Nonalternating Sequences Research Articles

Diadochokinesis Performance and Its Link to Cognitive Control: Alternating Versus Non-Alternating Diadochokinesis.

In a previous publication, we observed that maximum speech performance in a nonclinical sample of young adult speakers producing alternating diadochokinesis (DDK) sequences (e.g., rapidly repeating "pataka") was associated with cognitive control: Those with better cognitive switching abilities (i.e., switching flexibly between tasks or mental sets) showed higher DDK accuracy. To follow up on these results, we investigated whether this previously observed association is specific to the rapid production of alternating sequences or also holds for non-alternating sequences (e.g., "tatata"). For the same sample of 78 young adults as in our previous study, we additionally analyzed their accuracy and rate performance on non-alternating sequences to investigate whether executive control abilities (i.e., indices of speakers' updating, inhibition, and switching abilities) were more strongly associated with production of alternating, as compared with non-alternating, sequences. Of the three executive control abilities, only switching predicted both DDK accuracy and rate. The association between cognitive switching (and updating ability) and DDK accuracy was only observed for alternating sequences. The DDK rate model included a simple effect of cognitive switching, such that those with better switching ability showed slower diadochokinetic rates across the board. Thus, those with better cognitive ability showed more accurate (alternating) diadochokinetic production and slower maximum rates for both alternating and non-alternating sequences. These combined results suggest that those with better executive control have better control over their maximum speech performance and show that the link between cognitive control and maximum speech performance also holds for non-alternating sequences.

Thin smectic liquid crystalline fibrils of chiral rodlike particles.

Inspired by recent experimental work on virus-polymer mixtures, we study the properties of thin smectic fibrils composed of chiral rodlike particles using Monte Carlo simulations. Due to the interplay between surface energy, elastic deformation energy, and entropic effects, the fibril's layers relax into a twisted state. We focus our study on the layers' twist direction and map our results to the antiferromagnetic Ising model. In this view, the chiral interaction mimics an external field that drives the layers to have the same sense of twist. Besides, we determine the free energy difference and barrier height between an alternating and a nonalternating sequence of twisted layers composed of achiral rods and find that an alternating sequence is slightly preferred. We also see that the fibrils contract on increasing the chiral interaction strength and think that further studies on self-assembled functional materials can use our results.

Charge-Transfer Excited States and Proton Transfer in Model Guanine-Cytosine DNA Duplexes in Water

Characterization of the excited electronic states and relaxation processes in DNA systems is critical for understanding the physical basis of radiation damage. Spectroscopic studies have shown evidence of coupling between the relaxation dynamics of photoinduced charge-transfer states and interstrand proton transfer in DNA duplexes, where a deuterium isotope effect was observed for duplexes with alternating sequences but not with nonalternating sequences. We performed quantum mechanical/molecular mechanical (QM/MM) calculations of the vertical excitation energies and excited state proton potential energy curves for model DNA duplexes comprised of three guanine-cytosine pairs with alternating and nonalternating sequences in aqueous solution. Our calculations indicate that the intrastrand charge-transfer states are lower in energy for the alternating sequence than for the nonalternating sequence. The more accessible intrastrand charge-transfer states could provide a relaxation pathway coupled to interstrand proton transfer, thereby providing a possible explanation for the experimentally observed deuterium isotope effect in duplexes with alternating sequences.

Compositions as non-alternating sequences of partitions

Compositions are conceptualized as non alternating sequences of blocks of non-decreasing and strictly decreasing partitions. We find the generating function F(x; y; q) where x marks the size of the composition, y the number of parts and q the number of such partition blocks minus 1. We form these blocks starting on the left-hand-side of the composition and maximizing the size of each block. We also find the generating function for the total number of such blocks.

Alternating Reversed Scanning Sequence for Improved Within-Wafer Uniformity During Nonmelt Laser Annealing of Arsenic-Implanted Silicon

Beyond the 45-nm technology node, nonmelt laser thermal annealing (LTA) is a potential candidate to replace the spike rapid thermal annealing (RTA) for the formation of ultrashallow and highly activated source/drain extension junctions. However, one major drawback of LTA is that it is ineffective in the removal of implantation-induced damage. As such, arsenic deactivation, as a result of cluster formation due to the release of excess interstitials from the end-of-range (EOR) region, is observed when a post-LTA thermal budget is applied. Since conventional LTA comprises localized heating using a laser beam scanning the wafer front-side in a nonalternating sequence, different portions of the wafer will experience varying post-LTA thermal budget from the hotplate, depending on when the laser beam scans through it. Because dopant deactivation increases as the post-LTA thermal budget increases, severe degradation of the within-wafer uniformity is observed. To address this problem, a multiple-pulse, alternating reversed laser scanning technique is implemented to average out the differences in post-LTA thermal budget across the wafer between each pulse. Using such a scheme, the variations in subsequent dopant deactivation across the wafer is reduced and significant uniformity improvement of up to 50% is observed.

Attention Alters Visual Plasticity during Exposure-Based Learning

It is generally believed that attention enhances the processing of sensory information during perception and learning. Here we report that, contrary to common belief, attention limits the degree of plasticity induced by repeated exposure to image features. Specifically, daily exposure to oriented stimuli that are not linked to a specific task causes an orientation-specific improvement in perceptual performance along the "exposed" axes. This effect is modulated by attention: human subjects showed a larger improvement in orientation discrimination when attention is directed toward the location where stimuli are presented. However, the capacity to perform discriminations away from the exposed orientation is enhanced when the exposure stimuli are unattended. Importantly, the improvement in orientation discrimination at the unattended location leads to a robust enhancement in the discrimination of complex stimuli, such as natural texture images, with orientation components along the exposed axes, whereas the improvement in orientation discrimination at the attended location exhibits only weak transfer to complex stimuli. These results indicate that sensory adaptation by passive stimulus exposure should be viewed as a form of perceptual learning that is complementary to practice-based learning in that it reduces constraints on generalization.

Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

With the goal of developing a better understanding of the antiparasitic biological action of DB75, we have evaluated its interaction with duplex alternating and nonalternating sequence AT polymers and oligomers. These DNAs provide an important pair of sequences in a detailed thermodynamic analysis of variations in interaction of DB75 with AT sites. The results for DB75 binding to the alternating and nonalternating AT sequences are quite different at the fundamental thermodynamic level. Although the Gibbs energies are similar, the enthalpies for DB75 binding with poly(dA)·poly(dT) and poly(dA-dT)·poly(dA-dT) are + 3.1 and − 4.5 kcal/mol, respectively, while the binding entropies are 41.7 and 15.2 cal/mol·K, respectively. The underlying thermodynamics of binding to AT sites in the minor groove plays a key role in the recognition process. It was also observed that DB75 binding with poly(dA)·poly(dT) can induce T·A·T triplet formation and the compound binds strongly to the dT·dA·dT triplex.

DAUNOMYCIN BINDING TO DEOXYPOLYNUCLEOTIDES WITH ALTERNATING SEQUENCES: COMPLETE THERMODYNAMIC PROFILES OF HETEROGENEOUS BINDING SITES

ABSTRACT Complete thermodynamic binding profiles for the interaction of the anticancer drug, daunomycin with natural DNA and synthetic deoxypolynucleotides were described. Fluorescence titration method was used to estimate the equilibrium binding constants. Binding isotherms were found to be surprisingly complex in some cases, presumably because there were heterogeneous sites even in simple deoxypolynucleotides of repeating sequence. Some polynucleotides consisting of alternating sequence contain at least two different binding sites for daunomycin. The binding affinity of the primary binding sites of alternating and non-alternating sequences was found to differ by two orders of magnitude. An isothermal microtitration calorimeter was used to directly measure the binding enthalpy at 25°C with a high sensitivity. The binding enthalpy of poly[d(A-T)] was found to be −5.5 Kcal/mol, which was much lower than any other polynucleotides, while the binding constant of the high affinity sites, was similar. In this report, the complete thermodynamic profiles of daunomycin binding to deoxypolynucleotides were reliably shown for the first time.

Alternating and Non-alternating dG-dC Hexanucleotides Crystallize as CanonicalA-DNA

We have solved the single-crystal X-ray structures of two different hexanucleotides: the alternating sequence d(Gm5CGm5CGC), and the non-alternating sequence d(Gm5CCGGC). Both of these hexamers crystallize readily asA-DNA in the orthorhombic space groupC2221. Although hexanucleotides have been previously crystallized asZ-DNA, and in one case asB-DNA, this is the first time hexanucleotides have been crystallized asA-DNA. Both hexamers adopt a typicalA-conformation, which is surprisingly more similar to the structure ofA-DNA fibers than to otherA-DNA single crystals. The structure of d(Gm5CGm5CGC) was solved to a resolution of 2.1 Å (R-factor = 19.6%). This structure has all of the features characteristic of canonicalA-DNA, including it's helical repeat (11.2 bp/turn), helical rise (2.6 Å/bp), base-pair displacement (−4.7 Å), base inclination angle (16.9°), and sugar puckers that are predominantly 3′-endo. The lower resolution, non-alternating structure has similar overall average values for these parameters. We observed several sequence-dependent correlations in these parameters, especially in the d(CG) base step. These steps have lower twist and rise values, coupled with high roll angles as compared to d(GC) steps. The molecular interactions involved in crystal packing and the detailed structure of the bound water in the crystals, however, are similar to those of longer 8 and 10 bpA-DNA crystal structures. Although the structural effect of cytosine methylation onA-DNA appears to be minimal, this modification significantly affects the ability of these sequences to crystallise asA-DNA. In conclusion, we present theA-DNA forming class of hexanucleotides, a new crystallographic system for studying DNA structure at near atomic resolution.

Effect of base-pair sequence on the conformations and thermally induced transitions in oligodeoxyribonucleotides containing only AT base pairs

Tm curves, CD spectra, and kinetics results of the self-complementary DNA dodecamers d(A6T6), d(A3T3A3T3), d(A2T2A2T2A2T2), d(ATATATATATAT), and d(T6A6) demonstrate that the thermal transitions of these oligomers at low salt concentration involve a hairpin intermediate. At high salt concentrations (greater than 0.1 M Na+) only a duplex to denatured-strand transition appears to occur. The temperature and salt-concentration regions of the transitions are very sequence dependent. Alternating-type AT sequences have a lower duplex stability and a greater tendency to form hairpins than sequences containing more nonalternating AT base pairs. Of the two nonalternating sequences, d(T6A6) is significantly less stable than d(A6T6). Both oligomers have CD curves that are very similar to the unusual CD spectrum of poly(dA).poly(dT). The Raman spectra of these two oligomers are also quite similar, but at low temperature, small intensity differences in two backbone modes and three nucleoside vibrations are obtained. The hairpin to duplex transition for the AT dodecamers was examined by salt-jump kinetics measurements. The transition is faster than transitions for palindromic-sequence oligomers containing terminal GC base pairs. Stopped-flow kinetics studies indicate that the transition is second order and has a relatively low activation energy. The reaction rate increases with increasing ionic strength. These results are consistent with a three-step mechanism for the hairpin to duplex reaction: (i) fraying of the hairpin oligomers' terminal base pairs, (ii) a rate-determining bimolecular step involving formation of a cruciform-type intermediate from two hairpin oligomers with open terminal base pairs, and (iii) base-pair migration and formation in the intermediate to give the duplex.

Chemical probing of the B-Z transition in negatively supercoiled DNA.

An analysis of the B-to-Z transition as a function of supercoiling for a natural Z-DNA-forming sequence found in plasmid pBR322 is presented at nucleotide resolution. The analysis is based on reactivity to four chemical probes which exhibit hyperreactivity in the presence of Z-DNA: hydroxylamine, osmium tetroxide, diethyl pyrocarbonate and dimethyl sulfate. We find that the initial transition occurs largely within a 14 base pair region which is mostly alternating purines and pyrimidines. With increasing negative supercoiling. Z-DNA extends into flanking regions having less and less alternating character, first one direction and then in the other. Evidence of B-Z junctions is seen at four sites bracketing these three adjacent regions. One of these Z-forming regions contains the non-alternating sequence CTCCT, suggesting that such sequences can form Z-DNA without great difficulty if they are adjacent to alternating sequences. A plasmid containing three copies of a 61 base pair fragment bearing the entire Z-forming region shows equal reactivity of all three copies at any given superhelical density, implying that they compete equally and independently for the torsional strain energy which promotes the B-Z transition, and are unaffected by adjacent sequences more than 20-30 base pairs away.

Polarized Raman scattering from oriented single microcrystals of d(A5T5)2 and d(pTpT).

AbstractPolarized Raman spectra have been obtained from single microcrystals of the duplex of the decamer d(A5T5)2 using a Raman microscope. This is the first report of Raman spectra from a crystal of a deoxyoligomer that contains only long, nonalternating sequences of adenine and thymine. Sequences containing d(A)n and d(T)n are of interest in view of recent suggestions that they induce bends in DNA and that they might exist in a nonstandard B‐conformation. Polarized Raman spectra of a crystal of d(pTpT) have also been obtained. Both crystals display Raman bands whose intensities are very sensitive to the orientation of the crystal with respect to the direction of polarization of the incident laser beam. These spectra indicate that the helical axes of the oligonucleotides are parallel to the long axes of the crystals and that the d(A5T5)2 is not appreciably bent in the crystal. The Raman spectrum from the d(pTpT) crystal indicates that all of the furanose ring puckers are in a C2′‐endo configuration since only the C2′‐endo marker band at 835 ± 5 cm−1 is present. Crystals of d(A5T5)2 show measurable Raman intensities in both the 838‐ and 816‐cm−1 bands. This indicates the presence of both the C2′‐endo and C3′‐endo, or possibly other non‐C2′‐endo, furanose conformations. The 816‐cm−1 band is weak so that only a small fraction of the residues are estimated to be in the non‐C2′‐endo conformation. In both the d(pTpT) and d(A5T5)2 crystals the intensity of the bands due to vibrations of the backbone show only a small dependence on orientation of the crystals. This result is explained by the low symmetry of the puckered sugar rings. It is concluded that Raman spectra obtained from oligonucleotide crystals in which the orientation of the crystal axes to the laser polarization is not carefully controlled may contain intensity artifacts that are due to polarization effects.

Sequence dependent electrophoretic mobilities and melting temperatures for A-T containing oligodeoxyribonucleotides.

The electrophoretic mobilities and thermal melting properties of self complementary A-T containing dodecamer oligodeoxyribonucleotides have been investigated as a function of solution conditions. The oligomers contained tracts of nonalternating A-T base pairs of 2 (d(A2T2)3), 3 (d(A3T3)2), and 6 (d(A6T6] as well as the fully alternating (d(A-T)6) sequence. The melting temperature increased with the length of the nonalternating sequence and was approximately 12 degrees C higher in the d(A6T6) sequence than in the alternating oligomer. Under denaturing conditions all oligomers had the same electrophoretic mobility on acrylamide gels. Under conditions which favor duplex formation, the oligomers exhibited significant sequence dependent mobility differences. The mobilities of two oligomers, d(A-T)6 and d(A6-T6), were approximately equal and were less than those of the other oligonucleotides. The greatest mobility was observed for d(A2T2)3. These results are best explained by a model which requires bending at a junction of two or more continuous A or T bases with another sequence.

The subjective tempo difference between interaural and monaural sequences as a function of sequence length.

Previous research has demonstrated that the subjective tempo of sequences of clicks that alternate between ears is slower than that of nonalternating sequences. Although the stimulus onset asynchronies (SOAs) between the clicks are the same in both conditions, their perceptual onset asynchronies (POAs) differ by 25 msec at all SOA values between 40 and 2,130 msec. It has been suggested that this subjective tempo difference originates only after a few clicks have been processed. The present study shows this not to be the case: The POA difference between interaural and monaural click sequences could also be established with sequences comprising only a few clicks.

Auditory spatial alternation transforms auditory time.

Recent research has shown that a sequence of auditory events that is alternated between the ears is stretched out in auditory memory, as compared with nonalternating sequences. Although the stimulus-onset asynchronies (SOAs) of the interaural and monaural sequences were the same, the perceptual-onset asynchronies (POAs) differed by 24 msec. Because this result was only established for a restricted range of SOAs (125-250 msec), the present study tested a much larger range (40-2,130 msec). It turned out that the POA difference of 25 msec remained invariant over this whole range. Furthermore it was investigated how the angle of alternation affected the POA difference. It was found that (a) this difference increased linearly with increasing angular separation, and (b) the effects of SOA and angular separation on the POA difference were additive. The merits of six different attention-switching models were inspected to explain these results, but none of the models could describe the effects satisfactorily. We offer a new model, the space-time network, that copes not only with the present results but also explains several other studies reported in the literature.

Molecular-mechanical studies of Z-DNA: a comparison of the structural and energetic properties of Z- and B-DNA.

AbstractMolecular‐mechanical studies of the left‐handed Z‐DNA polymers have been carried out and the results compared with similar calculations on B‐DNA polymers. We have studied d(CGCGCG)2, d(GCGCGC)2 (and their 5‐methyl cytosine analogs), dG6·dC6, d(ATATAT)2, and d(TATATA)2 in both B‐ and Z‐forms. For the left‐handed Z helices, we considered the ZI and ZII model of Quigley and co‐workers [Wang, A. H., Quigley, G. J., Kolpak, F. J., Crawford, J. L., van Boom, J. H., van der Marel, G. & Rich, A. (1979) Nature (London) 282, 680–686], the actual “Z spermidine” and “Z spermine” structures of Quigley and the model‐built structure of Chandresekharan et al. [Arnott, S., Chandresekharan, R., Bindsall, D. L., Leslie, A. G. W. & Ratliff, R. L. (1980) Nature 283, 743–745]. The major conclusions of this study are as follows. (1) The stabilization of Z‐DNA relative to B‐DNA occurs as one increases the “effective” dielectric constant or adds counterions, consistent with observations of Z‐DNA only under high salt conditions. (2) The ZII polymer is calculated to be more stable than the ZI polymer. It is not yet clear whether the greater stability of ZII than ZI is a real effect or an artifact caused by the lack of inclusion of specific solvation effects in these calculations. (3) The greater tendency of the 5‐methyl cytosine analog of poly(dG‐dC)·poly(dG‐dC) to undergo the B → Z transition is found in our calculations and is due to destabilizing base–base and base–phosphate interactions, which are greater in the B‐ than in the Z‐form of the 5‐methyl cytosine polymer. (4) There are no large sequence‐dependent effects on the relative stabilities, and the AT polymers are calculated to be as likely to form Z‐helices as the GC polymers. In addition, the relative stability of a nonalternating sequence in the conformation is only slightly less than that found for alternating sequences.