Meaning to Form: Measuring Systematicity as Information

A longstanding debate in semiotics centers on the relationship between linguistic signs and their corresponding semantics: is there an arbitrary relationship between a word form and its meaning, or does some systematic phenomenon pervade? For instance, does the character bigram \textit{gl} have any systematic relationship to the meaning of words like \textit{glisten}, \textit{gleam} and \textit{glow}? In this work, we offer a holistic quantification of the systematicity of the sign using mutual information and recurrent neural networks. We employ these in a data-driven and massively multilingual approach to the question, examining 106 languages. We find a statistically significant reduction in entropy when modeling a word form conditioned on its semantic representation. Encouragingly, we also recover well-attested English examples of systematic affixes. We conclude with the meta-point: Our approximate effect size (measured in bits) is quite small---despite some amount of systematicity between form and meaning, an arbitrary relationship and its resulting benefits dominate human language.Comment: Accepted for publication at ACL 201

Qualitative extension of the EC′ Zone Diagram to a molecular catalyst for a multi-electron, multi-substrate electrochemical reaction

Traverse the EC′ Zone Diagram with a molecular H 2 -evolving electrocatalyst through systematic variation of the acid p K a , scan rate, acid concentration and catalyst concentration

Responses to altered oxygen tension are distinct between human stem cells of high and low chondrogenic capacity

Abstract Background Lowering oxygen from atmospheric level (hyperoxia) to the physiological level (physioxia) of articular cartilage promotes mesenchymal stem cell (MSC) chondrogenesis. However, the literature is equivocal regarding the benefits of physioxic culture on preventing hypertrophy of MSC-derived chondrocytes. Articular cartilage progenitors (ACPs) undergo chondrogenic differentiation with reduced hypertrophy marker expression in hyperoxia but have not been studied in physioxia. This study sought to delineate the effects of physioxic culture on both cell types undergoing chondrogenesis. Methods MSCs were isolated from human bone marrow aspirates and ACP clones were isolated from healthy human cartilage. Cells were differentiated in pellet culture in physioxia (2 % oxygen) or hyperoxia (20 % oxygen) over 14 days. Chondrogenesis was characterized by biochemical assays and gene and protein expression analysis. Results MSC preparations and ACP clones of high intrinsic chondrogenicity (termed high-GAG) produced abundant matrix in hyperoxia and physioxia. Poorly chondrogenic cells (low-GAG) demonstrated a significant fold-change matrix increase in physioxia. Both high-GAG and low-GAG groups of MSCs and ACPs significantly upregulated chondrogenic genes; however, only high-GAG groups had a concomitant decrease in hypertrophy-related genes. High-GAG MSCs upregulated many common hypoxia-responsive genes in physioxia while low-GAG cells downregulated most of these genes. In physioxia, high-GAG MSCs and ACPs produced comparable type II collagen but less type I collagen than those in hyperoxia. Type X collagen was detectable in some ACP pellets in hyperoxia but reduced or absent in physioxia. In contrast, type X collagen was detectable in all MSC preparations in hyperoxia and physioxia. Conclusions MSC preparations and ACP clones had a wide range of chondrogenicity between donors. Physioxia significantly enhanced the chondrogenic potential of both ACPs and MSCs compared with hyperoxia, but the magnitude of response was inversely related to intrinsic chondrogenic potential. Discrepancies in the literature regarding MSC hypertrophy in physioxia can be explained by the use of low numbers of preparations of variable chondrogenicity. Physioxic differentiation of MSC preparations of high chondrogenicity significantly decreased hypertrophy-related genes but still produced type X collagen protein. Highly chondrogenic ACP clones had significantly lower hypertrophic gene levels, and there was little to no type X collagen protein in physioxia, emphasizing the potential advantage of these cells

Physioxia promotes the articular chondrocyte-like phenotype in human chondroprogenitor-derived self-organized tissue

Introduction: Biomaterial-based tissue engineering has not successfully reproduced the structural architecture or functional mechanical properties of native articular cartilage. In scaffold-free tissue engineering systems, cells secrete and organize the entire extracellular matrix over time in response to environmental signals such as oxygen level. In this study, we investigated the effect of oxygen on the formation of neocartilage from human-derived chondrogenic cells. Materials and Methods: Articular chondrocytes (ACs) and articular cartilage progenitor cells (ACPs) derived from healthy human adults were guided toward cell condensation by centrifugation onto plate inserts that were uncoated or coated with either agarose or fibronectin. Neocartilage discs were cultured at hyperoxic (20%) or physioxic (5%) oxygen levels, and biochemical, biomechanical, and molecular analyses were used to compare the cartilage produced by ACs versus ACPs. Results: Fibronectin-coated inserts proved optimal for growing cartilaginous discs from both cell types. In comparison with culture in hyperoxia, AC neocartilage cultured at physioxia exhibited a significant increase in chondrogenic gene expression, proteoglycan production, and mechanical properties with a concomitant decrease in collagen content. At both oxygen levels, ACP-derived neocartilage produced tissue with significantly enhanced mechanical properties and collagen content relative to AC-derived neocartilage. Both ACs and ACPs produced substantial collagen II and reduced levels of collagens I and X in physioxia relative to hyperoxia. Neocartilage from ACPs exhibited anisotropic organization characteristic of native cartilage with respect to collagen VI of the pericellular matrix when compared with AC-derived neocartilage; however, only ACs produced abundant surface-localized lubricin. Discussion and Conclusions: Guiding human-derived cells toward condensation and subsequent culture in physioxia promoted the articular cartilage tissue phenotype for ACs and ACPs. Unlike ACs, ACPs are clonable and highly expandable while retaining chondrogenicity. The ability to generate large tissues utilizing a scaffold-free approach from a single autologous progenitor cell may represent a promising source of neocartilage destined for cartilage repair

SERT: A Transfomer Based Model for Spatio-Temporal Sensor Data with Missing Values for Environmental Monitoring

Environmental monitoring is crucial to our understanding of climate change, biodiversity loss and pollution. The availability of large-scale spatio-temporal data from sources such as sensors and satellites allows us to develop sophisticated models for forecasting and understanding key drivers. However, the data collected from sensors often contain missing values due to faulty equipment or maintenance issues. The missing values rarely occur simultaneously leading to data that are multivariate misaligned sparse time series. We propose two models that are capable of performing multivariate spatio-temporal forecasting while handling missing data naturally without the need for imputation. The first model is a transformer-based model, which we name SERT (Spatio-temporal Encoder Representations from Transformers). The second is a simpler model named SST-ANN (Sparse Spatio-Temporal Artificial Neural Network) which is capable of providing interpretable results. We conduct extensive experiments on two different datasets for multivariate spatio-temporal forecasting and show that our models have competitive or superior performance to those at the state-of-the-art.Comment: 11 pages, 7 figure

Functional MRI Assessment of Renal Fibrosis in Rat Models

poster abstractIntroduction Renal fibrosis is a common consequence of chronic kidney diseases which affects a large population. Therefore, it is important to establish imaging based noninvasive biomarkers to monitor the progression or regression of renal fibrosis instead of biopsy. Magnetic resonance imaging (MRI) could provide both high spatial resolution and excellent tissue contrast for visualization of kidney morphology. Moreover, MRI is capable of assessing pseudo perfusion (Df) and perfusion fraction (Pf) with intra-voxel incoherent motion (IVIM) imaging (1), tissue oxygenation with T2* mapping (2), macromolecular composition with T1rho imaging (3) and kidney function (eGFR) with dynamic contrast enhanced (DCE) imaging (4). This study is aimed to evaluate the sensitivity of these MRI techniques to the renal fibrotic changes in a rat model. Methods A total of 4 rats were scanned at early (2-5 days) and late (25-35 days) time points after surgical intervention (unilateral ureteral obstruction to induce renal fibrosis) on a Siemens Tim Trio 3T scanner using an 80mm inner diameter 8-channel rat body coil (RAPID, USA) under a stable anesthetized condition. Axial images of 80mm FOV, 2mm slice thick and sub-millimeter in-place resolution were acquired for different functional MRI techniques with following parameters, respectively: IVIM with10 b-values of 0 - 750 s/mm2. T2*: with 10 TEs of 8 - 66 ms; T1rho: with 9 TSL times of 5 - 80 ms; DCE: with150 dynamic measurements at a temporal resolution of 1.01 s. before and after a 15s injection of 1.1 ml GD-DTPA through rat tail with a power injector. Functional data were processed and analyzed using custom MATLAB programs or analysis tools installed in the MRI console workstation. Results Figure 1 shows an anatomical image of the obstructed (R) and healthy (L) rat kidneys. Figures 2-4 show example T1rho map, IVIM Df map, and T2* map, respectively. Quantitative results based on ROI measurements are summarized in table 1. Changes consistent with the expected progression of fibrosis were observed in the obstructed kidney (R) while the healthy kidney (L) and muscle region remained stable. Figure 5 shows the DCE-MRI images at baseline as well as 45s, 95s and 240s after contrast infusion. The timing and intensity of signal changes are clearly different between two kidneys. Quantitative results of DCE-MRI data and comparison with PET study is reported in a separate abstract. Discussion High quality anatomical and functional images of rat kidney can be obtained on a clinical 3.0T MR scanner with dedicated small animal coils and optimized imaging techniques. The findings suggest that IVIM, T2*, T1rho and DCE can be used to assess and monitor different aspects of physiological changes in kidney fibrosis

Electrode initiated proton-coupled electron transfer to promote degradation of a nickel( ii ) coordination complex

Electrochemical analysis of a nickel compound that degrades permitted a peek into the decomposition mechanism

The Impact of Temporal Geopotential Variations on GPS

Lemoine et al. (2006) and Lemoine et al. (2010) showed that applying more detailed models of time-variable gravity (TVG) improved the quality of the altimeter satellite orbits (e.g. TOPEX/Poseidon, Jason-1, Jason-2). This modeling include application of atmospheric gravity derived from 6-hrly pressure fields obtained from the ECMWF and annual gravity variations to degree & order 20x20 in spherical harmonics derived from GRACE data. This approach allowed the development of a consistent geophysical model for application to altimeter satellite orbit determination from 1993 to 2011. In addition, we have also evaluated the impact of TVG modeling on the POD of Jason-1 and Jason-2 by application of a weekly degree & order four gravity coefficient time series developed using data from ten SLR & DORIS-tracked satellites from 1993 to 2011 (Lemoine et al., 2011)

Magnetic Resonance Diffusion Tensor Imaging and Diffusion Compartmental Modeling in an Animal Model of Chronic Kidney Disease

poster abstractPurpose: According to National Health and Nutrition Examination Survey (NHANES), Chronic Kidney Disease (CKD) affects 25% of the US population over age 601. Renal fibrosis, a common pathological consequence of CKD, is a progressive process that ultimately leads to end-stage renal failure that requires dialysis or kidney transplantation2. There is a compelling need for non-invasive biomarkers that track changes in the tissue microenvironment associated with CKD. Several studies using magnetic resonance diffusion tensor imaging (DTI) have been proposed as imaging biomarkers for CKD3. In this study, in addition to DTI, we explored a diffusion-compartmental modeling technique4 to study the microstructures of hypoxia induced animal models of CKD. Method: Preparation of the animal CKD model: Experiments were performed in 4 Wistar Rats using protocols approved by the Institutional Animal Care and Use Committee (IACUC). Two days prior to the first magnetic resonance imaging (MRI) scan; surgical intervention in right renal artery was performed in all the animals to create hypoxia induced renal fibrosis. The MRI scans were repeated at an interval of approximately one month. During the imaging session, the rats were sedated and kept in head-first supine position. MRI imaging: The MRI diffusion pulse sequence was a single-shot spin-echo echo-planar imaging (SS-SE-EPI) sequence with multiple diffusion-weighting b-values (i.e. 3 shells with b-values of 150, 300 and 450 s/mm2) and multiple diffusion-weighting directions at each shell (i.e., 10, 19 and 30, respectively). Diffusion directions in each shell and in the projected sphere with all directions (i.e., total 59) were optimized for uniform diffusion sampling in the spherical space5. The repetition time (TR) is 2200 ms and echo time (TE) is 73.6 ms. A total of four signal averages was performed. The imaging parameters were field-of-view (FOV) = 128 x 64 mm, matrix size = 128 x 64, isotropic voxel size of 1 mm3, and 20 oblique coronal slices. Image data processing: DTI derived parameters including axial diffusivity (Da), radial diffusivity (Dr), mean diffusivity (MD), and fractional anisotropy (FA) were computed6. The diffusion compartmental model originally proposed for the brain called neutrite orientation dispersion and density imaging (NODDI)4 was modified to fit the water diffusivities of kidneys. The NODDI model with Watson stick framework produces the volume fraction of stick like diffusion compartment that may explain the active diffusion (transport) of water in the interstitial space between renal tubules, ellipsoid like diffusion compartment that may explain diffusion inside renal tubule, and a fast isotropic diffusion to account for the pseudo-diffusion term relating to bulk vascular flow. The normalized diffusion intensity was fit with a non-linear mathematical model given by A = (1-Viso) (VicAic+(1-Vic) Aec) + VisoAiso ; where Vic and Viso are the volume fraction of active water transport and free diffusion compartments in the kidney, respectively. Aic, Aec and Aiso are the normalized diffusion signal contribution from stick, tubule and free diffusion compartments, respectively. In the raw DW data, the b-value=0 volume clearly shows three distinct layers in the rat kidney representing the inner medulla, outer medulla and cortex (Figure1). Non-overlapping ROI's were constructed from the b-value =0 images. Figure 1: The DTI and Diffusion compartmental modeling parameter for RAT Kidney 2 days after surgical intervention. The Cortex (C), the Outer Medulla (OM) and Inner Medulla (IM) are shown in raw b0 maps. The orientation of the images follows radiology convention. Results: On post-surgical day 2, the overall water diffusivity (i.e., mean diffusivity (MD)) decreased significantly in the outer medullae and inner medullae of the surgical kidneys (Figure 2 B green bars). In the compartmental model, the volume fraction of the stick (interstitial) diffusion compartment (Vic) in right outer and inner medulla was significantly increased compared to the left (Figure 2A blue bars), whereas the volume fraction of water diffusion inside the tubules (Vec = (1-Vic)) decreased significantly. In addition, isotropic free diffusion compartment (Viso) was significantly lower in the inner medullae of the right kidneys. The axial diffusivity (Da) that may describe the diffusion parallel to the tubules decreased significantly in outer and inter medullae of the right surgical kidneys (Figure 2 B blue bars). The radial diffusivity (Dr) that may describe the water diffusion perpendicularly to the renal tubules decreased significantly in only the outer medullae of the right kidneys (Figure 2B gray bars). While FA shows high value in the inner medullae for both left and right kidneys, no significant results were found between left and right kidneys and between two time points. Over the one-month period of time, right inner medullae continued the significant changes in the diffusivity measurements (Figure 2C and D, right groups), but the diffusivities remained similar in the outer medullae (Figure 2 C and D, middle groups). No significant findings were found in the renal cortices between the right and left kidneys on post-surgical day 2 (Figure 2 A and B). Interestingly, the right renal cortices did have significant increase in Vic and decreases in Da, Dr, and MD over the one-month time period (Figure 2 C and D). Figure 2: Diffusion Compartmental (Figure 2A) and DTI (Figure 2B) parameters for Right Cortex (RC) and Left Cortex (LC), Right Outer Medulla (ROM) and Left Outer Medulla (LOM) and Right Inner Medulla (RIM) and Left Inner Medulla (LIM) on post-surgical day 2. (Figure 2C) Is the time series study of diffusion compartmental parameters and (Figure 2D) for DTI parameters for the right kidneys at post-surgical day 2 and 30, respectively. The bars represent diffusion measurements of all four rats. The overhead connecting lines represent significant statistical student t-test with p-value < 0.01. Discussions and Conclusion: The DTI and NODDI analogous diffusion compartment derived parameters are sensitive to the micro-structural changes in kidneys after surgical hypoxia intervention. The outer and inner medullae appear most sensitive to the surgical hypoxia intervention as early as post-surgical day 2. The preliminary result suggests that water diffusion decreases due to renal fibrosis, and more so inside the Henle tubules. In post-surgical day 30, renal cortices start to show changes in water diffusivities while inner medullae continue pathological changes. The NODDI compartmental model shows promising preliminary results in revealing renal microenvironments under the influences of hypoxia induced renal fibrosis. Further study is required to optimize and validate the model

In vivo UTE-MRI reveals positive effects of raloxifene on skeletal bound water in skeletally mature beagle dogs

Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal bound water. The goal of this study was to determine if raloxifene induced alterations in skeletal hydration could be measured in vivo using ultra-short echotime magnetic resonance imaging (UTE-MRI). Twelve skeletally mature female beagle dogs (n=6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 ml/kg/day) or raloxifene (RAL, 0.5 mg/kg/day). Following six months of treatment, all animals underwent in vivo UTE-MRI of the proximal tibial cortical bone. UTE-MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene-treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (-20%) compared to vehicle-treated animals. These data provide the first evidence that drug-induced changes in skeletal hydration can be non-invasively assessed using UTE-MRI.Funding for this study was provided by NIH (AR 62002 and a BIRT supplement). Raloxifene was provided by through an MTA with Eli Lilly