bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust hex-dominant mesh generation using field-guided polyhedral agglomeration
Authors: Gao Xifeng , Jakob Wenzel , Tarini Marco , Panozzo Daniele
Published: July 2017

We propose a robust and efficient field-aligned volumetric meshing algorithm that produces hex-dominant meshes, i.e. meshes that are predominantly composed of hexahedral elements while containing a small number of irregular polyhedra. The latter are placed according to the singularities of two optimized guiding fields, which allow our method to generate meshes with an exceptionally high amount of isotropy.

The field design phase of our method relies on a compact quaternionic representation of volumetric octa-fields and a corresponding optimization that explicitly models the discrete matchings between neighboring elements. This optimization naturally supports alignment constraints and scales to very large datasets. We also propose a novel extraction technique that uses field-guided mesh simplification to convert the optimized fields into a hexdominant output mesh. Each simplification operation maintains topological validity as an invariant, ensuring manifold output. These steps easily generalize to other dimensions or representations, and we show how they can be an asset in existing 2D surface meshing techniques.

Our method can automatically and robustly convert any tetrahedral mesh into an isotropic hex-dominant mesh and (with minor modifications) can also convert any triangle mesh into a corresponding isotropic quad-dominant mesh, preserving its genus, number of holes, and manifoldness. We demonstrate the benefits of our algorithm on a large collection of shapes provided in the supplemental material along with all generated results.
Charted metropolis light transport
Authors: Pantaleoni Jacopo
Published: July 2017

In this manuscript, inspired by a simpler reformulation of primary sample space Metropolis light transport, we derive a novel family of general Markov chain Monte Carlo algorithms called
charted Metropolis-Hastings
, that introduces the notion of
sampling charts
to extend a given sampling domain and make it easier to sample the desired target distribution and escape from local maxima through coordinate changes. We further apply the novel algorithms to light transport simulation, obtaining a new type of algorithm called
charted Metropolis light transport
, that can be seen as a bridge between primary sample space and path space Metropolis light transport. The new algorithms require to provide only right inverses of the sampling functions, a property that we believe crucial to make them practical in the context of light transport simulation.
Water wave packets
Authors: Jeschke Stefan , Wojtan Chris
Published: July 2017

This paper presents a method for simulating water surface waves as a displacement field on a 2D domain. Our method relies on Lagrangian particles that carry packets of water wave energy; each packet carries information about an entire group of wave trains, as opposed to only a single wave crest. Our approach is unconditionally stable and can simulate high resolution geometric details. This approach also presents a straightforward interface for artistic control, because it is essentially a particle system with intuitive parameters like wavelength and amplitude. Our implementation parallelizes well and runs in real time for moderately challenging scenarios.
Animating elastic rods with sound
Authors: Schweickart Eston , James Doug L. , Marschner Steve
Published: July 2017

Sound generation methods, such as linear modal synthesis, can sonify a wide range of physics-based animation of solid objects, resolving vibrations and sound radiation from various structures. However, elastic rods are an important computer animation primitive for which prior sound synthesis methods, such as modal synthesis, are ill-suited for several reasons: large displacements, nonlinear vibrations, dispersion effects, and the geometrically singular nature of rods.

In this paper, we present physically based methods for simultaneous generation of animation and sound for deformable rods. We draw on Kirchhoff theory to simplify the representation of rod dynamics and introduce a generalized dipole model to calculate the spatially varying acoustic radiation. In doing so, we drastically decrease the amount of precomputation required (in some cases eliminating it completely), while being able to resolve sound radiation for arbitrary body deformations encountered in computer animation. We present several examples, including challenging scenes involving thousands of highly coupled frictional contacts.
Visual attribute transfer through deep image analogy
Authors: Liao Jing , Yao Yuan , Yuan Lu , Hua Gang , Kang Sing Bing
Published: July 2017

We propose a new technique for visual attribute transfer across images that may have very different appearance but have perceptually similar semantic structure. By visual attribute transfer, we mean transfer of visual information (such as color, tone, texture, and style) from one image to another. For example, one image could be that of a painting or a sketch while the other is a photo of a real scene, and both depict the same type of scene.

Our technique finds semantically-meaningful dense correspondences between two input images. To accomplish this, it adapts the notion of "image analogy" [Hertzmann et al. 2001] with features extracted from a Deep Convolutional Neutral Network for matching; we call our technique
deep image analogy.
A coarse-to-fine strategy is used to compute the nearest-neighbor field for generating the results. We validate the effectiveness of our proposed method in a variety of cases, including style/texture transfer, color/style swap, sketch/painting to photo, and time lapse.
Generic objective vortices for flow visualization
Authors: Günther Tobias , Gross Markus , Theisel Holger
Published: July 2017

In flow visualization, vortex extraction is a long-standing and unsolved problem. For decades, scientists developed numerous definitions that characterize vortex regions and their corelines in different ways, but none emerged as ultimate solution. One reason is that almost all techniques have a fundamental weakness: they are not invariant under changes of the reference frame, i.e., they are not objective. This has two severe implications: First, the result depends on the movement of the observer, and second, they cannot track vortices that are moving on arbitrary paths, which limits their reliability and usefulness in practice. Objective measures are rare, but recently gained more attention in the literature. Instead of only introducing a new objective measure, we show in this paper how all existing measures that are based on velocity and its derivatives can be made objective. We achieve this by observing the vector field in optimal local reference frames, in which the temporal derivative of the flow vanishes, i.e., reference frames in which the flow appears steady. The central contribution of our paper is to show that these optimal local reference frames can be found by a simple and elegant linear optimization. We prove that in the optimal frame, all local vortex extraction methods that are based on velocity and its derivatives become objective. We demonstrate our approach with objective counterparts to
λ
2
, vorticity and Sujudi-Haimes.
All's well that ends well
Authors: Vouga Etienne , Smith Breannan , Kaufman Danny M. , Tamstorf Rasmus , Grinspun Eitan
Published: July 2017

Iterative algorithms are frequently used to resolve simultaneous impacts between rigid bodies in physical simulations. However, these algorithms lack formal guarantees of termination, which is sometimes viewed as potentially dangerous, so failsafes are used in practical codes to prevent infinite loops. We show such steps are unnecessary. In particular, we study the broad class of such algorithms that are conservative and satisfy a minimal set of physical correctness properties, and which encompasses recent methods like Generalized Reflections as well as pairwise schemes. We fully characterize finite termination of these algorithms. The only possible failure cases can be detected, and we describe a procedure for modifying the algorithms to provably ensure termination. We also describe modifications necessary to guarantee termination in the presence of numerical error due to the use of floating-point arithmetic. Finally, we discuss the challenges dissipation introduce for finite termination, and describe how dissipation models can be incorporated while retaining the termination guarantee.
Fusing state spaces for markov chain Monte Carlo rendering
Authors: Otsu Hisanari , Kaplanyan Anton S. , Hanika Johannes , Dachsbacher Carsten , Hachisuka Toshiya
Published: July 2017

Rendering algorithms using Markov chain Monte Carlo (MCMC) currently build upon two different state spaces. One of them is the path space, where the algorithms operate on the vertices of actual transport paths. The other state space is the primary sample space, where the algorithms operate on sequences of numbers used for generating transport paths. While the two state spaces are related by the sampling procedure of transport paths, all existing MCMC rendering algorithms are designed to work within only one of the state spaces. We propose a first framework which provides a comprehensive connection between the path space and the primary sample space. Using this framework, we can use mutation strategies designed for one space with mutation strategies in the respective other space. As a practical example, we take a combination of manifold exploration and multiplexed Metropolis light transport using our framework. Our results show that the simultaneous use of the two state spaces improves the robustness of MCMC rendering. By combining efficient local exploration in the path space with global jumps in primary sample space, our method achieves more uniform convergence as compared to using only one space.
Dip transform for 3D shape reconstruction
Authors: Aberman Kfir , Katzir Oren , Zhou Qiang , Luo Zegang , Sharf Andrei , Greif Chen , Chen Baoquan , Cohen-Or Daniel
Published: July 2017

The paper presents a novel three-dimensional shape acquisition and reconstruction method based on the well-known Archimedes equality between fluid displacement and the submerged volume. By repeatedly dipping a shape in liquid in different orientations and measuring its volume displacement, we generate the
dip transform
: a novel volumetric shape representation that characterizes the object's surface. The key feature of our method is that it employs fluid displacements as the shape sensor. Unlike optical sensors, the liquid has no line-of-sight requirements, it penetrates cavities and hidden parts of the object, as well as transparent and glossy materials, thus bypassing all visibility and optical limitations of conventional scanning devices. Our new scanning approach is implemented using a dipping robot arm and a bath of water, via which it measures the water elevation. We show results of reconstructing complex 3D shapes and evaluate the quality of the reconstruction with respect to the number of dips.
Computational design and automated fabrication of kirchhoff-plateau surfaces
Authors: Pérez Jesús , Otaduy Miguel A. , Thomaszewski Bernhard
Published: July 2017

We propose a computational tool for designing Kirchhoff-Plateau Surfaces---planar rod networks embedded in pre-stretched fabric that deploy into complex, three-dimensional shapes. While Kirchhoff-Plateau Surfaces offer an intriguing and expressive design space, navigating this space is made difficult by the highly nonlinear nature of the underlying mechanical problem. In order to tackle this challenge, we propose a user-guided but computer-assisted approach that combines an efficient forward simulation model with a dedicated optimization algorithm in order to implement a powerful set of design tools. We demonstrate our method by designing a diverse set of complex-shaped Kirchhoff-Plateau Surfaces, each validated through physically-fabricated prototypes.
Understanding the impact of animated gesture performance on personality perceptions
Authors: Smith Harrison Jesse , Neff Michael
Published: July 2017

Applications such as virtual tutors, games, and natural interfaces increasingly require animated characters to take on social roles while interacting with humans. The effectiveness of these applications depends on our ability to control the social presence of characters, including their personality. Understanding how movement impacts the perception of personality allows us to generate characters more capable of fulfilling this social role. The two studies described herein focus on gesture as a key component of social communication and examine how a set of gesture edits, similar to the types of changes that occur during motion warping, impact the perceived personality of the character. Surprisingly, when based on thin-slice gesture data, people's judgments of character personality mainly fall in a 2D subspace rather than independently impacting the full set of traits in the standard Big Five model of personality. These two dimensions areplasticity, which includes extraversion and openness, andstability, which includes emotional stability, agreeableness, and conscientiousness. A set of motion properties is experimentally determined that impacts each of these two traits. We show that when these properties are systematically edited in new gesture sequences, we can independently influence the character's perceived stability and plasticity (and the corresponding Big Five traits), to generate distinctive personalities. We identify motion adjustments salient to each judgment and, in a series of perceptual studies, repeatedly generate four distinctly perceived personalities. The effects extend to novel gesture sequences and character meshes, and even largely persist in the presence of accompanying speech. This paper furthers our understanding of how gesture can be used to control the perception of personality and suggests both the potential and possible limits of motion editing approaches.
A deep learning approach for generalized speech animation
Authors: Taylor Sarah , Kim Taehwan , Yue Yisong , Mahler Moshe , Krahe James , Rodriguez Anastasio Garcia , Hodgins Jessica , Matthews Iain
Published: July 2017

We introduce a simple and effective deep learning approach to automatically generate natural looking speech animation that synchronizes to input speech. Our approach uses a sliding window predictor that learns arbitrary nonlinear mappings from phoneme label input sequences to mouth movements in a way that accurately captures natural motion and visual coarticulation effects. Our deep learning approach enjoys several attractive properties: it runs in real-time, requires minimal parameter tuning, generalizes well to novel input speech sequences, is easily edited to create stylized and emotional speech, and is compatible with existing animation retargeting approaches. One important focus of our work is to develop an effective approach for speech animation that can be easily integrated into existing production pipelines. We provide a detailed description of our end-to-end approach, including machine learning design decisions. Generalized speech animation results are demonstrated over a wide range of animation clips on a variety of characters and voices, including singing and foreign language input. Our approach can also generate on-demand speech animation in real-time from user speech input.
Aether
Authors: Anderson Luke , Li Tzu-Mao , Lehtinen Jaakko , Durand Frédo
Published: July 2017

Implementing Monte Carlo integration requires significant domain expertise. While simple samplers, such as unidirectional path tracing, are relatively forgiving, more complex algorithms, such as bidirectional path tracing or Metropolis methods, are notoriously difficult to implement correctly. We propose Aether, an embedded domain specific language for Monte Carlo integration, which offers primitives for writing concise and correct-by-construction sampling and probability code. The user is tasked with writing sampling code, while our compiler automatically generates the code necessary for evaluating PDFs as well as the book keeping and combination of multiple sampling strategies. Our language focuses on ease of implementation for rapid exploration, at the cost of run time performance. We demonstrate the effectiveness of the language by implementing several challenging rendering algorithms as well as a new algorithm, which would otherwise be prohibitively difficult.
A stiffly accurate integrator for elastodynamic problems
Authors: Michels Dominik L. , Luan Vu Thai , Tokman Mayya
Published: July 2017

We present a new integration algorithm for the accurate and efficient solution of stiff elastodynamic problems governed by the second-order ordinary differential equations of structural mechanics. Current methods have the shortcoming that their performance is highly dependent on the numerical stiffness of the underlying system that often leads to unrealistic behavior or a significant loss of efficiency. To overcome these limitations, we present a new integration method which is based on a mathematical reformulation of the underlying differential equations, an exponential treatment of the full nonlinear forcing operator as opposed to more standard partially implicit or exponential approaches, and the utilization of the concept of stiff accuracy which ensures that the efficiency of the simulations is significantly less sensitive to increased stiffness. As a consequence, we are able to tremendously accelerate the simulation of stiff systems compared to established integrators and significantly increase the overall accuracy. The advantageous behavior of this approach is demonstrated on a broad spectrum of complex examples like deformable bodies, textiles, bristles, and human hair. Our easily parallelizable integrator enables more complex and realistic models to be explored in visual computing without compromising efficiency.
Discovering and synthesizing humanoid climbing movements
Authors: Naderi Kourosh , Rajamäki Joose , Hämäläinen Perttu
Published: July 2017

This paper addresses the problem of offline path and movement planning for wall climbing humanoid agents. We focus on simulating bouldering, i.e. climbing short routes with diverse moves, although we also demonstrate our system on a longer wall. Our approach combines a graph-based high-level path planner with low-level sampling-based optimization of climbing moves. Although the planning problem is complex, our system produces plausible solutions to bouldering problems (short climbing routes) in less than a minute. We further utilize a k-shortest paths approach, which enables the system to discover alternative paths - in climbing, alternative strategies often exist, and what might be optimal for one climber could be impossible for others due to individual differences in strength, flexibility, and reach. We envision our system could be used, e.g. in learning a climbing strategy, or as a test and evaluation tool for climbing route designers. To the best of our knowledge, this is the first paper to solve and simulate rich humanoid wall climbing, where more than one limb can move at the same time, and limbs can also hang free for balance or use wall friction in addition to predefined holds.
Functionality-aware retargeting of mechanisms to 3D shapes
Authors: Zhang Ran , Auzinger Thomas , Ceylan Duygu , Li Wilmot , Bickel Bernd
Published: July 2017

We present an interactive design system to create functional mechanical objects. Our computational approach allows novice users to retarget an existing mechanical template to a user-specified input shape. Our proposed representation for a mechanical template encodes a parameterized mechanism, mechanical constraints that ensure a physically valid configuration, spatial relationships of mechanical parts to the user-provided shape, and functional constraints that specify an intended functionality. We provide an intuitive interface and optimization-in-the-loop approach for finding a valid configuration of the mechanism and the shape to ensure that higher-level functional goals are met. Our algorithm interactively optimizes the mechanism while the user manipulates the placement of mechanical components and the shape. Our system allows users to efficiently explore various design choices and to synthesize customized mechanical objects that can be fabricated with rapid prototyping technologies. We demonstrate the efficacy of our approach by retargeting various mechanical templates to different shapes and fabricating the resulting functional mechanical objects.
Bounding proxies for shape approximation
Authors: Calderon Stéphane , Boubekeur Tamy
Published: July 2017

Many computer graphics applications use simpler yet faithful approximations of complex shapes to conduct reliably part of their computations. Some tasks, such as physical simulation, collision detection, occlusion queries or free-form deformation, require the simpler proxy to strictly enclose the input shape. While there are algorithms that can output such bounding proxies on simple input shapes, most of them fail at generating a proper coarse approximant on real-world complex shapes, which may contain multiple components and have a high genus. We advocate that, before reducing the number of primitives to describe a shape, one needs to regularize it while maintaining the strict enclosing property, to avoid any geometric aliasing that makes the decimation unreliable. Depending on the scale of the desired approximation, the topology of the shape itself may indeed have to be first simplified, to let the subsequent geometric optimization be free from topological locks.

We propose a new bounding shape approximation algorithm which takes as input an arbitrary surface mesh, with potentially complex multi-component structures, and generates automatically a bounding proxy which is tightened on the input and can match even the coarsest levels of approximation. To sustain the nonlinear approximation process that may eventually abstract both geometry and topology, we propose to use an intermediate regularized representation in the form of a shape closing, computed in real time using a new fast morphological framework designed for efficient parallel execution. Once the desired level of approximation is reached in the shape closing, a coarse, tight and bounding polygonization of the proxy geometry is extracted using an adaptive meshing scheme. Our underlying representation is both geometry- and topology-adaptive and can be optionally controlled accurately by a user, through sizing and orientation fields, yielding an intuitive brush metaphor within an interactive proxy design environment. We provide extensive experiments on various kinds of input meshes and illustrate the potential applications of our method in scenarios that benefit greatly from coarse, tight bounding substitutes to the actual high resolution geometry of the original 3D model, including freeform deformation, physical simulation and level of detail generation for rendering.
Rho Protein: Roles and Mechanisms
Authors: Mitra Pallabi , Ghosh Gairika , Hafeezunnisa Md. , Sen Ranjan
Published: July 2017

At the end of the multistep transcription process, the elongating RNA polymerase (RNAP) is dislodged from the DNA template either at specific DNA sequences, called the terminators, or by a nascent RNA-dependent helicase, Rho. In Escherichia coli, about half of the transcription events are terminated by the Rho protein. Rho utilizes its RNA-dependent ATPase activities to translocate along the mRNA and eventually dislodges the RNAP via an unknown mechanism. The transcription elongation factor NusG facilitates this termination process by directly interacting with Rho. In this review, we discuss current models describing the mechanism of action of this hexameric transcription terminator, its regulation by different cis and trans factors, and the effects of the termination process on physiological processes in bacterial cells, particularly E. coli and Salmonella enterica Typhimurium.
Present and Future of Culturing Bacteria
Authors: Overmann Jörg , Abt Birte , Sikorski Johannes
Published: July 2017

The cultivation of bacteria is highly biased toward a few phylogenetic groups. Many of the currently underexplored bacterial lineages likely have novel biosynthetic pathways and unknown biochemical features. New cultivation concepts have been developed based on an improved understanding of the ecology of previously not-cultured bacteria. Particularly successful were improved media that mimic the natural types and concentrations of substrates and nutrients, high-throughput cultivation techniques, and approaches that exploit biofilm formation and bacterial interactions. Metagenomics and single-cell genomics can reveal unknown metabolic features of not-yet-cultured bacteria and, if complemented by culture-independent physiological analyses, will help to target functional novelty more efficiently. However, numerous novel types of bacteria that were initially enriched subsequently escaped isolation. Future cultivation work will therefore need to focus on improved subcultivation, purification, and preservation techniques to recover and utilize a larger fraction of microbial diversity.
Adaptive regulation of pancreatic acinar mitochondrial thiamin pyrophosphate uptake process: possible involvement of epigenetic mechanism(s)
Authors: Sabui Subrata , Subramanian Veedamali S. , Kapadia Rubina , Said Hamid M.
Published: July 2017

The essentiality of thiamin stems from its roles as a cofactor [mainly in the form of thiamin pyrophosphate (TPP)] in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive regulation. We addressed this issue using pancreatic acinar 266-6 cells (PAC 266-6) maintained under thiamin-deficient (DEF) and oversupplemented (OS) conditions, as well as thiamin-DEF and -OS transgenic mice carrying the SLC25A19 promoter. We found that maintaining PAC 266-6 under the thiamin-DEF condition leads to a significant induction in mitochondrial [3H]TPP uptake, as well as in the level of expression of the MTPPT protein and mRNA compared with thiamin-OS cells. Similar findings were observed in mitochondria from thiamin-DEF mice compared with thiamin-OS. Subsequently, we demonstrated that adaptive regulation of MTTP protein was partly mediated via transcriptional mechanism(s) via studies with PAC 266-6 transfected with the SLC25A19 promoter and transgenic mice carrying the SLC25A19 promoter. This transcriptional regulation appeared to be, at least in part, mediated via epigenetic mechanism(s) involving histone modifications. These studies report, for the first time, that the PAC mitochondrial TPP uptake process is adaptively regulated by the prevailing thiamin level and that this regulation is transcriptionally mediated and involves epigenetic mechanism(s).

NEW & NOTEWORTHY Our findings show, for the first time, that the mitochondrial thiamin pyrophosphate (MTPP) uptake process is adaptively regulated by the prevailing thiamin level in pancreatic acinar cells and this regulation is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting the SLC25A19 promoter.
Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment
Authors: Lyra-Leite Davi M. , Andres Allen M. , Petersen Andrew P. , Ariyasinghe Nethika R. , Cho Nathan , Lee Jezell A. , Gottlieb Roberta A. , McCain Megan L.
Published: July 2017

Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease.

NEW & NOTEWORTHY A new methodology has been developed to measure O2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix elasticity regulates basal mitochondrial function, whereas both matrix elasticity and tissue alignment regulate mitochondrial stress responses.
Muscle sympathetic nerve activity and volume-regulating factors in healthy pregnant and nonpregnant women
Authors: Charkoudian Nisha , Usselman Charlotte W. , Skow Rachel J. , Staab Jeffery S. , Julian Colleen G. , Stickland Michael K. , Chari Radha S. , Khurana Rshmi , Davidge Sandra T. , Davenport Margie H. , Steinback Craig D.
Published: July 2017

Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In nonpregnant humans, volume-regulatory factors including plasma osmolality, vasopressin, and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume-regulating factors, including plasma osmolality, plasma renin activity, and arginine vasopressin (AVP). We studied 46 healthy, normotensive young women (23 pregnant and 23 nonpregnant). We measured SNA, arterial pressure, plasma osmolality, plasma renin activity, AVP, and other volume-regulatory factors in resting, semirecumbent posture. Pregnant women had significantly higher resting SNA (38 ± 12 vs. 23 ± 6 bursts/min in nonpregnant women), lower osmolality, and higher plasma renin activity and aldosterone (all P < 0.05). Group mean values for AVP were not different between groups [4.64 ± 2.57 (nonpregnant) vs. 5.17 ± 2.03 (pregnant), P > 0.05]. However, regression analysis detected a significant relationship between individual values for SNA and AVP in pregnant ( r = 0.71, P < 0.05) but not nonpregnant women ( r = 0.04). No relationships were found for other variables. These data suggest that the link between AVP release and resting SNA becomes stronger in pregnancy, which may contribute importantly to blood pressure regulation in healthy women during pregnancy.

NEW & NOTEWORTHY Sympathetic nerve activity and blood volume are both elevated during pregnancy, but blood pressure is usually normal. Here, we identified a relationship between vasopressin and sympathetic nerve activity in pregnant but not nonpregnant women. This may provide mechanistic insights into blood pressure regulation in normal pregnancy and in pregnancy-related hypertension.
Walking economy is predictably determined by speed, grade, and gravitational load
Authors: Ludlow Lindsay W. , Weyand Peter G.
Published: July 2017

The metabolic energy that human walking requires can vary by more than 10-fold, depending on the speed, surface gradient, and load carried. Although the mechanical factors determining economy are generally considered to be numerous and complex, we tested a minimum mechanics hypothesis that only three variables are needed for broad, accurate prediction: speed, surface grade, and total gravitational load. We first measured steady-state rates of oxygen uptake in 20 healthy adult subjects during unloaded treadmill trials from 0.4 to 1.6 m/s on six gradients: −6, −3, 0, 3, 6, and 9°. Next, we tested a second set of 20 subjects under three torso-loading conditions (no-load, +18, and +31% body weight) at speeds from 0.6 to 1.4 m/s on the same six gradients. Metabolic rates spanned a 14-fold range from supine rest to the greatest single-trial walking mean (3.1 ± 0.1 to 43.3 ± 0.5 ml O2·kg-body−1·min−1, respectively). As theorized, the walking portion (V̇o2-walk =  V̇o2-gross– V̇o2-supine-rest) of the body’s gross metabolic rate increased in direct proportion to load and largely in accordance with support force requirements across both speed and grade. Consequently, a single minimum-mechanics equation was derived from the data of 10 unloaded-condition subjects to predict the pooled mass-specific economy (V̇o2-gross, ml O2·kg-body + load−1·min−1) of all the remaining loaded and unloaded trials combined ( n = 1,412 trials from 90 speed/grade/load conditions). The accuracy of prediction achieved ( r2 = 0.99, SEE = 1.06 ml O2·kg−1·min−1) leads us to conclude that human walking economy is predictably determined by the minimum mechanical requirements present across a broad range of conditions.

NEW & NOTEWORTHY Introduced is a “minimum mechanics” model that predicts human walking economy across a broad range of conditions from only three variables: speed, surface grade, and body-plus-load mass. The derivation/validation data set includes steady-state loaded and unloaded walking trials ( n = 3,414) that span a fourfold range of walking speeds on each of six different surface gradients (−6 to +9°). The accuracy of our minimum mechanics model ( r2 = 0.99; SEE = 1.06 ml O2·kg−1·min−1) appreciably exceeds that of currently used standards.
Edward F. Adolph Distinguished Lecture: Skin-deep insights into vascular aging
Authors: Kenney W. Larry
Published: July 2017

The skin is an accessible model circulation for studying vascular function and dysfunction across the lifespan. Age-related changes, as well as those associated with disease progression, often appear first in the cutaneous circulation. Furthermore, impaired vascular signaling and attendant endothelial dysfunction, the earliest indicators of cardiovascular pathogenesis, occur in a similar fashion across multiple tissue beds throughout the body, including the skin. Because microvascular dysfunction is a better predictor of long-term outcomes and adverse cardiovascular events than is large vessel disease, an understanding of age-associated changes in the control of the human cutaneous microcirculation is important. This review focuses on 1) the merits of using skin-specific methods and techniques to study vascular function, 2) microvascular changes in aged skin (in particular, the role of the endothelial-derived dilator nitric oxide), and 3) the impact of aging on heat-induced changes in skin vasodilation. While skin blood flow is controlled by multiple, often redundant, mechanisms, our laboratory has used a variety of distinct thermal provocations of this model circulation to isolate specific age-associated changes in vascular function. Skin-specific approaches and techniques, such as intradermal microdialysis coupled with laser-Doppler flowmetry (in vivo) and biochemical analyses of skin biopsy samples (in vitro), have allowed for the targeted pharmacodissection of the mechanistic pathways controlling skin vasoreactivity and study of the impact of aging and disease states. Aged skin has an attenuated ability to vasodilate in response to warm stimuli and to vasoconstrict in response to cold stimuli.
The Retinoid X Receptor-Selective Retinoid, LGD1069, Down-regulates Cyclooxygenase-2 Expression in Human Breast Cells through Transcription Factor Crosstalk: Implications for Molecular-Based Chemoprevention
Authors: Kong Gu , Kim Hee-Tae , Wu Kendall , DeNardo David , Hilsenbeck Susan G. , Xu Xiao-Chun , Lamph William W. , Bissonnette Reid , Dannenberg Andrew J. , Brown Powel H.
Published: July 2017

Retinoids and their derivatives can suppress the development of cancer in animals and in humans. We and others have shown that retinoid X receptor (RXR)-selective retinoids or “rexinoids” suppress the development of breast cancer in several animal models with minimal toxicity. LGD1069 (Bexarotene) is a potent RXR-selective retinoid with reduced toxicity compared with naturally occurring retinoids. In this study, we investigated the expression of LGD1069-modulated biomarkers. We previously did cDNA array analysis of LGD1069-treated breast cells using Affymetrix microarrays. These studies identified many LGD1069-regulated genes, one of which was cyclooxygenase-2 (COX-2). Because COX-2 inhibitors have been shown to prevent cancer in other model systems, we investigated whether LGD1069 inhibits the expression of COX-2 in mammary tissue and in normal human mammary epithelial cells (HMEC). In mouse mammary tumor virus-erbB2 mice treated with LGD1069, there was a marked decrease of COX-2 expression in both normal and malignant mammary tissues. The effect of LGD1069 on COX-2 expression was also investigated in normal human breast cells. COX-2 expression was markedly reduced by treatment with LGD1069 at the RNA and protein level in normal HMECs; LGD1069 suppressed COX-2 promoter activity. We also showed that LGD1069 inhibited activator protein (AP-1)-dependent transcription in these breast cells, and that suppression of COX-2 expression was due to sequestration of CBP/p300. These results from in vivo and in vitro studies suggest that LGD1069, an RXR-selective retinoid, inhibits COX-2 expression by suppression of COX-2 transcription in part through transrepression of the AP-1 transcription factor. Thus, RXR-selective retinoids that inhibit AP-1 activity and suppress COX-2 expression may be particularly promising drugs for breast cancer prevention. Furthermore, such RXR-selective retinoids may be most useful in combination with antiestrogens for more effective prevention of breast cancer in women at high risk of this disease.
RRP22 Is a Farnesylated, Nucleolar, Ras-Related Protein with Tumor Suppressor Potential
Authors: Elam Candice , Hesson Luke , Vos Michele D. , Eckfeld Kristin , Ellis Chad A. , Bell Aaron , Krex Dietmar , Birrer Michael J. , Latif Farida , Clark Geoffrey J.
Published: July 2017

Ras proteins are members of a superfamily of related small GTPases. Some members, such as Ras, are oncogenic. However, other members seem to serve as tumor suppressors, such as Rig and Noey2. We now identify and characterize a novel member of the Ras superfamily, RRP22. Like Ras, RRP22 can be posttranslationally modified by farnesyl. Unlike Ras, RRP22 inhibits cell growth and promotes caspase-independent cell death. Examination of human tumor cells shows that RRP22 is frequently down-regulated due to promoter methylation. Moreover, reexpression of RRP22 in an RRP22-negative neural tumor cell line impairs its growth in soft agar. Unusually for a Ras-related protein, RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel mechanism of action. Thus, we identify a new member of the Ras superfamily that can serve as a potential tumor suppressor.
Human Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Gliomas
Authors: Nakamizo Akira , Marini Frank , Amano Toshiyuki , Khan Asadullah , Studeny Matus , Gumin Joy , Chen Julianne , Hentschel Stephen , Vecil Giacomo , Dembinski Jennifer , Andreeff Michael , Lang Frederick F.
Published: July 2017

The poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor. Because it has been suggested that circulating bone marrow–derived stem cells can be recruited into solid organs in response to tissue stresses, we hypothesized that human bone marrow–derived mesenchymal stem cells (hMSC) may have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. To test this, we isolated hMSCs from bone marrow of normal volunteers, fluorescently labeled the cells, and injected them into the carotid artery of mice bearing human glioma intracranial xenografts (U87, U251, and LN229). hMSCs were seen exclusively within the brain tumors regardless of whether the cells were injected into the ipsilateral or contralateral carotid artery. In contrast, intracarotid injections of fibroblasts or U87 glioma cells resulted in widespread distribution of delivered cells without tumor specificity. To assess the potential of hMSCs to track human gliomas, we injected hMSCs directly into the cerebral hemisphere opposite an established human glioma and showed that the hMSCs were capable of migrating into the xenograft in vivo. Likewise, in vitro Matrigel invasion assays showed that conditioned medium from gliomas, but not from fibroblasts or astrocytes, supported the migration of hMSCs and that platelet-derived growth factor, epidermal growth factor, or stromal cell–derived factor-1α, but not basic fibroblast growth factor or vascular endothelial growth factor, enhanced hMSC migration. To test the potential of hMSCs to deliver a therapeutic agent, hMSCs were engineered to release IFN-β (hMSC-IFN-β). In vitro coculture and Transwell experiments showed the efficacy of hMSC-IFN-β against human gliomas. In vivo experiments showed that treatment of human U87 intracranial glioma xenografts with hMSC-IFN-β significantly increase animal survival compared with controls (P < 0.05). We conclude that hMSCs can integrate into human gliomas after intravascular or local delivery, that this engraftment may be mediated by growth factors, and that this tropism of hMSCs for human gliomas can be exploited to therapeutic advantage.
Gene Expression Profiling Allows Distinction between Primary and Metastatic Squamous Cell Carcinomas in the Lung
Authors: Talbot Simon G. , Estilo Cherry , Maghami Ellie , Sarkaria Inderpal S. , Pham Duy Khanh , O-charoenrat Pornchai , Socci Nicholas D. , Ngai Ivan , Carlson Diane , Ghossein Ronald , Viale Agnes , Park Bernard J. , Rusch Valerie W. , Singh Bhuvanesh
Published: July 2017

Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large “test” set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.
Role for the Nuclear Factor κB Pathway in Transforming Growth Factor-β1 Production in Idiopathic Myelofibrosis: Possible Relationship with FK506 Binding Protein 51 Overexpression
Authors: Komura Emiko , Tonetti Carole , Penard-Lacronique Virginie , Chagraoui Hédia , Lacout Catherine , LeCouédic Jean Pierre , Rameau Philippe , Debili Najet , Vainchenker William , Giraudier Stéphane
Published: July 2017

The release of transforming growth factor-β1 (TGF-β1) in the bone marrow microenvironment is one of the main mechanisms leading to myelofibrosis in murine models and probably in the human idiopathic myelofibrosis (IMF). The regulation of TGF-β1 synthesis is poorly known but seems regulated by nuclear factor κB (NF-κB). We previously described the overexpression of an immunophilin, FK506 binding protein 51 (FKBP51), in IMF megakaryocytes. Gel shift and gene assays show that FKBP51's overexpression in a factor-dependent hematopoietic cell line, induces a sustained NF-κB activation after cytokine deprivation. This activation correlates with a low level of IκBα. A spontaneous activation of NF-κB was also detected in proliferating megakaryocytes and in circulating CD34+ patient cells. In normal cells, NF-κB activation was only detected after cytokine treatment. The expression of an NF-κB superrepressor in FKBP51 overexpressing cells and in derived megakaryocytes from CD34+ of IMF patients revealed that NF-κB activation was not involved in the resistance to apoptosis after cytokine deprivation of these cells but in TGF-β1 secretion. These results highlight the importance of NF-κB's activation in the fibrosis development of this disease. They also suggest that FKBP51's overexpression in IMF cells could play an important role in the pathogenesis of this myeloproliferative disorder.