Harmonic Rhythm: The Essence of an Enjoyable Design Process

While production efficiency is the rule of modern life, design efficiency has not reached the happy level it could when dealing with the human actors of our environment because the process of design - and the production of a design - is not exactly an enjoyable one..

Presente y futuro de las empresas coreanas en el sector de energía e infraestructura argentinos, presencia china y otros desafíos a superar

This paper intends to carry out a study on the panorama facing the construction and energy companies of South Korea in Argentina. For this, an analysis is carried out on the operation of this type of companies from Korea at international level. In turn, a comparison is made about the operation of Chinese and Korean companies around the world. Finally, the biggest challenges of Korean companies that are in these sectors are exposed so that they can successfully enter the Argentine marketEn el presente trabajo se pretende realizar un estudio sobre el panorama que enfrentan las empresas constructoras y energéticas de Corea del Sur en Argentina. Para ello, se realiza un análisis sobre el funcionamiento de este tipo de empresas provenientes de Corea a nivel internacional. A su vez, se realiza una comparación sobre el funcionamiento de las empresas chinas y coreanas alrededor del mundo. Por último, se exponen los mayores retos de las compañías coreanas que están en estos sectores para que logren incursionar exitosamente en el mercado argentin

Presente y futuro de las empresas coreanas en el sector de energía e infraestructura argentinos, presencia china y otros desafíos a superar

En el presente trabajo se pretende realizar un estudio sobre el panorama que enfrentan las empresas constructoras y energéticas de Corea del Sur en Argentina. Para ello, se realiza un análisis sobre el funcionamiento de este tipo de empresas provenientes de Corea a nivel internacional. A su vez, se realiza una comparación sobre el funcionamiento de las empresas chinas y coreanas alrededor del mundo. Por último, se exponen los mayores retos de las compañías coreanas que están en estos sectores para que logren incursionar exitosamente en el mercado argentin

Presente y futuro de las empresas coreanas en el sector de energía e infraestructura argentinos: presencia china y otros desafíos a superar

Esta compilación de ensayos continúa con la sección economía y consta de un artículo, escrito por Ih Joon Chang, que analiza la participación de las empresas coreanas en el sector de energía e infraestructura argentino. Chang realiza un recorrido por las características de las empresas coreanas del rubro, su presencia en el mercado mundial y latinoamericano, en particular, y la posición avasallante de las inversiones de China, para responder a la pregunta de por qué las empresas coreanas no tienen una participación importante en el mercado argentino, a pesar de que nuestro país es uno de los que posee mayores recursos energéticos de la región y que, a su vez, es un demandante de inversión en infraestructura y energía. Su respuesta se basa en la identificación de dificultades en las áreas de financiamiento, calidad institucional, burocracia y derecho laboral, de modo que en su conclusión plantea una serie de recomendaciones destinadas a favorecer el intercambio superando estos obstáculos.Facultad de Ciencias Jurídicas y Sociale

Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

<p>Abstract</p> <p>Purpose</p> <p>This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from <it>Michelia compressa</it>, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells.</p> <p>Methods</p> <p>The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay.</p> <p>Results</p> <p>Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9.</p> <p>Conclusions</p> <p>Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.</p

G-Protein coupled receptors: structure and function in drug discovery

The G-protein coupled receptors (GPCRs) superfamily comprise similar proteins arranged into families or classes thus making it one of the largest in the mammalian genome. GPCRs take part in many vital physiological functions making them targets for numerous novel drugs. GPCRs share some distinctive features, such as the seven transmembrane domains, they also differ in the number of conserved residues in their transmembrane domain. Here we provide an introductory and accessible review detailing the computational advances in GPCR pharmacology and drug discovery. An overview is provided on family A-C GPCRs; their structural differences, GPCR signalling, allosteric binding and cooperativity. The dielectric constant (relative permittivity) of proteins is also discussed in the context of site-specific environmental effects

Low-cell-number, single-tube amplification (STA) of total RNA revealed transcriptome changes from pluripotency to endothelium

Table S1. Summary of the sequencing results. The alignments against the GRCh38 genome assembly (Aligned Reads) were counted for exon reads (exon) and transcript reads based on GENCODE v22. Intronic counts (intron) were defined by transcript counts minus exon ones. Nontranscript reads were used to obtain tRNA counts (tRNA) based on the tRNA database of GENCODE v22. Nontranscript and non-tRNA reads were used for counts on repetitive sequences (repeats) based on RepeatMasker. Those not belonging to any category were defined as unannotated reads (unannotated). The counting of exonic features was based on the “gene_type” attribute in GENCODE v22. The percentages of mature miRNA reads were defined by reads aligned exclusively to the mature “miRNA” feature divided by reads aligned to the “miRNA_primary_transcript” feature of miRBase v21. (DOCX 42 kb

Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP)

ObjectiveThe Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients.MethodsThese data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP.ResultsAs of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0–11.6) years; median follow-up time was 5.2 (range 0–10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias.ConclusionsSince the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab.Trial registration numberNCT00493298

Barriers to women entering surgical careers: a global study into medical student perceptions

Background Barriers to female surgeons entering the field are well documented in Australia, the USA and the UK, but how generalizable these problems are to other regions remains unknown. Methods A cross-sectional survey was developed by the International Federation of Medical Students' Associations (IFMSA)'s Global Surgery Working Group assessing medical students' desire to pursue a surgical career at different stages of their medical degree. The questionnaire also included questions on students' perceptions of their education, resources and professional life. The survey was distributed via IFMSA mailing lists, conferences and social media. Univariate analysis was performed, and statistically significant exposures were added to a multivariate model. This model was then tested in male and female medical students, before a further subset analysis by country World Bank income strata. Results 639 medical students from 75 countries completed the survey. Mentorship [OR 3.42 (CI 2.29–5.12) p = 0.00], the acute element of the surgical specialties [OR 2.22 (CI 1.49–3.29) p = 0.00], academic competitiveness [OR 1.61 (CI 1.07–2.42) p = 0.02] and being from a high or upper-middle-income country (HIC and UMIC) [OR 1.56 (CI 1.021–2.369) p = 0.04] all increased likelihood to be considering a surgical career, whereas perceived access to postgraduate training [OR 0.63 (CI 0.417–0.943) p = 0.03], increased year of study [OR 0.68 (CI 0.57–0.81) p = 0.00] and perceived heavy workload [OR 0.47 (CI 0.31–0.73) p = 0.00] all decreased likelihood to consider a surgical career. Perceived quality of surgical teaching and quality of surgical services in country overall did not affect students' decision to pursue surgery. On subset analysis, perceived poor access to postgraduate training made women 60% less likely to consider a surgical career [OR 0.381 (CI 0.217–0.671) p = 0.00], whilst not showing an effect in the men [OR 1.13 (CI 0.61–2.12) p = 0.70. Concerns about high cost of training halve the likelihood of students from low and low-middle-income countries (LICs and LMICs) considering a surgical career [OR 0.45 (CI 0.25–0.82) p = 0.00] whilst not demonstrating a significant relationship in HIC or UMIC countries. Women from LICs and LMICs were 40% less likely to consider surgical careers than men, when controlling for other factors [OR 0.59 CI (0.342–1.01 p = 0.053]. Conclusion Perceived poor access to postgraduate training and heavy workload dissuade students worldwide from considering surgical careers. Postgraduate training in particular appears to be most significant for women and cost of training an additional factor in both women and men from LMICs and LICs. Mentorship remains an important and modifiable factor in influencing student's decision to pursue surgery. Quality of surgical education showed no effect on student decision-making