Mutation pattern is not effected by sample collection.

<p><b>(A-B)</b> Lego plot of single-nucleotide variants plotted by sequence context for variants with allelic fractions > 0.05 and < 0.95. Samples collected in <b>A)</b> EDTA tubes and <b>B)</b> Streck tubes were combined and plots show the sum of the three samples.</p

Microarray results.

<p>Microarray results.</p

Sequencing coverage is not effected by sample collection tube.

<p><b>(A-B)</b> Box plots of the read coverage for target regions binned by GC content for samples collected in <b>A)</b> EDTA tubes or <b>B)</b> Streck tubes. For all box plots, the central box indicates values in the range 25^th-75^th percentile of all values for that subset of data with the central line indicating the median. Whiskers extend 1.5x from the lower and upper boundaries of the central box with points outside that range indicated as black circles.</p

WES variant calls.

<p>WES variant calls.</p

DNA extraction and sequencing metrics.

<p>DNA extraction and sequencing metrics.</p

Evaluación del horno de curado de tabaco por convección forzada usco-madr1

Teniendo como base la infraestructura existente de un horno tradicional de curado de tabaco, se rediseño e implementó en él un sistema de intercambio de calor por convección forzada que funciona con cisco de café como combustible. Este horno de curado de tabaco por convección forzada USCO-MADR fue evaluado durante el periodo de cosecha, lográndose un manejo controlado de las variables de temperatura y humedad relativa dentro de él durante las tres etapas del curado de la hoja de tabaco; el equipo utilizado tuvo un excelente desempeño al emplear cisco de café como combustible con los siguientes consumos durante el proceso de curado: en la fase de “amarillamiento”, 8,92 kilogramos por hora; en la de “secado de paño y fijación de color”, 17,75 kilogramos por hora; y en la de “secado de vena”, 19,29 kilogramos por hora; el análisis comparativo de los costos operativos del horno evaluado, con los ajustes propuestos a éste, permiten presentarlo a la cadena de tabaco como una alternativa promisoria.A traditional oven for curing tobacco leaves was redesigned (based on existing infrastructure); a forced-convection heat exchan- ger system was implemented in it which worked with coffee hulls as fuel. This oven (called a forced-convection tobacco leaf curing oven) was evaluated during the harvesting season. It was found that temperature and relative humidity inside the furnace could be controlled with this assembly during the three stages involved in curing tobacco leaves. The equipment used performed excellently when using coffee hulls as fuel, having the following approximate consumption during curing: 8.92 kilograms per hour during the yellowing stage, 17.75 kilograms per hour during the leaf drying and color fixation phase and 19.29 kilograms per hour during the stem drying stage. Comparative analysis of the oven’s operating costs along with the proposed adjustments to be made to it would allow its implementation as a promising alternative in the existing tobacco chain

Intronic mutations in 18 TSC NMI subjects.

<p>The locations of 18 splice site mutations identified are shown relative to the canonical consensus sequences present at the 3’ exon region, the branch site, and the 5’ exon region.</p

Correlation between clinical features and mutation status in 53 NMI subjects.

<p>(A) The proportion of subjects with 2, 3, or 4 organs affected; with heterozygous or mosaic mutations, or persistent NMI status. P = 0.003. (B) The number of major symptoms seen for each subject sorted according to mutation status. Note that differing levels of mosaicism have different symbols according to allele frequency (AF). (C) Age at the time of clinical evaluation, sorted according to mutation status. Het, heterozygous; Mos, mosaic. P values determined by chi square test (A) and Mann-Whitney unpaired test (B and C). Results with p < 0.05 are considered statistically significant.</p

Impact of ectopic expression of <i>Src</i>^E527K in parental OE19 on lapatinib sensitivity and cell signalling.

<p><b>A,</b> Dose-response curves for lapatinib in the non-transduced parental OE19 (OE19 ^Mock), transduced with GFP (OE19 ^GFP), wild-type <i>Src</i> (OE19 ^{Src wild-type}) or <i>Src</i>^E527K mutation (OE19 ^{Src E527K}). The calculated values of IC₅₀ for lapatinib was >1,000 nM in OE19 ^{Src E527K} cells. Values were presented as relative cellular viability relative to vehicle-treated controls with the mean ± S.E. of quadruplicate from a representative experiment. The <i>p</i> value calculated by two-way ANOVA was 0.376 for mock <i>vs</i> control (GFP), <0.0001 for control <i>vs</i> wild-type Src, and <0.0001 for control <i>vs Src</i>^E527K. <b>B,</b> Relative cell viability lapatinib in the non-transduced parental OE19 (OE19 ^Mock), transduced with GFP (OE19 ^GFP), wild-type <i>Src</i> (OE19 ^{Src wild-type}) or <i>Src</i>^E527K mutation (OE19 ^{Src E527K}). The <i>p</i> values were calculated by two-tailed <i>t</i>-test. Values were presented as relative cellular viability relative to vehicle-treated controls with the mean ± S.E. of quadruplicate from a representative experiment. <b>C,</b> Immunoblots showing changes of various signalling proteins after treatment with 1 µM concentration of lapatinib or saracatinib, either alone or combination, in the OE19 cells with or without Src ^E527K transduction.</p

Pie charts displaying the mutation types and frequencies in 53 TSC NMI subjects.

<p>(A) Proportion of subjects with mutations identified vs. remaining as persistent NMI. (B) Proportion of mutations in <i>TSC1</i> vs. <i>TSC2</i>. (C) Proportion of heterozygous vs. mosaic mutations. (D) Different types of identified mutations.</p