State and output feedback design for robust tracking of linear systems with rate limited actuators

A design technique (Control of Uncertain Systems with Bounded Inputs, Tarbouriech S, Garcia G, (Eds), Lecture Notes in Control and Information Sciences, vol. 227 , Springer: Berlin, 1997; 173–186) recently proposed for stabilization of a linear system with rate‐limited actuators is utilized to design feedback laws that cause the system output to track a desired command signal. This design technique combines two design techniques recently developed for linear systems with position limited actuators, piecewise‐linear LQ control (Automatica, 1994; 30 : 403–416) and low‐and‐high gain feedback (IEEE Trans. Automat. Control, 1996; 41 : 368–378), and hence takes advantage of both design techniques, while avoiding their disadvantages. In the case that only the output is available for feedback, the performance of the state feedback law is preserved by the use of a fast observer. An open‐loop exponentially unstable fighter aircraft is used to demonstrate the effectiveness of the proposed control design method. Copyright © 2002 John Wiley & Sons, Ltd.     

Synthesis of deramciclane* labeled with tritium in various positions

[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐³H]camphor and via [3‐³H]phenylborneol converted to [3‐³H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐³H]camphor gave an overall yield of 22%. Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐³H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐³H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐³H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [³H]NaBH₄ gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd.     

Immunoregulatory Factor Released From a Cell Line Derived From Human Decidual Tissue

ABSTRACT: The culture supernatant of the TTK-1 cell line, established from human decidual tissue, was found to contain a factor that strongly suppressed the mixed lymphocyte reaction (MLR). The mechanism of the MLR-suppressive activity as well as the biochemical characterization of this factor was analyzed. The TTK-1 supernatant suppressed the MLR much more strongly than the culture supernatants of the three other malignant cell lines examined. The molecular weight of this factor was estimated to be between 43 kilodaltons (kd) and 67 kd by gel filtration chromatography. The TTK-1 supernatant also suppressed the proliferation of the interleukin 2 (IL-2)-dependent T cell lines, but did not suppress that of the IL-2-independent T cell lines, suggesting that the TTK-1 supernatant inhibited the action of IL-2 and subsequently suppressed the MLR. The fact that the TTK-1 cell line originated from human decidual tissue might imply the important role of this factor in immunological fetomaternal balance.     

Clinical experience with the use of rhG‐CSF in secondary autoimmune neutropenia

This paper outlines the impact of granulocyte‐colony stimulating factor (G‐CSF) used as a single modality therapy in 17 patients with secondary autoimmune neutropenia (S‐AIN) who had been treated a multiple number of times previously. Fifteen of these patients had demonstrable antineutrophil antibodies and two had cellular S‐AIN with haemopoietic inhibitory T‐cells present in the marrow. Prior to treatment, all had had problems with infection. All patients responded within 7 days of commencement of treatment. Provided G‐CSF neutrophil counts were maintained above 1 × 10⁹/l, no further infections occurred. This was achievable by using G‐CSF administered as infrequently as once every 8 days. Eight of the 17 patients remained on G‐CSF, although five switched to the glycosylated form because of side‐effects. None have developed osteoporosis despite 47.29 patient years of total experience with G‐CSF. In conclusion both glycosylated and nonglycosylated G‐CSF can be used effectively in treating AIN on a long‐term basis.     

Differences in SLE disease activity between patients of Caucasian and South‐East Asian/Chinese background in an Australian hospital

Aim: We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method: There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results: Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions: South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.     

Necrotizing soft tissue infections

Necrotizing soft tissue infections (NSTI) represent a spectrum of diseases characterized by extensive rapidly progressive necrosis that may involve the skin, subcutaneous tissues, fascia or muscle. Their progress is extremely fast, leading often to sepsis and septic shock that ends up in multiple organ failure with abrupt and high mortality. A variety of classification systems have been developed based on parameters such as anatomic location of the disease or microbiology. There are a number of factors that predispose to the spread of these soft tissue infections, such as delays in recognition, immune suppression, diabetes mellitus and advanced age. The use of broad‐spectrum antibiotics tends to mask the severity of the underlying infection, modulates the clinical presentation, and even delays hospital admission. The most important factor affecting outcome in NSTI is early diagnosis and aggressive radical surgical treatment. The medical records of 13 patients who had been treated for NSTI from 1996 to 2005 were reviewed, retrospectively. There were eight men (61.5%) and five (38.5%) women. Mean age was 56 years (range 27–73). Seven cases of infection involved the perineal region (54%), two the lower limb, one the upper limb and three the abdominal wall/trunk. The most common associated comorbidity was diabetes mellitus in five patients (38.5%). A single organism was identified in two (15%) and multiple organisms in 11 (85%) patients. Necrotizing aponeurositis Type I was the most common of the polymicrobial necrotizing infections. Overall survival was 85%, and the mean hospital stay for survivors was 35 days (range 17–92).     

Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen.

BACKGROUND: Alternaria alternata is one of the most important allergenic fungi worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for several fungal allergens. OBJECTIVE: The present study's objective was to clone the MtDH from an A. alternata cDNA library, express and purify the recombinant non-fusion protein and test its IgE-binding properties. Methods A cDNA library prepared from A. alternata hyphae and spores was screened for mannitol dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum homologue as a probe. The resulting clone was sequenced and heterologously expressed in Escherichia coli as a recombinant non-fusion protein, which was purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence analysis revealed an identity of 75% and a homology of 86% between the MtDHs of A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A. alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION: Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the ascomycete A. alternata that might be suitable for improving diagnostic and therapeutic procedures.     

Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.