Micro-DRIFTS for small area hyper-black spectroscopy.

We have developed a low-cost micro-diffuse reflectance infrared Fourier transform spectroscopic (micro-DRIFTS) setup for measuring the reflectance of small area diffuse samples. The system performance is characterized and then demonstrated on small area vertically aligned carbon nanotube (VACNT) samples. We find that our system can measure samples with a spatial resolution of approximately 140 µm with sensitivities of 10s of ppm in the 2 µm - 18 µm spectral window. Our uncertainty budget is presented along with how our measured reflectance can be equated to directional-hemispherical reflectance.

Extreme laser pulse-energy measurements by means of photon momentum.

Extreme lasers capable of short, high-energy pulses are probing the frontiers of science and advancing practical technology. The utility of such lasers increases with their average power delivery, which enables faster data acquisition, higher flux of laser-driven particle and radiation sources and more efficient material processing. However, the same extreme energies and electric field strengths of these lasers are currently preventing their direct and high accuracy measurement for these experimental applications. To overcome this limitation, we use the momentum of the laser pulses as a measurement proxy for their energy. When light reflects from an ideal mirror, its momentum is transferred to the mirror, but its energy is reflected. We demonstrate here a force-sensing mirror configuration to measure laser pulse energies up to 100 J/pulse (10 ns duration, 10 Hz repetition rate) from a kilowatt-level average power multi-slab laser operated at the HiLASE facility of the Czech Academy of Sciences. We combine a radiation-pressure power meter with a charge integrator photodiode to form what we refer to as a Radiation Pressure Energy Meter. To our knowledge, this is the first demonstration of a high-accuracy, non-absorbing, SI traceable primary standard measurement of both single and average pulse energies of a 1-kW-average-power pulsed laser source. With this, we demonstrate a practical method for in-situ calibration of the traditional thermal instruments (pyroelectric detectors) currently used for indirect measurements of energy and power of such extreme lasers.

siRNA high throughput screening identifies regulators of chloropicrin and hydrogen fluoride injury in human corneal epithelial cell models.

Corneal injuries induced by various toxicants result in similar clinical presentations such as corneal opacity and neovascularization. Many studies suggest that several weeks post-exposure a convergence of the molecular mechanisms drives these progressive pathologies. However, chemical agents vary in toxicological properties, and early molecular responses are anticipated to be somewhat dissimilar for different toxicants. We chose 3120 targets from the Dharmacon Human Druggable genome to screen for chloropicrin (CP) and hydrogen fluoride (HF) corneal injury as we hypothesized that targets identified in vitro may be effective as therapeutic targets in future studies. Human immortalized corneal epithelial cells (SV40-HCEC) were used for screening. Cell viability and IL-8 were analyzed to down-select hits into validation studies, where multiplex cytokine analysis and high content analysis were performed to understand toxicant effect and target function. Some endpoints were also evaluated in a second human immortalized corneal epithelial cell line, TCEpi. Over 20 targets entered validation studies for CP and HF; of these, only three targets were shared: NR3C1, RELA, and KMT5A. These findings suggest that early molecular responses to different toxicants may be somewhat distinctive and present dissimilar targets for possible early intervention.

High-accuracy room temperature planar absolute radiometer based on vertically aligned carbon nanotubes.

We have developed a planar absolute radiometer for room temperature (PARRoT) that will replace the legacy C-series calorimeter as the free-space continuous-wave laser power detector standard at the National Institute of Standards and Technology (NIST). This instrument will lower the combined relative expanded measurement uncertainty (k = 2) from 0.84 % to 0.13 %. PARRoT's performance was validated by comparing its response against a transfer standard silicon trap detector traceable to NIST's primary standard laser optimized cryogenic radiometer (LOCR) and against the C-series calorimeter. On average, these comparisons agreed to better than 0.008 % and 0.05 %, respectively.

High amplification laser-pressure optic enables ultra-low uncertainty measurements of the optical laser power at kilowatt levels.

We present the first measurements of kilowatt laser power with an uncertainty less than 1 %. These represent progress toward the most accurate measurements of laser power above 1 kW at 1070 nm wavelength and establish a more precise link between force metrology and laser power metrology. Radiation pressure, or photon momentum, is a relatively new method of non-destructively measuring laser power. We demonstrate how a multiple reflection optical system amplifies the pressure of a kilowatt class laser incoherently to improve the signal to noise ratio in a radiation pressure-based measurement. With 14 incoherent reflections of the laser, we measure a total uncertainty of 0.26 % for an input power of 10 kW and 0.46 % for an input power of 1 kW at the 95 % confidence level. These measurements of absolute power are traceable to the SI kilogram and mark a state-of-the-art improvement in measurement precision by a factor of four.

Miniature force sensor for absolute laser power measurements via radiation pressure at hundreds of watts.

We present a small power meter that detects the radiation pressure of an incident high-power laser. Given its small package and non-destructive interaction with the laser, this power meter is well suited to realizing a robust real-time, high-accuracy power measurement in laser-based manufacturing environments. The incident laser power is determined through interferometric measurement of displacement of a 20 mm diameter high reflectivity mirror, mounted at the center of a dual element spiral flexure. This device can measure laser power from 25 W to 400 W with a 260 m W/H z noise floor and ≤ 3.2% expanded uncertainty. We validate our device against a calibrated thermopile with simultaneous measurements of an unpolarized 1070 nm laser and report good agreement between the two systems. Finally, by referencing to an identical mechanical spring that does not see the incident laser, we suppress vibration noise in the power measurement by 14.8 dB over a 600 Hz measured bandwidth. This is an improvement over other radiation pressure based power meters that have previously been demonstrated.

Simplified kilogram traceability for high-power laser measurement using photon momentum radiometers.

Photon momentum radiometers measure the force imparted by a reflected laser beam to determine the laser's optical power. This requires high-accuracy calibration of the force sensors using milligram and microgram mass artifacts. Calibrated test masses can therefore be used to provide traceability of these radiometers to the International System of Units, but low-noise calibration at these mass levels is difficult. Here, we present the improvement in calibration capability that we have gained from implementing a robotic mass delivery system. We quantify this in terms of the specific nuances of force measurements as implemented for laser power metrology.

Calibration of free-space and fiber-coupled single-photon detectors.

We measure the detection efficiency of single-photon detectors at wavelengths near 851 nm and 1533.6 nm. We investigate the spatial uniformity of one free-space-coupled single-photon avalanche diode and present a comparison between fusion-spliced and connectorized fiber-coupled single-photon detectors. We find that our expanded relative uncertainty for a single measurement of the detection efficiency is as low as 0.70% for fiber-coupled measurements at 1533.6 nm and as high as 1.78% for our free-space characterization at 851.7 nm. The detection-efficiency determination includes corrections for afterpulsing, dark count, and count-rate effects of the single-photon detector with the detection efficiency interpolated to operation at a specified detected count rate.

Feedback Control of a Nonlinear Electrostatic Force Transducer.

We document a feedback controller design for a nonlinear electrostatic transducer that exhibits a strong unloaded resonance. Challenging features of this type of transducer include the presence of multiple fixed points (some of which are unstable), nonlinear force-to-deflection transfer, effective spring-constant softening due to electrostatic loading and associated resonance frequency shift. Furthermore, due to the utilization of lowpass filters in the electronic readout circuitry, a significant amount of transport delay is introduced in the feedback loop. To stabilize this electro-mechanical system, we employ an active disturbance-rejecting controller with nonlinear force mapping and delay synchronization. As demonstrated by numerical simulations, the combination of these three control techniques stabilizes the system over a wide range of electrode deflections. The proposed controller shows good setpoint tracking and disturbance rejection, and improved settling time, compared to the sensor alone.

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue.

Inline laser power measurement by photon momentum.

We present a novel measurement scheme and instrumentation for quantifying laser power by means of photon momentum. The optical design is optimized such that the incoming laser beam is minimally perturbed and is available for other purposes along the incoming beam axis. Additionally, the geometry of the instrument gives access to the small but measurable transmittance between two passive mirrors that face the force sensor. The force sensor is based on a commercially available weighing instrument ("scale") that has a temporal response of approximately 5 s and a readability of approximately 1 µg (∼2 W). Our measurement results demonstrate beam profile and power for 500 W, but the mirror and mass (or force) calibration are suitable for very high power up to 50 kW and beyond. The optics are based on commercially available, off-the-shelf mirrors optimized for the angle of incidence and maximum reflectance at the wavelength of 1070 nm. The size of the complete instrument has an input aperture of Ø75 mm, but this constraint is only a matter of optimizing the beam path and box geometry.

Spectral, spatial, and survivability evaluation of a flash-dried plasma-etched nanotube spray coating.

We demonstrate improved manufacturability of spectrally flat detectors for visible to mid-infrared wavelengths by characterizing a carbon nanotube spray coating compatible with lithium tantalate and other thermal sensors. Compared against previous spray coatings, it demonstrated the highest responsivity yet attained due to both higher absorptivity and thermal diffusivity, while also being matured to a commercially available product. It demonstrated spectral nonuniformity from 300 nm to 12 µm less than 1% with uncertainty (k=2) under 0.4%. The spatial nonuniformity of the assembled sensor was less than 0.5% over the central half (4 mm) of the absorber. As with previous developments employing isotropic carbon nanotube coatings, the absorber surface was sufficiently robust to withstand cleaning by compressed air blast and survived repeated vacuum cycling without measurable impact upon responsivity.

Portable, high-accuracy, non-absorbing laser power measurement at kilowatt levels by means of radiation pressure.

We describe a non-traditional optical power meter which measures radiation pressure to accurately determine a laser's optical power output. This approach traces its calibration of the optical watt to the kilogram. Our power meter is designed for high-accuracy and portability with the capability of multi-kilowatt measurements whose upper power limit is constrained only by the mirror quality. We provide detailed uncertainty evaluation and validate experimentally an average expanded relative uncertainty of 0.016 from 1 kW to 10 kW. Radiation pressure as a power measurement tool is unique to the extent that it does not rely on absorption of the light to produce a high-accuracy result. This permits fast measurements, simplifies power scalability, and allows high-accuracy measurements to be made during use of the laser for other applications.

Onsite multikilowatt laser power meter calibration using radiation pressure.

We have demonstrated the calibration of a thermal power meter against a radiation pressure power meter in the range of 20 kW in a manufacturing test environment. The results were compared to a traditional calorimeter-based laboratory calibration undertaken at the National Institute of Standards and Technology. The results are reported, and the effects of nonideal conditions typical of measurements in low-stability environments are discussed.

Planar hyperblack absolute radiometer.

The absolute responsivity of a planar cryogenic radiometer fabricated from micromachined silicon and having carbon nanotubes, as the absorber and thermistor were measured in the visible and far infrared (free-field terahertz) wavelength range by means of detector-based radiometry. The temperature coefficient of the thermistor near 4.8 K and noise equivalent power were evaluated along with independent characterization of the window transmittance and specular reflectance of the nanotube absorber. Measurements of absolute power by means of electrical substitution are compared to the German national standard and the uncertainty of the radiometer responsivity as a function of wavelength is summarized.

Identification and validation of vesicant therapeutic targets using a high-throughput siRNA screening approach.

Sulfur mustard [SM, bis-(2-chloroethyl) sulfide] is a highly reactive bifunctional alkylating agent that has been used as a vesicating agent in warfare scenarios to induce severe lung, skin, and eye injury. SM cutaneous lesions are characterized by both vesication and severe inflammation, but the molecular mechanisms that lead to these signs and symptoms are not well understood. There is a pressing need for effective therapeutics to treat this injury. An understanding of the molecular mechanisms of injury and identification of potential therapeutic targets is necessary for rational therapeutic development. We have applied a high-throughput small interfering RNA (siRNA) screening approach to the problem of SM cutaneous injury in an effort to meet these needs. Our siRNA screening efforts have initially focused on SM-induced inflammation in cutaneous injury since chronic inflammation after exposure appears to play a role in progressive clinical pathology, and intervention may improve clinical outcome. Also, targets that mitigate cellular injury should reduce the inflammatory response. Historical microarray data on this injury were mined for targets and pathways implicated in inflammation, and a siRNA library of 2,017 targets was assembled for screening. Primary screening and library deconvolution were performed using human HaCaT keratinocytes and focused on cell death and inflammatory markers as end points. Using this in vitro approach, we have identified and validated novel targets for the potential treatment of SM-induced cutaneous injury.

Morphological and Electrical Characterization of MWCNT Papers and Pellets.

Six types of commercially available multiwall carbon nanotube soot were obtained and prepared into buckypapers by pellet pressing and by filtration into a paper. These samples were evaluated with respect to thickness, compressibility and electrical conductivity. DC conductivity results by two-point and four-point (van der Pauw) measurement methods as a function of preparation parameters are presented. Topology was investigated qualitatively by way of scanning electron microscopy and helium ion microscopy and from this, some generalizations about the nanotube structural properties and manufacturing technique with respect to conductivity are given.

Computational Design of Phosphotriesterase Improves V-Agent Degradation Efficiency.

Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target. Here we describe a library of computationally designed variants of phosphotriesterase (PTE), an enzyme that is known to break down OPs. The mutations G208D, F104A, K77A, A80V, H254G, and I274N broadly improve catalytic efficiency of VX and VR hydrolysis without impacting the structure of the enzyme. The mutation I106 A improves catalysis of VR and L271E abolishes activity, likely due to disruptions of PTE's structure. This study elucidates the importance of these residues and contributes to the design of enzymatic OP scavengers with improved efficiency.

Use of radiation pressure for measurement of high-power laser emission.

We demonstrate a paradigm in absolute laser radiometry where a laser beam's power can be measured from its radiation pressure. Using an off-the-shelf high-accuracy mass scale, a 530 W Yb-doped fiber laser, and a 92 kW CO(2) laser, we present preliminary results of absolute optical power measurements with inaccuracies of better than 7% to 13%. We find negligible contribution from radiometric (thermal) forces. We also identify this scale's dynamic-force noise floor for a 0.1 Hz modulation frequency as 4 µN/Hz(1/2) or, as optical power sensitivity, 600 W/Hz(1/2).

Chronic caloric restriction attenuates a loss of sulfatide content in PGC-1α-/- mouse cortex: a potential lipidomic role of PGC-1α in neurodegeneration.

Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a key regulator of energy metabolism and lipid homeostasis in multiple highly oxidative tissues, has been implicated in the metabolic derangements of diabetes and obesity. However, relatively less is known regarding its role in neurological functions. Using shotgun lipidomics, we investigated the lipidome of mouse cerebral cortex with generalized deficiency of PGC-1α (PGC-1α(-/-)) versus wild-type (WT) mice under standard diet and chronically calorically restricted conditions. Specific deficiency in sulfatide, a myelin-specific lipid class critically involved in maintaining neurological function, was uncovered in the cortex of PGC-1α(-/-) mice compared with WT mice at all ages examined. Chronic caloric restriction (CR) for 22 months essentially restored the sulfatide reduction in PGC-1α(-/-) mice compared with WT, but sulfatide reduction was not restored in PGC-1α(-/-) with CR for a short term (i.e., 3 months). Mechanistic studies uncovered and differentiated the biochemical mechanisms underpinning the two conditions of altered sulfatide homeostasis. The former is modulated through PGC-1α-MAL pathway, whereas the latter is under the control of LXR/RXR-apoE metabolism pathway. These results suggest a novel mechanistic role of PGC-1α in sulfatide homeostasis, provide new insights into the importance of PGC-1α in neurological functions, and indicate a potential therapeutic approach for treatment of deficient PGC-1α-induced alterations in sulfatide homeostasis.