Designed binary mixtures for subcritical organic Rankine cycles based on multiobjective optimization

The use of binary zeotropic mixtures as working fluids applied to Organic Rankine Cycles (ORCs) is investigated in this paper. In total, six (6) hydrocarbons and (2) hydrofluorocarbons are considered, leading to twenty-eight (28) possible binary combinations. The mixtures were tested with a basic Rankine cycle while using the heat source temperature as independent variable, which assumed six different values, ranging from 80 °C to 180 °C, in steps of 20 °C. The simulations aimed to identify the ideal mixtures that maximized the net power and exergetic efficiency, and minimized the heat exchanger’s global conductance for a given temperature of the heat source. The optimization process relied on a genetic algorithm and the selection of the best mixtures, on a non-dominated sorting method (NDS), which returned Pareto fronts gathering the best solutions. While no one specific ideal mixture was identified, the results showed that the range of the so-called ideal mixtures narrows as the heat source temperature increases, with mixtures including fluids like R245fa and pentane being good options, whereas at low temperature, a larger number of fluid mixtures perform well. Finally, a scale analysis is proposed and shows that the maximal net power varies linearly with a Number of Transfer Units (NTU) factor while its slope depends on the heat source temperature. The latter analysis is compared with the results obtained with the Pareto front and NDS, showing that both sets of results agree well while correlated by a single constant for the entire temperature range covered in the present study

COCCIÓN DE LADRILLOS MACIZOS EN HORNOS A FUEGO DORMIDO Y CONTINUO Y DETERMINACION DE SUS PROPIEDADES MECÁNICAS

El artículo presenta la cocción de ladrillos macizos en horno natural tipo fuego dormido y en un horno continuo tipo Hoffman ,los cuales fueron fabricados en la ladrillera la Pradera, y la comparación de sus propiedades mecánicas, a las cuales se les realizaron ensayos de tasa de absorción inicial, inmersión durante 24 horas, resistencia a la compresión y módulo de rotura o flexión de acuerdo la norma técnica Colombina NTC- 4017 “Métodos para muestreo y ensayos de unidades de mampostería y otros productos de arcilla”. Para los ensayos de resistencia a la compresión y módulo de rotura se utilizó una máquina Universal tipo Pinzuar PU-100 y el software estadístico Statgraphics. Los resultados se compararon entre la cocción en los dos hornos y con los valores de referencia establecidos en la norma NTC 4205 unidades de mampostería de arcilla cocida, ladrillos y bloques cerámicos

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals, 2005–2010

<p>Abstract</p> <p>Background</p> <p>Hospital-acquired infections caused by multiresistant gram-negative bacteria are difficult to treat and cause high rates of morbidity and mortality. The analysis of antimicrobial resistance trends of gram-negative pathogens isolated from hospital-acquired infections is important for the development of antimicrobial stewardship programs. The information obtained from antimicrobial resistant programs from two hospitals from Mexico will be helpful in the selection of empiric therapy for hospital-acquired gram-negative infections.</p> <p>Findings</p> <p>Two thousand one hundred thirty two gram-negative bacteria collected between January 2005 and December 2010 from hospital-acquired infections occurring in two teaching hospitals in Mexico were evaluated. <it>Escherichia coli</it> was the most frequently isolated gram-negative bacteria, with >50% of strains resistant to ciprofloxacin and levofloxacin. <it>Klebsiella</it> spp. showed resistance rates similar to <it>Escherichia coli</it> for ceftazidime (33.1% vs 33.2%), but exhibited lower rates for levofloxacin (18.2% vs 56%). Of the samples collected for the third most common gram-negative bacteria, <it>Pseudomonas aeruginosa</it>, >12.8% were resistant to the carbapenems, imipenem and meropenem. The highest overall resistance was found in <it>Acinetobacter</it> spp. <it>Enterobacter</it> spp. showed high susceptibility to carbapenems.</p> <p>Conclusions</p> <p><it>E. coli</it> was the most common nosocomial gram-negative bacilli isolated in this study and was found to have the second-highest resistance to fluoroquinolones (>57.9%, after <it>Acinetobacter</it> spp. 81.2%). This finding represents a disturbing development in a common nosocomial and community pathogen.</p

The Complete Mutatome and Clonal Architecture of Del(5q)

Abstract Cytogenetic abnormalities are found in around half of MDS patients (pts) and have both clinical impact and may be subtype-defining, e.g. in 5q-syndrome. Interstitial deletion of the long arm of chr.5 [del(5q)] is the most common aberration (almost 20% of cases with abnormal cytogenetics). Del(5q) is heterogeneous, occurring as a sole abnormality or in combination, with the deleted region often truncated within or extended and/or beyond the CDR boundaries. Isolated del(5q) is frequently shorter and confers a more favorable prognosis with regard to survival and lenalidomide (LEN) responsiveness, while del(5q) in the context of a complex karyotype (CK) imparts a poor prognosis. In addition to chromosomal lesions, somatic mutations can contribute to the pathogenesis of MDS, including del(5q). We theorized that recognition of molecular defects in MDS with del(5q) may clarify the pathogenic mechanisms behind this lesion and help explain the clinical heterogeneity. We analyzed 225 pts with myeloid neoplasia and del(5q) using WES (n= 107 samples) and targeted multiplexed PCR (top 60 most frequently mutated genes) (n =133 samples); serial analysis was performed in 15 pts studied at ≥2 time points, 11 during LEN therapy and 4 upon relapse/progression. A total of 116 samples had a CK with other lesions such as -7/del(7q) found in 31% cases, and 18% had -17/del(17p). WES (average depth >60x) was followed by a bioanalytic pipeline, detecting ≥1 mutated gene in 71% of cases. Candidate somatic alterations were found in 357 genes and selected for further analysis. When focused on hemizygous mutations within the retained 5q allele, CSNK1A1 mutations were the most common, found in 4 pts, while other genes were only sporadically affected. Among heterozygous mutations on the non-deleted portion of del(5q) and other chromosomes (Chr), we found several novel mutations, in addition to TP53 (n=26), DNMT3A (n=8), PRPF8 (n =8), RUNX1 (n=5), TET2 (n=5), and ASXL1 (n=4), among others. Furthermore, LOH/haploinsuffciency of genes on 7q (e.g., LUC7L2, CUX1, EZH2 and MLL3) appears to be a common defect seen in pts with non-isolated del(5q), suggesting synergistic functional defects. When functionally grouping gene mutations, DNA methylation family (8 cases) and transcription factor mutations (29 cases) were associated with advanced disease (AD) and a CK. Heterozygous mutations in TP53 (34%) or deletions involving the TP53 locus (23%) resulted in total of 42% of cases carrying either TP53 LOH or mutation. TP53 lesions were more common in pts with AD vs. low risk. (21 vs. 5 p =.0008). In contrast, TP53 mutations are found in 8-10% of cases of MDS. A total of 34 pts were treated with LEN and subgrouped into responders (n=17) vs. refractory (n=9) with an overall response rate of 65%. When mutational profiles were compared, the presence of TP53 mutations did not preclude responsiveness to LEN. CK was present in 12% of responders vs. 67% of refractory pts. The most frequent Chr abnormalities were -7/7q (0% vs. 67% in responders vs. refractory) and 17p-(6% vs. 67% in responders vs. refractory) suggestive of their role in LEN resistance. In addition to cross sectional analysis, our WES study using paired Germline/tumor samples followed by deep sequencing facilitated analyses of clonal architecture by examining clonal dynamics over time. Assessment of del(5q) clone size by allelic imbalance combined with clonal burden by VAF allowed us to reconstruct the clonal hierarchy: in 73% of cases, del(5q) appeared to be the initial defect followed by subsequent mutations (e.g., TP53, DNMT3A, IDH2). In contrast, in 24% of cases, TP53, RUNX1, JARID2, were the primary defect followed by a subclonal del(5q) events. Serial samples collected before and after therapy demonstrated that responses were associated with decreased clonal burden for del(5q) but persistence of certain mutations. In refractory cases, persistent subclonal lesions and the appearance of new lesions were associated with progression. For example, pts with TP53, LAMB4, EPHA6 progressed and acquired additional lesions such as CSMD2 or KCND2, and did not see the disappearance of TP53 alterations upon treatment. In conclusion, no unifying somatic defect was found in pts with del(5q) regardless if the deletion event was primary or subclonal. Most commonly associated lesions were not present on the retained 5q alleles but rather other chr yet modified clinical behavior, including responsiveness to LEN. Disclosures Bejar: Celgene: Consultancy, Honoraria; Alexion: Other: ad hoc advisory board; Genoptix Medical Laboratory: Consultancy, Honoraria, Patents & Royalties: MDS prognostic gene signature. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees

A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period.

AIM:We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. MATERIAL AND METHODS:In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. RESULTS:In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). CONCLUSION:The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance