Surface plasmon resonance evaluation of various aminoglycoside-RNA hairpin interactions reveals low degree of selectivity

Aminoglycoside antibiotics, which are able to selectively bind to RNA, are considered to be an important lead in RNA-targeting drug discovery. In this study, surface plasmon resonance (SPR) was employed to explore the interaction of aminoglycosides with known tobramycin-binding RNA hairpins (aptamers) and an unrelated RNA hairpin. It was established that aminoglycosides have multiple interactions with RNA hairpins. Unexpectedly, the different hairpins showed comparable affinity for a set of related aminoglycosides. The observed absence of selectivity presents an extra hurdle in the discovery of novel aminoglycosides as specific drugs that target defined RNA hairpins.     

Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form

As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis.     

基于动态贝叶斯网络的语音识别及音素切分研究

研究了一种基于动态贝叶斯网络(dynamic bayesian networks, DBN)的语音识别建模方法,利用GMTK(graphical model tool kits)工具构建音素级音频流DBN语音训练和识别模型,同时与传统的基于隐马尔可夫的语音识别结果进行比较,并给出词与音素的切分结果.实验表明,在各种信噪比测试条件下,基于DBN的语音识别结果与基于HMM的语音识别结果相当,并表现出一定的抗噪性,音素的切分结果也比较准确.     

Using a test-specification format in automatic test-programgeneration

The author suggests that if the information necessary for testing a digital IC or printed-circuit board is kept and transferred in a standardized format, testing will be much easier. He describes the concept of a test-specification format (TSF) and reports the results of experiments with two candidate TSFs. The first, Tandem, is a restricted implementation that uses ITF, aPhilips internal language, to specify tests. The practical use of a TSF was studied by evaluating NCF (neutral code format), a well-documented and stable language. Although the two languages investigated were not true TSFs, the author shows that placing a language between CAD and test systems creates a powerful environment that could greatly reduce test-preparation time and test costs     

Chronic dissection of the thoracic aorta in a patient with tuberculous pleuro-pericarditis

The production of mycotoxins by Alternaria alternata in cellulosic ceiling tiles was examined with thin-layer chromatography and high-performance liquid chromatography procedures. Alternariol and alternariol monomethyl ether were found in ceiling tile extracts, whereas extracts of control rice cultures of all three isolates produced these mycotoxins plus altenuene and altertoxin I. Extensive fungal growth and mycotoxin production occurred in the ceiling tiles at relative humidities of 84-89% and 97%.     

Corticotropin-dependent Cushing's syndrome in older people: presentation of five cases and therapeutical use of ketoconazole

BACKGROUND: Cushing's syndrome is a rare disorder. The corticotropin (ACTH)-dependent form of this syndrome generally results either from excessive ACTH secretion by a pituitary adenoma or ectopic secretion by a malignant tumor. Theoretically, the latter type can be assumed to occur more frequently in old age as the incidence of malignancy increases. METHODS: Diagnostic procedures for these five cases of Cushing's syndrome consisted of 24-hour urinary cortisol excretion, plasma ACTH and serum cortisol levels, oCRH stimulatory test, low-dose and high-dose dexamethasone suppression tests, CT scan or MR imaging of the pituitary region, and bilateral inferior petrosal sinus sampling. Patients were treated with ketoconazole, if possible, and evaluated according to clinical response and 24-hour urinary cortisol excretion. PATIENTS: The five cases presented were selected on the basis of age--75 years or older--from a total of about 100 patients presenting with Cushing's syndrome. In only three cases were signs of hypercorticism found on clinical examination. The other two patients were evaluated for adrenocortical excess because of severe hypokalemia and the fortuitous finding of enlarged adrenal glands on CT scan, respectively. RESULTS: As a result of endocrine testing, pituitary-dependent Cushing's disease was suspected in three patients and ectopic Cushing's syndrome in two patients. Imaging techniques demonstrated only one pituitary adenoma in the first three patients and a lung tumor in one of the latter two patients. Inferior petrosal sinus sampling confirmed the suspected origin of the Cushing's syndrome in the three patients in which this procedure was performed. All three patients with pituitary-dependent Cushing's disease underwent successful clinical and biochemical treatment with ketoconazole. CONCLUSION: Pituitary-dependent Cushing's disease may occur more frequently in patients older than 75 years of age than has previously been assumed. Because surgical treatment is not always easily tolerated by older patients, the steroidogenesis inhibitor, ketoconazole, can be a valuable alternative for the control of hypercorticism.     

PEP: An interactive programming system with an Algol-like programming language

PEP (Program Editor and Processor) is an interactive programming system based on an Algol-like language. It is intended to replace BASIC as a system for interactive program development on small computers (LSI-11). The language processed by the system allows declaration of variables, constants and procedures; it has structured statements for conditional and repetitive execution of program parts. We describe design and implementation of the system and give our impressions after 1 year of experience with the system.     

Recycling GTL catalysts—A new challenge

The Fischer Tropsch synthesis of motor fuel from natural gas on a large scale may become significant in the near future for economic and environmental reasons. This process requires solid-phase catalysts containing large amounts of cobalt (catalyst) and traces of platinum group metals or rhenium (promoter). The economic data presented in this paper shows why recycling of those metals will be mandatory. Several recycling processes will be presented along with their technical challenges, most of which can be handled by Umicore using its know how and experience in the recycling of cobalt and the precious metals.     

Novel aza peptide inhibitors and active-site probes of papain-family cysteine proteases

Recent characterization of multiple classes of functionalized azapeptides as effective covalent inhibitors of cysteine proteases prompted us to investigate O-acyl hydroxamates and their azapeptide analogues for use as activity-based probes (ABPs). We report here a new class of azaglycine-containing O-acylhydroxamates that form stable covalent adducts with target proteases. This allows them to be used as ABPs for papain family cysteine proteases. A second class of related analogues containing a novel O-acyl hydroxyurea warhead was found to function as covalent inhibitors of papain-like proteases. These inhibitors can be easily synthesized on solid support, which allows rapid optimization of compounds with improved selectivity and potency for a given target enzyme. We present here one such optimized inhibitor that showed selective inhibition of falcipain 1, a protease of the malaria-causing parasite, Plasmodium falciparum.