Attosecond impulsive stimulated X-ray Raman scattering in liquid water.

We report the measurement of impulsive stimulated x-ray Raman scattering in neutral liquid water. An attosecond pulse drives the excitations of an electronic wavepacket in water molecules. The process comprises two steps: a transition to core-excited states near the oxygen atoms accompanied by transition to valence-excited states. Thus, the wavepacket is impulsively created at a specific atomic site within a few hundred attoseconds through a nonlinear interaction between the water and the x-ray pulse. We observe this nonlinear signature in an intensity-dependent Stokes Raman sideband at 526 eV. Our measurements are supported by our state-of-the-art calculations based on the polarization response of water dimers in bulk solvation and propagation of attosecond x-ray pulses at liquid density.

Toward ultrafast soft x-ray spectroscopy of organic photovoltaic devices.

Novel ultrafast x-ray sources based on high harmonic generation and at x-ray free electron lasers are opening up new opportunities to resolve complex ultrafast processes in condensed phase systems with exceptional temporal resolution and atomic site specificity. In this perspective, we present techniques for resolving charge localization, transfer, and separation processes in organic semiconductors and organic photovoltaic devices with time-resolved soft x-ray spectroscopy. We review recent results in ultrafast soft x-ray spectroscopy of these systems and discuss routes to overcome the technical challenges in performing time-resolved x-ray experiments on photosensitive materials with poor thermal conductivity and low pump intensity thresholds for nonlinear effects.

Delivery of stable ultra-thin liquid sheets in vacuum for biochemical spectroscopy.

The development of ultra-thin flat liquid sheets capable of running in vacuum has provided an exciting new target for X-ray absorption spectroscopy in the liquid and solution phases. Several methods have become available for delivering in-vacuum sheet jets using different nozzle designs. We compare the sheets produced by two different types of nozzle; a commercially available borosillicate glass chip using microfluidic channels to deliver colliding jets, and an in-house fabricated fan spray nozzle which compresses the liquid on an axis out of a slit to achieve collision conditions. We find in our tests that both nozzles are suitable for use in X-ray absorption spectroscopy with the fan spray nozzle producing thicker but more stable jets than the commercial nozzle. We also provide practical details of how to run these nozzles in vacuum.

Interaction of an intense few-cycle infrared laser pulse with an ultrathin transparent liquid sheet.

We experimentally study the interaction between intense infrared few-cycle laser pulses and an ultrathin (∼2 µm) flat liquid sheet of isopropanol running in vacuum. We observe a rapid decline in transmission above a critical peak intensity of 50 TW/cm2 of the initially transparent liquid sheet, and the emission of a plume of material. We find both events are due to the creation of a surface plasma and are similar to processes observed in dielectric solids. After calculating the electron density for different laser peak intensities, we find an electron scattering rate of 0.3 fs-1 in liquid isopropanol to be consistent with our data. We study the dynamics of the plasma plume to find the expansion velocity of the plume front.

Prior CT imaging history for patients who undergo whole-body CT for acute traumatic injury and are discharged home from the emergency department.

BACKGROUND: Recurrent CT imaging is believed to significantly increase lifetime malignancy risk. We previously reported that high acuity, admitted trauma patients who received a whole-body CT in the emergency department (ED) had a history of prior CT imaging in 14% of cases. The primary objective of this study was to determine the CT imaging history for trauma patients who received a whole-body CT but were ultimately deemed safe for discharge directly home from the ED. METHODS: This was a retrospective cohort study conducted at an academic ED. All trauma patients who were discharged directly home from the ED after whole-body CT were analyzed. The decision to utilize whole-body CT was at the discretion of the caring physician during the study period. Clinical data for the most recent trauma visit was recorded in a structured fashion on a standardized data collection instrument utilizing the hospital system electronic medical record (EMR). Subsequently, study investigators reviewed a shared, electronic radiological archive for the 6-hospital system to evaluate prior CT exposure for each patient. RESULTS: 165 patients were in the study group. The mean age of the study group was 39+/- 16 years old, 40% were female and 64% were Hispanic. The most common mechanism of injury in our study group was motor vehicle crash (MVC) (66%). In our study group, 25% had at least one prior CT. The most common prior studies performed were: CT abdomen/pelvis (13%), CT head (9.1%), CT face (6.7%), and CT chest (1.8%). Within a multivariate logistic regression model we found that the large majority of patient characteristics and mechanisms of injury were not associated with a positive prior CT imaging history. CONCLUSION: We found a positive history for prior CT for 25% of trauma patients who received whole-body CT scan but were discharged from the ED to home.

Amplification of intense light fields by nearly free electrons.

Light can be used to modify and control properties of media, as in the case of electromagnetically induced transparency or, more recently, for the generation of slow light or bright coherent XUV and X-ray radiation. Particularly unusual states of matter can be created by light fields with strengths comparable to the Coulomb field that binds valence electrons in atoms, leading to nearly-free electrons oscillating in the laser field and yet still loosely bound to the core [1,2]. These are known as Kramers-Henneberger states [3], a specific example of laser-dressed states [2]. Here, we demonstrate that these states arise not only in isolated atoms [4,5], but also in rare gases, at and above atmospheric pressure, where they can act as a gain medium during laser filamentation. Using shaped laser pulses, gain in these states is achieved within just a few cycles of the guided field. The corresponding lasing emission is a signature of population inversion in these states and of their stability against ionization. Our work demonstrates that these unusual states of neutral atoms can be exploited to create a general ultrafast gain mechanism during laser filamentation.

High-order harmonic source spanning up to the oxygen K-edge based on filamentation pulse compression.

We present a 0.2 TW sub-two-cycle 1.8 µm carrier-envelope-phase stable source based on two-stage pulse compression by filamentation for driving high-order harmonic generation extending beyond the oxygen K absorption edge. The 1 kHz repetition rate, high temporal resolution enabled by the short 11.8 fs driving pulse duration, and bright high-order harmonics generated in helium make this an attractive source for solid-state and molecular-dynamics studies.

Individualized Levels System and Systematic Stimulus Pairing to Reduce Multiply Controlled Aggression of a Child With Autism Spectrum Disorder.

Research has shown that physical aggression is common in individuals with autism spectrum disorder (ASD). Interventions for multiply controlled aggression may be complex and difficult to implement with fidelity. As a result, the probability of treatment efficacy for this class of behavior may suffer. We designed an individualized levels system to reduce the physical aggression of an 11-year-old female with ASD. We then employed a systematic stimulus pairing procedure to facilitate generalization. Results suggest individualized levels systems can suppress multiply controlled aggression and that systematic stimulus pairing is an effective way to transfer treatment effects from trained therapists to caregivers.

Time-resolved x-ray absorption spectroscopy with a water window high-harmonic source.

Time-resolved x-ray absorption spectroscopy (TR-XAS) has so far practically been limited to large-scale facilities, to subpicosecond temporal resolution, and to the condensed phase. We report the realization of TR-XAS with a temporal resolution in the low femtosecond range by developing a tabletop high-harmonic source reaching up to 350 electron volts, thus partially covering the spectral region of 280 to 530 electron volts, where water is transmissive. We used this source to follow previously unexamined light-induced chemical reactions in the lowest electronic states of isolated CF4+ and SF6+ molecules in the gas phase. By probing element-specific core-to-valence transitions at the carbon K-edge or the sulfur L-edges, we characterized their reaction paths and observed the effect of symmetry breaking through the splitting of absorption bands and Rydberg-valence mixing induced by the geometry changes.

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation.

The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in preosteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and postnatal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification. The decrease in bone accrual, as well as the associated increase in skeletal fragility, was due to a reduction in osteoblast function. In vitro, osteoblasts derived from knockout mice display a reduced osteogenic potential, and an assessment of bone-developmental markers in Rptor knockout osteoblasts revealed a transcriptional profile consistent with an immature osteoblast phenotype suggesting that osteoblast differentiation was stalled early in osteogenesis. Metabolic labeling and an assessment of cell size of Rptor knockout osteoblasts revealed a significant decrease in protein synthesis, a major driver of cell growth. These findings demonstrate that mTORC1 plays an important role in skeletal development by regulating mRNA translation during preosteoblast differentiation.

Laser vaporization of cirrus-like ice particles with secondary ice multiplication.

We investigate the interaction of ultrashort laser filaments with individual 90-µm ice particles, representative of cirrus particles. The ice particles fragment under laser illumination. By monitoring the evolution of the corresponding ice/vapor system at up to 140,000 frames per second over 30 ms, we conclude that a shockwave vaporization supersaturates the neighboring region relative to ice, allowing the nucleation and growth of new ice particles, supported by laser-induced plasma photochemistry. This process constitutes the first direct observation of filament-induced secondary ice multiplication, a process that strongly modifies the particle size distribution and, thus, the albedo of typical cirrus clouds.

Brief report: the differential roles of mTORC1 and mTORC2 in mesenchymal stem cell differentiation.

Adipocytes (AdCs) and osteoblasts (OBs) are derived from mesenchymal stem cells (MSCs) and differentiation toward either lineage is both mutually exclusive and transcriptionally controlled. Recent studies implicate the mammalian target of rapamycin (mTOR) pathway as important in determining MSC fate, with inhibition of mTOR promoting OB differentiation and suppressing AdC differentiation. mTOR functions within two distinct multiprotein complexes, mTORC1 and mTORC2, each of which contains the unique adaptor protein, raptor or rictor, respectively. While compounds used to study mTOR signaling, such as rapamycin and related analogs, primarily inhibit mTORC1, prolonged exposure can also disrupt mTORC2 function, confounding interpretation of inhibitor studies. As a result, the relative contribution of mTORC1 and mTORC2 to MSC fate determination remains unclear. In this study, we generated primary mouse MSCs deficient in either Rptor (RapKO) or Rictor (RicKO) using the Cre/loxP system. Cre-mediated deletion of Rptor or Rictor resulted in impaired mTORC1 and mTORC2 signaling, respectively. Under lineage-inductive culture conditions, RapKO MSCs displayed a reduced capacity to form lipid-laden AdCs and an increased capacity to form a mineralized matrix. In contrast, RicKO MSCs displayed reduced osteogenic differentiation capacity and enhanced adipogenic differentiation potential. Taken together, our findings reveal distinct roles for mTORC1 and mTORC2 in MSC lineage commitment.

Splenopancreatic ductal adenocarcinoma with multiorgan metastasis in a northern water snake (Nerodia sipedon).

A 16-yr-old northern water snake (Nerodia sipedon) presented with a large, firm midcoelomic swelling. A complete blood count, survey radiographs, coelomic ultrasound, and fine needle aspirate of the mass were performed. Survey radiographs revealed a soft tissue opacity mass. Ultrasonographic examination confirmed the presence of the mass but could not aid in its visceral localization. After 2 weeks, the snake presented again because of continued anorexia and poor quality of life. Euthanasia was performed. Gross necropsy revealed a multilobulated mass attached to and effacing the splenopancreas. Histologically, the mass was composed of cuboidal to columnar neoplastic epithelial cells forming tubules surrounded by variable amounts of fibrovascular stroma. Histological examination and immunohistochemical staining of other tissues revealed local invasion in the subserosa and tunica muscularis of the stomach, metastasis within the liver, in the mesovarium, and an intravascular metastasis within the ventricle of the heart surrounded by a thrombus.

Identification of seven loci affecting mean telomere length and their association with disease.

Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.

Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect.

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19,713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r=0.42; P-value=3.60 × 10(-61)) than father-offspring correlation (r=0.33; P-value=7.01 × 10(-5)), and a significant positive association with paternal age at offspring birth (ß=0.005; P-value=7.01 × 10(-5)). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10(-30)) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10(-23)) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10(-10)). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

Lifting the "FOG" with laser generated visual-cueing.

BACKGROUND AND PURPOSE: To ascertain whether freezing of gait (FOG) and stride reduction (SR) may be relieved by the use of an attachable, adjustable laser (the Mobilaser). METHODS: Seven parkinsonian patients with FOG and SR were randomized in an open-label, randomized, cross-over clinical study at a tertiary referral center. The Mobilaser was attached to a 4-wheeled walker by Velcro and switched on, producing an adjustable red line, which the subjects stepped on or over while ambulating a standardized course. The length of time each subject took, and the number of freezes they experienced traversing the course, using a 4-wheeled walker with the device turned on and off, were compared. RESULTS: A total of 7 patients were investigated; however, one was excluded from the study due to severe deconditioning, prohibiting completion of the testing. Of the 6 enrolled, all subjects took less time to ambulate the course using the attachable, adjustable laser than without it (Wilcoxon signed-rank test, P=0.03). In addition, the total number of freezes was less in all 6 subjects when using the device than without it. No adverse events occurred during the trial. DISCUSSION AND CONCLUSIONS: The Mobilaser is potentially an effective and safe device for alleviating parkinsonian FOG and SR.

A comprehensive space management model for facilitating programmatic research.

In FY04, the authors developed and implemented models to manage existing and incremental research space, and to facilitate programmatic research, at the University of Arizona College of Medicine. Benchmarks were set for recovery of total sponsored research dollars and for facilities and administrative (F&A) dollars/net square foot (nsf) of space, based on college-wide metrics. Benchmarks were applied to units (departments, centers), rather than to individual faculty. Performance relative to the benchmark was assessed using three-year moving averages, and applied to existing blocks of space. Space was recaptured or allocated, in all cases to programmatic themes, using uniform policies. F&A revenues were returned on the basis of performance relative to a benchmark. During the first two years after implementation of the model (FY05 and FY06), and for the 24 units occupying research space, median total sponsored research revenue/nsf increased from $393.96 to $474.46 (20.4%), and median F&A revenue/nsf increased from $57.42 to $91.86 (60.0%). These large increases in median values are driven primarily from redistribution and recapturing of space. Recruiting policies for unit heads were developed to facilitate joint hires among units. In combination, these policies created a comprehensive space management model for facilitating programmatic research. Although challenges remain in implementing the programmatic recruitment strategy, and selected modifications to the original policy were introduced later (e.g., research space for newly recruited junior faculty is now exempted from calculations for three years), overall, the models have created a climate of transparency that is now accepted and that allows efficient and equitable management of research space.