Optimal combined word-length allocation and architectural synthesis of digital signal processing circuits

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Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Dissociation of molecular aggregates under high hydrostatic pressure: the influence of water structure on Benzene cluster solubility

In some critical conditions water can solvate hydrophobic molecules, becoming a powerful solvent for nonpolar agents. To discuss the pressure effect on hydrated benzene clusters we carried out six consecutive 5000 ps (pico seconds) molecular dynamics simulations of benzene molecules in water cubic boxes at different pressure conditions, ranging from 1 bar to 5 kbar. Radius of gyration, diffusion coefficient, radial atomic pair distribution functions, number of hydrogen bonds between water molecules and the solvent accessible surface were monitored. Results showed that above 3 kbar the second hydration layer structure vanishes and the benzene clusters start to break up gradually. Up to 2 kbar, the solubility and diffusion of benzene molecules are inversely proportional to the increase of the pressure and above 3 kbar this behavior is inverted

Hydrogen Bonding of Carboxylic Acids in Aqueous Solutions—UV Spectroscopy, Viscosity, and Molecular Simulation of Acetic Acid

The UV spectra of aqueous acetic acid solutions up to 2M were investigated. At these wavelengths, the carboxylic acids exhibit an absorption peak, attributed to the C=O group, which shifts when hydrogen bonds are formed.. The measured spectra were best fitted to several bands, either of Gaussian or Lorentzian shape, which can be explained as several types of structural units formed by hydrogen bonds established between acetic acid and water molecules and between acetic acid molecules themselves. Molecular dynamics simulation of these mixtures was also performed, confirming the occurrence of several types of hydrogen bonds and showing the presence of dimers at higher concentrations. The viscosity and density of these solutions were also measured at different concentrations and temperatures. These results give a more complete picture of the hydrogen bond network of the system.Instituto de Física de Líquidos y Sistemas Biológico

Mycobacterium paratuberculosis sheep type strain in Uruguay: evidence for a wider geographic distribution in South America

Johne's disease (JD) is an economically important disease of ruminants caused by Mycobacterium avium paratuberculosis (MAP), which also infects other species including humans. Two major MAP strain types are currently recognized: sheep (S) and cattle (C) types. Information on JD prevalence and MAP types infecting small ruminants in South America is limited, and all but one of the MAP types reported from this region are of the C type. This study describes clinicopathological, molecular and microbiological findings in 11 cases of JD caused by a type S MAP strain, and estimated true within-flock prevalence in a ~735-sheep operation in Uruguay. Postmortem examination and histology (hematoxylin-eosin and Ziehl-Neelsen stains) of samples from 41 selected sheep revealed lymphohistiocytic/granulomatous enteritis and mesenteric lymphadenitis in 11 animals, with moderate/severe multibacillary lesions in 6 clinical cases, and minimal/mild paucibacillary lesions in 5 sub-clinical cases. Immunohistochemistry using an antibody against Mycobacterium bovis that cross-reacts with MAP (2 cases), and transmission electron microscopy (1 case), revealed myriads of intrahistiocytic mycobacteria. MAP was isolated in one case and detected by PCR in 6 cases. The S type of MAP was identified using a multiplex PCR that distinguishes between S and C types, and PCR-REA. The estimated true within-flock prevalence was ≤ 2.3%. This represents the first communication on within-flock prevalence of JD associated with a type S MAP strain in South America and the second documentation of this strain in the subcontinent. Additional studies are required to better understand the molecular epidemiology of the different MAP types in the region.Centro de Diagnóstico e Investigaciones Veterinaria

Structure-based functional inference of hypothetical proteins from Mycoplasma hyopneumoniae

Enzootic pneumonia caused by Mycoplasma hyopneumoniae is a major constraint to efficient pork production throughout the world. This pathogen has a small genome with 716 coding sequences, of which 418 are homologous to proteins with known functions. However, almost 42% of the 716 coding sequences are annotated as hypothetical proteins. Alternative methodologies such as threading and comparative modeling can be used to predict structures and functions of such hypothetical proteins. Often, these alternative methods can answer questions about the properties of a model system faster than experiments. In this study, we predicted the structures of seven proteins annotated as hypothetical in M. hyopneumoniae, using the structure-based approaches mentioned above. Three proteins were predicted to be involved in metabolic processes, two proteins in transcription and two proteins where no function could be assigned. However, the modeled structures of the last two proteins suggested experimental designs to identify their functions. Our findings are important in diminishing the gap between the lack of annotation of important metabolic pathways and the great number of hypothetical proteins in the M. hyopneumoniae genome

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7