades involved in glial scar formation has been difficult mostly because of the in vivo nature of the process.\nIn this context, we studied here the mechanisms of glial scar assembly/disassembly in vitro to identify potential pharmacological targets for therapeutic interventions. To achieve this goal we will use the classical 2-Dimensional (2D) astroglial cultures, but we will also develop 3-dimensional (3D) astroglial cultures by using nanotube matrixes to attempt to better reproduce the in vivo situation. The results of this thesis showed that meningeal macrophages or ischemia-activated macrophages induce astroglial retraction and formation of scar-like structures in vitro. Scar-forming astrocytes over-express GFAP, S100B and TLR2-4. Using the NF-?B antagonist BAY-11-7082 we demonstrated that scar formation and its density is partially NF-?B dependent. Finally, in 3D astroglial culture grown on hydromatrix nanotubes, we showed that DAMPs can induce astroglial polarization but not the formation of the glial scar in vitro. We conclude that TLR/ NF-?B pathway is probably implicated in the glial scar formation or stabilization and that DAMPs and macrophages are necessary for the formation of glial scars in vitro.Fil: Mannava, Raja Sekhar. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Efficient simulation of communication systems on a desktop grid

Simulation is an important part of the design cycle of modern communication systems. As communication systems grow more sophisticated, the computational burden of these simulations can become excessive. The need to rapidly bring systems to market generally precludes the use of a single computer, and drives a demand for parallel computation. While this demand could be satisfied by the development of dedicated infrastructure, a more efficient option is to harness the unused computational cycles of underutilized desktop computers located throughout the organization.;In this thesis, a new paradigm for parallelizing communication simulations is proposed and developed. A desktop grid is created by running a compute engine as a background job on existing computers located throughout the University. The compute engine takes advantage of unused cycles to run simulations, and reports its results back to a server. The simulation itself is developed and launched from a client machine using Matlab, an application that has widespread acceptance within the communications industry. To obviate the need for a Matlab license on every machine running the compute engine, the simulation is first compiled to stand-alone executable code, and the executable and input data files are distributed to the grid machines over the Internet. To illustrate the performance improvement, a campaign of 16 distinct simulations corresponding to the IEEE 802.11a standard is run over the grid. Each compute engine executes a single simulation corresponding to one of eight modulation and coding schemes and one of two channel models. The improvement in execution time is quantified by a tool that was developed to monitor the activity of the grid

Primary Care Nurse Attitudes, Beliefs and Confidence Levels Regarding Alcohol Abuse and Its Treatment: Impact of Educational Intervention.

Alcohol abuse has been a major burden on the society. In the fight against it a key issue the education of the primary care nurses has been ignored. This study evaluates the effect of education program on the attitudes, beliefs, and confidence levels of primary care nurses regarding alcohol abuse and its treatment. Data from the Project Mainstream educational intervention were used with permission from the investigators. Two hundred one students and faculty of nursing at Vanderbilt University participated in the intervention, which was designed to train primary care providers in the Brief Negotiated Intervention technique for early detection and treatment of alcohol problems. Participants completed questionnaires before and after the educational intervention. Analysis of the data using paired samples t-test and one way analysis of variance showed statistically significant positive change in the nurses\u27 attitudes, beliefs, and confidence levels regarding alcohol abuse and its treatment after the educational intervention. This study has shown the importance of educational intervention in dealing with alcohol abuse

An investigation of phenolic glycoside and condensed tannin homeostasis in \u3ci\u3ePopulus\u3c/i\u3e by salicyl alcohol feeding to cell cultures and by transgenic manipulation of the sucrose transporter, \u3ci\u3ePTSUT4, in planta\u3c/i\u3e

Secondary metabolites play an important role in plant protection against biotic and abiotic stress. In Populus, phenolic glycosides (PGs) and condensed tannins (CTs) are two such groups of compounds derived from the common phenylpropanoid pathway. The basal levels and the inducibility of PGs and CTs depend on genetic as well as environmental factors, such as soil nitrogen (N) level. Carbohydrate allocation, transport and sink strength also affect PG and CT levels. A negative correlation between the levels of PGs and CTs was observed in several studies. However, the molecular mechanism underlying such relation is not known. We used a cell culture system to understand negative correlation of PGs and CTs. Under normal culture conditions, neither salicin nor higher-order PGs accumulated in cell cultures. Several factors, such as hormones, light, organelles and precursors were discussed in the context of aspen suspension cells’ inability to synthesize PGs. Salicin and its isomer, isosalicin, were detected in cell cultures fed with salicyl alcohol, salicylaldehyde and helicin. At higher levels (5 mM) of salicyl alcohol feeding, accumulation of salicins led to reduced CT production in the cells. Based on metabolic and gene expression data, the CT reduction in salicin-accumulating cells is partly a result of regulatory changes at the transcriptional level affecting carbon partitioning between growth processes, and phenylpropanoid CT biosynthesis. Based on molecular studies, the glycosyltransferases, GT1-2 and GT1-246, may function in glycosylation of simple phenolics, such as salicyl alcohol in cell cultures. The uptake of such glycosides into vacuole may be mediated to some extent by tonoplast localized multidrug-resistance associated protein transporters, PtMRP1 and PtMRP6. In Populus, sucrose is the common transported carbohydrate and its transport is possibly regulated by sucrose transporters (SUTs). SUTs are also capable of transporting simple PGs, such as salicin. Therefore, we characterized the SUT gene family in Populus and investigated, by transgenic analysis, the possible role of the most abundantly expressed member, PtSUT4, in PG-CT homeostasis using plants grown under varying nitrogen regimes. PtSUT4 transgenic plants were phenotypically similar to the wildtype plants except that the leaf area-to-stem volume ratio was higher for transgenic plants. In SUT4 transgenics, levels of non-structural carbohydrates, such as sucrose and starch, were altered in mature leaves. The levels of PGs and CTs were lower in green tissues of transgenic plants under N-replete, but were higher under N-depleted conditions, compared to the levels in wildtype plants. Based on our results, SUT4 partly regulates N-level dependent PG-CT homeostasis by differential carbohydrate allocation

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse model

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse modelrnRaja Vuyyuru and Wulf O. BöcherrnHepatitis B is a liver disease caused by Hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead either to liver disease or liver cancer. Acute infection is self limiting in most adults, resulting in clearance of virus from blood and liver and the development of lasting immunity. However 5% of acutely infected patients do not resolve primary HBV infection, leading to chronic infection with persistent viral replication in the liver. The strength of the initial antiviral immune response elicited to Hepatitis B determines the subsequent clinical outcome. A strong and broad T cell response leads to spontaneous resolution. Conversely, a weak T cell response favours viral persistence and establishment of chronic disease. While treatments using interferon-alpha or nucleos(t)ide analogues can reduce disease progression, they rarely lead to complete recovery. The lack of a suitable small animal model hampered efforts to understand the mechanisms responsible for immune failure in these chronic patients.rnIn current study we used Trimera mice to study the efficacy of potential vaccine candidates using HBV loaded dendritic cells in HBV chronic infection in vivo. The Trimera mouse model is based on Balb/c mice implanted with SCID mouse bone marrow and human peripheral blood mononuclear cells (PBMC) from HBV patients, and thus contains the immune system of the donor including their HBV associated T cell defect.rnIn our present study, strong HBV specific CD4+ and CD8+ T cell responses were enhanced by therapeutic vaccination in chronic HBV patients. These T cell responses occurred independently of either the course of the disease or the strength of their underlying HBV specific T cell failure. These findings indicate that the Trimera mouse model represents a novel experimental tool for evaluating potential anti-HBV immunotherapeutic agents. This in vivo data indicated that both the HBV specific CD4+ cell and CD8+ responses were elicited in the periphery. These HBV specific T cells proliferated and secreted cytokines upon restimulation in Trimera mice. The observation that these HBV specific T cells are not detectable directly ex vivo indicates that they must be immune tolerant or present at a very low frequency in situ. HBV specific T cell responses were suppressed in Trimera mice under viremic conditions, suggesting that viral factors might be directly involved in tolerizing or silencing antiviral T cell responses. Thus, combination of an effective vaccine with antiviral treatment to reduce viremia might be a more effective therapeutic strategy for the future. Such approaches should be tested in Trimera mice generated in HBV or HBs expressing transgenic mice before conducting clinical trials.r

Experimental evaluation of select servers and firewalls under denial of service security attacks

Internet security requires newer prevention mechanisms to be implemented on web-servers and routers. Firewall/Intrusion Prevention mechanisms (IPS) can be deployed on host servers or routers as an added line of defense against Internet attacks. In this thesis, we evaluate performance of security mechanisms provided by these devices against Distributed Denial of Service (DDoS) attacks. The host based firewalls on Windows servers-2003 and 2008 were evaluated. In this thesis, we also evaluated Juniper Networks Netscreen-5GT firewall/IPS, and Cisco ASA-5510/IPS that are used in protecting web-servers against DDoS attacks. It was found that the host based firewalls and protection mechanisms on the windows servers were not capable of defending against the DDoS attacks. Our performance evaluation showed the computing resource of the servers to be completely exhausted under these attacks. The evaluation of firewalls and IPS under different loads of attack had varying performance in supporting the number of web connections

Temporal effects of fescue toxicosis and heat stress on rat physiology and hepatic gene expression

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Title from title screen of research.pdf file (viewed on February 29, 2008)Vita.Thesis (Ph. D.) University of Missouri-Columbia 2007.Fescue toxicosis results from intake of toxins in fescue containing an endophytic fungus, Neotyphodium coenophialum. Time-related changes in rats associated with intake of an endophyte-infected fescue diet (E+) were evaluated under thermoneutral (TN), and both short- and long-term heat stress (HS) conditions. Short-term E+ intake decreased feed intake and growth rate under both conditions, whereas rats exhibited signs of adaptation during long-term exposure with better recovery occurring under TN conditions. Rats fed an E+ diet did not change core temperature during TN, but under HS conditions they exhibited a short-term increase in core temperature above control level. However, there was adaptive return of this temperature to TN level with long-term exposure. Short-term E+ intake at TN decreased serum glucose, urea nitrogen, alkaline phosphatase, and cholesterol; whereas long-term E+ intake under these conditions resulted in complete adaptation. In contrast, short-term E+ intake at HS did not affect serum biochemistry, while long-term intake decreased all the above mentioned serum parameters. Serum prolactin level was decreased during both short- or long-term TN and HS conditions. The E+ diet decreased hepatic antioxidant gene expression, with even greater reduction as a result of HS. Long-term E+ intake and HS increased expression of cytochrome P450 and detoxification pathways, respectively. Genes associated with immune response increased with long-term E+ at TN, but decreased with E+ diet at HS. Similarly, genes coding for chaperone and DNA repair decreased with long-term E+ at TN, but increased with E+ and HS. Recovery observed in E+ rats at TN could be attributed to increased gene expression for detoxification and immune response, whereas decreased antioxidant and immune response associated genes could contribute to distress associated with E+ at HS. Fescue toxicosis results from intake of toxins in fescue containing an endophytic fungus, Neotyphodium coenophialum. Time-related changes in rats associated with intake of an endophyte-infected fescue diet (E+) were evaluated under thermoneutral (TN), and both short- and long-term heat stress (HS) conditions. Short-term E+ intake decreased feed intake and growth rate under both conditions, whereas rats exhibited signs of adaptation during long-term exposure with better recovery occurring under TN conditions. Rats fed an E+ diet did not change core temperature during TN, but under HS conditions they exhibited a short-term increase in core temperature above control level. However, there was adaptive return of this temperature to TN level with long-term exposure. Short-term E+ intake at TN decreased serum glucose, urea nitrogen, alkaline phosphatase, and cholesterol; whereas long-term E+ intake under these conditions resulted in complete adaptation. In contrast, short-term E+ intake at HS did not affect serum biochemistry, while long-term intake decreased all the above mentioned serum parameters. Serum prolactin level was decreased during both short- or long-term TN and HS conditions. The E+ diet decreased hepatic antioxidant gene expression, with even greater reduction as a result of HS. Long-term E+ intake and HS increased expression of cytochrome P450 and detoxification pathways, respectively. Genes associated with immune response increased with long-term E+ at TN, but decreased with E+ diet at HS. Similarly, genes coding for chaperone and DNA repair decreased with long-term E+ at TN, but increased with E+ and HS. Recovery observed in E+ rats at TN could be attributed to increased gene expression for detoxification and immune response, whereas decreased antioxidant and immune response associated genes could contribute to distress associated with E+ at HS.Includes bibliographical reference

The Fatal Accident at Biodiversity Flyover in Hyderabad - A Case Study

Urban disasters, Traffic is unavoidable due to increase in density of vehicles without adding more road space to the city. This is demanding for more flyovers, grade separators to avoid congestion at the junctions. Hyderabad is congesting with many junctions adding up to the heavy traffic and waiting time, energy, fuel and polluting the city with noise and air pollution. For economic benefit and decongestion of major junctions, Flyovers were planned and constructed. To meet this demand in Gachibowli and Hi-Tech city area, a flyover was constructed by MVR Infra projects near biodiversity junction. The present paper describes the incident of fatal accident taken place on November 23, 2019. The study also reveals aftermath actions taken by the government of Telangana and suggested various sections in the Indian penal codes for such incidents

An Internal Current Controlled BLDC Motor Drive Supplied with PV Fed High Voltage Gain DC-DC Converter

The paper presents an efficient speed control of brushless DC (BLDC) motor drive for photo-voltaic (PV) system fed system. A high-gain DC-DC converter is employed in the system to boost the PV system low output voltage to a level required for the drive system. High-gain DC-DC converter is operated in closed-loop mode to attain accurate and steady output. The converter (VSI) for BLDC is switched at fundamental frequency and thus reducing high frequency switching losses. Internal current control method is developed and employed for the speed control of PV fed BLDC motor. The appropriateness of the internal current controller for the speed control of PV fed BLDC motor is verified for increamental speed with fixed torque and decreamental speed with fixed torque operating conditions. The system is developed and results are developed using MATLAB/SIMULINK softwar