Abstract: The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5′ end.

Abstract: Charge-splitting networks, optoelectronic devices, methods for making optoelectronic devices, power generation systems utilizing such devices and method for making charge-splitting networks are disclosed. An optoelectronic device may include a porous nano-architected (e.g., surfactant-templated) film having interconnected pores that are accessible from both the underlying and overlying layers. A pore-filling material substantially fills the pores. The interconnected pores have diameters of about 1-100 nm and are distributed in a substantially uniform fashion with neighboring pores separated by a distance of about 1-100 nm. The nano-architected porous film and the pore-filling, material have complementary charge-transfer properties with respect to each other, i.e., one is an electron-acceptor and the other is a hole-acceptor. The nano-architected porous, film may be formed on a substrate by a surfactant temptation technique such as evaporation-induced self-assembly.

Abstract: Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5′ and 3′ to the CpG-motif on immunostimulatory activity. Cell proliferation and secretion of IL-12 and IL-6 in mouse spleen cell cultures, and spleen weights of mice increased significantly when a non-ionic linkage was placed at least four or more internucleoside linkages away from the CpG-motif in the 5′-flanking sequence. When the non-ionic linkage was placed closer than three internucleoside linkages in the 5′-flanking sequence to the CpG-motif, immunostimulatory activity was suppressed compared with that observed with the unmodified parent oligo.

Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.

Abstract: The invention provides new processes for synthesizing oligonucleotides that allow for deprotection of the oligonucleotide under more rapid and/or more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups. The invention also provides oligonucleotides containing any of a variety of base labile functionalities and methods for using such oligonucleotides.

Abstract: The invention relates to the therapeutic use of oligonucleotides or oligonucleotide analogs as immunostimulatory agents in immunotherapy applications. The invention provides methods for enhancing the immune response caused by immunostimulatory oligonucleotide compounds.

Abstract: An exemplary power supply provides low power dissipation in standby mode by disabling the start-up circuit and by implementing variable frequency operation independent of the feedback signal. A standby mode detection circuit automatically implements the variable frequency operation, and an under voltage lockout signal implements the start-up circuit disable. Once the start time expires or when feedback control enables, the start-up circuit is disabled so that it dissipates negligible power. A voltage controlled oscillator responsive to the rectified DC line voltage provides for variable frequency operation in standby mode. The frequency output of the VCO is inversely proportional to the line voltage—as line voltage increases the switching frequency decreases, which decreases the output power.

Abstract: High dielectric constant capacitors are made from a dielectric ink of lead-magnesium-niobate and lead oxide powders. Dielectric inks are made by mixing the dielectric powders with a suitable organic vehicle which can be used to coat one or more glass-based green tapes. Buried capacitors are made by coating an overlying and an underlying green tape with a conductor such as silver. Capacitors can also be made by adjusting the organic vehicle and forming a green tape from the dielectric powders. These dielectric green tapes each can be coated with a conductive layer and stacked, the conductive layers connected in parallel. The resultant multilayer capacitors have a very high dielectric constant, while eliminating the need for very large area capacitors, as compared to single layer capacitors.

Abstract: A polymer surface in contact with a liquid crystal medium is exposed to polarized light, whereby a covalently bound anisotropic component of the polymer surface aligns in response to the polarized light. Alignment of the anisotropic component causes alignment of the liquid crystal medium. An interference pattern of two polarized lights causes the covalently bound anisotropic component to form microgrooves on the polymer surface. A liquid crystal cell includes at least one polymer surface that has a covalently bound anisotropic component that can align in response to polarized light and a liquid crystal in contact with the polymer surface.

Abstract: The invention provides new primary phosphoramidate internucleoside linkages that are less sterically constrained than existing phosphoramidate linkages, as well as oligonucleotides containing such linkages and processes for making and methods for using such oligonucleotides.

Abstract: The invention provides new reagents and processes for synthesizing oligonucleotides, including stereoselective oligonucleotide synthesis. In a first aspect, the invention provides novel monomer synthons for the synthesis of oligonucleotides. Monomer synthons according to this aspect of the invention are useful in the synthesis of oligonucleotides and can be used in place of the well known beta-cyanoethyl phosphoramidite monomer synthon in the phosphoramidite synthesis procedure. Certain monomer synthons according to this aspect of the invention are useful in this procedure for producing oligonucleotides having defined stereochemistry.In a second aspect, the invention provides processes for synthesizing monomer synthons according to the invention, including diastereomerically enriched or purified monomer synthons.

Abstract: The invention provides new reagents and an improved process for synthesizing oligonucleotides that contain methylphosphonate internucleoside linkages. The reagents and process utilize a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups.

Abstract: The invention provides oligonucleotides containing methyl phosphotriester linkages and processes for making and methods for using such oligonucleotides.

Abstract: The present invention comprises a novel method of incorporating a tritium label at one or more predetermined sites within an oligonucleotide. In particular, the method comprises contacting a nascent, support-bound oligonucleotide having a free 5' hydroxyl group with a suitable oxidizing agent to oxidize the alcohol to an aldehyde, followed by reducing the aldehyde thereby formed with a suitable tritium labeled reducing agent such as ?.sup.3 H!NaBH.sub.4 to yield the 5' terminal alcohol with a 5' tritium label. Normal automated synthesis can then be continued to yield the oligonucleotide of desired length having the tritium label in the desired location. The oligonucleotides thereby produced have higher specific activity than those previously known in the art. According, in a second aspect, the present invention provides oligonucleotides having high specific acitivity.

Abstract: The present invention comprises a method for quickly and efficiently detritylating oligonucleotides synthesized by standard chemical techniques. The method comprises contacting a 5'-DMT oligonucleotide with the H.sup.+ form of a "DOWEX," "AMBERLYST" or "AMBERLITE" ion-exchange resin for about 10 minutes to about 2 hours. The method is particularly advantageous when used in large scale synthesis. The method is quicker than the standard acetic acid method and eliminates much of the post-detritylation processing associated with the acetic acid method.

Abstract: The present invention provides new mononucleotide synthons useful in the synthesis of oligonucleotides having from one to all P-chiral centers that are predominantly and independently in the R or S configuration. The invention also provides methods of synthesizing these synthons, methods of synthesizing oligonucleotides having from one to all P-chiral centers predominantly and independently in the R or S configuration, and such oligonucleotides. Oligonucleotides synthesized with the novel synthons are useful for modulating nucleic acid expression, both in vitro and in vivo, as well as in traditional hybridization assays.

Abstract: The present invention comprises a novel method of incorporating a tritium label at one or more predetermined sites within an oligonucleotide. In particular, the method comprises contacting a nascent, support-bound oligonucleotide having a free 5' hydroxyl group with a suitable oxidizing agent to oxidize the alcohol to an aldehyde, followed by reducing the aldehyde thereby formed with a suitable tritium labeled reducing agent such as [.sup.3 H]NaBH.sub.4 to yield the 5' terminal alcohol with a 5' tritium label. Normal automated synthesis can then be continued to yield the oligonucleotide of desired length having the tritium label in the desired location. The oligonucleotides thereby produced have higher specific activity than those previously known in the art. According, in a second aspect, the present invention provides oligonucleotides having high specific activity.

Abstract: The present invention comprises a novel method of incorporating radiolabels and other type of labels at one or more predetermined sites within an oligonucleotide. In particular, the method comprises contacting a nascent, support-bound oligonucleotide having an unprotected 5' hydroxyl group with a suitable activating agent, followed by contacting the resulting activated nascent oligonucleotide with a labeled, Y-protected mononucleotide having an unprotected 3'-hydroxyl, thereby condensing the labeled mononucleotide and nascent oligonucleotide. Normal automated synthesis can then be continued to yield the oligonucleotide of desired length having the label in the desired location. This method advantageously yields oligonucleotides with high specific activity. The oligonucleotides thereby produced are useful for determining the pharmacokinetics and biodistribution of their non-radiolabeled counterparts, both in vitro and in vivo.

Abstract: A method for fabricating a gate-to-drain overlapped MOS transistor in which gate-to-drain capacitance is lower and a structure thereby. A pad oxide layer is formed over a substrate having a first conductive layer with a first pattern formed on a first gate oxide layer, and etchback process is performed until surface part and a predetermined upper parts of the both side walls of the first conductive layer is exposed. As a result, a second conductive layers with a second pattern is formed and a second gate oxide layer thicker than the first gate oxide layer is formed.