Feedback system design with an uncertain plant

A method is developed to design a fixed-parameter compensator for a linear, time-invariant, SISO (single-input single-output) plant model characterized by significant structured, as well as unstructured, uncertainty. The controller minimizes the H(infinity) norm of the worst-case sensitivity function over the operating band and the resulting feedback system exhibits robust stability and robust performance. It is conjectured that such a robust nonadaptive control design technique can be used on-line in an adaptive control system

Ensaio regional de variedades de milho na Região Sul - safra 2008/09.

A rede regional de ensaios de variedades de Milho tem por objetivo avaliar o comportamento de variedades comerciais de milho na região sul do Brasil. O resultado dos ensaios é publicado anualmente no Livro das Indicações Técnicas para o Cultivo de Milho e de Sorgo no RS. Esses resultados também servem para determinação do Valor de Cultivo e Uso (VCU), com vistas à extensão da indicação de uso de cultivares comerciais para o RS

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p

P. falciparum and P. vivax Epitope-Focused VLPs Elicit Sterile Immunity to Blood Stage Infections

In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against a 10,000 Pb/Pf sporozoite challenge, VLPs carrying the CS non-repeat B cell eptiopes were minimally-to-non-protective. One-to-three CS-specific CD4/CD8 T cell sites were also fused to VLPs, which primed CS-specific as well as WHcAg-specific T cells. However, a VLP carrying only the 3 T cell domains failed to protect against a sporozoite challenge, indicating a requirement for anti-CS repeat Abs. A VLP carrying 2 CS repeat B cell epitopes and 3 CS T cell sites in alum adjuvant elicited high titer anti-CS Abs (endpoint dilution titer \u3e1x106) and provided 80–100% protection against blood stage malaria. Using a similar strategy, VLPs were constructed carrying P. vivax CS repeat B cell epitopes (WHc-Pv-78), which elicited high levels of anti-CS Abs and conferred 99% protection of the liver against a 10,000 Pb/Pv sporozoite challenge and elicited sterile immunity to blood stage infection. These results indicate that immunization with epitope-focused VLPs carrying selected B and T cell epitopes from the P.falciparum and P. vivax CS proteins can elicit sterile immunity against blood stage malaria. Hybrid WHcAg-CS VLPs could provide the basis for a bivalent P. falciparum/P. vivax malaria vaccine

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Is it better to treat chronic hepatitis B as early as possible?—Con

Ideally, treatment of chronic hepatitis B in its early stage prior to irreversible liver damage should be most effective in preventing adverse clinical outcome. However, currently available treatments have low efficacy in achieving sustained response among patients in the early phase of chronic hepatitis B infection when the immune response to hepatitis B virus is weak. This review will provide evidence why a ‘wait and monitor’ approach is appropriate for chronic hepatitis B patients who are in the immune tolerant phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73513/1/j.1440-1746.2004.03660.x.pd

RNAi for Treating Hepatitis B Viral Infection

Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-α and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection

Developmental Regulation of Hepatitis B Virus Biosynthesis by Hepatocyte Nuclear Factor 4α

The host cellular factors that promote persistent viral infections in vivo are, in general, poorly understood. Utilizing the hepatitis B virus (HBV) transgenic mouse model of chronic infection, we demonstrate that the nuclear receptor, hepatocyte nuclear factor 4α (HNF4α, NR2A1), is essential for viral biosynthesis in the liver. The dependency of HBV transcription on HNF4α links viral biosynthesis and persistence to a developmentally regulated transcription factor essential for host viability

Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (-) chronic inactive HBV patients from active carriers

<p>Abstract</p> <p>Background and Aims</p> <p>ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (-) chronic active or inactive patients in Pakistani population.</p> <p>Materials and methods</p> <p>In a cross-sectional, cohort study, 567 HBeAg (-) patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (-) chronic active and inactive patients compared using receiver operation characteristic (ROC) curves.</p> <p>Results</p> <p>Of 567 HBeAg (-) patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (-) inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female) and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group.</p> <p>Conclusions</p> <p>Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (-) chronic active and inactive patients.</p

Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates is a prevalent, persistent and disabling disorder

<p>Abstract</p> <p>Background</p> <p>ADHD is a common and disabling disorder, with an increased risk for coexisting disorders, substance abuse and delinquency. In the present study, we aimed at exploring ADHD and criminality. We estimated the prevalence of ADHD among longer-term prison inmates, described symptoms and cognitive functioning, and compared findings with ADHD among psychiatric outpatients and healthy controls.</p> <p>Methods</p> <p>At Norrtälje Prison, we approached 315 male inmates for screening of childhood ADHD by the Wender Utah Rating Scale (WURS-25) and for present ADHD by the Adult ADHD Self-Report Screener (ASRS-Screener). The response rate was 62%. Further, we assessed 34 inmates for ADHD and coexisting disorders. Finally, we compared findings with 20 adult males with ADHD, assessed at a psychiatric outpatient clinic and 18 healthy controls.</p> <p>Results</p> <p>The estimated prevalence of adult ADHD among longer-term inmates was 40%. Only 2 out of 30 prison inmates confirmed with ADHD had received a diagnosis of ADHD during childhood, despite most needed health services and educational support. All subjects reported lifetime substance use disorder (SUD) where amphetamine was the most common drug. Mood and anxiety disorders were present among half of subjects; autism spectrum disorder (ASD) among one fourth and psychopathy among one tenth. Personality disorders were common; almost all inmates presented conduct disorder (CD) before antisocial personality disorder (APD). Prison inmates reported more ADHD symptoms during both childhood and adulthood, compared with ADHD psychiatric outpatients. Further, analysis of executive functions after controlling for IQ showed both ADHD groups performed poorer than controls on working memory tests. Besides, on a continuous performance test, the ADHD prison group displayed poorer results compared with both other groups.</p> <p>Conclusions</p> <p>This study suggested ADHD to be present among 40% of adult male longer-term prison inmates. Further, ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders, severely affected prison inmates with ADHD. Besides, inmates showed poorer executive functions also when controlling for estimated IQ compared with ADHD among psychiatric outpatients and controls. Our findings imply the need for considering these severities when designing treatment programmes for prison inmates with ADHD.</p