Suppression of alias and replica noises in phase holograms using fractal topologies.

Two-dimensional fractal topologies featuring (scaling) self-similarity, dense set of Bragg (diffraction) peaks, and inherent rotation symmetry, which are not achievable with regular grid-matrix geometries, exhibit optical robustness against structural damage and noise immunity of optical transmission paths. In this work, we numerically and experimentally demonstrate phase holograms using fractal plane-divisions. By taking advantage of the symmetries of the fractal topology, we propose numerical algorithms to design the fractal holograms. This algorithm solves the inapplicability of the conventional iterative Fourier transform algorithm (IFTA) method and enables efficient optimizations of millions of adjustable parameters in the optical element. Experimental samples show that the alias and replica noises in the image plane of fractal holograms are clearly suppressed, facilitating applications for high-accuracy and compact requirements.

Preparation and in vivo investigation of oligomeric proanthocyanidins cross-linked collagen serving as synthesized tissue regeneration membrane.

In this study, type I collagen membranes were prepared using oligomeric proanthocyanidins (OPCs) as the cross-linking agent. The fabricated materials were evaluated to be applied as guided tissue regeneration membranes for periodontal defects. The mechanical strength of the cross-linked collagen membranes, namely OPCs-Col films, using different concentrations of OPCs ranged from 30 to 60 kPa. The cross-linked collagen membranes had better thermal stability than non-cross-linked one and could effectively resist the decomposition in collagenase solution as long as fifty days. The results of material characterization showed that 10% OPCs-Col film was ideal for our purpose. In vitro study using L929 and MG-63 cells revealed that 10% OPCs-Col film had great biocompatibility while OPC was demonstrated to be not cytotoxic as glutaraldehyde and genipin but even promote L929 cells. The material was further studied for in vivo studies with two models, subcutaneous and cranium defects in rat. The subcutaneous test showed that the regeneration membrane degraded till one month and the inflammatory response also reduced with implantation time. When implanted into the cranium defect, no lesions of the brain were caused and new bone tissue was observed inside the material. The results of in vivo studies showed that the synthesized membrane was helpful for tissue regeneration with long degradation time. The tissue regeneration membranes can barrier the rapid growing soft tissue, in order to save the capacity for the growth of neo bone.

Performance comparison of III-V//Si and III-V//InGaAs multi-junction solar cells fabricated by the combination of mechanical stacking and wire bonding.

The integration of III-V and Si multi-junction solar cells as photovoltaic devices has been studied in order to achieve high photovoltaic conversion efficiency. However, large differences in the coefficients of thermal expansion and the lattice parameters of GaAs, Si, and InGaAs have made it difficult to obtain high-efficiency solar cells grown as epilayers on Si and InP substrates. In this paper, two types of devices, including GaInP/GaAs stacked on Si (GaInP/GaAs//Si) and GaInP/GaAs stacked on InGaAs (GaInP/GaAs//InGaAs), are fabricated via mechanical stacking and wire bonding technologies. Mechanically stacked GaInP/GaAs//Si and GaInP/GaAs//InGaAs triple-junction solar cells are prepared via glue bonding. Current-voltage measurements of the two samples are made at room temperature. The short-circuit current densities of the GaInP/GaAs//Si and GaInP/GaAs//InGaAs solar cells are 13.37 and 13.66 mA/cm2, while the open-circuit voltages of these two samples are measured to be 2.71 and 2.52 V, respectively. After bonding the GaInP/GaAs dual-junction with the Si and InGaAs solar cells, the conversion efficiency is relatively improved by 32.6% and 30.9%, respectively, compared to the efficiency of the GaInP/GaAs dual-junction solar cell alone. This study demonstrates the high potential of combining mechanical stacked with wire bonding and ITO films to achieve high conversion efficiency in solar cells with three or more junctions.

Relationship between calorimetric profiles and differential melting curves for natural DNAs.

Many experiments demonstrate that regions with higher GC-content in natural DNAs unwind at higher temperatures adsorbing more heat than equivalently sized regions with lower GC-content. This simple observation implies that normalized calorimetric melting profiles (calorimetric cDMCs) will not be equivalent differential melting curves (DMCs). We propose simple expressions for long natural and random DNA sequences to reciprocally convert DMCs and corresponding calorimetric cDMCs. The expressions are confirmed by the Poland-Fixman-Freire method and an approach based upon mixtures of homopolymeric duplexes. Using these expressions and experimental calorimetric data, we demonstrate that the average relative deviation between DMC and cDMC is proportional to the temperature melting range of the helix-coil transition ΔT. Corresponding difference between melting temperatures is proportional to ΔT2. In general, sequence and ionic conditions influence the deviation through their effect on ΔT. On the basis of the developed approach, we propose a method to determine the thermodynamic melting temperature (ratio of calorimetric enthalpy and entropy of the helix-coil transition) for natural DNAs from optical DMCs without calorimetric experiments.

Estimation of the diversity between DNA calorimetric profiles, differential melting curves and corresponding melting temperatures.

The Poland-Fixman-Freire formalism was adapted for modeling of calorimetric DNA melting profiles, and applied to plasmid pBR 322 and long random sequences. We studied the influence of the difference (HGC -HAT ) between the helix-coil transition enthalpies of AT and GC base pairs on the calorimetric melting profile and on normalized calorimetric melting profile. A strong alteration of DNA calorimetrical profile with HGC -HAT was demonstrated. In contrast, there is a relatively slight change in the normalized profiles and in corresponding ordinary (optical) normalized differential melting curves (DMCs). For fixed HGC -HAT , the average relative deviation (S) between DMC and normalized calorimetric profile, and the difference between their melting temperatures (Tcal -Tm ) are weakly dependent on peculiarities of the multipeak fine structure of DMCs. At the same time, both the deviation S and difference (Tcal -Tm ) enlarge with the temperature melting range of the helix-coil transition. It is shown that the local deviation between DMC and normalized calorimetric profile increases in regions of narrow peaks distant from the melting temperature.

Determination of melting temperature and temperature melting range for DNA with multi-peak differential melting curves.

Many factors that change the temperature position and interval of the DNA helix-coil transition often also alter the shape of multi-peak differential melting curves (DMCs). For DNAs with a multi-peak DMC, there is no agreement on the most useful definition for the melting temperature, Tm, and temperature melting width, ΔT, of the entire DNA transition. Changes in Tm and ΔT can reflect unstable variation of the shape of the DMC as well as alterations in DNA thermal stability and heterogeneity. Here, experiments and computer modeling for DNA multi-peak DMCs varying under different factors allowed testing of several methods of defining Tm and ΔT. Indeed, some of the methods give unreasonable "jagged" Tm and ΔT dependences on varying relative concentration of DNA chemical modifications (rb), [Na(+)], and GC content. At the same time, Tm determined as the helix-coil transition average temperature, and ΔT, which is proportional to the average absolute temperature deviation from this temperature, are suitable to characterize multi-peak DMCs. They give smoothly varying theoretical and experimental dependences of Tm and ΔT on rb, [Na(+)], and GC content. For multi-peak DMCs, Tm value determined in this way is the closest to the thermodynamic melting temperature (the helix-coil transition enthalpy/entropy ratio).

DNA combing on low-pressure oxygen plasma modified polysilsesquioxane substrates for single-molecule studies.

Molecular combing and flow-induced stretching are the most commonly used methods to immobilize and stretch DNA molecules. While both approaches require functionalization steps for the substrate surface and the molecules, conventionally the former does not take advantage of, as the latter, the versatility of microfluidics regarding robustness, buffer exchange capability, and molecule manipulation using external forces for single molecule studies. Here, we demonstrate a simple one-step combing process involving only low-pressure oxygen (O2) plasma modified polysilsesquioxane (PSQ) polymer layer to facilitate both room temperature microfluidic device bonding and immobilization of stretched single DNA molecules without molecular functionalization step. Atomic force microscopy and Kelvin probe force microscopy experiments revealed a significant increase in surface roughness and surface potential on low-pressure O2 plasma treated PSQ, in contrast to that with high-pressure O2 plasma treatment, which are proposed to be responsible for enabling effective DNA immobilization. We further demonstrate the use of our platform to observe DNA-RNA polymerase complexes and cancer drug cisplatin induced DNA condensation using wide-field fluorescence imaging.

Comparative thermal and thermodynamic study of DNA chemically modified with antitumor drug cisplatin and its inactive analog transplatin.

Antitumor activity of cisplatin is exerted by covalent binding to DNA. For comparison, studies of cisplatin-DNA complexes often employ the very similar but inactive transplatin. In this work, thermal and thermodynamic properties of DNA complexes with these compounds were studied using differential scanning calorimetry (DSC) and computer modeling. DSC demonstrates that cisplatin decreases thermal stability (melting temperature, Tm) of long DNA, and transplatin increases it. At the same time, both compounds decrease the enthalpy and entropy of the helix-coil transition, and the impact of transplatin is much higher. From Pt/nucleotide molar ratio rb=0.001, both compounds destroy the fine structure of DSC profile and increase the temperature melting range (ΔT). For cisplatin and transplatin, the dependences δTm vs rb differ in sign, while δΔT vs rb are positive for both compounds. The change in the parameter δΔT vs rb demonstrates the GC specificity in the location of DNA distortions. Our experimental results and calculations show that 1) in contrast to [Pt(dien)Cl]Cl, monofunctional adducts formed by transplatin decrease the thermal stability of long DNA at [Na(+)]>30mM; 2) interstrand crosslinks of cisplatin and transplatin only slightly increase Tm; 3) the difference in thermal stability of DNA complexes with cisplatin vs DNA complexes with transplatin mainly arises from the different thermodynamic properties of their intrastrand crosslinks. This type of crosslink appears to be responsible for the antitumor activity of cisplatin. At any [Na(+)] from interval 10-210mM, cisplatin and transplatin intrastrand crosslinks give rise to destabilization and stabilization, respectively.

Recent advances toward the development of inhibitors to attenuate tumor metastasis via the interruption of lectin-ligand interactions.

Aberrant glycosylation is a well-recognized phenomenon that occurs on the surface of tumor cells, and the overexpression of a number of ligands (such as TF, sialyl Tn, and sialyl Lewis X) has been correlated to a worse prognosis for the patient. These unique carbohydrate structures play an integral role in cell-cell communication and have also been associated with more metastatic cancer phenotypes, which can result from binding to lectins present on cell surfaces. The most well studied metastasis-associated lectins are the galectins and selectins, which have been correlated to adhesion, neoangiogenesis, and immune-cell evasion processes. In order to slow the rate of metastatic lesion formation, a number of approaches have been successfully developed which involve interfering with the tumor lectin-substrate binding event. Through the generation of inhibitors, or by attenuating lectin and/or carbohydrate expression, promising results have been observed both in vitro and in vivo. This article briefly summarizes the involvement of lectins in the metastatic process and also describes different approaches used to prevent these undesirable carbohydrate-lectin binding events, which should ultimately lead to improvement in current cancer therapies.

Temporal behavior of DNA thermal stability in the presence of platinum compounds. Role of monofunctional and bifunctional adducts.

Penetrating into cell nuclei, antitumor drug cisplatin sequentially forms various intermediate and final adducts destroying local DNA structure. The demonstrated disappearance of the fine structure of melting curve of long DNAs along with a strong decrease in melting enthalpy conforms to the structural impact. However, the negative thermal effect (δT(m)) caused by cisplatin is relatively small if neutral medium is used in melting experiments. Cisplatin's inactive analogs transplatin and diethylenetriaminechloroplatinum {Pt[(dien)Cl]Cl} also distort DNA structure but their thermal effect is even positive. We have found that the use of alkaline medium in melting experiments strengthens the negative thermal effect for cisplatin. For transplatin and Pt[(dien)Cl]Cl, the thermal effect becomes negative that makes it qualitatively consistent with structural distortions. Those changes are explained by elimination of nonspecific electrostatic stabilization of DNA under platination. Additionally, alkaline medium fixes intermediate states of DNA platination and makes them stable against heating. These results allowed us to monitor δT(m) under binding of platinum compounds to DNA and their further transformation. The kinetic and thermal characteristics of monofunctional and bifunctional adducts were evaluated. It has been demonstrated that monofunctional adducts of cisplatin, transplatin and Pt[(dien)Cl]Cl produce approximately the same thermal destabilization. Cisplatin intrastrand crosslinks cause a two-fold stronger thermal destabilization than its monofunctional adducts. The value of δT(m) for cisplatin's final adducts is ten times larger than for transplatin. This difference mainly comes from the much stronger thermal destabilizing power of cisplatin's intrastrand crosslinks, which are responsible for antitumor activity of this compound.

Thermal stability of DNA with interstrand crosslinks.

Although many anticancer drugs exert their biological activity by forming DNA interstrand crosslinks (ICLs), the thermodynamics of biologically relevant long crosslinked DNAs has not been intensively studied in contrast to short duplexes. Here, we carry out computer modeling of the shift of melting temperature of long DNAs caused by ICLs taking into account crosslinking effect in itself and concomitant local alterations in the free energy (δG) of the helix-coil transition at sites of ICLs. Depending on δG, DNA interstrand crosslinks at per nucleotide concentration r = 0.05 can change the melting temperature by value from -17 to +47°C, and the influence weakly depends on DNA sequence and GC content. A change in melting temperature caused by introduction of interstrand crosslinking in modified DNA at sites of modifications also depends on δG and varies from 0 to +12°C. Comparison with experiment for the three platinum crosslinking compounds demonstrates utility of the theoretical method for understanding how crosslinking compounds can influence the melting behavior. On the basis of the method, interdependence of local distortions and crosslinking in itself was studied for thermal effect of ICLs. A method for evaluating the nature of the structural alteration that produces a change in thermal stability for short crosslinked DNA is also proposed. The methods can be used for comparative thermodynamic characterization of various DNA crosslinking agents.

Thermostability of the N-terminal RNA-binding domain of the SARS-CoV nucleocapsid protein: experiments and numerical simulations.

Differential scanning calorimetry, circular dichroism spectroscopy, nuclear magnetic resonance spectroscopy, and numerical simulations were used to study the thermostability of the N-terminal RNA-binding domain (RBD) of the SARS-CoV nucleocapsid protein. The transition temperature of the RBD in a mixing buffer, composed of glycine, sodium acetate, and sodium phosphate with 100 mM sodium chloride, at pH 6.8, determined by differential scanning calorimetry and circular dichroism, is 48.74 degrees C. Experimental results showed that the thermal-induced unfolding-folding transition of the RBD follows a two-state model with a reversibility >90%. Using a simple Go-like model and Langevin dynamics we have shown that, in agreement with our experiments, the folding of the RBD is two-state. Theoretical estimates of thermodynamic quantities are in reasonable agreement with the experiments. Folding and thermal unfolding pathways of the RBD also were experimentally and numerically studied in detail. It was shown that the strand beta(1) from the N-terminal folds last and unfolds first, while the remaining beta-strands fold/unfold cooperatively.