Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization.

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Th1-type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen.

There is a need for new adjuvants that will induce immune responses to subunit vaccines. We show that a short peptide, named Hp91, whose sequence corresponds to an area within the endogenous molecule high mobility group box (HMGB1) protein 1 potentiates cellular immune responses to peptide antigen and cellular and humoral immune responses to protein antigen in vivo. Hp91 promoted the in vivo production of the immunomodulatory cytokines, IFN-γ, TNF-α, IL-6, and IL-12 (p70), as well as antigen-specific activation of CD8+ T cells. These results demonstrate the ability of a short immunostimulatory peptide to serve as an adjuvant for subunit vaccines.

Optimization and theoretical modeling of polymer microlens arrays fabricated with the hydrophobic effect.

High-performance polymer microlens arrays were fabricated by means of withdrawing substrates of patterned wettability from a monomer solution. The f-number (f(#)) of formed microlenses was controlled by adjustment of monomer viscosity and surface tension, substrate dipping angle and withdrawal speed, the array fill factor, and the number of dip coats used. An optimum withdrawal speed was identified at which f(#) was minimized and array uniformity was maximized. At this optimum, arrays of f/3.48 microlenses were fabricated with one dip coat with uniformity of better than Deltaf/f +/- 3.8%. Multiple dip coats allowed for production of f/1.38 lens arrays and uniformity of better than Deltaf/f +/-5.9%. Average f(#)s were reproducible to within 3.5%. A model was developed to describe the fluid-transfer process by which monomer solution assembles on the hydrophilic domains. The model agrees well with experimental trends.

Cationic two-photon induced polymerization with high dynamic range.

Cationic-induced two-photon photo-polymerization is demonstrated at 710 nm, using an isopropylthioxanthone / diarylidonium salt initiating system for the cationic polymerization of an epoxide. In-situ monitoring of the polymer conversion using interferometry allows for determination of the polymerization threshold J2th, polymerization rate R and its dependence of initiator's concentration z. Best J2th achieved is 1 GW/cm 2 , with a dynamic range of > 100, i.e. the material can be fully polymerized at intensities > 100 times the threshold level without damage. The R is found to be proportional to the m=1.7 power of the intensity, or R =[C(J-J2th)]m =[C(J-J2th)]1.7 , which implies a significantly stronger localization of the photochemical response than that of free radical photoinitiators. Both R and J2th significantly improve when the concentration z of the initiator (onium salt) increases, reduction of J2th exhibiting z -m trend.

Characterization of a polymer microlens fabricated by use of the hydrophobic effect.

We report a means of fabricating hydrophilic domains in a hydrophobic background by lithographically patterning an adhesive hydrophobic layer. Polymer microlenses were fabricated on these substrates by use of a dip-coating technique. Various lens shapes (circular, elliptical, square) were fabricated on a variety of substrates (SiO(2), SiN, GaAs, InP, etc.), ranging in size from 2 to 500 microm in diameter, with fill factors of up to 90%. Plano-convex and double-convex lenses were fabricated, with f-numbers as low as 1.38 and 1.2, respectively. Optimum lens surfaces deviated from spherical by just +/-5 nm . The lenses are stable at room temperature and exhibit minimal degradation after 24 h at 105 degrees C. The transfer of these polymer lenses to an underlying substrate was also demonstrated.

Massively parallel low-cost pick-and-place of optoelectronic devices by electrochemical fluidic processing.

We describe a novel electrochemical technique for the nonlithographic, fluidic pick-and-place assembly of optoelectronic devices by electrical and optical addressing. An electrochemical cell was developed that consists of indium tin oxide (ITO) and n -type silicon substrates as the two electrode materials and deionized water (R = 18 MOmega) as the electrolytic medium between the two electrodes. 0.8-20-microm-diameter negatively charged polystyrene beads, 50-100-microm-diameter SiO(2) pucks, and 50-microm LED's were successfully integrated upon a patterned silicon substrate by electrical addressing. In addition, 0.8-microm-diameter beads were integrated upon a homogeneous silicon substrate by optical addressing. This method can be applied to massively parallel assembly (>1000 x 1000 arrays) of multiple types of devices (of a wide size range) with very fast (a few seconds) and accurate positioning.

Three-dimensional optical data storage in a fluorescent dye-doped photopolymer.

We propose a new, to our knowledge, monolithic multilayer optical storage medium in which data may be stored through the diffusional redistribution of fluorescent molecules within a polymer host. The active portion of the medium consists of a photopolymer doped with a fluorescent dye that is polymerized at the focal point of a high-numerical-aperture lens. We believe that as fluorescent molecules bond to the polymer matrix they become more highly concentrated in the polymerized regions, resulting in the modulated data pattern. Since data readout is based on detection of fluorescence rather than index modulation as in other photopolymer-based memories, the problems of media shrinkage and optical scatter are of less concern. An intensity threshold observed in the recording response of this material due to the presence of inhibitor molecules in the photopolymer allows for the three-dimensional confinement of recorded bits and therefore multilayer recording. The nonlinear recording characteristics of this material were investigated through a simple model of photopolymerization and diffusion and verified experimentally. Both single-layer and multilayer recordings were demonstrated.

Three-dimensional holographic stamping of multilayer bit-oriented nonlinear optical media.

The requirements and limitations on the use of a volume holographic element for the simultaneous optical stamping of multilayer data into a three-dimensional (3D) bit-oriented material that exhibits a suitable sensitivity threshold are investigated. The expected performance of such a holographic stamping element is examined through a model of the coherent noise effects that result from the interference of the many data layers with one another. We show that higher signal-to-noise values may be achieved through the use of semicoherent light during the readout of the hologram. The main limitations to this technique arise from the bandwidth requirements on the holographic element, the degree of nonlinearity required of the bit-oriented media, and the tolerance requirements for the optical exposure levels. As a demonstration of the concept, a two-layer stamping element is fabricated and used to simultaneously stamp two layers of data into a 3D dye-doped photopolymer storage medium.

Free-space parallel multichip interconnection system.

A parallel data-communication scheme is described for interchip communication with free-space optics. We present a proof-of-concept and feasibility demonstration of a practical modular packaging approach in which free-space optical interconnect modules can be simply integrated on top of an electronic multichip module (MCM). Our packaging architecture is based on a modified folded 4-f imaging system that is implemented with off-the-shelf optics, conventional electronic packaging techniques, and passive assembly techniques to yield a potentially low-cost packaging solution. The prototype system, as built, supports 48 independent free-space channels with eight separate laser and detector chips, in which each chip consists of a one-dimensional array of 12 devices. All chips are assembled on a single ceramic carrier together with three silicon complementary metal-oxide semiconductor chips. Parallel optoelectronic (OE) free-space interconnections are demonstrated at a speed of 200 MHz. The system is compact at only 10 in.(3) (~164 cm(3)) and is scalable because it can easily accommodate additional chips as well as two-dimensional OE device arrays for increased interconnection density.

Cross talk and ghost talk in a microbeam free-space optical interconnect system with vertical-cavity surface-emitting lasers, microlenses, and metal-semiconductor-metal detectors.

A diffraction-based beam-propagation model is used to study optical cross talk in microbeam free-space optical interconnection (FSOI) systems. The system consists of VCSEL's, microlenses, and metal-semiconductor-metal (MSM) detectors, with the detectors modeled as amplitude gratings with low contrast ratio (based on experimental results). Different possible cross-talk sources are studied. Results show that, in an optimized system, the cross talk caused by diffractive scattering is not an issue. However, in such systems the principal reflection from a MSM detector surface creates two problems: VCSEL coupling and ghost talk. The coupling of the reflected beam into the VCSEL's may cause power oscillation (and increase the bit error rate), whereas ghost talk will limit the distance-bandwidth product of the interconnect system. This optical system is also abstracted in hspice together with the laser driver and receiver circuits to analyze ghost talk in this system. Results show that at high speed (1 Gbit/s or more) these effects negatively affect system performance.

Two-photon holography in a 3D photopolymer host-guest matrix.

We demonstrate for the first time two-photon induced holographic recording at an arbitrary point in three dimensional photopolymeric cube by overlapping two coherent pulses from a 200 femtosecond Ti: Sapphire tunable laser operating at 710 nm. Spatial overlap is achieved by a novel pupil division method. The polymer material is made of epoxy host, which is fully polymerized and filled with liquid photopolymerisable formulation comprising acrylate type monomer and two-photon photoinitiator. Measured diffraction efficiency is measured to be 3.5%.

Two-photon holography in 3-D photopolymer host-guest matrix: errata.

: Correction to References. Commercial codes of the chemicals are added.

Optomechanical design and characterization of a printed-circuit-board-based free-space optical interconnect package.

We present a proof of concept and a feasibility demonstration of a practical packaging approach in which free-space optical interconnects (FSOI's) can be integrated simply on electronic multichip modules (MCM's) for intra-MCM-board interconnects. Our system-level packaging architecture is based on a modified folded 4f imaging system that has been implemented with only off-the-shelf optics, conventional electronic packaging, and passive-assembly techniques to yield a potentially low-cost and manufacturable packaging solution. The prototypical system as built supports 48 independent FSOI channels with 8 separate laser and detector chips, for which each chip consists of a one-dimensional array of 12 devices. All the chips are assembled on a single substrate that consists of a printed circuit board or a ceramic MCM. Optical link channel efficiencies of greater than 90% and interchannel cross talk of less than -20 dB at low frequency have been measured. The system is compact at only 10 in.3 (25.4 cm3) and is scalable, as it can easily accommodate additional chips as well as two-dimensional optoelectronic device arrays for increased interconnection density.

Characterization of dielectric and electro-optic properties of PLZT 9/65/35 films on sapphire for electro-optic applications.

Lead lanthanum zirconate titanate (PLZT) thin films were deposited on r-plane sapphire at low temperatures by RF triode magnetron sputtering using lead compensated hot-pressed targets. To obtain fully perovskite phase in the films, two types of post-deposition processing were investigated: rapid thermal annealing (RTA) and furnace annealing (FA). Dielectric and electro-optic properties of PLZT films were found to be strongly dependent on annealing conditions. The peak dielectric constant of the films were 1200 and 2800 with Curie temperatures of 110 degrees C and 190 degrees C after RTA and FA processing, respectively. The dielectric losses in the films were fairly low; tan deltas were less than 0.02 after RTA and less than 0.04 after FA processing. The films showed good optical transmission characteristics after annealing and an anomalously large effective quadratic electro-optic effect was observed in one furnace annealed film.

Speed and energy analysis of digital interconnections: comparison of on-chip, off-chip, and free-space technologies.

We model and compare on-chip (up to wafer scale) and off-chip(multichip module) high-speed electrical interconnections withfree-space optical interconnections in terms of speed performance andenergy requirements for digital transmission in large-scalesystems. For all technologies the interconnections are firstmodeled and optimized for minimum delay as functions of theinterconnection length for both one-to-one and fan-outconnections. Then energy requirements are derived as functions ofthe interconnection length. Free-space optical interconnectionsthat use multiple-quantum-well modulators or vertical-cavitysurface-emitting lasers as transmitters are shown to offer aspeed-energy product advantage as high as 30 over that of the electrical interconnection technologies.

Small-signal-equivalent circuits for a semiconductor laser.

Passive electrical circuits whose voltage and current equations are exactly equivalent to the small-signal rate equations of a semiconductor laser are derived to model an electrically modulated laser (verified to be the same as that given in the literature), an optically modulated laser (i.e., a laser used as an optical amplifier), and a multimode laser. These circuits offer a fast and efficient simulation tool with little computational complexity in which the small-signal assumption (i.e., small modulation range) is neither violated nor insufficient for the simulation.

Photorefractive Beam splitter for Free-Space Optical Interconnections.

A photorefractive beam splitter (PRBS) is introduced as an alternative to a polarizing beam splitter (PBS) for coupling optical power into reflective modulators in a free-space optical interconnection system. The PRBS uses a single diffraction grating recorded in a photorefractive material to redirect the incident laser light into the first diffraction order and onto the modulators. Reflected interconnection light not matching the Bragg angle criteria transmits uncoupled through the beam splitter. Experimental results show that the PRBS provides better, more uniform transmission for off-axis beams than the currently used PBS.

Biorthogonally accessed three-dimensional two-photon memory for relational database operations.

Memory bandwidth is a bottleneck for very large database machines. Parallel-access three-dimensional two-photon memories have the potential of achieving enormous throughput (>100 Gbit/s) and capacity (1 Tbit/cm(3)) [Appl. Opt. 29, 2058 (1990)] and, consequently, are well suited for this application. Our analysis shows that some operations can be completed more than 2 orders of magnitude faster with this type of memory than with a system based on serial-access storage. These particular memories have a further feature of being accessible in orthogonal directions. We show that this property, used in conjunction with a three-dimensional data-organization scheme designed for this approach, leads to improved performance by permitting the user a choice of accessing strategies for a given operation.

Experimental characterization of a two-photon memory.

We demonstrate the recording of 100 planes of digital images in a page-oriented two-photon memory and characterize the images in terms of signal-to-noise ratio and bit error rate. Possible error sources in the recording are discussed, and methods for compensating for some of these effects are presented. Looking at the distributions of the normalized bit intensities, we are able to estimate the minimum achievable bit error rate for this system.