171 research outputs found
Thermodynamic behavior of short oligonucleotides in microarray hybridizations can be described using Gibbs free energy in a nearest-neighbor model
While designing oligonucleotide-based microarrays, cross-hybridization
between surface-bound oligos and non-intended labeled targets is probably the
most difficult parameter to predict. Although literature describes
rules-of-thumb concerning oligo length, overall similarity, and continuous
stretches, the final behavior is difficult to predict. The aim of this study
was to investigate the effect of well-defined mismatches on hybridization
specificity using CodeLink Activated Slides, and to study quantitatively the
relation between hybridization intensity and Gibbs free energy (Delta G),
taking the mismatches into account. Our data clearly showed a correlation
between the hybridization intensity and Delta G of the oligos over three orders
of magnitude for the hybridization intensity, which could be described by the
Langmuir model. As Delta G was calculated according to the nearest-neighbor
model, using values related to DNA hybridizations in solution, this study
clearly shows that target-probe hybridizations on microarrays with a
three-dimensional coating are in quantitative agreement with the corresponding
reaction in solution. These results can be interesting for some practical
applications. The correlation between intensity and Delta G can be used in
quality control of microarray hybridizations by designing probes and
corresponding RNA spikes with a range of Delta G values. Furthermore, this
correlation might be of use to fine-tune oligonucleotide design algorithms in a
way to improve the prediction of the influence of mismatching targets on
microarray hybridizations.Comment: 32 pages on a single pdf fil
The effects of mismatches on hybridization in DNA microarrays: determination of nearest neighbor parameters
Quantifying interactions in DNA microarrays is of central importance for a
better understanding of their functioning. Hybridization thermodynamics for
nucleic acid strands in aqueous solution can be described by the so-called
nearest-neighbor model, which estimates the hybridization free energy of a
given sequence as a sum of dinucleotide terms. Compared with its solution
counterparts, hybridization in DNA microarrays may be hindered due to the
presence of a solid surface and of a high density of DNA strands. We present
here a study aimed at the determination of hybridization free energies in DNA
microarrays. Experiments are performed on custom Agilent slides. The solution
contains a single oligonucleotide. The microarray contains spots with a perfect
matching complementary sequence and other spots with one or two mismatches: in
total 1006 different probe spots, each replicated 15 times per microarray. The
free energy parameters are directly fitted from microarray data. The
experiments demonstrate a clear correlation between hybridization free energies
in the microarray and in solution. The experiments are fully consistent with
the Langmuir model at low intensities, but show a clear deviation at
intermediate (non-saturating) intensities. These results provide new
interesting insights for the quantification of molecular interactions in DNA
microarrays.Comment: 31 pages, 5 figure
Doping Engineering Enables Highly Conductive and Thermally Stable n-Type Organic Thermoelectrics with High Power Factor
This work exploits the scope of doping engineering as an enabler for better-performing and thermally stable n-type organic thermoelectrics. A fullerene derivative with polar triethylene glycol type side chain (PTEG-1) is doped either by "coprocessing doping" with n-type dopants such as n-DMBI and TBAF or by "sequential doping" through thermal deposition of Cs2CO3. Solid-state diffusion of Cs2CO3 appears to dope PTEG-1 in the strongest manner, leading to the highest electrical conductivity of similar to 17.5 S/cm and power factor of 32 mu W/(m K-2). Moreover, the behavior of differently doped PTEG-1 films under thermal stress is examined by electric and spectroscopic means. Cs2CO3-doped films are most stable, likely due to a coordinating interaction between the polar side chain and Cs+-based species, which immobilizes the dopant. The high power factor and good thermal stability of Cs2CO3-doped PTEG-1 make it very promising for tangible thermoelectric applications
Observation of Quantum Interference in Molecular Charge Transport
As the dimensions of a conductor approach the nano-scale, quantum effects
will begin to dominate its behavior. This entails the exciting possibility of
controlling the conductance of a device by direct manipulation of the electron
wave function. Such control has been most clearly demonstrated in mesoscopic
semiconductor structures at low temperatures. Indeed, the Aharanov-Bohm effect,
conductance quantization and universal conductance fluctuations are direct
manifestations of the electron wave nature. However, an extension of this
concept to more practical emperatures has not been achieved so far. As
molecules are nano-scale objects with typical energy level spacings (~eV) much
larger than the thermal energy at 300 K (~25 meV), they are natural candidates
to enable such a break-through. Fascinating phenomena including giant
magnetoresistance, Kondo effects and conductance switching, have previously
been demonstrated at the molecular level. Here, we report direct evidence for
destructive quantum interference in charge transport through two-terminal
molecular junctions at room temperature. Furthermore, we show that the degree
of interference can be controlled by simple chemical modifications of the
molecule. Not only does this provide the experimental demonstration of a new
phenomenon in quantum charge transport, it also opens the road for a new type
of molecular devices based on chemical or electrostatic control of quantum
interference
Evidence for Quantum Interference in SAMs of Arylethynylene Thiolates in Tunneling Junctions with Eutectic Ga-In (EGaIn) Top-Contacts
This paper compares the current density (J) versus applied bias (V) of self-assembled monolayers (SAMs) of three different ethynylthiophenol-functionalized anthracene derivatives of approximately the same thickness with linear-conjugation (AC), cross-conjugation (AQ), and broken-conjugation (AH) using liquid eutectic Ga-In (EGaIn) supporting a native skin (~1 nm thick) of Ga2O3 as a nondamaging, conformal top-contact. This skin imparts non-Newtonian rheological properties that distinguish EGaIn from other top-contacts; however, it may also have limited the maximum values of J observed for AC. The measured values of J for AH and AQ are not significantly different (J ≈ 10-1 A/cm2 at V = 0.4 V). For AC, however, J is 1 (using log averages) or 2 (using Gaussian fits) orders of magnitude higher than for AH and AQ. These values are in good qualitative agreement with gDFTB calculations on single AC, AQ, and AH molecules chemisorbed between Au contacts that predict currents, I, that are 2 orders of magnitude higher for AC than for AH at 0 < |V| < 0.4 V. The calculations predict a higher value of I for AQ than for AH; however, the magnitude is highly dependent on the position of the Fermi energy, which cannot be calculated precisely. In this sense, the theoretical predictions and experimental conclusions agree that linearly conjugated AC is significantly more conductive than either cross-conjugated AQ or broken conjugate AH and that AQ and AH cannot necessarily be easily differentiated from each other. These observations are ascribed to quantum interference effects. The agreement between the theoretical predictions on single molecules and the measurements on SAMs suggest that molecule-molecule interactions do not play a significant role in the transport properties of AC, AQ, and AH.
Sporadic hemangioblastomas are characterized by cryptic VHL inactivation
Abstract
Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.http://deepblue.lib.umich.edu/bitstream/2027.42/110224/1/40478_2014_Article_167.pd
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