A convergent Born series for solving the inhomogeneous Helmholtz equation in arbitrarily large media

We present a fast method for numerically solving the inhomogeneous Helmholtz equation. Our iterative method is based on the Born series, which we modified to achieve convergence for scattering media of arbitrary size and scattering strength. Compared to pseudospectral time-domain simulations, our modified Born approach is two orders of magnitude faster and nine orders of magnitude more accurate in benchmark tests in 1-dimensional and 2-dimensional systems

Blind focusing through strongly scattering media using wavefront shaping with nonlinear feedback

Scattering prevents light from being focused in turbid media. The effect of scattering can be negated through wavefront shaping techniques when a localized form of feedback is available. Even in the absence of such a localized reporter, wavefront shaping can blindly form a single diffraction-limited focus when the feedback response is nonlinear. We developed and experimentally validated a model that accurately describes the statistics of this blind focusing process. We show that maximizing the nonlinear feedback signal does not always result in the formation of a focus. Using our model, we can calculate the minimal requirements to blindly focus light through strongly scattering media.Comment: 13 pages, 4 figure

Model-based wavefront shaping microscopy

Wavefront shaping is increasingly being used in modern microscopy to obtain distortion-free, high-resolution images deep inside inhomogeneous media. Wavefront shaping methods typically rely on the presence of a 'guidestar' in order to find the optimal wavefront to mitigate the scattering of light. However, this condition cannot be satisfied in most biomedical applications. Here, we introduce a novel, guidestar-free wavefront shaping method in which the optimal wavefront is computed using a digital model of the sample. The refractive index model of the sample, that serves as the input for the computation, is constructed in-situ by the microscope itself. In a proof of principle imaging experiment, we demonstrate a large improvement in the two-photon fluorescence signal through a diffuse medium, outperforming the state-of-the-art wavefront shaping techniques by a factor of 21

Optimizing field-of-view of deep-tissue scanning microscopy

For centuries, the optical microscope has been a crucial instrument for new biological findings, as microscopes were the first devices allowing to observe the internal processes of the cell. Unfortunately, this observation requires the use of thin samples, as biological tissue scatters the incoming light, resulting in a blurred image. An ever increasing number of deep-tissue imaging technique have pushed the penetration depth of the optical microscope. Methods such as adaptive optics [1] allow focusing inside biological tissue by correcting for scattering introduced by the sample. However, adaptive optics methods can only correct for image distortions caused by scattering over a single small area (i.e., field-of-view) within tissue. Please click Additional Files below to see the full abstract

Nonuniform high-gamma (60-500 Hz) power changes dissociate cognitive task and anatomy in human cortex

High-gamma-band (\u3e60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that induced high-gamma-band (60-500 Hz) power changes are more heterogeneous than currently understood. Using single-word repetition tasks in six human subjects, we showed that functional responsiveness of different ECoG high-gamma sub-bands can discriminate cognitive task (e.g., hearing, reading, speaking) and cortical locations. Power changes in these sub-bands of the high-gamma range are consistently present within single trials and have statistically different time courses within the trial structure. Moreover, when consolidated across all subjects within three task-relevant anatomic regions (sensorimotor, Broca\u27s area, and superior temporal gyrus), these behavior- and location-dependent power changes evidenced nonuniform trends across the population. Together, the independence and nonuniformity of power changes across a broad range of frequencies suggest that a new approach to evaluating high-gamma-band cortical activity is necessary. These findings show that in addition to time and location, frequency is another fundamental dimension of high-gamma dynamics

Assessing the reactive surface area of soils and the association of soil organic carbon with natural oxide nanoparticles using ferrihydrite as proxy

Assessment of the surface reactivity of natural metal-(hydr)oxide nanoparticles is necessary for predicting ion adsorption phenomena in soils using surface complexation modeling. Here, we describe how the equilibrium concentrations of PO4, obtained with 0.5 M NaHCO3 extractions at different solution-to-soil ratios, can be interpreted with a state-of-the-art ion adsorption model for ferrihydrite to assess the reactive surface area (RSA) of agricultural top soils. Simultaneously, the method reveals the fraction of reversibly adsorbed soil PO4 (R-PO4). The applied ion-probing methodology shows that ferrihydrite is a better proxy than goethite for consistently assessing RSA and R-PO4. The R-PO4 pool agrees well with ammonium oxalate (AO)-extractable phosphorus, but only if measured as orthophosphate. The RSA varied between ∼2 and 20 m2/g soil. The corresponding specific surface area (SSA) of the natural metal-(hydr)oxide fraction is ∼350–1400 m2/g, illustrating that this property is highly variable and cannot be represented by a single value based on the AO-extractable oxide content. The soil organic carbon (SOC) content of our top soils increases linearly not only with the increase in RSA but remarkably also with the increase in mean particle size (1.5–5 nm). To explain these observations, we present a structural model for organo-mineral associations based on the coordination of SOC particles to metal-(hydr)oxide cores.Universidad de Costa Rica/[]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro de Investigaciones Agronómicas (CIA

Imaging with extrinsic Raman labels

In two separate examples we demonstrate the use of extrinsic Raman scattering probes for imaging of biological samples. First, the distribution of cholesterol in a rat eye lens is determined with the use of the Raman scattered light from filipin, a molecule which binds specifically to cholesterol. The protein distribution in the same eye lens was obtained by using the 1450-cm-1 CH2 and CH3 bending modes as an intrinsic marker for protein. It appears that the cholesterol is concentrated in the membranes of the eye lens fibers, whereas the protein is distributed more evenly. Second, we demonstrate that phenotyping of lymphocytes can be done by using the Raman scattering of (antibody-coated) polystyrene spheres. The lymphocyte population was also fluorescently labeled with anti-CD4-FITC to demonstrate that Raman and fluorescence labeling can be used simultaneously. Finally, we discuss the potential advantages and disadvantages of using Raman labels

Paradoxical down-regulation of p16INK4a mRNA with advancing age in Acute Myeloid Leukemia

Aging is generally considered to be the consequence of stem cell attrition caused by the activity of tumor suppressor pathways that censor potentially malignant clones by eliciting apoptosis or senescence. An important effector of aging is the cyclindependent kinase inhibitor p16INK4a, which is also a known suppressor of cancer. The expression of p16INK4a is very low or absent in young organisms but increases with advancing age. We recently showed that, unlike healthy cells, acute myeloid leukemia (AML) derived blasts show a down-regulation of p16INK4a mRNA with increasing age. Based on this observation we hypothesize that suppression of defense mechanisms which protect older cells against cellular and DNA damage might facilitate oncogenesis in older individuals

Evi1 Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of All-Trans Retinoic Acid on Flt3-ITD/Npm1c-Driven Acute Myeloid Leukemia Cells.

All-trans retinoic acid (atRA) has a dramatic impact on the survival of patients with acute promyelocytic leukemia, but its therapeutic value in other types of acute myeloid leukemia (AML) has so far remained unclear. Given that AML is a stem cell-driven disease, recent studies have addressed the effects of atRA on leukemic stem cells (LSCs). atRA promoted stemness of MLL-AF9-driven AML in an Evi1-dependent manner but had the opposite effect in Flt3-ITD/Nup98-Hoxd13-driven AML. Overexpression of the stem cell-associated transcription factor EVI1 predicts a poor prognosis in AML, and is observed in different genetic subtypes, including cytogenetically normal AML. Here, we therefore investigated the effects of Evi1 in a mouse model for cytogenetically normal AML, which rests on the combined activity of Flt3-ITD and Npm1c mutations. Experimental expression of Evi1 on this background strongly promoted disease aggressiveness. atRA inhibited leukemia cell viability and stem cell-related properties, and these effects were counteracted by overexpression of Evi1. These data further underscore the complexity of the responsiveness of AML LSCs to atRA and point out the need for additional investigations which may lay a foundation for a precision medicine-based use of retinoids in AML

Patients with mild traumatic brain injury and acute neck pain at the emergency department are a distinct category within the mTBI spectrum:a prospective multicentre cohort study

Background: Acute neck pain (ANP) has recently been demonstrated to be a predictor of persistent posttraumatic complaints after mild traumatic brain injury (mTBI). The aim of this study was to determine specific characteristics of patients with ANP following mTBI, their posttraumatic complaints and relationship with functional outcome. Methods: Data from a prospective follow-up study of 922 mTBI patients admitted to the emergency department (ED) in three level-one trauma centres were analysed. Patients were divided into two groups: 156 ANP patients and 766 no acute neck pain (nANP) patients. Posttraumatic complaints were evaluated 2 weeks and 6 months post-injury using standardized questionnaires and functional outcome was evaluated at 6 months with the Glasgow Outcome Scale Extended (GOSE). Results: ANP patients were more often female (p < 0.01), younger (38 vs. 47 years, p < 0.01) with more associated acute symptoms at the ED (p < 0.05) compared to nANP patients. More motor vehicle accidents (12% vs. 6%, p = 0.01) and less head wounds (58% vs. 73%, p < 0.01) in ANP patients indicated 'high-energy low-impact' trauma mechanisms. ANP patients showed more posttraumatic complaints 2 weeks and 6 months post-injury (p < 0.05) and more often incomplete recovery (GOSE < 8) was present after 6 months (56% vs. 40%, p = 0.01). Conclusions: MTBI patients with acute neck pain at the ED constitute a distinct group within the mTBI spectrum with specific injury and demographic characteristics. Early identification of this at risk group already at the ED might allow specific and timely treatment to avoid development of incomplete recovery