Development of low-alcohol isotonic beer by interrupted fermentation

Alcohol-free beer with isotonic properties is getting more popular and its production can be carried out by different production strategies; however, interrupted fermentation is still a challenge. Therefore, the objective of this study was to develop a low-alcohol isotonic beer (<0.5% v/v) by interrupted fermentation. Moreover, the major objective is to compare the developed product to commercial beverages (sports drinks, ‘Pilsen' regular beer, alcohol-free beers and low-alcohol isotonic beer). The beverages were evaluated based on pH, alcohol content (% v/v), total titratable acidity (mEq L⁻¹), osmolality (mOsmol kg⁻¹), bitterness International Bitterness Units, colour European Brewery Convention, total phenolic compounds (mg L⁻¹ gallic acid), reducing and total sugars (%) and Na and K contents (mg L⁻¹). The developed low-alcohol isotonic beer presented characteristics similar to sports drinks, with the advantage of being richer in phenolic compounds and suitable osmolality. Despite salts were added in its formulation, the grades attributed to all beers employed in the sensory evaluation, as well as the purchase intention did not present significant differences.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields

cDNA selection was used to isolate coding sequences from cosmids mapping to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere. The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cerevisiae SMT3 protein, whose gene was previously isolated as a suppressor of mutations in the MIF2 gene. The yeast MIF2 gene encodes an essential centromeric protein and shows homology to mammalian CENP-C, an integral component of active kinetochores. SMT3A was found to be highly homologous to two other recently isolated human genes, suggesting the presence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants. Moreover, all predicted proteins show significant homology to ubiquitin. The proposed role of yeast SMT3 as centromeric protein and the strong evolutionary conservation of the SMT3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore.     

A survey of parental knowledge about car seats in children

Motor vehicle accidents are the main cause of death and disability between 1 and 4 years of age. Since 1980 the Academy of Pediatrics has been promoting the correct use of car seats. The major reason that car seats are not fulfilling their full potential is their incorrect or lack of use. In order to evaluate parental knowledge about car seat use for children and their actual use in the population visiting HURRA, a survey was performed which demonstrated that only 57.6% of the parents interviewed had infant car seats and that only 83.3% of owners actually use it. As many as 94.4% had correct knowledge about car seat use, but the majority of correct information was not provided by the medical staff. The majority of parents use seat belts for their own protection but a significantly smaller percentage use car seats for their own children.     

Predictive equation for acquisition of hepatitis B in hospital workers in a general hospital

A cross-sectional study was performed to obtain risk factors for hepatitis B disease, HBsAg carriers and immunised personnel, among 2470 workers in a general hospital in Madrid, Spain. The data obtained were analyzed with multiple logistic regression to obtain beta coefficients for variables. The results of the analysis show that being a nurse or being regularly exposed to blood are the most important risk factors for hepatitis B acquisition. The length of time working at the same job activity was also a risk factor. The resulting beta coefficients allow the construction for a hepatitis non-immunised, HBsAg carrier and immunised HBV status, which can select subjects for a hepatitis B vaccination program.     

Pulse-stream VLSI neural networks mixing analog and digitaltechniques

The pulse-stream technique, which represents neural states as sequences of pulses, is reviewed. Several general issues are raised, and generic methods appraised, for pulsed encoding, arithmetic, and intercommunication schemes. Two contrasting synapse designs are presented and compared. The first is based on a fully analog computational form in which the only digital component is the signaling mechanism itself-asynchronous, pulse-rate encoded digital voltage pulses. In this circuit, multiplication occurs in the voltage/current domain. The second design uses more conventional digital memory for weight storage, with synapse circuits based on pulse stretching. Integrated circuits implementing up to 15000 analog, fully programmable synaptic connections are described. A demonstrator project is described in which a small robot localization network is implemented using asynchronous, analog, pulse-stream devices.     

Fast Parallel Reordering and Isomorphism Testing of k -Trees

In this paper two problems on the class of k -trees, a subclass of the class of chordal graphs, are considered: the fast reordering problem and the isomorphism problem. An O(log ² n) time parallel algorithm for the fast reordering problem is described that uses O(nk(n-k)/\kern -1ptlog n) processors on a CRCW PRAM proving membership in the class NC for fixed k . An O(nk(k+1)!) time sequential algorithm for the isomorphism problem is obtained representing an improvement over the O(n ² k(k+1)!) algorithm of Sekharan (the second author) [10]. A parallel version of this sequential algorithm is presented that runs in O(log ² n) time using O((nk((k+1)!+n-k))/log n) processors improving on a parallel algorithm of Sekharan for the isomorphism problem [10]. Both the sequential and parallel algorithms use a concept introduced in this paper called the kernel of a k -tree.