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Recently, microneedle patches have been explored for extracting interstitial fluid with the goal of extracting temporally relevant, clinical-grade information for human health monitoring. As compared to traditional hypodermic needles, the sub-millimeter scale of microneedles allows for the creation of micropores providing access into human skin interstitial fluid while minimizing interactions with blood vessels and nerves, leading to painless insertion with little to no bleeding. An essential sub-component is the actuator, responsible for driving the microneedle into the skin with a precise force and velocity to ensure reliable insertion. Reliability, in this case, consists of two criteria: the ability of the microneedle to 1) penetrate the skin, and 2) withstand penetration forces without mechanical failure. Evaluation of these criteria requires a thorough understanding of the non-linear, time-dependent interactions between the microneedle and the skin during insertion, including rupture and tearing of the skin on the micron scale, and the resultant stresses on the microneedle. To this end, a comprehensive finite-element model was developed to simulate the microneedle insertion process. This analysis yielded a prediction of complete microneedle insertion without failure of the microneedle and an estimated insertion force of 0.055 N per microneedle, well within the capability of the actuator system considered. This insertion force was validated using experimental data obtained through microneedle insertion in whole skin samples. The model was then used to perform several parametric studies, yielding valuable insights for possible future design improvements.

Hydrogen sulfide, Nitrogen Dioxide, and sulfur dioxide are highly toxic gases with health effects at ppb and ppm levels in air. These compounds occur in industrial operations as well as in environmental atmospheric polluted air. Traditionally, microfabricated electrochemical gas sensors use photolithography processes for patterning of the electrodes and defining the electrode geometry for high surface area to increase the sensor gas sensitivity. We present herein a series of gas sensor designs fabricated via laser ablation of sputtered Au films. For these sensors, the laser ablation step itself takes less than two hours to pattern up to 60 sensors. The sensors are fabricated on a porous hydrophobic substrate made of layers of a Teflon woven mesh, and the 400 nm gold film was sputtered onto a 100 nm tungsten adhesion layer. A total of 60 sensors was patterned in a 6 by 10 grid per substrate with each sensor having a footprint of 15 mm x 15 mm. An image of some of the sensors and their corresponding designs are illustrated in figure 1. Laser ablation was performed by an Optec WS-Flex USP femtosecond 1030 nm laser. The pulse frequency was set to 400 kHz and both the speed and jump speed were set to 200 mm/s. The laser power is nominally 4 W and the power percentage setting was determined for each substrate by patterning a test array onto the substrate in increments of 2%. From this test array, the lowest power that completely ablated the gold could be determined and that was used for the remaining sensor ablation. Images of the etched surface area shown in the figure 1. Surface analysis with EDS using SEM microscope indicated the composition of the layers and effective removal of the gold from the Teflon sheet without damage to the Teflon porosity in the woven mesh, figure 2. The sensor electrodes were assembled by lamination between several plastic layers and then an electrolyte was added. The assembled sensors were diced from the assembled 10x6 sensor wafer and individual sensors were connected to a potentiostat and tested via exposure to the various pollutant gases. The current response of these amperometric sensors was measured and found to be linear with respect to concentration in the low ppm range. This work illustrates an alternative to photolithography for the preparation of thin film gas porous electrodes for use in amperometric gas sensors. Figure 1

This paper presents fabrication approaches for magnesium (Mg) microstructures embedded in biodegradable polymers using through-mold Mg electrodeposition and metal- transfer-molding. Biodegradable implantable electronics have garnered increasing interest from the medical community for the monitoring and treatment of transient diseases. Magnesium is a biodegradable metal with desirable properties, and the ability to micropattern Mg thick films (i.e., about >1 µm) with direct microelectromechanical systems (MEMS) integration would sup- port the development of more sophisticated and clinically relevant biodegradable devices and microsystems. Magnesium microstruc- tures were electroplated through micropatterned water-soluble molds in a nonaqueous electrolyte and transfer molded into a biodegradable polymer. Electroplated Mg compared favorably with commercial Mg foil based on elemental composition, crystal orientation, electrical resistivity, and corrosion behavior. Mag- nesium electroplated to a thickness of up to 50 µ ms howed a grain size of ∼10 µm, and minimum feature dimensions of 100 µm in width and spacing. Completely biodegradable Mg and poly-L-lactic acid constructs were demonstrated. The application of Mg thick films toward biodegradable energy sources was explored through the fabrication and testing of biodegradable Mg/Fe batteries. The batteries exhibited a capacity and power of up to 2.85 mAh and 39 µW, respectively. Results confirmed the advantages of electrodeposited Mg microstructures for biodegradable MEMS applications. (2014-0103)

Metallic magnetic materials have desirable magnetic properties, including high permeability, and high saturation flux density, when compared with their ferrite counterparts. However, eddy-current losses preclude their use in many switching converter applications, due to the challenge of simultaneously achieving sufficiently thin laminations such that eddy currents are suppressed (e.g., 500 nm-1 μm for megahertz frequencies), while simultaneously achieving overall core thicknesses such that substantial power can be handled. A CMOS-compatible fabrication process based on robot-assisted sequential electrodeposition followed by selective chemical etching has been developed for the realization of a core of substantial overall thickness (tens to hundreds of micrometers) comprised of multiple, stacked permalloy (Ni80Fe20) nanolaminations. Tests of toroidal inductors with nanolaminated cores showed negligible eddy-current loss relative to total core loss even at a peak flux density of 0.5 T in the megahertz frequency range. To illustrate the use of these cores, a buck power converter topology is implemented with switching frequencies of 1-2 MHz. Power conversion efficiency greater than 85% with peak operating flux density of 0.3-0.5 T in the core and converter output power level exceeding 5 W was achieved.

tion are often outweighed by disadvantages related to the increased noise levels associated with such jets. Better predictions of Coanda jet noise would allow the Coanda effect to be more widely applied, and its potential to be fully realized. This paper applies the method of characteristics to a steady two-dimensional axisymmetric supersonic flow in order to determine the location of the first shock cell downstream of the nozzle. This phenomenon has previously been found to be particularly important in determining both the OASPL and peak frequency of the broadband high-frequency Shock-Associated Noise (BBSAN) emitted by a given jet configuration. 10, 20 The current work has also illuminated the relationship between cell location and flow characteristics, and thus the effect of jet operating conditions on BBSAN can now be determined. 11 The relationship between cell location and jet breakaway is also under investigation. Predictions are compared with experimental results obtained using flow visualization techniques. This work is in the process of being extended so that the Rankine-Hugoniot conditions can be used to predict the shock cell structure (and thus the BBSAN) along the entire jet. 22

Bio-electrodes have traditionally been made of materials such as metal and silicon that are much stiffer than the tissue from which they record or stimulate. This difference in mechanical compliance can cause incomplete or ineffective contact with the tissue. The electrode stiffness has also been hypothesized to cause chronic low-grade injury and scar-tissue encapsulation, reducing stimulation and recording efficiency. As an initial step to resolve these issues with electrode performance, we have developed and characterized electrically-functional, low-Young's modulus, microcable-shaped neuroelectrodes and demonstrated electrophysiological recording functionality. The microcable geometry gives the electrodes a similar footprint to traditional wire and microwire neuroelectrodes, while reducing the difference in Young's modulus from nervous tissue by orders of magnitude. The electrodes are composed of PDMS and thin-film gold, affording them a high-level of compliance that is well suited for in vivo applications. The composite Young's modulus of the electrode was experimentally determined to be 1.81 ± 0.01 MPa. By incorporating a high-tear-strength silicone, Sylgard 186, the load at failure was increased by 92%, relative to that of the commonly used Sylgard 184. The microcable electrodes were also electromechanically tested, with measurable conductivity (220 kΩ) at an average 8% strain (n = 2) after the application of 200% strain. Electrophysiological recording is demonstrated by wrapping the electrode around a peripheral nerve, utilizing the compliance and string-like profile of the electrode for effective recording in nerve tissue.

This study addresses the temperature dependence of the enthalpy of formation for several unimolecular quadruplexes in the presence of excess monovalent salt. We examined a series of biologically significant guanine-rich DNA sequences: thrombin binding aptamer (TBA) (d(G2T2G2TGTG2T2G2), PS2.M, a catalytically active aptamer (d(GTG3TAG3CG3T2G2)), and the human telomere repeat (HT) (d(AG3(T2AG3)3)). Using CD spectra and UV melting, we confirmed the presence of quadruplex structures and established the temperature range in which quadruplex conformation is stable. We then performed ITC experiments, adding DNA to a solution containing excess NaCl or KCl. In this approach, only several additions are made, and only the enthalpy of quadruplex formation is measured. This measurement was repeated at different temperatures to determine the temperature dependence of the enthalpy change accompanying quadruplex formation. To control for the effect of nonspecific salt interactions during DNA folding, we repeated the experiment by replacing the quadruplex-forming sequences with a similar but nonfolding sequence. Dilution enthalpies were also subtracted to obtain the final enthalpy value involving only the quadruplex folding process. For all sequences studied, quadruplex formation was exothermic but with an increasing magnitude with increasing temperature. These results are discussed in terms of the change in heat capacity associated with quadruplex formation. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 302–309, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

We have imaged a $\sim$6 arcminute$^2$ region in the Bo\"otes Deep Field using the 350 $\mu$m-optimised second generation Submillimeter High Angular Resolution Camera (SHARC II), achieving a peak 1$\sigma$ sensitivity of $\sim$5 mJy. We detect three sources above 3$\sigma$, and determine a spurious source detection rate of 1.09 in our maps. In the absence of $5\sigma$ detections, we rely on deep 24 $\mu$m and 20 cm imaging to deduce which sources are most likely to be genuine, giving two real sources. From this we derive an integral source count of 0.84$^{+1.39}_{-0.61}$ sources arcmin$^{-2}$ at $S>13$ mJy, which is consistent with 350 $\mu$m source count models that have an IR-luminous galaxy population evolving with redshift. We use these constraints to consider the future for ground-based short-submillimetre surveys.

The conformation of the guanine quadruplex formed by the human telomere (HT) repeat in solutions containing physiological concentrations of K+ ions has been a topic of intensive investigation during the past several years. Of particular interest are the directionality of the overall folding pattern, i.e., parallel, antiparallel, or a combination of these two modes, and the alternation, if any, of the glycosidic bond conformation between syn and anti. An additional issue involves resolving mixtures of conformations when more than one species is present. We approach these questions using selective substitution of riboguanosine, rG, for deoxyriboguanosine, dG. Using a combination of circular dichroism, gel electrophoresis, equilibrium ultracentrifugation, and imino proton NMR, we are able to show that these modifications can yield sequences which fold into parallel or antiparallel conformations consisting of one or two strands. We also demonstrate that chimeric editing of the HT sequence permits isolating one of two conformational isomers existing in solution in the presence of KCl. The ability to engineer and control quadruplex folding motifs illustrated here with HT may prove useful more generally for a variety of quadruplex-forming sequences.

Planar or two-dimensional (2D) microelectrode arrays (MEAs), which are used for in vitro culturing of neurons and tissue slices, have been in existence for over 30 years. However, in order to study complex network morphologies and tissue slices which contain substantial 3D neuronal structures, 3D MEAs with microfluidic ports are required. Integrated fabrication of 3D MEAs with embedded microfluidic ports for nutrient perfusion through these relatively thick tissues typically requires non-planar lithography, which is not easily accomplished. This paper reports a laser-scribing technique coupled with electroplating to fabricate 3D MEAs coupled with microfluidic ports. An excimer laser has been used to define patterns in a polymer mold layer that is conformally vapor-deposited on a 3D microfluidic SU-8 substrate. Metal is electroplated through this mold to fabricate electrodes at multiple heights. To demonstrate 3D MEAs, a standard design was chosen consisting of an array of three-dimensional protrusions (‘towers’) optionally with microfluidic functionality on which electrodes can be formed extending to the top of each tower. Additional electrodes are formed on the substrate resulting in a multi-level electrode structure. Since microfluidics can exist both in the substrate as well as along the towers, a coupled three-dimensional electrical and microfluidic functionality is achieved. The resulting 3D MEAs have been analyzed electrically using impedance spectroscopy and baseline noise measurements. They have further been evaluated fluidically using micro-particle image velocimetry measurements.

Nucleic acid quadruplexes, based on the guanine quartet, can arise from one or several strands, depending on the sequence. Those consisting of a single strand are usually folded in one of two principal topologies: antiparallel, in which all or half of the guanine stretches are antiparallel to each other, or parallel, in which all guanine stretches are parallel to each other. In the latter, all guanine nucleosides possess the anti conformation about the glycosidic bond, while in the former, half possess the anti conformation, and half possess the syn conformation. While antiparallel is the more common fold, examples of biologically important, parallel quadruplexes are becoming increasingly common. Thus, it is of interest to understand the forces that determine the quadruplex fold. Here, we examine the influence of individual nucleoside conformation on the overall folding topology by selective substitution of rG for dG. We can reverse the antiparallel fold of the thrombin binding aptamer (TBA) by this approach. Additionally, this substitution converts a unimolecular quadruplex into a bimolecular one. Similar reverse substitutions in the all-RNA analogue of TBA result in a parallel to antiparallel change in topology and alter the strand configuration from bimolecular to unimolecular. On the basis of the specific substitutions made, we conclude that the strong preference of guanine ribonucleosides for the anti conformation is the driving force for the change in topology. These results demonstrate how conformational properties of guanine nucleosides govern not only the quadruplex folding topology but also impact quadruplex molecularity and provide a means to control these properties.

Stabilization of nucleic acid structures results from a balance of multiple interactions, including electrostatics, base stacking, hydrophobic interactions, hydrogen bonding, van der Waals forces, etc. Nucleic acid quadruplexes are unusual structures in that their formation is driven by specific binding of metal ions. This unique mode of metal binding, which is tightly coupled to oligonucleotide folding, can engender correspondingly unique solution behavior. In particular, we show that addition of many cosolvents, such as primary aliphatic alcohols, increases the thermal stability of quadruplexes, as determined by melting temperature, Tm, in direct contrast to the response of duplexes to the same admixture of solvents. Thermal stability is observed to increase as the dielectric constant of the composite solvent decreases. This behavior suggests a dominant role for electrostatics in quadruplex formation and stability. Additional studies done with other cosolvents and solutes suggest that, in some cases, other forces may come into play, including the possibility of direct interaction with the quadruplex structure. Nonetheless, many cosolvents and small molecules, such as ethanol, dimethylformamide, and betaine, stabilize the quadruplex conformation in sharp distinction to their destabilization of DNA duplexes. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 91–101, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

We report the detection of a 3.6sigma 350micron-selected source in the Bootes Deep Field. The source, the first Short-wavelength Submillimeter-selected Galaxy (SSG 1), was discovered as part of a blank field extragalactic survey using the 350micron-optimised Submillimeter High Angular Resolution Camera (SHARC II) at the Caltech Submillimeter Observatory. With multiwavelength photometry from NOAO-NDWFS (R and I band), FLAMEX (J and K_s), Spitzer (IRAC and MIPS) and the Westerbork 1.4GHz Deep Survey (radio upper limit), we are able to constrain the photometric redshift using different methods, all of which suggest a redshift of close to 1. In the absence of long-wavelength submillimeter data we use SED templates to infer that this source is an ultraluminous infrared galaxy (ULIRG) with a dust temperature of 30+/-5 K, occupying a region of luminosity-temperature space shared by modarate redshift ISO-selected ULIRGs (rather than high redshift SCUBA-selected SMGs). SHARC II can thus select SMGs with moderately "warm'' dust that might be missed in submillimeter surveys at longer wavelengths.

Recent X-ray crystallographic studies on the human telomere sequence d[AGGG(TTAGGG)3] revealed a unimolecular, parallel quadruplex structure in the presence of potassium ions, while earlier NMR results in the presence of sodium ions indicated a unimolecular, antiparallel quadruplex. In an effort to identify and isolate the parallel form in solution, we have successfully ligated into circular products the single-stranded human telomere and several modified human telomere sequences in potassium-containing solutions. Using these sequences with one or two terminal phosphates, we have made chemically ligated products via creation of an additional loop. Circular products have been identified by polyacrylamide gel electrophoresis, enzymatic digestion with exonuclease VII and electrospray mass spectrometry in negative ion mode. Optimum pH for the ligation reaction of the human telomere sequence ranges from 4.5 to 6.0. Several buffers were also examined, with MES yielding the greatest ligation efficiency. Human telomere sequences with two phosphate groups, one each at the 3′ and 5′ ends, were more efficient at ligation, via pyrophosphate bond formation, than the corresponding sequences with only one phosphate group, at the 5′ end. Circular dichroism spectra showed that the ligation product was derived from an antiparallel, single-stranded guanine quadruplex rather than a parallel single-stranded guanine quadruplex structure.

Nucleic acid quadruplexes are composed of guanine quartets stabilized by specific metal ions. X-ray diffraction can provide high-resolution information on the structure and metal binding properties of quadruplexes, but only if they can be crystallized. NMR can provide detailed information on the solution structure of such quadruplexes but little quantitative data concerning the metal binding site. Here we apply extended X-ray absorption fine structure (EXAFS) measurements to characterize the metal ion binding site, in frozen solution, of the unimolecular quadruplex formed by the thrombin binding aptamer, d(G(2)T(2)G(2)TGTG(2)T(2)G(2)) (TBA), in the presence of Pb(2+) ions. The Pb L(III) -edge X-ray absorption spectrum of this metal-DNA complex is very similar to that we obtain for a Pb(2+)-stabilized quartet system of known structure constructed from a modified guanine nucleoside (G1). The Fourier transforms of the Pb(2+) complexes with both TBA and G1 show a first-shell interaction at about 2.6 A, and a weaker, broader shell at 3.5-4.0 A. Quantitative analysis of the EXAFS data reveals the following: (i) very close agreement between interatomic distances at the metal coordination site for the Pb(2+)-G1 complex determined by EXAFS and by X-ray crystallography; (ii) similarly close agreement between interatomic distances measured by EXAFS for the Pb(2+)-G1 and Pb(2+)-TBA complexes. These results provide strong evidence for binding of the Pb(2+) ion in the region between the two quartets in the Pb(2+)-TBA complex, coordinated to the eight surrounding guanine O6 atoms. The specific binding of Pb(2+) to DNA examined here may be relevant to the genotoxic effects of this environmentally important heavy metal. Furthermore, these results demonstrate the utility of EXAFS as a method for quantitative characterization of specific metal binding sites in nucleic acids in solution.

A decade ago, the Chief Executive Officer of Albert Einstein Healthcare Network (AEHN), anticipating a tumultuous and largely unpredictable period in its industry, undertook to convert this organization from one that was basically stable and complacent to one that was agile, “nimble, and change-hardy”. This case study, while briefly addressing AEHN's approaches to business strategy and organization design, focuses primarily on the human resource strategy that emerged over time to foster the successful attainment of organizational agility. Although exploratory, the study suggests a number of lessons for those who are—or will be—studying or trying to create and sustain this promising new organizational paradigm. © 2001 John Wiley & Sons, Inc.

The thrombin aptamer is a 15-mer oligodeoxyribonucleotide that folds into a unimolecular quadruplex consisting of a stack of two guanine quartets connected by two external loops and one central loop and possesses a high affinity for thrombin. We have undertaken a systematic examination, in KCl, of the thermodynamic stability of thrombin aptamer analogues containing sequence modifications in one or more of the loops, as well as in the number of quartets. UV melting studies have been carried out to obtain the relevant thermodynamic parameters for these aptamers. van't Hoff analysis of these data, with a two-state model for unimolecular denaturation, gave excellent fits to the experimental observations. Thermodynamic analysis indicates that the central loop sequence in the parent aptamer is optimal for stability. Modifications in this or other loops can effect either DeltaH degrees, DeltaS degrees, or both. Addition of a single G at the 5'-end decreases stability while addition of a G at the 3'-end increases stability. Differential scanning calorimetry experiments on the thrombin aptamer reveal that a heat capacity change, not detected by UV measurements, accompanies the unfolding of the aptamer.

Among the many unusual conformations of DNA and RNA, quadruplex structures, based on the guanine quartet, possess several unique properties. These properties, along with the general features of guanine quadruplexes, are described in the context of possible roles for these structures in biological systems. A variety of experimental observations supporting the notion that quadruplexes are important in vivo is presented, including proteins known to specifically bind to quadruplex structures, guanine-rich DNA, and RNA sequences endowed with the potential for forming quartet-based structures in telomeres and regulatory regions, such as gene promoters, quadruplexes as DNA aptamer folding motifs arising from in vitro selection experiments, and potential chemotherapeutic, quadruplex-forming oligonucleotides. Taken together, all of these observations argue cogently not only for the presence of quadruplexes in biological systems but also for their significance in terms of their roles in various biological processes. © 2001 John Wiley & Sons, Inc. Biopolymers (Nucleic Acid Sci) 56: 209–227, 2001

In this paper we examine the cosmological constraints of the recent DIRBE and FIRAS detection of the extragalactic background light between 125-5000 microns on the metal and star formation histories of the universe., Comment: 38 pages and 9 figures. Accepted for publications in The Astrophysical Journal

The solution structure and dynamical properties of the potassium-stabilized, hairpin dimer quadruplex formed by the oligonucleotide d(G3T4G3) have been elucidated by a combination of high-resolution NMR and molecular dynamics simulations. Refinement calculations were carried out both in vacuo, without internally coordinated K+ cations, and in explicit water, with internally coordinated K+ cations. In the latter case, the electrostatic interactions were calculated using the particle mesh Ewald (PME) method. The NMR restraints indicate that the K+ quadruplex has a folding arrangement similar to that formed by the same oligonucleotide in the presence of sodium, but with significant local differences. Unlike the Na+ quadruplex, the thymine loops found in K+ exhibit considerable flexibility, and appear to interconvert between two preferred conformations. Furthermore, the NMR evidence points toward K+-stabilized guanine quartets of slightly larger diameter relative to the Na+-stabilized structure. The characteristics of the quartet stem are greatly affected by the modeling technique employed: caged cations alter the size and symmetry of the quartets, and explicit water molecules form hydration spines within the grooves. These results provide insight into those factors that determine the overall stability of hairpin dimer quadruplexes and the effects of different cations in modulating the relative stability of the dimeric hairpin and linear, four-stranded, quadruplex forms.

Ligands capable of specific recognition of RNA structures are of interest in terms of the principles of molecular recognition as well as potential chemotherapeutic applications. We have approached the problem of identifying small molecules with binding specificity for the RNA double helix through application of the DOCK program [Kuntz, I. D., Meng, E. C., and Shoichet, B. K. (1994) Acc. Chem. Res. 27, 117-123], a structure-based method for drug discovery. A series of lead compounds was generated through a database search for ligands with shape complementarity to the RNA deep major groove. Compounds were then evaluated with regard to their fit into the minor groove of B DNA. Those compounds predicted to have an optimal fit to the RNA groove and strong discrimination against DNA were examined experimentally. Of the 11 compounds tested, 3, all aminoglycosides, exhibited pronounced stabilization of RNA duplexes against thermal denaturation with only marginal effects on DNA duplexes. One compound, lividomycin, was examined further, and shown to facilitate the ethanol-induced B to A transition in calf thymus DNA. Fluorine NMR solvent isotope shift measurements on RNA duplexes containing 5-fluorouracil provided evidence that lividomycin binds in the RNA major groove. Taken together, these results indicate that lividomycin recognizes the general features of the A conformation of nucleic acids through deep groove binding, confirming the predictions of our DOCK analysis. This approach may be of general utility for identifying ligands possessing specificity for additional RNA structures as well as other nucleic acid structural motifs.

We have targeted the d[G(AG)5]. d[C(TC)5] duplex for triplex formation at neutral pH with either d[G(AG)5] or d[G(TG)5]. Using a combination of gel electrophoresis, uv and CD spectra, mixing and melting curves, along with DNase I digestion studies, we have investigated the stability of the 2:1 pur*pur.pyr triplex, d[G(AG)5]*d[G(AG)5].d[C(TC)5], in the presence of MgCl2. This triplex melts in a monophasic fashion at the same temperature as the underlying duplex. Although the uv spectrum changes little upon binding of the second purine strand, the CD spectrum shows significant changes in the wavelength range 200-230 nm and about a 7 nm shift in the positive band near 270 nm. In contrast, the 1:1:1 pur/pyr*pur.pyr triplex, d[G(TG)5]*d[G(AG)5].d[C(TC)5], is considerably less stable thermally, melting at a much lower temperature than the underlying duplex, and possesses a CD spectrum that is entirely negative from 200 to 300 nm. Ethidium bromide undergoes a strong fluorescence enhancement upon binding to each of these triplexes, and significantly stabilizes the pur/pyr*pur.pyr triplex. The uv melting and differential scanning calorimetry analysis of the alternating sequence duplex and pur*pur.pyr triplex shows that they are lower in thermodynamic stability than the corresponding 10-mer d(G3A4G3). d(C3T4C3) duplex and its pur*pur.pyr triplex under identical solution conditions.

The mechanical and electrochemical properties of magnesium are favorable for biomedical and energy storage applications. However, magnesium microfabrication has been limited to sub-micron-thick film technologies (i.e., sputtering or evaporation). This paper presents three magnesium microfabrication approaches for thicknesses greater than 10 μm: 1) laser-cutting and 2) chemical etching of 70-μm-thick commercial magnesium foil; and 3) through-mold electroplating of magnesium from non-aqueous solution. The fabrication technologies are compared on minimum feature size, morphology, uniformity, composition and electrical resistivity. Preliminary results confirmed that the 50-μm-thick electroplated material composition compared favorably with commercial magnesium foil. The measured electrical resistivities of commercial and electrodeposited magnesium were 5.3 μΩ·cm and 8.7 μΩ·cm, respectively. Thick magnesium microstructures can be fabricated through several means to serve a broad range of MEMS-based applications.

Two-dimensional 1H NMR studies on the dimeric hairpin quadruplex formed by d(G3T4G3) in the presence of either NaCl or KCl are presented. In the presence of either salt, the quadruplex structure is characterized by half the guanine nucleosides in the syn conformation about the glycosidic bond, the other half in the anti conformation, as reported for other similar sequences. However, 1H NOESY and 1H-31P heteronuclear correlation experiments demonstrate that the deoxyguanosines do not strictly alternate between syn and anti along individual strands. Thus we find the following sequences with regard to glycosidic bond conformation: 5'-G1SG2SG3AT4AT5A-T6AT7AG8SG9AG10A-3' and 5'-G11SG12AG13AT14AT1 5AT16AT17AG18SG19SG20A-3', where S and A denote syn and anti, respectively. This represents the first experimental evidence for a nucleic acid structure containing two sequential nucleosides in the syn conformation. The stacking interactions of the resulting quadruplex quartets and their component bases have been evaluated using unrestrained molecular dynamics calculations and energy component analysis. These calculations suggest that the sequential syn-syn/anti-anti and syn-anti quartet stacks are almost equal in energy, whereas the anti-syn stack, which is not present in our structure, is energetically less favorable by about 4 kcal/mol. Possible reasons for this energy difference and its implications for the stability of quadruplex structures are discussed.

NASA's Cosmic Background Explorer ( COBE 1 ) carries three scientific instruments to make precise measurements of the spectrum and anisotropy of the cosmic microwave background (CMB) radiation on angular scales greater than 7° and to conduct a search for a diffuse cosmic infrared background (CIB) radiation with 0.7° angular resolution. Data from the Far-InfraRed Absolute Spectrophotometer (FIRAS) show that the spectrum of the CMB is that of a blackbody of temperature T=2.73±0.06 K, with no deviation from a blackbody spectrum greater than 0.25% of the peak brightness. The first year of data from the Differential Microwave Radiometers (DMR) show statistically significant CMB anisotropy. The anisotropy is consistent with a scale invariant primordial density fluctuation spectrum. Infrared sky brightness measurements from the Diffuse InfraRed Background Experiment (DIRBE) provide new conservative upper limits to the CIB. Extensive modeling of solar system and galactic infrared foregrounds is required for further improvement in the CIB limits.

The National Aeronautics and Space Administration (NASA) has flown the COBE satellite to observe the Big Bang and the subsequent formation of galaxies and large-scale structure. Data from the Far-Infrared Absolute Spectrophotometer (FIRAS) show that the spectrum of the cosmic microwave background is that of a black body of temperature T = 2.73 ± 0.06 K, with no deviation from a black-body spectrum greater than 0.25% of the peak brightness. The data from the Differential Microwave Radiometers (DMR) show statistically significant cosmic microwave background anisotropy, consistent with a scale-invariant primordial density fluctuation spectrum. Measurements from the Diffuse Infrared Background Experiment (DIRBE) provide new conservative upper limits to the cosmic infrared background. Extensive modeling of solar system and galactic infrared foregrounds is required for further improvement in the cosmic infrared background limits.

Interaction of the antimalarial drugs quinacrine and chloroquine with DNA has been studied extensively in order to understand the origin of their biological activity. These studies have shown that they bind to DNA through an intercalative mode and show little sequence specificity. All previous experiments were carried out using the racemic form of these drugs. We have investigated the binding of the enantiomeric forms of quinacrine and chloroquine to synthetic polynucleotides poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly (dG-dC), and found interesting differences in their binding parameters. Quinacrine enantiomers have a much higher binding affinity for the two polynucleotides compared to those of chloroquine. The negative enantiomers were found to have higher binding affinity than the positive ones. The binding constant for the binding of quinacrine(-) to poly(dG-dC).poly(dG-dC) was found to be about 3 times that of quinacrine(+). The differences in these binding affinities were further confirmed by equilibrium dialysis of the complexes of the polynucleotides with the racemic form of the drugs, which resulted in the enrichment of the dialysate with the positive enantiomer. CD spectra of the enantiomers and their polynucleotide complexes are reported. Changes in the fluorescence properties of quinacrine in the presence of the two polynucleotides are also described. Biological implications of these findings are discussed.

The interactions of spermine and polyamine analogues with synthetic polynucleotides of various base sequences complexed with ethidium bromide (EB) were investigated using measurements of fluorescence intensity and steady-state fluorescence polarization. Spermine and polyamine analogues displaced some but not all of the EB bound to poly(dA-dT).poly(dA-dT) or poly(dG-dC).poly(dG-dC), suggesting that polyamines may stabilize these polynucleotides in a conformation with reduced affinity for EB. Modifications of the aliphatic backbone of spermine have pronounced effects on its ability to displace EB from poly(dA-dT).poly(dA-dT) but not from poly-(dG-dC).poly(dG-dC). Spermine and some but not all of the polyamine analogues caused fluorescence depolarization when they interacted with the complex of EB and poly(dA-dT).poly-(dA-dT). Neither spermine nor any of the analogues, however, induced fluorescence depolarization in the complex of EB with poly(dG-dC).poly(dG-dC) or poly(dA).poly(dT). This suggests that spermine and some spermine analogues induce structural changes specific to alternating A-T sequences.

In an effort to probe the structure and stability of the CH + -C base pair in DNA, we have studied the conformation of the deoxydecanucleotide d(C 3 T 4 C 3 ) at pH 5.5, using 1 H-NMR and UV absorption spectroscopy. Lowering the pH of a solution containing d(C 3 T 4 C 3 ) is accompanied by the induction of six new imino proton NMR resonances in a region (15.415.8 ppm) downfield from where either T-H 3 or G-H1 Watson-Crick (W-C)-paired imino protons normally resonate

Two-dimensional (2D) 1H-NMR spectroscopy has been used to analyze the structure of d(GCTTAAGC)2 and its interaction with berenil in solution. Nuclear Overhauser enhancement connectivities enabled sequential assignments of nearly all proton resonances in the self-complementary octamer duplex and demonstrated that the oligonucleotide is primarily in a B-type conformation. No major conformational changes were observed by the addition of berenil, but proton resonances of the two adenosine nucleotides shifted substantially. Intermolecular nuclear Overhauser effects between berenil and the DNA duplex revealed that the drug binds via the minor groove of d(GCTTAAGC)2 in the A.T-base-pair region. At 18 degrees C the twofold symmetry of the duplex is preserved on berenil binding. However, strongly shifted proton resonances broadened significantly. A model is proposed for the berenil-d(GCTTAAGC)2 complex involving fast exchange of berenil between two equivalent symmetry-related binding sites, which span the 5'-TAA-3' region and are asymmetrically disposed with respect to the dyad axis of the duplex. These results are compared with previous studies on the berenil-d(GCAATTGC)2 complex.

We present constraints on the nature of the first galaxies selected at 350 μm. The sample includes galaxies discovered in the deepest blank-field survey at 350 μm (in the Bootes Deep Field) and also later serendipitous detections in the Lockman Hole. In determining multiwavelength identifications, the 350 μm position and map resolution of the second generation Submillimeter High Angular Resolution Camera are critical, especially in the cases where multiple radio sources exist and the 24 μm counterparts are unresolved. Spectral energy distribution templates are fitted to identified counterparts, and the sample is found to comprise IR-luminous galaxies at 1 < z < 3 predominantly powered by star formation. The first spectrum of a 350 μm selected galaxy provides an additional confirmation, showing prominent dust grain features typically associated with star-forming galaxies. Compared to submillimeter galaxies selected at 850 and 1100 μm, galaxies selected at 350 μm have a similar range of far-infrared color temperatures. However, no 350 μm selected sources are reliably detected at 850 or 1100 μm. Galaxies in our sample with redshifts 1 < z < 2 show a tight correlation between the far- and mid-infrared flux densities, but galaxies at higher redshifts show a large dispersion in their mid- to far-infrared colors. This implies a limit to which the mid-IR emission traces the far-IR emission in star-forming galaxies. The 350 μm flux densities (15 < S 350 < 40 mJy) place these objects near the Herschel/SPIRE 350 μm confusion threshold, with the lower limit on the star formation rate density suggesting the bulk of the 350 μm contribution will come from less luminous infrared sources and normal galaxies. Therefore, the nature of the dominant source of the 350 μm background—star-forming galaxies in the epoch of peak star formation in the universe—could be more effectively probed using ground-based instruments with their angular resolution and sensitivity offering significant advantages over space-based imaging.

The binding of spermine to the d(m 5 CGm 5 CGm 5 CG) duplex has been studied by proton and phosphorus nuclear magnetic resonance techniques in order to investigate the mobility and nature of spermine bound to the resulting Z -DNA complex. A characterization of the B to Z transition as a function of increasing spermine concentration demonstrated doubling of the non-exchangeable proton and the phosphorus peaks at a ratio of about 1:1 (spermine/duplex) and a re-simplification of the spectrum at 2:1 (spermine/duplex) where about 90% or the DNA was fully converted into the Z -form. However, some of the Z -DNA proton chemical shifts differed between the 1:1 and 2:1 titration points. Since these differences involved primarily the exchangeable terminal imino and amino protons, they could result from end effects. Discrepancies were generally not observed with the non-terminal proton shifts nor with the phosphorus shifts. These proton and phosphorus chemical shift changes are fully consistent with a, B to Z transition. Complexed spermine peaks appear about 0.1 parts per million upfield from the uncomplexed form. The spermine and both the B and Z -DNA hexamer signals are noticeably broadened at the 1:1 ratio but the remaining signals re-sharpen at the 2:1 ratio. Both one-dimensional and two-dimensional studies revealed negative nuclear Overhauser effect (NOE) contacts between each spermine proton. Therefore, spermine has a longer correlation time than that observed for unbounded spermine. These results are contrasted with the positive NOE contacts observed for the B -DNA-spermine complexes reported by Wemmer et al. using the dodecamer d(CGCGAATTCGCG) 2 and reported here using the hexamer d(ATGCAT) 2 . While the mobility of spermine in the Z -DNA complex is significantly less than that of the B -DNA complex, no clear evidence of intermolecular spermine-DNA proton NOE contacts is observed.

The interaction of ethidium, a DNA intercalator, with the poly(dA).poly(dT) duplex and the poly (dA).2poly(dT) triplex has been investigated by a variety of spectrophotometric and hydrodynamic techniques. The fluorescence of ethidium is increased when either the duplex or triplex form is present. Binding constants, determined from absorbance measurements, indicate that binding to the triple helical form is substantially stronger than to the duplex, with a larger binding site size (2.8 base triplets compared to 2.4 base pairs). Furthermore, while binding to poly(dA).poly(dT) shows strong positive cooperativity, binding to the triplex is noncooperative. Thermal denaturation experiments demonstrate that ethidium stabilizes the triple helix. Binding to either form induces a weak circular dichroism band in the visible wavelength region, while in the region around 310 nm, there is a band that is strongly dependent on the degree of saturation of the duplex, and which is positive for the duplex but negative for the triplex. Both fluorescence energy transfer and quenching studies provide evidence of intercalation of ethidium in both duplex and triplex complexes. Binding of ethidium leads to an initial decrease in viscosity for both the duplex and triplex structures, followed by an increase, which is greater for the duplex. Taken together, these results strongly suggest that ethidium binds to the poly (dA).2poly(dT) triple helix via an intercalative mechanism.

The concept and operation of the Differential Microwave Radiometers (DMR) instrument aboard NASA's Cosmic Background Explorer satellite are reviewed, with emphasis on the software identification and subtraction of potential systematic effects. Preliminary results obtained from the first six months of DMR data are presented, and implications for cosmology are discussed.

In this paper, we report the results of a rapid and room temperature integration approach for the selective and structured deposition of carbon nanotubes (CNTs) into three-dimensional microstructures. The approach exploits electrophoretic deposition (EPD) from an aqueous suspension of CNTs, together with suitably patterned and electrically-energized microstructure-bearing substrates. Uniform 2-D and 3-D micropatterns of CNTs on wafer scale have been achieved in less than 4 minutes with controllable thicknesses ranging from 133nm to several micrometers. Orientation of the deposited CNTs was observed in microstructures with certain dimensions. Surface hydrophobicity of the microstructures was found to be critical in achieving well-defined micropatterning of CNTs. A hydrophobic microstructure surface leads to the selective patterning profiles of CNTs, while a hydrophilic surface induces CNTs assembly over the entire microstructure, with resultant loss of selectivity. This approach can be further extended to fabricate 3-D micropatterns with multilayer materials on flexible substrate through the aid of transfer micromolding techniques.

The binding of mithramycin A to the d(A1T2G3C4A5T6) duplex was investigated by 1H NMR and found to be similar to that of its analogue chromomycin A3. In the presence of Mg2+, mithramycin binds strongly to d(ATGCAT)2. On the basis of the two-dimensional NOESY spectrum, the complex formed possesses C2 symmetry at a stoichiometry of two drugs per duplex (2:1) and is in slow chemical exchange on the NMR time scale. NOESY experiments reveal contacts from the E-pyranose of mithramycin to the terminal and nonterminal adenine H2 proton of DNA and from the drug hydroxyl proton to both G3NH2 protons, C4H1' proton, and A5H1' proton. These data place the drug chromophore and E pyranose on the minor groove side of d(ATGCAT)2. NOE contacts from the A-, B-, C-, and D-pyranoses of mithramycin to several deoxyribose protons suggest that the A- and B-rings are oriented along the sugar-phosphate backbone of G3-C4, while the C- and D-rings are located along the sugar-phosphate backbone of A5-T6. These drug-DNA contacts are very similar to those found for chromomycin binding to d(ATGCAT)2. Unlike chromomycin, the NOESY spectrum of mithramycin at the molar ratio of one drug per duplex reveals several chemical exchange cross-peaks corresponding to the drug-free and drug-bound proton resonances. From the intensity of these cross-peaks and the corresponding diagonal peaks, the off-rate constant was estimated to be 0.4 s-1. These data suggest that the exchange rate of mithramycin binding to d(ATGCAT)2 is faster than that of chromomycin.

The existence of DNA triple helices in vitro has been known for some time. Recent evidence suggesting that DNA triplexes exist in vivo and showing their potential for chemotherapeutic applications has renewed interest in these triple-strand conformations. However, little structural information is currently known about these unusual nucleic acid forms. We have induced and stabilized triple-helical (dA)10.2(dT)10 with MgCl2 at neutral pH. UV mixing curves demonstrate a 1:2 (dA)10 to (dT)10 stoichiometry at suitable MgCl2 concentrations. Thermal denaturation profiles establish a melting mechanism characterized by the initial loss of the third strand, followed by dissociation of the remaining duplex. The circular dichroic spectrum of the triplex form is distinct from that of a duplex equimolar in (dA)10. NMR studies show that magnesium-induced triplex formation is accompanied by an upfield shift of several imino proton resonances present before stabilization of the triplex form with MgCl2 and the induction of new upfield imino proton resonances. Nuclear Overhauser effect spectroscopy measurements on both undeuterated and C8--H-deuterated (dA)10.2(dT)10 triplexes demonstrate dipolar contacts between resolvable imino proteins and both adenine C8--H and C2--H aromatic protons. Hence, MgCl2 stabilizes a triplex structure in which thymine N3--H imino protons are involved in both Watson-Crick and Hoogsteen base pairing.

We have stabilized the d(A)10.2d(T)10 and d(C+LT4C+3).d(G3A4G3).d(C3T4C3) triple helices with either NaCl or MgCl2 at pH 5.5. UV mixing curves demonstrate a 1:2 stoichiometry of purine to pyrimidine strands under the appropriate conditions of pH and ionic strength. Circular dichroic titrations suggest a possible sequence-independent spectral signature for triplex formation. Thermal denaturation profiles indicate the initial loss of the third strand followed by dissociation of the underlying duplex with increasing temperature. Depending on the base sequence and ionic conditions, the binding affinity of the third strand for the duplex at 25 degrees C is two to five orders of magnitude lower than that of the two strands forming the duplex. Thermodynamic parameters for triplex formation were determined for both sequences in the presence of 50 mM MgCl2 and/or 2.0 M NaCl. Hoogsteen base pairs are 0.22-0.64 kcal/mole less stable than Watson-Crick base pairs, depending on ionic conditions and base composition. C+.G and T.A Hoogsteen base pairs appear to have similar stability in the presence of Mg2+ ions at low pH.

This paper reports a laser-assisted fabrication scheme for three-dimensional (3-D) electrodeposited metal structures into high aspect ratio trenches. A polymer (parylene C) is conformally deposited onto a highly nonplanar surface, selectively laser ablated, and used as an electroplating mold to fabricate metallic structures. Laser ablation of high-resolution (< 10 mum) features is performed using a 248 nm KrF Excimer laser. The ablation parameters for the parylene layer have been characterized for various film thicknesses. Metal lines of 2 mum thickness, and 2.5 mum width have been electroplated into 300 mum deep silicon trenches. The minimum resolution achieved is less than 5 mum. This process can potentially be applied toward the fabrication of embedded inductors, high density electrodes, buried interconnects or high voltage circuitry in CMOS and MEMS devices.

This paper reports the design, fabrication and experimental characterization of ultraminiaturized, axial-flux, permanent-magnet (PM) generators intended for milliwatt range systems. The miniaturization of PM machines is attractive because scaling laws are favorable, but integration of ultra-small permanent magnets is challenging. The generators are 2-pole, multi-turn, 2-mm diameter machines. A single-phase, open-circuit voltage of 51 mVrms has been measured at 392 krpm, which approximately corresponds to 3.6 mW of DC power to a load resistance at the point of maximum power transfer, indicating that this approach shows great promises for milliwatt-scale power devices.

We present images taken with the first deployed astronomical instrument to use multiplexed superconducting bolometers. The Fabry-Perot Interferometer Bolometer Research Experiment (FIBRE), a broadband submillimeter spectrometer, took these images as a detector investigation at the Caltech Submillimeter Observatory (CSO). FIBRE's detectors are superconducting bilayer transition edge sensor (TES) bolometers read out by a SQUID multiplexer. An order-sorted Fabry-Perot provides illumination of a 16-element linear bolometer array, resulting in five orders at a spectral resolution of around 1200 covering the 350 micron atmospheric band. We present multiwavelength images of Jupiter, Venus and the high-mass star-forming region G34.3+0.2 taken with this instrument at several wavelengths in the 350 micron band, separated by approximately 8 microns. These images have validated the use of multiplexed superconducting bolometers in an astronomical application and have helped inform the design of our future instruments.

In the presence of certain metal ions, DNA and RNA can form guanine quadruplex structures, which have been proposed to play a functional role in a variety of biological processes. An 18-nucleotide DNA oligomer, PS2.M, d(GTG3TAG3CG3T2G2), was previously reported to bind hemin and the resulting complex exhibited peroxidase activity. It was proposed that PS2.M folds unimolecularly into an antiparallel quadruplex with unusual, single-base loops and terminal guanines positioned in adjacent quartets. Here we describe structural and stability properties of PS2.M alone in different buffers and metal ions, using gel electrophoresis, circular dichroism (CD), ultraviolet (UV)-visible spectroscopies, and one-dimensional 1H nuclear magnetic resonance (NMR). Native gel behavior of PS2.M in the presence of either Na+ or Pb2+ suggests the formation of unimolecular structures but, in the presence of K+, both unimolecular and multistranded structures are observed. In the presence of Pb2+ ions, PS2.M forms a unimolecular quadruplex containing three guanine quartets. CD titrations reveal that binding of Pb2+ ions to PS2.M is stoichiometric, and a single lead cation suffices to fully fold PS2.M. The PS2.M–Na+ system also forms a similar unimolecular quadruplex. In the presence of K+, the PS2.M–K+ system forms mixed species. With increasing time and PS2.M concentration, the contribution of unimolecular species decreases while that of multimolecular species increases, and this behavior is independent of buffer media. These results suggest that the catalytically active form, studied in the presence of K+, may be a parallel, multistranded quadruplex rather than an antiparallel, unimolecular quadruplex. © 2006 Wiley Periodicals, Inc. Biopolymers 82:558–569, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

This paper presents a simplified fabrication method to make highly elevated electrical signal lines up to 700 /spl mu/m in height from the substrates. The immediate application is a bioMEMS device that requires high aspect ratio three-dimensional (3D) multi-electrode arrays (MEA) to detect signals from deep within 3D networks of neurons. The demonstrated method generated thick electroplated metal lines on excimer laser patterned parylene molds. The directionality of the laser beam makes it possible to achieve practically straight patterns on the inclined sidewalls in addition to the bottom surface, which are several hundred microns below. 3D multi-electrodes on various elevation surfaces and insulation of parylene coating were efficiently implemented by using the directionality of excimer lasers and the conformal coating of parylene.

Formation of intramolecular tetraplex structures by the thrombin-binding DNA aptamer (TBA) in the presence of K(+), Pb(2+), Ba(2+), Sr(2+) and Mn(2+) has been studied by vibrational spectroscopy. All tetraplex structures contain G-G Hoogsteen type base pairing, both C2'endo/anti and C2'endo/syn deoxyguanosine glycosidic conformations and local B like form DNA phosphate geometries. Addition of Pb(2+) ions modifies the structure by interacting at the level of the guanine carbonyl groups. The very important downshift of the guanine C6=O6 carbonyl vibration mode in the TBA spectrum induced by the addition of one Pb(2+) ion per TBA molecule is in agreement with a localization of the metal ion between both guanine quartets. FTIR melting experiments show an important stabilization of the tetraplex structure upon addition of Pb(2+) ions (DeltaT = 15 degrees C). This strong interaction of lead cations may be correlated with a change in the geometry of the cage formed by the two guanine quartets. A similar but weaker effect is observed for barium and strontium cations.

Far-infrared detector arrays such as the 16x32 superconducting bolometer array for the SAFIRE instrument (flying on the SOFIA airborne observatory) require systems of readout and control electronics to provide translation between a user-driven, digital PC and the cold, analog world of the cryogenic detector. In 2001, the National Institute of Standards and Technology (NIST) developed their Mark III electronics for purposes of control and readout of their 1x32 SQUID Multiplexer chips. We at NASA s Goddard Space Flight Center acquired a Mark 111 system and subsequently designed upgrades to suit our and our collaborators purposes. We developed an arbitrary, programmable multiplexing system that allows the user to cycle through rows in a SQUID array in an infinite number of combinations. We provided hooks in the Mark III system to allow readout of signals from outside the Mark 111 system, such as telescope status information. Finally, we augmented the heart of the system with a new feedback algorithm implementation, flexible diagnostic tools, and informative telemetry.

The Fabry-Perot Interferometer Bolometer Research Experiment FIBRE, a protoype submillimeter spectrometer for astronomical observations, is based on a helium-cooled scanning Fabry-Perot and superconducting transition edge sensor bolometers (TES). The TES design takes advantage of a recently discovered method of excess noise reduction by depositing lateral normal metal bars on these devices. A SQUID multiplexer is used to read out the individual detector pixels. The spectral resolving power of the instrument is provided by a Fabry-Perot spectrometer. The outgoing light from the Fabry-Perot passes onto a low resolution grating for order sorting. A linear bolometer array consisting of 16 elements detects this dispersed light, capturing 5 orders simultaneously from one position on the sky. With tuning of the Fabry-Perot over one free spectral range, a spectrum covering Δλ/λ =1/7 at a resolution of ~1/1200 can be achieved. This spectral resolution is sufficient to resolve doppler broadened line emission from external galaxies. FIBRE operates in the 350 μm and 450 μm bands. These bands cover line emission from the important PDR tracers neutral carbon [CI] and carbon monoxide CO. The spectrometer is used at the Caltech Submillimeter Observatory for astronomical observations.

We have been developing an architecture for producing large format, two-dimensional arrays of close-packedbolometers, which will enable far-infrared to millimeter wavelength ( l =100 mÐ2 mm) cameras and spectrometers toobtain images and spectra orders of magnitude faster than present instruments. The low backgrounds achieved in theseinstruments require very sensitive detectors with NEPs ranging from 10 Ð17 to 10 Ð19 W/ Hz. Superconducting transitionedge sensor bolometers can be close-packed using the Pop-Up Detector (PUD) format, and SQUID multiplexersoperating at the detector base temperature can be intimately coupled to them. The array unit cell is 8 ´ 32 pixels, using 32-element detector and multiplexer components. We have fabricated an engineering model array with this technologyfeaturing a very compact, modular approach for large format arrays. We report on the production of the 32-elementcomponents for the arrays. Planned instruments using this array architecture include the Submillimeter and Far-InfraRedExperiment (SAFIRE) on the SOFIA airborne observatory, the South Pole Imaging Fabry-Perot Interferometer (SPIFI)for the AST/RO observatory, the Millimeter Bolometer Camera for the Atacama Cosmology Telescope (MBC/ACT),and the Redshift O Z O Early Universe Spectrometer (ZEUS).Keywords: bolometer array, superconducting transition edge sensor, SQUID multiplexer, SOFIA, AST/RO, ACT

Upcoming major NASA missions such as the Einstein Inflation Probe and the Single Aperture Far-Infrared Observatory require arrays of detectors with thousands of elements, operating at temperatures near l00 mK and sensitive to wavelengths from approx. 100 microns to approx. 3 mm. Such detectors represent a substantial enabling technology for these missions, and must be demonstrated soon in order for them to proceed. In order to make rapid progress on detector development, the cryogenic testing cycle must be made convenient and quick. We have developed a cryogenic detector characterization system capable of testing superconducting detector arrays in formats up to 8 x 32, read out by SQUID multiplexers. The system relies on the cooling of a two-stage adiabatic demagnetization refrigerator immersed in a liquid helium bath. This approach permits a detector to be cooled from 300K to 50 mK in about 4 hours, so that a test cycle begun in the morning will be over by the end of the day. Tine system is modular, with two identical immersible units, so that while one unit is cooling, the second can be reconfigured for the next battery of tests. We describe the design, construction, and performance of this cryogenic detector testing facility.