Tunable narrow-linewidth laser at 2†µm wavelength for gravitational wave detector research.

We present and characterize a narrow-linewidth external-cavity diode laser at 2 µm, and show that it represents a low-cost, high-performance alternative to fiber lasers for research into 2 µm photonic technologies for next-generation gravitational-wave detectors. A linewidth of 20 kHz for a 10 ms integration time was measured without any active stabilization, with frequency noise of ∼ 15 Hz/Hz between 3 kHz and 100 kHz. This performance is suitable for the generation of quantum squeezed light, and we measure intensity noise comparable to that of master oscillators used in current gravitational wave interferometers. The laser wavelength is tunable over a 120 nm range, and both the frequency and intensity can be modulated at up to 10 MHz by modulating the diode current. These features also make it suitable for other emerging applications in the 2 µm wavelength region including gas sensing, optical communications and LIDAR.

Erratum: Bright Solitonic Matter-Wave Interferometer [Phys. Rev. Lett. 113, 013002 (2014)].

This corrects the article DOI: 10.1103/PhysRevLett.113.013002.

Time-of-flight detection of ultra-cold atoms using resonant frequency modulation imaging.

Resonant frequency modulation imaging is used to detect free falling ultra-cold atoms. A theoretical comparison of fluorescence imaging (FI) and frequency modulation imaging (FMI) is made, indicating that for low optical depth clouds, FMI accomplished a higher signal-to-noise ratio under conditions necessary for a 200 µm spatially resolved atom interferometer. A 750 ms time-of-flight measurement reveals near atom shot-noise limited number measurements of 2×106 Bose-condensed Rb87 atoms. The detection system is applied to high precision spinor BEC based atom interferometer.

Non-destructive shadowgraph imaging of ultra-cold atoms.

An imaging system is presented that is capable of far-detuned non-destructive imaging of a Bose-Einstein condensate with the signal proportional to the second spatial derivative of the density. Whilst demonstrated with application to Rb85, the technique generalizes to other atomic species and is shown to be capable of a signal-to-noise of ∼25 at 1 GHz detuning with 100 in-trap images showing no observable heating or atom loss. The technique is also applied to the observation of individual trajectories of stochastic dynamics inaccessible to single shot imaging. Coupled with a fast optical phase locked loop, the system is capable of dynamically switching to resonant absorption imaging during the experiment.

Simultaneous Precision Gravimetry and Magnetic Gradiometry with a Bose-Einstein Condensate: A High Precision, Quantum Sensor.

A Bose-Einstein condensate is used as an atomic source for a high precision sensor. A 5×10^{6} atom F=1 spinor condensate of ^{87}Rb is released into free fall for up to 750 ms and probed with a T=130 ms Mach-Zehnder atom interferometer based on Bragg transitions. The Bragg interferometer simultaneously addresses the three magnetic states |m_{f}=1,0,-1⟩, facilitating a simultaneous measurement of the acceleration due to gravity with a 1000 run precision of Δg/g=1.45×10^{-9} and the magnetic field gradient to a precision of 120 pT/m.

Bright solitonic matter-wave interferometer.

We present the first realization of a solitonic atom interferometer. A Bose-Einstein condensate of 1×10(4) atoms of rubidium-85 is loaded into a horizontal optical waveguide. Through the use of a Feshbach resonance, the s-wave scattering length of the 85Rb atoms is tuned to a small negative value. This attractive atomic interaction then balances the inherent matter-wave dispersion, creating a bright solitonic matter wave. A Mach-Zehnder interferometer is constructed by driving Bragg transitions with the use of an optical lattice colinear with the waveguide. Matter-wave propagation and interferometric fringe visibility are compared across a range of s-wave scattering values including repulsive, attractive and noninteracting values. The solitonic matter wave is found to significantly increase fringe visibility even compared with a noninteracting cloud.

An atomic Fabry-Perot interferometer using a pulsed interacting Bose-Einstein condensate.

We numerically demonstrate atomic Fabry-Perot resonances for a pulsed interacting Bose-Einstein condensate (BEC) source transmitting through double Gaussian barriers. These resonances are observable for an experimentally-feasible parameter choice, which we determined using a previously-developed analytical model for a plane matter-wave incident on a double rectangular barrier system. Through numerical simulations using the non-polynomial Schödinger equation-an effective one-dimensional Gross-Pitaevskii equation-we investigate the effect of atom number, scattering length, and BEC momentum width on the resonant transmission peaks. For [Formula: see text]Rb atomic sources with the current experimentally-achievable momentum width of [Formula: see text] [[Formula: see text]], we show that reasonably high contrast Fabry-Perot resonant transmission peaks can be observed using (a) non-interacting BECs, (b) interacting BECs of [Formula: see text] atoms with s-wave scattering lengths [Formula: see text] ([Formula: see text] is the Bohr radius), and (c) interacting BECs of [Formula: see text] atoms with [Formula: see text]. Our theoretical investigation impacts any future experimental realization of an atomic Fabry-Perot interferometer with an ultracold atomic source.

Computer-generated schematic diagrams of protein structures.

Computer-generated pictures are essential for studying and comparing the structures of proteins that have been solved by x-ray crystallography. Stereoscopic pairs produced by a computer program are particularly useful in providing an intelligible portrayal of the molecular topology.

Single-chain antigen-binding proteins.

Single-chain antigen-binding proteins are novel recombinant polypeptides, composed of an antibody variable light-chain amino acid sequence (VL) tethered to a variable heavy-chain sequence (VH) by a designed peptide that links the carboxyl terminus of the VL sequence to the amino terminus of the VH sequence. These proteins have the same specificities and affinities for their antigens as the monoclonal antibodies whose VL and VH sequences were used to construct the recombinant genes that were expressed in Escherichia coli. Three of these proteins, one derived from the sequence for a monoclonal antibody to growth hormone and two derived from the sequences of two different monoclonal antibodies to fluorescein, were designed, constructed, synthesized, purified, and assayed. These proteins are expected to have significant advantages over monoclonal antibodies in a number of applications.

In vivo tumor targeting of a recombinant single-chain antigen-binding protein.

We describe here the first in vivo targeting of tumors with a single-chain antigen-binding protein. The molecule, which was constructed and expressed in Escherichia coli, is a novel recombinant protein composed of a variable light-chain (VL), amino acid sequence of an immunoglobulin tethered to a variable heavy-chain (VH) sequence by a designed peptide. We show that this protein, derived from the DNA sequence of the variable regions of the antitumor monoclonal antibody B6.2, has the same in vitro antigen-binding properties as the B6.2 Fab' fragment. Comparative pharmacokinetic studies in athymic mice demonstrate much more rapid alpha and beta phases of plasma clearance for the single-chain antigen-binding protein than for the Fab' fragment, as well as an extremely rapid whole-body clearance. Half-life values for alpha and beta phases of single-chain antigen-binding protein clearance were 2.4 minutes and 2.8 hours, respectively, versus 14.8 minutes and 7.5 hours for Fab'. Furthermore, the single-chain antigen-binding protein molecule did not show accumulation in the kidney as did the Fab' molecule or, as previously shown, the F(ab')2 molecule. Despite its rapid clearance, the single-chain antigen-binding protein showed uptake in a human tumor xenograft comparable to that of the Fab' fragment, resulting in tumor to normal tissue ratios comparable to or greater than those obtained with the Fab' fragment. These studies thus demonstrate the in vivo stability of recombinant single-chain antigen-binding proteins and their potential in some diagnostic and therapeutic clinical applications in cancer and other diseases.

Fast machine-learning online optimization of ultra-cold-atom experiments.

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our 'learner' discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system.

Crystallization and preliminary X-ray diffraction studies of a pea lectin-methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside complex.

The seed lectin isolated from garden peas (Pisum sativum) has been co-crystallized with methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside in the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions a = 64.3 A, b = 73.4 A and C = 108.5 A. The asymmetric unit contains one pea lectin dimer (alpha 2 beta 2). The crystals are suitable for high-resolution structure analysis.

Structure of ferricytochrome c' from Rhodospirillum molischianum at 1.67 A resolution.

The structure of ferricytochrome c' from Rhodospirillum molischianum has been crystallographically refined to 1.67 A resolution using a combination of reciprocal space and restrained least-squares refinement methods. The final crystallographic R-factor for 30,533 reflections measured with I greater than sigma (I) between infinity and 1.67 A is 0.188. The final model incorporates 1944 unique protein atoms (of a total of 1972) together with 194 bound solvent molecules. The structure has been analysed with respect to its detailed conformational properties, secondary structural features, temperature factor behavior, bound solvent sites, and heme geometry. The asymmetric unit of the cytochrome c' crystal contains a dimer composed of chemically identical 128-residue polypeptide chains. Although the refined structure shows the monomers to be very similar, examination of the differences that do occur allows an evaluation of how different lattice contacts affect protein conformation and solvent binding. In particular, comparison of solvent binding sites in the two subunits allows identification of a common set that are not altered by lattice interactions. The preservation of these solvent interactions in different lattice environments suggests that they play a structural role in protein stabilization in solution. The refined structure additionally reveals some new features that relate to the ligand binding properties and unusual mixed-spin state character of cytochrome c'. Finally, comparison of the heme binding geometry in cytochrome c' and other structurally unrelated c-type cytochromes shows that two alternative, but sterically favorable, conformational variants occur among the seven examples examined.

X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.

X-ray crystallographic analysis of 5-(4'-substituted phenyl)sulfanyl-2,4-diaminoquinazoline inhibitors in ternary complex with Candida albicans dihydrofolate reductase (DHFR) and NADPH revealed two distinct modes of binding. The two compounds with small 4'-substituents (H and CH3) were found to bind with the phenyl group oriented in the plane of the quinazoline ring system and positioned adjacent to the C-helix. In contrast, the more selective inhibitors with larger 4'-substituents (tert-butyl and N-morpholino) were bound to the enzyme with the phenyl group perpendicular to the quinazoline ring and positioned in the region of the active site that typically binds the dihydronicotinamide moiety of NADPH. The cofactor appeared bound to DHFR but with the disordered dihydronicotinamide swung away from the protein surface and into solution. This unusual inhibitor binding mode may play an important role in the high DHFR selectivity of these compounds and also may provide new ideas for inhibitor design.

Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo.

To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the P1 and P2' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2' linkers. With an N-methylamide at P3', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3'-P4' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC(50) values of

Measurement of the acid-labile subunit of the insulin-like growth factor binding protein complex in human serum: a comparison of four immunoassays.

The acid-labile subunit (ALS) of the high molecular weight insulin-like growth factor binding protein complex is a liver-derived glycoprotein which is regulated by growth hormone and serves as a serum marker of growth hormone action. We have compared the measurement of ALS by four immunoassay methods (two RIAs, two ELISAs) utilizing various polyclonal and monoclonal antibodies raised against natural or recombinant human ALS, or synthetic ALS peptides. Despite the variety of methodologies and reagents, results obtained by the four methods were highly correlated for 125 sera from various patient groups, and when compared for individual groups of sera from healthy children and adults, growth hormone-deficient children and adults, and subjects with acromegaly. Some weaker correlations among methods were seen when measuring ALS levels in groups of sera from pregnant subjects and subjects with chronic renal failure. An assay using antibodies raised against recombinant ALS yielded lower apparent values than the other methods in patient sera, the discrepancy probably being attributable to a difference in standardization. We conclude that a variety of assay formats and reagents can yield serum ALS values of potential clinical utility.

A purified bovine serum albumin preparation contains an insulin-like growth factor (IGF) binding protein-3 fragment that forms ternary complexes selectively with IGF-II and the acid-labile subunit.

Among the six insulin-like growth factor binding proteins (IGFBP), only IGFBP-3 and IGFBP-5 form ternary complexes with IGFs and the acid-labile sunbunit (ALS). In a commercial, highly-purified BSA preparation, ternary complex formation was detected using radio-labeled IGF-II and human serum-derived ALS, with precipitation by ALS antiserum. In contrast, no complexes with radio-labeled IGF-I were detected under the same conditions. Size-fractionation of the BSA on Superose-12 showed the peak of ternary complex forming activity at approximately 30 kDa. To purify the active factor, a solution of the BSA was pumped onto a [Gly(1)]IGF-II affinity column, and eluted fractions were lyophilized and applied to a C18 HPLC column. The eluted fractions showing ternary complex forming activity maintained a preference for IGF-II in forming ternary complexes and a slight preference in forming binary complexes with IGF-II rather than IGF-I. By silver staining after non-reducing SDS-PAGE, the peak activity in the HPLC-eluted fractions appeared as 30 kDa and 21-24 kDa bands. Amino-terminal sequencing of this peak activity revealed bovine IGFBP-3. These results demonstrate that amino-terminal proteolyzed bovine IGFBP-3 is present in a highly purified BSA preparation. In contrast to intact human IGFBP-3 and IGFBP-5, this form of bovine IGFBP-3 forms ternary complexes preferentially with IGF-II rather than IGF-I.

Fate and toxicity of temephos applied to an intertidal mangrove community.

The distribution, persistence, and toxicity of the mosquito larvicide temephos was monitored following aerial applications to an intertidal mangrove community in Lee County, Florida. The amount of temephos penetrating to the mangrove floor ranged from 15 to 70% of the amount entering the upper leaf canopy, with 50-60% of that applied remaining on the mangrove leaves. Rainfall caused an additional influx of temephos from the leaves to the mangrove floor. Residues were detected in intertidal water at 2 h, but not 4 h after application. However, temephos was observed to persist in simulated tidal pools and on mangrove leaves for up to 72 h and in oysters for up to 48 h after application. Marine organisms placed in cages at 3 test sites and a control site were monitored for toxic effects. Mortality among natural mosquito larvae was simultaneously monitored. Mysids (Mysidopsis bahia) exhibited a significant mortality at one site during 1 of 3 applications monitored; however, no correlation was observed between mortality and temephos concentration in water. No significant mortality was observed for the other organisms, which included: brown shrimp (Panaeus aztecus), grass shrimp (Palaemonetes pugio), juvenile snook (Centropomis undecimalis) and sheepshead minnow (Cyprinodon variegatus).

Detection of elephant endotheliotropic herpesvirus type 1 in asymptomatic elephants using TaqMan real-time PCR.

This study assessed the feasibility of identifying asymptomatic viral shedders using a novel TaqMan real-time PCR on trunk washes and swabs from the conjunctiva, palate and vulva of elephants. Six elephants from a UK collection were sampled weekly over a period of 11 weeks for this study. The herd prevalence of elephant endotheliotropic herpesvirus-1 (EEHV-1) was 100 per cent by PCR. The virus DNA was detected in all the sampling sites; however, the prevalence of virus DNA in the conjunctiva swabs was higher. In addition, Asian elephants from two continental European collections were sampled once and one animal tested positive on a trunk wash. The virus from this animal was phylogenetically typed as EEHV-1A based on 231 nucleotides of the terminase gene.