Copy number variations and cognitive phenotypes in unselected populations

IMPORTANCE: The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE: To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS: The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES: Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS: Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1 Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P = 1.06e-04) among 248 (≥250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (≥1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P = .005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P = 1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE: Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health.

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Copy&Paste façanes procedurals per skylineEngine

L’objectiu d’aquest projecte és el desenvolupament d’una eina d’alt nivell pel modelatged’edificis procedurals que permeti copiar i enganxar parts arbitràries d’un edifici en un altre.Els edificis procedurals es basen en l’execució iterativa d’un conjunt de regles, que es podenrepresentar per un graf d’operacions. Per tant, l’operació de copiar i enganxar es centra enla reescriptura dels grafs de regles amb l’objectiu de modificar els edificis per tal de duraquesta tasca. Donat que es treballa sobre la plataforma de recerca anomenada skylineEngine,que s’executa sobre el programari Houdini 3D, l’aplicació també estarà implementada a sobred’aquesta plataforma

Psychophysical estimation of acid intensity and determination of sweet-acid interaction in a fish paste containing glycerol

In a fish paste made with cooked Brazilian flathead (Percophis brasiliensis), glycerol (17%), sodium chloride (1.5%) and potassium sorbate (0.1%) the following acid percentages: 0.2; 0.4; 0.6; 0.8, 1 and 1.5% w/w were incorporated to determine the relationship between added acetic acid and the sensorially perceived intensity, and the effects of the combination of sweet-acid tastes. Tests for paired comparison, ranking and structured verbal scales for sweet and acid attributes and psychophysical test were carried out. There was a perceptible difference among samples for differences of 0.4 units of acid concentration. Samples indicated as sweeter by 89.47% of the judges were those containing a lesser acid concentration. A reduction in glycerol sweetness when increasing acid levels was observed. Acetic acid reduced the sweetness of glycerol and inversely glycerol reduced the acidity of acetic acid. The data obtained with the magnitude estimation test agree with Steven's law.

Effect of preparation practices and the cowpea cultivar Vigna unguiculata L.Walp on the quality and content of myo-inositol phosphate in akara (fried bean paste)

Akara is one of Brazil's national treasures prepared from cowpea (Vigna unguiculata L.Walp), grated onions and salt and deep-fried in crude palm oil. The results of this study on akara preparation methods showed that, in general, cowpeas were soaked for up 3 hours at room temperature, and the seed coats were then removed. The akara makers preferred the olho de pombo cultivar, because of its cream hue, or the macassar cultivar because it produces a crispier paste. The seeds purchased from street markets had lower ranges of InsP6, InsP5, and InsP4 (1.03-7.62 ∝mol.g- 1; 0.14-1.31 ∝mol.g- 1; and 0.0-0.10 ∝mol.g- 1, respectively) than both the paste and akara (6.72-19.24 ∝mol.g- 1; 1.29-4.57 ∝mol.g- 1; 0.0-0.76 ∝mol.g- 1; 3.31-13.71 ∝mol.g- 1; 0.0-4.48 ∝mol.g- 1; and 0.0-1.32 ∝mol.g- 1). These results suggest that other beans or cowpea varieties have been used in the preparation of akara and that the phytate levels do not affect its nutritional quality.

Effect of huitlacoche (Ustilago maydis DC Corda) paste addition on functional, chemical and textural properties of tortilla chips

AbstractThis study analyzed the addition of huitlacoche paste (HP) in baked tortilla chips (TC), evaluating its effects on functional, physicochemical and structural changes during processing. Two blue corn grains were nixtamalized, stone milled, air dried and milled to obtain flour; commercial blue corn flour (TM1) and commercial TC (TM2) were used as controls. Additions of 0, 3, 6 and 9% of HP were formulated; masas were prepared at 55% moisture content (MC), precooked and baked in an industrial machine. TC crispiness was influenced by grain characteristics and percentage of HP. Huitlacoche paste addition caused an increase in total dietary fiber (from 5.27 to 14.54%), total soluble phenolics content (from 17.52 to 37.60 mg GAE/100 g) and antioxidant capacity (from 6.74 to 7.98 μmol TE/g) in TC. Results suggest that tortilla chips added with huitlacoche can be an alternative to prepare this traditional edible fungus and produce healthier snacks, not fried and enriched with bioactive compounds.

General regulations and orders, 1804

Bound with: The manual and platoon exercises, &c., &c. (51 p.) and: General orders and observations on the movement and field exercise of infantry (16 p.) Inscribed on front paste-down: L. Colonel Brock. Also inscribed: Maj. Genl T.A. Smith late of the 1st. Rifle Regt. Bookplate of Robert B. Taylor, Norfolk. On front flyleaf: lengthy, two-page transcription in ink, headed /Copy/Circular/ dated "Horse Guards, 25th May '07" and signed: "Harry Calvert Adjt. General.

General regulations and orders, 1804

Bound with: The manual and platoon exercises, &c., &c. (51 p.) and: General orders and observations on the movement and field exercise of infantry (16 p.) Inscribed on front paste-down: L. Colonel Brock. Also inscribed: Maj. Genl T.A. Smith late of the 1st. Rifle Regt. Bookplate of Robert B. Taylor, Norfolk. On front flyleaf: lengthy, two-page transcription in ink, headed /Copy/Circular/ dated "Horse Guards, 25th May '07" and signed: "Harry Calvert Adjt. General.

Probate (copy) of the Last Will and Testament of Thomas Clark Street of Stamford Township

Probate (copy) of the Last Will and Testament of Thomas Clark Street of Stamford Township. This is a printed copy which is signed by Charles A. Mittleberger, student at law, Oct. 18, 1872.

Indenture between Samuel DeVeaux Woodruff and Her Majesty the Queen (copy)

Indenture between Samuel DeVeaux Woodruff and Her Majesty the Queen (copy) regarding Lots no. 20 and 21 in the 5th and 6th Concessions in the Town of Grantham (handwritten 3 pages), Aug. 16, 1880

Form letter: a printed, 2 1/2 page copy of Jarvis Conklin and Co. Mortgage, Loans and Municipal Bonds letter to S.D. Woodruff, signed by James Conklin

Form letter: a printed, 2 1/2 page copy of Jarvis Conklin and Co. Mortgage, Loans and Municipal Bonds letter to S.D. Woodruff, signed by James Conklin, n.d.

Receipt (copy) for the amount received from Burton and Bro. for the sum of $944.00 paid in full

Receipt (copy) for the amount received from Burton and Bro. for the sum of $944.00 paid in full for stumpage on berths 192 and 198. It is signed by S.D. Woodruff, May 24, 1878.

Second copy of the memorandum respecting differences between the approximate and final estimate but this one has “memorandum of extras of Brown and McDonall contract” written on the outer page

Second copy of the memorandum respecting differences between the approximate and final estimate but this one has “memorandum of extras of Brown and McDonall contract” written on the outer page (3 pages, handwritten), n.d.

Voucher from the Engineer Department of Port Dalhousie and Thorold Railway Extension for W.G. Thompson for the Northern Division. There are attached notes from the Welland Railway Company to John Mitchell for putting up shelves; to William Waud, staff; and to William Martin to repair the office (copy), June 10, 1857

Voucher from the Engineer Department of Port Dalhousie and Thorold Railway Extension for W.G. Thompson for the Northern Division. There are attached notes from the Welland Railway Company to John Mitchell for putting up shelves; to William Waud, staff; and to William Martin to repair the office (copy), June 10, 1857.

Pay roll voucher #20 from the Engineer Department of Port Dalhousie and Thorold Railway Extension, for the Northern Division approved by F. Shanly, chief engineer and W.G. Thompson, assistant engineer (copy) June 1857

Pay roll voucher #20 from the Engineer Department of Port Dalhousie and Thorold Railway Extension, for the Northern Division approved by F. Shanly, chief engineer and W.G. Thompson, assistant engineer (copy) June 1857.