A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration and regeneration: part 2, non-invasive imaging.

Peripheral neuroregenerative research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, novel biomarkers can elucidate regenerative mechanisms and open new avenues for research. Without such measures, clinical decision-making is impaired, and research becomes more costly, time-consuming, and sometimes infeasible. Part 1 of this two-part scoping review focused on neurophysiology. In part 2, we identify and critically examine many current and emerging non-invasive imaging techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration, and regeneration: part 1, neurophysiology.

Peripheral neuroregeneration research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures that can serve as biomarkers of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, such biomarkers can elucidate regeneration mechanisms and open new avenues for research. Without these measures, clinical decision-making falls short, and research becomes more costly, time-consuming, and sometimes infeasible. As a companion to Part 2, which is focused on non-invasive imaging, Part 1 of this two-part scoping review systematically identifies and critically examines many current and emerging neurophysiological techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

On the survival of the quantum depletion of a condensate after release from a magnetic trap.

We present observations of the high momentum tail in expanding Bose-Einstein condensates of metastable Helium atoms released from a harmonic trap. The far-field density profile exhibits features that support identification of the tails of the momentum distribution as originating in the in-situ quantum depletion prior to release. Thus, we corroborate recent observations of slowly-decaying tails in the far-field beyond the thermal component. This observation is in conflict with the hydrodynamic theory, which predicts that the in-situ depletion does not survive when atoms are released from a trap. Indeed, the depleted tails even appear stronger in the far-field than expected before release, and we discuss the challenges of interpreting this in terms of the Tan contact in the trapped gas. In complement to these observations, full quantum simulations of the experiment show that, under the right conditions, the depletion can persist into the far field after expansion. Moreover, the simulations provide mechanisms for survival and for the the large-momentum tails to appear stronger after expansion due to an acceleration of the depleted atoms by the mean-field potential. However, while in qualitative agreement, the final depletion observed in the experiment is much larger than in the simulation.

Trap frequency measurement with a pulsed atom laser.

We describe a novel method of single-shot trap frequency measurement for a confined Bose-Einstein Condensate, which uses an atom laser to repeatedly sample the mean velocity of trap oscillations as a function of time. The method is able to determine the trap frequency to an accuracy of 39 ppm (16 mHz) in a single experimental realization, improving on the literature by a factor of three. Further, we show that by employing a reconstructive aliasing approach our method can be applied to trap frequencies more than a factor of 3 greater than the sampling frequency.

Measurement of a helium tune-out frequency: an independent test of quantum electrodynamics.

Despite quantum electrodynamics (QED) being one of the most stringently tested theories underpinning modern physics, recent precision atomic spectroscopy measurements have uncovered several small discrepancies between experiment and theory. One particularly powerful experimental observable that tests QED independently of traditional energy level measurements is the "tune-out" frequency, where the dynamic polarizability vanishes and the atom does not interact with applied laser light. In this work, we measure the tune-out frequency for the 23S1 state of helium between transitions to the 23P and 33P manifolds and compare it with new theoretical QED calculations. The experimentally determined value of 725,736,700(260) megahertz differs from theory [725,736,252(9) megahertz] by 1.7 times the measurement uncertainty and resolves both the QED contributions and retardation corrections.

Direct Measurement of the Forbidden 2

We present the detection of the highly forbidden 2^{3}S_{1}→3^{3}S_{1} atomic transition in helium, the weakest transition observed in any neutral atom. Our measurements of the transition frequency, upper state lifetime, and transition strength agree well with published theoretical values and can lead to tests of both QED contributions and different QED frameworks. To measure such a weak transition, we develop two methods using ultracold metastable (2^{3}S_{1}) helium atoms: low background direct detection of excited then decayed atoms for sensitive measurement of the transition frequency and lifetime, and a pulsed atom laser heating measurement for determining the transition strength. These methods could possibly be applied to other atoms, providing new tools in the search for ultraweak transitions and precision metrology.

Bell correlations between spatially separated pairs of atoms.

Bell correlations are a foundational demonstration of how quantum entanglement contradicts the classical notion of local realism. Rigorous validation of quantum nonlocality have only been achieved between solid-state electron spins, internal states of trapped atoms, and photon polarisations, all weakly coupling to gravity. Bell tests with freely propagating massive particles, which could provide insights into the link between gravity and quantum mechanics, have proven to be much more challenging to realise. Here we use a collision between two Bose-Einstein condensates to generate spin entangled pairs of ultracold helium atoms, and measure their spin correlations along uniformly rotated bases. We show that correlations in the pairs agree with the theoretical prediction of a Bell triplet state, and observe a quantum mechanical witness of Bell correlations with [Formula: see text] significance. Extensions to this scheme could find promising applications in quantum metrology, as well as for investigating the interplay between quantum mechanics and gravity.

Kinetics of the γ-δ phase transition in energetic nitramine-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine.

The solid, secondary explosive nitramine-octahydro-1,3,5,7-tetranitro-1,3,5,7 or HMX has four different stable polymorphs which have different molecular conformations, crystalline structures, and densities, making structural phase transitions between these nontrivial. Previous studies of the kinetics of the ß-δ HMX structural transition found this to happen by a nucleation and growth mechanism, where growth was governed by the heat of fusion, or melting, even though the phase transition temperature is more than 100 K below the melting point. A theory known as virtual melting could easily justify this since the large volume difference in the two phases creates a strain at their interface that can lower the melting point to the phase transition temperature through a relaxation of the elastic energy. To learn more about structural phase transitions in organic crystalline solids and virtual melting, here we use time-resolved X-ray diffraction to study another structural phase transition in HMX, γ-δ. Again, second order kinetics are observed which fit to the same nucleation and growth model associated with growth by melting even though the volume change in this transition is too small to lower the melting point by interfacial strain. To account for this, we present a more general model illustrating that melting over a very thin layer at the interface between the two phases reduces the total interfacial energy and is therefore thermodynamically favorable and can drive the structural phase transition in the absence of large volume changes. Our work supports the idea that virtual melting may be a more generally applicable mechanism for structural phase transitions in organic crystalline solids.

Ghost imaging with atoms.

Ghost imaging is a counter-intuitive phenomenon-first realized in quantum optics-that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recover a 'ghost' image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms, which originate from s-wave scattering of two colliding Bose-Einstein condensates. We use higher-order Kapitza-Dirac scattering to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference, and enable tests of Einstein-Podolsky-Rosen entanglement and Bell's inequalities with atoms.

Gene expression profile of pulpitis.

The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

Precision Measurement for Metastable Helium Atoms of the 413 nm Tune-Out Wavelength at Which the Atomic Polarizability Vanishes.

We present the first measurement for helium atoms of the tune-out wavelength at which the atomic polarizability vanishes. We utilize a novel, highly sensitive technique for precisely measuring the effect of variations in the trapping potential of confined metastable (2^{3}S_{1}) helium atoms illuminated by a perturbing laser light field. The measured tune-out wavelength of 413.0938(9_{stat})(20_{syst}) nm compares well with the value predicted by a theoretical calculation [413.02(9) nm] which is sensitive to finite nuclear mass, relativistic, and quantum electrodynamic effects. This provides motivation for more detailed theoretical investigations to test quantum electrodynamics.

X-ray transmission movies of spontaneous dynamic events.

We describe a new x-ray radiographic imaging system which allows for continuous x-ray transmission imaging of spontaneous dynamic events. We demonstrate this method on thermal explosions in three plastic bonded formulations of the energetic material octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine. We describe the x-ray imaging system and triggering developed to enable the continuous imaging of a thermal explosion.

Overexpression of KLF13 and FGFR3 in oral cancer cells.

KLF13 and FGFR3 have important cellular functions and each is believed to play a role in cancer. KLF13 is a transcription factor required for the expression of several oncogenes. FGFR3 is a fibroblast growth factor receptor that initiates a signaling cascade leading to the activation of numerous cellular pathways. Here we show that KLF13 and FGFR3 are overexpressed in oral cancer cells. We also show that artificially reducing cellular levels of KLF13 and FGFR3 decreases cell proliferation and increases sensitivity to ionizing radiation. These data suggest that KLF13 and FGFR3 contribute to malignancy in oral cancer cells and may be useful biomarkers for early detection and possible targets for therapy.

A novel tactile sensation measurement system for qualifying touch perception.

The feel of films, wrapping paper, cardboards, and other packaging materials are important to the commercial success of foods. It is known from people's self-report studies that different surfaces provoke different subjective responses. There are several mechanical parameters, including friction, roughness, compliance, and thermal properties, which are important to the sensory feel. This paper describes the design, construction, and use of a multisensory measurement system for tactile sensation that can be used to evaluate the feel of different packaging materials. The experiments were conducted by sliding or pressing an artificial fingertip with embedded sensors against the surfaces of different samples which were fixed on a force table. The roughness, friction coefficients, compliance, and rate of change in the temperature were obtained. Forty volunteers were asked to touch and rate the samples by filling in questionnaires about how they felt. Strong correlations were found between people's feelings and the physical measurements.

Intercomparison of calorimetry, Raman spectroscopy, and second harmonic generation applied to solid-solid phase transitions.

This paper compares several different observables for use in measuring the kinetics of solid-solid phase transitions. Relative advantages and disadvantages for each technique are described, and a direct comparison of results is made for the beta to delta polymorphic phase transition of the energetic nitramine, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine.

Direct observation of the phenomenology of a solid thermal explosion using time-resolved proton radiography.

We present a new phenomenology for burn propagation inside a thermal explosion based on dynamic radiography. Radiographic images were obtained of an aluminum cased solid cylindrical sample of a plastic bonded formulation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine. The phenomenology observed is ignition followed by cracking in the solid accompanied by the propagation of a radially symmetric front of increasing proton transmission. This is followed by a further increase in transmission through the sample, ending after approximately 100 micros. We show that these processes are consistent with the propagation of a convective burn front followed by consumption of the remaining solid by conductive particle burning.

Excision of the nifD element in the heterocystous cyanobacteria.

Heterocyst differentiation in cyanobacteria is accompanied by developmentally regulated DNA rearrangements that occur within the nifD, fdxN, and hupL genes. These genetic elements are excised from the genome by site-specific recombination during the latter stages of differentiation. The nifD element is excised by the recombinase, XisA, located within the element. Our objective was to examine the XisA-mediated excision of the nifD element. To accomplish this, we observed the ability of XisA to excise substrate plasmids that contained the flanking regions of the nifD element in an E. coli host. Using PCR directed mutagenesis, nucleotides in the nifD element flanking regions in substrate plasmids were altered and the effect on recombination was determined. Results indicate that only certain nucleotides within and surrounding the direct repeats are involved in excision. In some nucleotide positions, the presence of a purine versus a pyrimidine greatly affected recombination. Our results also indicated that the site of excision and branch migration occurs in a 6 bp region within the direct repeats.

Multiplexed immunobead-based assay for detection of oral cancer protein biomarkers in saliva.

OBJECTIVE: For clinical applications of biomarkers, there is a need for multiplex assays using high throughput platforms. The objective of this study was to determine the efficacy of Luminex Multianalyte Profiling (xMAP) technology for measurement of salivary proteins and to evaluate whether multiplex assays are as effective as single-plex assays and enzyme-linked immunosorbent assay (ELISA). RESULTS: The average levels of interleukin-8 (IL-8) from the single-plex assay were 3313.2 +/- 3759.8 pg ml(-1) [oral squamous cell carcinoma (OSCC), n = 20] and 1061.7 +/- 1978.8 pg ml(-1) (control, n = 20). The IL-1beta average levels from the single-plex assay were 945.2 +/- 1134.8 pg ml(-1) (OSCC, n = 20) and 314.2 +/- 444.8 pg ml(-1) (control, n = 20). The average levels of IL-8 from the multiplex assay were 2834.9 +/- 3385.6 pg ml(-1) (OSCC, n = 20) and 947.3 +/- 2036.8 pg ml(-1) (control, n = 20). The IL-1beta average levels from the multiplex assay were 1013.5 +/- 1221.1 pg ml(-1) (OSCC, n = 20) and 376.3 +/- 576.3 pg ml(-1) (control, n = 20). The correlation coefficient between Luminex and ELISA assay for IL-8 (n = 19) and IL-1beta (n = 19) was 0.91 and 0.84, respectively. CONCLUSION: Luminex xMAP single-plex and multiplex assays are as effective as ELISA assays for quantification of proteins in saliva. Both IL-8 and IL-1beta were expressed at significantly higher levels in OSCC subjects than in the matched healthy control subjects.

An orthotopic floor-of-mouth model for locoregional growth and spread of human squamous cell carcinoma.

The molecular investigation of head and neck cancer targets requires the utilization and optimization of established animal models to characterize the effects of gene transcription and protein expression on invasion and metastasis. Floor-of-the-mouth murine models have been developed to study tumor growth, invasion, and metastasis of murine squamous cell carcinoma (SCC) cells in immunocompetent mice and invasion and metastasis of human SCC cells in nude mice. However, there are tumor cell lines that do not produce tumors in mice, using standard techniques, thus reducing the utility of the model to study specific genetic or treatment conditions. Furthermore, these techniques require large tumor volumes raising the possibility of airway compromise. In this report, we detail significant modifications to the orthotopic floor-of-mouth murine model for human SCC to facilitate predictable growth of a large panel of University of Michigan SCC cell lines. Furthermore, we describe the use of bioluminescence and micro-computed tomography to monitor tumor growth and bony invasion.

First Report of Sclerotinia Stem Rot of Chickpea Caused by Sclerotinia sclerotiorum in North Dakota and Washington.

Chickpea (Cicer arietinum L.) is cultivated as a rotational crop in the cereal-based production system in the U.S. Pacific Northwest (PNW) and its production is expanding to other northern tier states. During July 2005, symptoms of Sclerotinia stem rot were observed on chickpea cv. Dwelley and Dylan in fields near Spangle, WA and Carrington, ND, respectively, with disease incidence of approximately ≤1% in affected areas at both locations. Symptoms included stem whitening, wilting, and stem breakage. Occasionally, white fluffy mycelium was observed; however, production of sclerotia on infected plants was rarely observed. Sclerotinia sclerotiorum was isolated from diseased stems collected from both states. The isolates produced a ring of sclerotia near the edge of potato dextrose agar (PDA) plates in 7 days and produced neither conidia nor other fruiting bodies in culture after 30 days. PCR amplification of the rDNA internal transcribed spacer region from two representative isolates and subsequent digestion with restriction enzymes, Mbo I and Taq I, produced identical banding patterns to previously identified isolates of S. sclerotiorum from pea from the PNW (2). Chickpea cvs. Dwelley and Spanish White (eight plants of each) were inoculated by fastening mycelial agar plugs from an actively growing colony on PDA onto the stems with Parafilm. Symptoms of stem whitening were observed as early as 2 days after inoculation, and the lesions extended upward and downward from the inoculation site. Wilting and stem breakage were also observed. Control inoculations of four plants of each cultivar with PDA plugs without mycelium produced no visible symptoms. S. sclerotiorum was consistently reisolated from inoculated plants but not from control plants. Chickpea had been grown in the PNW for more than 20 years without any reported incidence of Sclerotinia stem rot although the disease has been reported from Arizona (3) and Asian countries (1). This is likely because of the upright growth habit of the chickpea plant coupled with relatively dry conditions late in the growing season. Previous chickpea cultivars were very susceptible to Ascochyta blight, an early-season disease of chickpea in the PNW that reduced chickpea stands and canopy coverage. Current cultivars possess much improved resistance to Ascochyta blight, allowing greater vegetative growth to occur and creating microenvironmental conditions conducive to Sclerotinia stem rot. In North Dakota, where humid conditions prevail late in the growing season, symptoms of Sclerotinia stem rot had been observed in previous years but had not been documented because of a recent history of chickpea cultivation there. To our knowledge, this is the first report of confirmed Sclerotinia stem rot of chickpea in North Dakota and Washington. References: (1) G. J. Boland and R. Hall. Can. J. Plant Pathol. 16:93, 1994. (2) I. Jimenez-Hidalgo et al. Phytopathology (Abstr.) 94(suppl.):S47, 2004. (3) M. E. Matheron and M. Porchas. Plant Dis. 84:1250, 2000.