Microarray-based ultra-high resolution discovery of genomic deletion mutations

BACKGROUND: Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low. RESULTS: Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size. CONCLUSIONS: Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence

Solvent effects on the three-photon absorption cross-section of a highly conjugated fluorene derivative

Herein, we report the study of the three-photon absorption cross-section dependence on solvents parameters for a highly conjugated organic dye, 2,2(\u27)-(4,4(\u27)-(1E,1(\u27)E)-2,2(\u27)-(9,9-didecyl-9H-fluorene-2,7-diyl) bis(ethene-2,1-diyl)bis(4,1-phenylene))dibenzo[d]thiazole (A-pi-pi-pi-A). The three-photon absorption cross-section was measured for this organic dye in solution in four different solvents with polarity function, Delta f between 0.162 and 0.247. The experiments show how the solvent\u27s reorientation of the electrons and polarity contribute to the 3PA cross-section. Multiphoton-absorption experiments of A-pi-pi-pi-A in all four different solvents were performed with a tunable OPG pumped by a 25 picosecond Nd-YAG laser

The impact of the pi-electron conjugation length on the three-photon absorption cross section of fluorene derivatives

The three-photon absorption cross sections of three different fluorene derivatives, with extended pi-electron conjugation lengths was experimentally measured and compared with shorter pi-electron conjugation length analogs. The effect of the conjugation length on the three-photon absorption cross section sigma(3)\u27 of this family of molecules has been elucidated. It is demonstrated that sigma(3)\u27 of the asymmetric compound D-pi-pi-pi-A is 6.6 times larger than its shorter configuration D-pi-A, while for the symmetric compounds D-pi-pi-pi-D and A-pi-pi-pi-A a two-fold enhancement was found relative to their shorter conjugation length analogs. Measurements of the three-photon excitation of these compounds in THF solution (10(-3)M) were accomplished with a tunable optical pulse generation pumped by a 25 ps Nd-YAG laser

Thermally controlled preferential molecular aggregation state in a thiacarbocyanine dye

Herein we report the experimental and theoretical study of the temperature dependence of a thiacarbocyanine dye in its monomer, H- and J-aggregates states. We demonstrate the ability to control the ratio of monomer, H- and/or J-aggregates with heat. We link such a control to the conformation dependence of the molecule. An alternative way to gain access to the dominating species without changing the concentration as a complete switching mechanism between all the present species is proposed. The results presented in this work lead to a better understanding of thiacarbocyanine dye\u27s behavior

One- and Two-Photon Stimulated Emission Depletion of a Sulfonyl-Containing Fluorene Derivative

One- and two-photon stimulated emission transitions were investigated by the fluorescence quenching of a sulfonyl-containing fluorene compound, 2,7-bis(4-(phenylsulfonyl)styryl)-9,9-didecyl-9H-fluorene (1), in solution at room temperature using a picosecond pump-probe technique. The nature of stimulated transitions under various fluorescence excitation and quenching conditions was analyzed theoretically, and good agreement with experimental data was demonstrated. Two-photon stimulated transitions S1f S0 were shown for 1 at λq) 1064 nm, representing the first report of two-photon stimulated emission depletion (STED) in a molecular system. The two-photon stimulated emission cross section, δ2PE(λq), of fluorene 1 was estimated to be ∼240-280 GM, suggesting that this compound may be a good candidate for use in two-photon STED microscopy. 1

Linear and nonlinear optical characterizations of a monomeric symmetric squaraine-based dye in solution

The photophysical properties of a symmetric squaryllium dye, namely, 2,4-bis[4-(N,N-dibutylamino)-2-hydroxyphenyl] squaraine (SQ), in its monomer form in acetone solution, have been thoroughly studied by means of one-photon absorption (1PA) and two-photon absorption (2PA), excitation anisotropy, fluorescence emission, fluorescence quantum yield, and excited state absorption. The results show that there is a strong one-photon allowed absorption band in the near IR region associated with intramolecular charge transfer. Higher one-photon allowed and forbidden singlet excited states were also revealed by absorption and excitation anisotropy. A relatively high fluorescence quantum yield (0.44) was measured for this dye. The nonlinear optical characterization of SQ in solution confirms the ability of squaraine dyes to be used as good two-photon absorbers. Additionally, it was found that this dye presents both saturable and reverse saturable absorption effects. Density functional theory calculations of the 1PA and 2PA electronic spectra of SQ were carried out to support the experimental data. A detailed analysis of the symmetry and energy of the orbitals involved in the lowest five electronic transitions is presented and discussed in relation to the behavior observed experimentally

Two-Photon Interferometry for High-Resolution Imaging

We discuss advantages of using non-classical states of light for two aspects of optical imaging: creating of miniature images on photosensitive substrates, which constitutes the foundation for optical lithography, and imaging of micro objects. In both cases, the classical resolution limit given by the Rayleigh criterion is approximately a half of the optical wavelength. It has been shown, however, that by using multi-photon quantum states of the light field, and multi-photon sensitive material or detector, this limit can be surpassed. We give a rigorous quantum mechanical treatment of this problem, address some particularly widespread misconceptions and discuss the requirements for turning the research on quantum imaging into a practical technology.Comment: Presented at PQE 2001. To appear in Special Issue of Journal of Modern Optic

Improving the Targeting of Treatment: Evidence from College Remediation

At an annual cost of roughly $7 billion nationally, remedial coursework is one of the single largest interventions intended to improve outcomes for underprepared college students. But like a costly medical treatment with non-trivial side effects, the value of remediation overall depends upon whether those most likely to benefit can be identified in advance. This NBER working paper uses administrative data and a rich predictive model to examine the accuracy of remedial screening tests, either instead of or in addition to using high school transcript data to determine remedial assignment. The authors find that roughly one in four test-takers in math and one in three test-takers in English are severely mis-assigned under current test-based policies, with mis-assignments to remediation much more common than mis-assignments to college-level coursework. Using high school transcript information—either instead of or in addition to test scores—could significantly reduce the prevalence of assignment errors. Further, the choice of screening device has significant implications for the racial and gender composition of both remedial and college-level courses. Finally, if institutions took account of students’ high school performance, they could remediate substantially fewer students without lowering success rates in college-level courses

Remedial Placement Testing in Community Colleges: What Resources Are Required, and What Does It Cost?

In this paper, the authors estimate the costs to colleges and students of remedial placement systems at community college. Using the ingredients method, they catalog the inputs required to perform placement tests and price these inputs out to derive the total cost of assigning students to either college-level or remedial courses. The authors use detailed data from three community colleges for their costs analysis. The authors find that colleges spend $30–$44 per student per subject (English or math) on assessing students for placement into remediation. Student time represents a substantial proportion of the total burden of placement testing; when this time is included, the total costs rise to $54–$71 per student per subject. These amounts appear low compared with the costs of “treatment” (remediation) and compared with the costs of misplacement of students into remediation instead of college-level courses

Mega three-photon absorption cross-section enhancement in pseudoisocyanine J-aggregates

Herein we report an extraordinary three-photon absorption cross-section (sigma(3)(\u27)) enhancement in J-aggregates supramolecular systems. The much higher value of sigma(3)(\u27) in PIC J-aggregate (2.5x10(-71) cm(6) s(2) ph(-2)) compared to typical values obtained in organic molecules (10(-80) cm(6) s(2) ph(-2)) is attributed to the strong molecular transition dipole moment coupling in the supramolecular assembly. Three-photon absorption of PIC J-aggregates and monomer aqueous solutions were measured using the well known open aperture Z-scan technique pumping with a 25 ps pulse laser-OPG system at 1720 nm. This novel result opens new expectations for applications of supramolecular systems in bioimaging and medicine