Institute for Biomedical Engineering

Computer vision applications have come to rely increasingly on superpixels in recent years, but it is not always clear what constitutes a good superpixel algorithm. In an effort to understand the benefits and drawbacks of existing methods, we empirically compare five state-of-the-art superpixel algorithms for their ability to adhere to image boundaries, speed, memory efficiency, and their impact on segmentation performance. We then introduce a new superpixel algorithm, simple linear iterative clustering (SLIC), which adapts a k-means clustering approach to efficiently generate superpixels. Despite its simplicity, SLIC adheres to boundaries as well as or better than previous methods. At the same time, it is faster and more memory efficient, improves segmentation performance, and is straightforward to extend to supervoxel generation.

New theoretical and practical concepts are presented for considerably enhancing the performance of magnetic resonance imaging (MRI) by means of arrays of multiple receiver coils. Sensitivity encoding (SENSE) is based on the fact that receiver sensitivity generally has an encoding effect complementary to Fourier preparation by linear field gradients. Thus, by using multiple receiver coils in parallel scan time in Fourier imaging can be considerably reduced. The problem of image reconstruction from sensitivity encoded data is formulated in a general fashion and solved for arbitrary coil configurations and k-space sampling patterns. Special attention is given to the currently most practical case, namely, sampling a common Cartesian grid with reduced density. For this case the feasibility of the proposed methods was verified both in vitro and in vivo. Scan time was reduced to one-half using a two-coil array in brain imaging. With an array of five coils double-oblique heart images were obtained in one-third of conventional scan time. Magn Reson Med 42:952-962, 1999.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results.

Aerosols serve as cloud condensation nuclei (CCN) and thus have a substantial effect on cloud properties and the initiation of precipitation. Large concentrations of human-made aerosols have been reported to both decrease and increase rainfall as a result of their radiative and CCN activities. At one extreme, pristine tropical clouds with low CCN concentrations rain out too quickly to mature into long-lived clouds. On the other hand, heavily polluted clouds evaporate much of their water before precipitation can occur, if they can form at all given the reduced surface heating resulting from the aerosol haze layer. We propose a conceptual model that explains this apparent dichotomy.

The authors develop and estimate a conceptual model of how different aspects of customers’ relationships with the brand community influence their intentions and behaviors. The authors describe how identification with the brand community leads to positive consequences, such as greater community engagement, and negative consequences, such as normative community pressure and (ultimately) reactance. They examine the moderating effects of customers’ brand knowledge and the brand community's size and test their hypotheses by estimating a structural equation model with survey data from a sample of European car club members.

Rice (Oryza sativa), a major staple food, is usually milled to remove the oil-rich aleurone layer that turns rancid upon storage, especially in tropical areas. The remaining edible part of rice grains, the endosperm, lacks several essential nutrients, such as provitamin A. Thus, predominant rice consumption promotes vitamin A deficiency, a serious public health problem in at least 26 countries, including highly populated areas of Asia, Africa, and Latin America. Recombinant DNA technology was used to improve its nutritional value in this respect. A combination of transgenes enabled biosynthesis of provitamin A in the endosperm.

Quantification of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. However, converting the biological information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biological environment. Electrochemical biosensors provide an attractive means to analyze the content of a biological sample due to the direct conversion of a biological event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Additional measurement techniques, which have been shown useful in combination with electrochemical detection, are also summarized, such as the electrochemical versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochemical sensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.

Titanium dioxide is a common additive in many food, personal care, and other consumer products used by people, which after use can enter the sewage system and, subsequently, enter the environment as treated effluent discharged to surface waters or biosolids applied to agricultural land, incinerated wastes, or landfill solids. This study quantifies the amount of titanium in common food products, derives estimates of human exposure to dietary (nano-) TiO(2), and discusses the impact of the nanoscale fraction of TiO(2) entering the environment. The foods with the highest content of TiO(2) included candies, sweets, and chewing gums. Among personal care products, toothpastes and select sunscreens contained 1% to >10% titanium by weight. While some other crèmes contained titanium, despite being colored white, most shampoos, deodorants, and shaving creams contained the lowest levels of titanium (<0.01 μg/mg). For several high-consumption pharmaceuticals, the titanium content ranged from below the instrument detection limit (0.0001 μg Ti/mg) to a high of 0.014 μg Ti/mg. Electron microscopy and stability testing of food-grade TiO(2) (E171) suggests that approximately 36% of the particles are less than 100 nm in at least one dimension and that it readily disperses in water as fairly stable colloids. However, filtration of water solubilized consumer products and personal care products indicated that less than 5% of the titanium was able to pass through 0.45 or 0.7 μm pores. Two white paints contained 110 μg Ti/mg while three sealants (i.e., prime coat paint) contained less titanium (25 to 40 μg Ti/mg). This research showed that, while many white-colored products contained titanium, it was not a prerequisite. Although several of these product classes contained low amounts of titanium, their widespread use and disposal down the drain and eventually to wastewater treatment plants (WWTPs) deserves attention. A Monte Carlo human exposure analysis to TiO(2) through foods identified children as having the highest exposures because TiO(2) content of sweets is higher than other food products and that a typical exposure for a US adult may be on the order of 1 mg Ti per kilogram body weight per day. Thus, because of the millions of tons of titanium-based white pigment used annually, testing should focus on food-grade TiO(2) (E171) rather than that adopted in many environmental health and safety tests (i.e., P25), which is used in much lower amounts in products less likely to enter the environment (e.g., catalyst supports, photocatalytic coatings).

More than 3000 per- and polyfluoroalkyl substances (PFASs) are, or have been, on the global market, yet most research and regulation continues to focus on a limited selection of rather well-known long-chain PFASs, particularly perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their precursors. Continuing to overlook the vast majority of other PFASs is a major concern for society. We provide recommendations for how to proceed with research and cooperation to tackle the vast number of PFASs on the market and in the environment.

Three‐dimensional (3‐D) structural parameters derived from lower‐dimensional measurements using indirect morphometric methods may be strongly biased if the measured objects deviate from the assumed structure model. With the introduction of 3‐D microscopic measuring techniques it is possible to obtain a complete depiction of complex spatial structures. As a consequence, new 3‐D methods have recently been developed for the estimation of morphometric parameters such as volume, surface area and connectivity by direct processing of the 3‐D images. Structure thickness is an important morphometric parameter which is usually defined for specific structure models only. In this paper we propose a general thickness definition for arbitrary structures allowing us to calculate the mean structure thickness and the thickness distribution of 3‐D objects in a direct way and independently of an assumed structure model. Additionally, an efficient implementation for the practical usage of the method is described using distance transformation. The new method is applied to trabecular bone structures measured with a 3‐D micro‐computed tomography system.

Abstract. Anthropogenic increases in atmospheric greenhouse gas concentrations are the main driver of current and future climate change. The integrated assessment community has quantified anthropogenic emissions for the shared socio-economic pathway (SSP) scenarios, each of which represents a different future socio-economic projection and political environment. Here, we provide the greenhouse gas concentrations for these SSP scenarios – using the reduced-complexity climate–carbon-cycle model MAGICC7.0. We extend historical, observationally based concentration data with SSP concentration projections from 2015 to 2500 for 43 greenhouse gases with monthly and latitudinal resolution. CO2 concentrations by 2100 range from 393 to 1135 ppm for the lowest (SSP1-1.9) and highest (SSP5-8.5) emission scenarios, respectively. We also provide the concentration extensions beyond 2100 based on assumptions regarding the trajectories of fossil fuels and land use change emissions, net negative emissions, and the fraction of non-CO2 emissions. By 2150, CO2 concentrations in the lowest emission scenario are approximately 350 ppm and approximately plateau at that level until 2500, whereas the highest fossil-fuel-driven scenario projects CO2 concentrations of 1737 ppm and reaches concentrations beyond 2000 ppm by 2250. We estimate that the share of CO2 in the total radiative forcing contribution of all considered 43 long-lived greenhouse gases increases from 66 % for the present day to roughly 68 % to 85 % by the time of maximum forcing in the 21st century. For this estimation, we updated simple radiative forcing parameterizations that reflect the Oslo Line-By-Line model results. In comparison to the representative concentration pathways (RCPs), the five main SSPs (SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) are more evenly spaced and extend to lower 2100 radiative forcing and temperatures. Performing two pairs of six-member historical ensembles with CESM1.2.2, we estimate the effect on surface air temperatures of applying latitudinally and seasonally resolved GHG concentrations. We find that the ensemble differences in the March–April–May (MAM) season provide a regional warming in higher northern latitudes of up to 0.4 K over the historical period, latitudinally averaged of about 0.1 K, which we estimate to be comparable to the upper bound (∼5 % level) of natural variability. In comparison to the comparatively straight line of the last 2000 years, the greenhouse gas concentrations since the onset of the industrial period and this studies' projections over the next 100 to 500 years unequivocally depict a “hockey-stick” upwards shape. The SSP concentration time series derived in this study provide a harmonized set of input assumptions for long-term climate science analysis; they also provide an indication of the wide set of futures that societal developments and policy implementations can lead to – ranging from multiple degrees of future warming on the one side to approximately 1.5 ∘C warming on the other.

Model projections suggest that although increased temperature and decreased soil moisture will act to reduce global crop yields by 2050, the direct fertilization effect of rising carbon dioxide concentration ([CO2]) will offset these losses. The CO2 fertilization factors used in models to project future yields were derived from enclosure studies conducted approximately 20 years ago. Free-air concentration enrichment (FACE) technology has now facilitated large-scale trials of the major grain crops at elevated [CO2] under fully open-air field conditions. In those trials, elevated [CO2] enhanced yield by approximately 50% less than in enclosure studies. This casts serious doubt on projections that rising [CO2] will fully offset losses due to climate change.

Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (k(cat) and K(m)) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 microg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

Variations in solar radiation incident at Earth's surface profoundly affect the human and terrestrial environment. A decline in solar radiation at land surfaces has become apparent in many observational records up to 1990, a phenomenon known as global dimming. Newly available surface observations from 1990 to the present, primarily from the Northern Hemisphere, show that the dimming did not persist into the 1990s. Instead, a widespread brightening has been observed since the late 1980s. This reversal is reconcilable with changes in cloudiness and atmospheric transmission and may substantially affect surface climate, the hydrological cycle, glaciers, and ecosystems.

A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of < 200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd-DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath-hold.

The global spread of epidemics, rumors, opinions, and innovations are complex, network-driven dynamic processes. The combined multiscale nature and intrinsic heterogeneity of the underlying networks make it difficult to develop an intuitive understanding of these processes, to distinguish relevant from peripheral factors, to predict their time course, and to locate their origin. However, we show that complex spatiotemporal patterns can be reduced to surprisingly simple, homogeneous wave propagation patterns, if conventional geographic distance is replaced by a probabilistically motivated effective distance. In the context of global, air-traffic-mediated epidemics, we show that effective distance reliably predicts disease arrival times. Even if epidemiological parameters are unknown, the method can still deliver relative arrival times. The approach can also identify the spatial origin of spreading processes and successfully be applied to data of the worldwide 2009 H1N1 influenza pandemic and 2003 SARS epidemic.

The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. During aging and disease, plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. The introduction of three-dimensional (3D) measuring techniques in bone research makes it possible to capture the actual architecture of cancellous bone without assumptions of the structure type. This requires, however, new methods that make direct use of the 3D information. Within the framework of a BIOMED I project of the European Union, we analyzed a total of 260 human bone biopsies taken from five different skeletal sites (femoral head, vertebral bodies L2 and L4, iliac crest, and calcaneus) from 52 donors. The samples were measured three-dimensionally with a microcomputed tomography scanner and subsequently evaluated with both traditional indirect histomorphometric methods and newly developed direct ones. The results show significant differences between the methods and in their relation to the bone volume fraction. Based on the direct 3D analysis of human bone biopsies, it appears that samples with a lower bone mass are primarily characterized by a smaller plate-to-rod ratio, and to a lesser extent by thinner trabecular elements.

The remarkable Hubble Space Telescope(HST) data sets from the CANDELS, HUDF09, HUDF12, ERS, and BoRG/HIPPIES programs have allowed us to map the evolution of the rest-frame UV luminosity function (LF) from z 10 to z 4. We develop new color criteria that more optimally utilize the full wavelength coverage from the optical, near-IR, and mid-IR observations over our search fields, while simultaneously minimizing the incompleteness and eliminating redshift gaps. We have identified 5859, 3001, 857, 481, 217, and 6 galaxy candidates at z 4, z 5, z 6, z 7, z 8, and z 10, respectively, from the 1000 arcmin 2 area covered by these data sets. This sample of >10,000 galaxy candidates at z 4 is by far the largest assembled to date with HST. The selection of z 4-8 candidates over the five CANDELS fields allows us to assess the cosmic variance; the largest variations are at z 7. Our new LF determinations at z 4 and z 5 span a 6 mag baseline and reach to -16 AB mag. These determinations agree well with previous estimates, but the larger samples and volumes probed here result in a more reliable sampling of >L* galaxies and allow us to reassess the form of the UV LFs. Our new LF results strengthen our earlier findings to s 3.4 significance for a steeper faint-end slope of the UV LF at > z 4, with evolving from a = - 1.64 0.04 at z 4 to a = - 2.06 0.13 at z 7 (and a = - 2.02 0.23 at z 8), consistent with that expected from the evolution of the halo mass function. We find less evolution in the characteristic magnitude M * from z 7 to z 4; the observed evolution in the LF is now largely represented by changes in f*. No evidence for a non-Schechter-like form to the z 4-8 LFs is found. A simple conditional LF model based on halo growth and evolution in the M/L ratio + - z ( (