bluuebunny/crossref_metadata_2025 huggingface dataset:
M–H–BR3 and M–Br–BR3 interactions in rhodium and nickel complexes of an ambiphilic phosphine–thioether–borane ligand
Authors: Cowie Bradley E. , Emslie David J.H.
Published: April 2018

Reaction of [Rh(μ-Cl)(CO)(TXPB)] (1; TXPB = 2,7-di-tert-butyl-5-diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene) with NaBH4 yielded square planar [Rh(μ-H)(CO)(TXPB)] (2) in which the hydride ligand bridges between rhodium and the borane unit of TXPB. The Rh–H, Rh–B, and Rh–Cipso distances are short at 1.84(5), 2.456(6), and 2.568(5) Å, respectively, whereas the B–H bond, 1.59(6) Å, falls at the longer end of the usual range. Compound 2 is compared with the previously reported series of rhodium TXPB complexes: [RhX(CO)(TXPB)] {X = F (3), Cl (1), Br (4), I (5)}. Compound 4 in this series features the only crystallographically characterized example of an M–Br–BR3 interaction, and to expand this area, [NiBr(μ-Br)(TXPB)] (6) was prepared via the reaction of [NiBr2(dme)2] (dme = 1,2-dimethoxyethane) with TXPB. An X-ray crystal structure of light purple 6 revealed a square-planar geometry with a strong B–Br interaction {B–Br = 2.311(6) Å; ∑(C–B–C) = 344.5(7)°}. An 11B NMR chemical shift of 23 ppm was observed for 6, indicating that an appreciable B–Br interaction is maintained in solution. No signals were observed in the 31P{1H} NMR spectrum at room temperature, whereas a broadened 31P signal was observed at −20 °C, evolving into a sharp singlet at −67 °C. This behaviour suggests that at room temperature, square planar 6 exists in equilibrium with a paramagnetic tetrahedral isomer, present at a level below that detectable through Evans magnetic measurements.
Uniform zinc thioporphyrazine nanosphere by self-assembly and the photocatalytic performance
Authors: Yang Changjun , Gao Lanchang , Zhang Bingguang , Zhang Zehui , Deng Kejian
Published: April 2018

A novel strategy for the synthesis of zinc thioporphyrazine nanospheres is presented. The uniform spheres were fabricated through a polymerization reaction without using any template or emulsifier, which result from the covalent links between zinc tetra(2,3-bis(pentenylthio)porphyrazine (ZnPz) possessing eight long flexible chains in periphery and each with one terminal olefin group. A possible mechanism to explain the self-assembly of ZnPz nanospheres was also illuminated through monitoring nanosphere formation by means of transmission electron microscopy (TEM). More importantly, ZnPz nanospheres can effectively activate dioxygen in aqueous media under simulated sunlight irradiation, and showed significantly improved photocatalytic activity for the degradation of Rhodamine B (RhB) as compared to monomeric ZnPz. Furthermore, the reactive oxygen species derived from ZnPz nanospheres under light irradiation were determined by electron paramagnetic resonance (EPR) technology, indicating that singlet oxygen ([Formula: see text]O[Formula: see text] and hydroxyl radical (•OH) are the major reactive oxygen species. The facile synthetic methodology and the enhanced photocatalytic performance of the ZnPz nanospheres endow this novel material with the potential of being an efficient biomimetic photocatalyst for wastewater treatment.
Mating trackways of a fossil giant millipede
Authors: Whyte Martin A.
Published: April 2018

Three closely associated arthropleurid trackways,
Diplichnites cuithensis
, from the Lower Carboniferous of Fife, Scotland, exhibit signs of interaction between track-makers. An extra file of footprints is found on the downslope side of two trackways (A and C), the upslope side of another (B). These additional files of footprints suggest that either: each trackway resulted from two arthropleurids of different sizes walking in tandem, matching their footprints exactly on one side for some distance; or that one arthropleurid was partially mounted on the back of another producing the three parallel files. It is here argued that the latter is correct and that this represents evidence of mating behaviour in arthropleurids.
Interactive High-Quality Green-Screen Keying via Color Unmixing
Authors: Aksoy Yağiz , Aydin Tunç Ozan , Pollefeys Marc , Smolić Aljoša
Published: April 2018

Due to the widespread use of compositing in contemporary feature films, green-screen keying has become an essential part of postproduction workflows. To comply with the ever-increasing quality requirements of the industry, specialized compositing artists spend countless hours using multiple commercial software tools, while eventually having to resort to manual painting because of the many shortcomings of these tools. Due to the sheer amount of manual labor involved in the process, new green-screen keying approaches that produce better keying results with less user interaction are welcome additions to the compositing artist’s arsenal. We found that—contrary to the common belief in the research community—production-quality green-screen keying is still an unresolved problem with its unique challenges. In this article, we propose a novel green-screen keying method utilizing a new energy minimization-based
color unmixing
algorithm. We present comprehensive comparisons with commercial software packages and relevant methods in literature, which show that the quality of our results is superior to any other currently available green-screen keying solution. It is important to note that, using the proposed method, these high-quality results can be generated using only one-tenth of the manual editing time that a professional compositing artist requires to process the same content having all previous state-of-the-art tools at one’s disposal.
Hexahedral-Dominant Meshing
Authors: Sokolov Dmitry , Ray Nicolas , Untereiner Lionel , Lévy Bruno
Published: April 2018

This article introduces a method that generates a hexahedral-dominant mesh from an input tetrahedral mesh. It follows a three-step pipeline similar to the one proposed by Carrier Baudoin et al.: (1) generate a frame field, (2) generate a pointset
P
that is mostly organized on a regular grid locally aligned with the frame field, and (3) generate the hexahedral-dominant mesh by recombining the tetrahedra obtained from the constrained Delaunay triangulation of
P
.

For step (1), we use a state-of-the-art algorithm to generate a smooth frame field. For step (2), we introduce an extension of Periodic Global Parameterization to the volumetric case. As compared with other global parameterization methods (such as CubeCover), our method relaxes some global constraints to avoid creating degenerate elements, at the expense of introducing some singularities that are meshed using non-hexahedral elements. For step (3), we build on the formalism introduced by Meshkat and Talmor, fill in a gap in their proof, and provide a complete enumeration of all the possible recombinations, as well as an algorithm that efficiently detects all the matches in a tetrahedral mesh.

The method is evaluated and compared with the state of the art on a database of examples with various mesh complexities, varying from academic examples to real industrial cases. Compared with the method of Carrier-Baudoin et al., the method results in better scores for classical quality criteria of hexahedral-dominant meshes (hexahedral proportion, scaled Jacobian, etc.). The method also shows better robustness than CubeCover and its derivatives when applied to complicated industrial models.
Scalable Locally Injective Mappings
Authors: Rabinovich Michael , Poranne Roi , Panozzo Daniele , Sorkine-Hornung Olga
Published: April 2018

We present a scalable approach for the optimization of flip-preventing energies in the general context of simplicial mappings and specifically for mesh parameterization. Our iterative minimization is based on the observation that many distortion energies can be optimized indirectly by minimizing a family of simpler proxy energies. Minimization of these proxies is a natural extension of the local/global minimization of the ARAP energy. Our algorithm is simple to implement and scales to datasets with millions of faces. We demonstrate our approach for the computation of maps that minimize a conformal or isometric distortion energy, both in two and three dimensions. In addition to mesh parameterization, we show that our algorithm can be applied to mesh deformation and mesh quality improvement.
Deep Correlations for Texture Synthesis
Authors: Sendik Omry , Cohen-Or Daniel
Published: April 2018

Example-based texture synthesis has been an active research problem for over two decades. Still, synthesizing textures with nonlocal structures remains a challenge. In this article, we present a texture synthesis technique that builds upon convolutional neural networks and extracted statistics of pretrained deep features. We introduce a structural energy, based on correlations among deep features, which capture the self-similarities and regularities characterizing the texture. Specifically, we show that our technique can synthesize textures that have structures of various scales, local and nonlocal, and the combination of the two.
Deep Compositing Using Lie Algebras
Authors: Duff Tom
Published: April 2018

Deep compositing is an important practical tool in creating digital imagery, but there has been little theoretical analysis of the underlying mathematical operators. Motivated by finding a simple formulation of the merging operation on
OpenEXR
-style deep images, we show that the Porter-Duff
over
function is the operator of a Lie group. In its corresponding Lie algebra, the splitting and mixing functions that
OpenEXR
deep merging requires have a particularly simple form. Working in the Lie algebra, we present a novel, simple proof of the uniqueness of the mixing function.

The Lie group structure has many more applications, including new, correct resampling algorithms for volumetric images with alpha channels, and a deep image compression technique that outperforms that of
OpenEXR
.
Real-Time Geometry, Albedo, and Motion Reconstruction Using a Single RGB-D Camera
Authors: Guo Kaiwen , Xu Feng , Yu Tao , Liu Xiaoyang , Dai Qionghai , Liu Yebin
Published: April 2018

This article proposes a real-time method that uses a single-view RGB-D input (a depth sensor integrated with a color camera) to simultaneously reconstruct a casual scene with a detailed geometry model, surface albedo, per-frame non-rigid motion, and per-frame low-frequency lighting, without requiring any template or motion priors. The key observation is that accurate scene motion can be used to integrate temporal information to recover the precise appearance, whereas the intrinsic appearance can help to establish true correspondence in the temporal domain to recover motion. Based on this observation, we first propose a shading-based scheme to leverage appearance information for motion estimation. Then, using the reconstructed motion, a volumetric albedo fusing scheme is proposed to complete and refine the intrinsic appearance of the scene by incorporating information from multiple frames. Since the two schemes are iteratively applied during recording, the reconstructed appearance and motion become increasingly more accurate. In addition to the reconstruction results, our experiments also show that additional applications can be achieved, such as relighting, albedo editing, and free-viewpoint rendering of a dynamic scene, since geometry, appearance, and motion are all reconstructed by our technique.
Network Structure Inference, A Survey
Authors: Brugere Ivan , Gallagher Brian , Berger-Wolf Tanya Y.
Published: April 2018

Networks represent relationships between entities in many complex systems, spanning from online social interactions to biological cell development and brain connectivity. In many cases, relationships between entities are unambiguously known: are two users “friends” in a social network? Do two researchers collaborate on a published article? Do two road segments in a transportation system intersect? These are directly observable in the system in question. In most cases, relationships between nodes are not directly observable and must be inferred: Does one gene regulate the expression of another? Do two animals who physically co-locate have a social bond? Who infected whom in a disease outbreak in a population?

Existing approaches for inferring networks from data are found across many application domains and use specialized knowledge to infer and measure the quality of inferred network for a specific task or hypothesis. However, current research lacks a rigorous methodology that employs standard statistical validation on inferred models. In this survey, we examine (1) how network representations are constructed from underlying data, (2) the variety of questions and tasks on these representations over several domains, and (3) validation strategies for measuring the inferred network’s capability of answering questions on the system of interest.
Approximation Algorithms for Minimum-Load
k
-Facility Location
Authors: Ahmadian Sara , Behsaz Babak , Friggstad Zachary , Jorati Amin , Salavatipour Mohammad R. , Swamy Chaitanya
Published: April 2018

We consider a facility-location problem that abstracts settings where the cost of serving the clients assigned to a facility is incurred by the facility. Formally, we consider the
minimum-load k-facility location
(ML
k
FL) problem, which is defined as follows. We have a set
F
of facilities, a set
C
of clients, and an integer
k
≥ 0. Assigning client
j
to a facility
f
incurs a connection cost
d
(
f
,
j
). The goal is to open a set
F
⊆
F
of
k
facilities and assign each client
j
to a facility
f
(
j
)∈
F
so as to minimize max

f
∈

F
∑

j
∈
C
:
f
(
j
)=
f

d
(
f
,
j
); we call ∑

j
∈
C
:
f
(
j
)=
f

d
(
f
,
j
) the
load
of facility
f
. This problem was studied under the name of min-max star cover in References [3, 7], who (among other results) gave bicriteria approximation algorithms for ML
k
FL for when
F
=
C
. ML
k
FL is rather poorly understood, and only an
O
(
k
)-approximation is currently known for ML
k
FL,
even for line metrics
.

Our main result is the
first polytime approximation scheme
(PTAS) for ML
k
FL on line metrics (note that no non-trivial true approximation of any kind was known for this metric). Complementing this, we prove that ML
k
FL is strongly
NP
-hard on line metrics. We also devise a quasi-PTAS for ML
k
FL on tree metrics. ML
k
FL turns out to be surprisingly challenging even on line metrics and resilient to attack by a variety of techniques that have been successfully applied to facility-location problems. For instance, we show that (a) even a configuration-style LP-relaxation has a bad integrality gap and (b) a multi-swap
k
-median style local-search heuristic has a bad locality gap. Thus, we need to devise various novel techniques to attack ML
k
FL.

Our PTAS for line metrics consists of two main ingredients. First, we prove that there always exists a near-optimal solution possessing some nice structural properties. A novel aspect of this proof is that we first move to a mixed-integer LP (MILP) encoding of the problem and argue that a MILP-solution minimizing a certain potential function possesses the desired structure and then use a rounding algorithm for the generalized-assignment problem to “transfer” this structure to the rounded integer solution. Complementing this, we show that these structural properties enable one to find such a structured solution via dynamic programming.
Generating Realistic Synthetic Population Datasets
Authors: Wu Hao , Ning Yue , Chakraborty Prithwish , Vreeken Jilles , Tatti Nikolaj , Ramakrishnan Naren
Published: April 2018

Modern studies of societal phenomena rely on the availability of large datasets capturing attributes and activities of synthetic, city-level, populations. For instance, in epidemiology, synthetic population datasets are necessary to study disease propagation and intervention measures before implementation. In social science, synthetic population datasets are needed to understand how policy decisions might affect preferences and behaviors of individuals. In public health, synthetic population datasets are necessary to capture diagnostic and procedural characteristics of patient records without violating confidentialities of individuals. To generate such datasets over a large set of categorical variables, we propose the use of the maximum entropy principle to formalize a generative model such that in a statistically well-founded way we can optimally utilize given prior information about the data, and are unbiased otherwise. An efficient inference algorithm is designed to estimate the maximum entropy model, and we demonstrate how our approach is adept at estimating underlying data distributions. We evaluate this approach against both simulated data and US census datasets, and demonstrate its feasibility using an epidemic simulation application.
Behavior2Vec
Authors: Chen Hung-Hsuan
Published: April 2018

Most studies on recommender systems target at increasing the click through rate, and hope that the number of orders will increase as well. We argue that clicking and purchasing an item are different behaviors. Thus, we should probably apply different strategies for different objectives, e.g., increase the click through rate, or increase the order rate. In this article, we propose to generate the distributed representations of users’ viewing and purchasing behaviors on an e-commerce website. By leveraging on the cosine distance between the distributed representations of the behaviors on items under different contexts, we can predict a user’s next clicking or purchasing item more precisely, compared to several baseline methods. Perhaps more importantly, we found that the distributed representations may help discover interesting analogies among the products. We may utilize such analogies to explain how two products are related, and eventually apply different recommendation strategies under different scenarios. We developed the Behavior2Vec library for demonstration. The library can be accessed at https://github.com/ncu-dart/behavior2vec/.
Exact Algorithms for Terrain Guarding
Authors: Ashok Pradeesha , Fomin Fedor V. , Kolay Sudeshna , Saurabh Saket , Zehavi Meirav
Published: April 2018

Given a 1.5-dimensional terrain
T
, also known as an
x
-monotone polygonal chain, the T
errain
G
uarding
problem seeks a set of points of minimum size on
T
that
guards
all of the points on
T
. Here, we say that a point
p
guards a point
q
if no point of the line segment
pq
is strictly below
T
. The T
errain
G
uarding
problem has been extensively studied for over 20 years. In 2005 it was already established that this problem admits a constant-factor approximation algorithm (SODA 2005). However, only in 2010 King and Krohn (SODA 2010) finally showed that T
errain
G
uarding
is NP-hard. In spite of the remarkable developments in approximation algorithms for T
errain
G
uarding
, next to nothing is known about its parameterized complexity. In particular, the most intriguing open questions in this direction ask whether, if parameterized by the size
k
of a solution guard set, it admits a subexponential-time algorithm and whether it is fixed-parameter tractable. In this article, we answer the first question affirmatively by developing an
n

O
(√
k
)

-time algorithm for both D
iscrete
T
errain
G
uarding
and C
ontinuous
T
errain
G
uarding
. We also make non-trivial progress with respect to the second question: we show that D
iscrete
O
rthogonal
T
errain
G
uarding
, a well-studied special case of T
errain
G
uarding
, is fixed-parameter tractable.
SUMOylation regulates germinal vesicle breakdown and the Akt/PKB pathway during mouse oocyte maturation
Authors: Feitosa Weber Beringui , Morris Patricia L.
Published: April 2018

SUMOylation, a process of posttranslational modification of proteins by the small ubiquitin-related modifier (SUMO) family of proteins, is known to be involved in yeast and mammalian somatic cell-cycle regulation. However, the identities of the SUMO-modified oocyte targets are largely unknown and the functional role(s) for SUMOylation during mammalian oocyte maturation remains unclear. On the basis of studies in non-germline cells, protein kinase B/Akt is a potential SUMOylation target in the mouse oocyte, where it plays an essential role in cell-cycle resumption and progression during maturation. This study investigated the temporal patterns and prospective role(s) for interactions between SUMOylation and Akt serine-phosphorylation during oocyte meiotic resumption. Pharmacological inhibition of SUMOylation significantly decreased follicular fluid meiosis-activating sterol-induced cell-cycle resumption in oocytes matured in vitro and negatively affected the phosphorylation and nuclear translocation of Akt. Similarly, nuclear localization of cyclin D1, a downstream target of Akt activation, was significantly decreased following SUMOylation inhibition. Together these data show that SUMO and the posttranslational process of SUMOylation are involved in cell-cycle resumption during murine oocyte maturation and exert a regulatory influence on the Akt pathway during germinal vesicle breakdown.
Role of ion channels in the functional response of conjunctival goblet cells to dry eye
Authors: Puro Donald G.
Published: April 2018

Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing >70% of the eye’s refractive power. However, for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye. In freshly excised rat conjunctiva, perforated-patch recordings demonstrated that a ≥10% rise in osmolarity triggers goblet cells to rapidly generate a ~15-mV hyperpolarization due to the oxidant-dependent activation of ATP-sensitive K+ (KATP) channels. High-resolution membrane capacitance measurements used to monitor exocytosis revealed that this hyperpolarization results in an approximately fourfold boost in exocytotic activity evoked by cholinergic input, which in vivo occurs via a neural reflex and depends chiefly on calcium influxing down its electro-gradient. We discovered that this adaptive response is transient. During 30–80 min of hyperosmolarity, development of a depolarizing nonspecific cation conductance fully counterbalances the KATP-driven hyperpolarization and thereby eliminates the exocytotic boost. We conclude that hyperosmotic-induced hyperpolarization is a previously unappreciated mechanism by which goblet cells respond to transient ocular dryness. Loss of this voltage increase during long-term dryness/hyperosmolarity may account for the clinical conundrum that goblet cells in chronically dry eyes can remain filled with mucin even though the tear film is hyperosmotic and mucin-deficient.
Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects
Authors: Sabui Subrata , Kapadia Rubina , Ghosal Abhisek , Schneider Michael , Lambrecht Nils W. G. , Said Hamid M.
Published: April 2018

Intestinal absorption of the water-soluble vitamins biotin and pantothenic acid is carrier mediated and involves the sodium-dependent multivitamin transporter (SMVT; product of the SLC5A6 gene). We recently observed that intestinal-specific (conditional) knockout of the mouse Slc5a6 gene (SMVT-cKO) is associated with growth retardation, the development of spontaneous and severe inflammation, abnormal histology in the large intestine, altered gut permeability, and early death. Our aim in this study was to examine the possibility that biotin and pantothenic acid oversupplementation (BPS) of the SMVT-cKO mice could reverse the above-described abnormalities. BPS was provided in the drinking water to mice before conception, to dams during pregnancy and lactation, and to the SMVT-cKO mice throughout their life. Our findings showed that such a regimen prevents early death, as well as normalizes the growth rate, intestinal integrity, pathology, and inflammation in SMVT-cKO mice. These findings provide clear evidence for a role for biotin and/or pantothenic acid in the maintenance of normal intestinal integrity and health.
Role of lipolysis in postoral and oral fat preferences in mice
Authors: Sclafani Anthony , Ackroff Karen
Published: April 2018

Fatty acid receptors in the mouth and gut are implicated in the appetite for fat-rich foods. The role of lipolysis in oral- and postoral-based fat preferences of C57BL/6J mice was investigated by inhibiting lipase enzymes with orlistat. Experiment 1 showed that postoral lipolysis is required: mice learned to prefer (by 70%) a flavored solution paired with intragastric infusions of 5% soybean oil but not a flavor paired with soybean oil + orlistat (4 mg/g fat) infusions. Experiments 2–4 tested the oral attraction to oil in mice given brief choice tests that minimize postoral effects. In experiment 2, the same low orlistat dose did not reduce the strong (83–94%) preference for 2.5 or 5% soybean oil relative to fat-free vehicle in 3-min tests. Mice in experiment 3 given choice tests between two fat emulsions (2% triolein, corn oil, or soybean oil) with or without orlistat at a high dose (250 mg/g fat) preferred triolein (72%) and soybean oil (67%) without orlistat to the oil with orlistat but were indifferent to corn oil with and without orlistat. In experiment 4, mice preferred 2% triolein (62%) or soybean oil (89%) to vehicle when both choices contained orlistat (250 mg/g fat). Fatty acid receptors are thus essential for postoral but not oral-based preferences. Both triglyceride and fatty acid taste receptors may mediate oral fat preferences.
Deficiency of selenoprotein S, an endoplasmic reticulum resident oxidoreductase, impairs the contractile function of fast-twitch hindlimb muscles
Authors: Addinsall Alex B. , Wright Craig R. , Shaw Chris S. , McRae Natasha L. , Forgan Leonard G. , Weng Chia-Heng , Conlan Xavier A. , Francis Paul S. , Smith Zoe M. , Andrikopoulos Sofianos , Stupka Nicole
Published: April 2018

Selenoprotein S (Seps1) is an endoplasmic reticulum (ER) resident antioxidant implicated in ER stress and inflammation. In human vastus lateralis and mouse hindlimb muscles, Seps1 localization and expression were fiber-type specific. In male Seps1+/− heterozygous mice, spontaneous physical activity was reduced compared with wild-type littermates ( d = 1.10, P = 0.029). A similar trend was also observed in Seps1−/− knockout mice ( d = 1.12, P = 0.051). Whole body metabolism, body composition, extensor digitorum longus (EDL), and soleus mass and myofiber diameter were unaffected by genotype. However, in isolated fast EDL muscles from Seps1−/− knockout mice, the force frequency curve (FFC; 1–120 Hz) was shifted downward versus EDL muscles from wild-type littermates ( d = 0.55, P = 0.002), suggestive of reduced strength. During 4 min of intermittent, submaximal (60 Hz) stimulation, the genetic deletion or reduction of Seps1 decreased EDL force production ( d = 0.52, P < 0.001). Furthermore, at the start of the intermittent stimulation protocol, when compared with the 60-Hz stimulation of the FFC, EDL muscles from Seps1−/− knockout or Seps1+/− heterozygous mice produced 10% less force than those from wild-type littermates ( d = 0.31, P < 0.001 and d = 0.39, P = 0.015). This functional impairment was associated with reduced mRNA transcript abundance of thioredoxin-1 ( Trx1), thioredoxin interacting protein ( Txnip), and the ER stress markers Chop and Grp94, whereas, in slow soleus muscles, Seps1 deletion did not compromise contractile function and Trx1 ( d = 1.38, P = 0.012) and Txnip ( d = 1.27, P = 0.025) gene expression was increased. Seps1 is a novel regulator of contractile function and cellular stress responses in fast-twitch muscles.
Time course of compensatory physiological responses to central hypovolemia in high- and low-tolerant human subjects
Authors: Xiang Lusha , Hinojosa-Laborde Carmen , Ryan Kathy L. , Rickards Caroline A. , Convertino Victor A.
Published: April 2018

Lower body negative pressure (LBNP) simulates hemorrhage in human subjects. Most subjects (67%) exhibited high tolerance (HT) to hypovolemia, while the remainder (33%) had low tolerance (LT). To investigate the mechanisms for decompensation to central hypovolemia in HT and LT subjects, we characterized the time course of total peripheral resistance (TPR), heart rate (HR), and muscle sympathetic nerve activity (MSNA) during LBNP to tolerance determined by the onset of decompensation (presyncope, PS). We hypothesized that 1) maximum (Max) TPR, HR, and MSNA would coincide, and 2) PS would result from simultaneous decreases in TPR, HR, and MSNA in LT and HT subjects but occur earlier in LT than in HT subjects. Max TPR was lower and occurred earlier in LT ( n = 59) than in HT ( n = 113) subjects (LT: 24 ± 1 mmHg·min·1−1at 756 ± 31 s; HT: 28 ± 1 mmHg·min·1−1at 1,265 ± 37 s, P < 0.01). Max TPR occurred several minutes before PS. During subsequent decrease in TPR, HR and MSNA continued to increase. Max HR (LT: 111 ± 2 beat/min at 923 ± 27 s; HT: 130 ± 2 beats/min at 1489 ± 23 s, P < 0.01) occurred several seconds before PS. Higher MSNA ( P < 0.01) was attained in HT ( n = 10; 51 ± 5 bursts/min at max TPR; 54 ± 5 bursts/min at max HR) than LT subjects ( n = 4; 41 ± 8 bursts/min at max TPR; 39 ± 8 bursts/min at max HR). The onset of cardiovascular decompensation is a biphasic process in which vasodilation occurs before bradycardia and sympathetic withdrawal. This pattern was similar in LT and HT but occurred earlier in LT subjects. We conclude that sudden bradycardia plays a critical role in the determination of tolerance to central hypovolemia.
Effects of aging and exercise training on leg hemodynamics and oxidative metabolism in the transition from rest to steady-state exercise: role of cGMP signaling
Authors: Piil Peter , Jørgensen Tue Smith , Egelund Jon , Rytter Nicolai , Gliemann Lasse , Bangsbo Jens , Hellsten Ylva , Nyberg Michael
Published: April 2018

Aging is associated with slower skeletal muscle O2 uptake (V̇o2) kinetics; however, the mechanisms underlying this effect of age are unclear. Also, the effects of exercise training in elderly on the initial vascular and metabolic response to exercise remain to be elucidated. We measured leg hemodynamics and oxidative metabolism in the transition from rest to steady-state exercise engaging the knee-extensor muscles in young ( n = 15, 25 ± 1 yr) and older ( n = 15, 72 ± 1 yr) subjects before and after a period of aerobic high-intensity exercise training. To enhance cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, the older group had a slower ( P <0.05) increase in femoral arterial blood flow and leg vascular conductance in the transition from rest to steady-state exercise at low- and moderate-intensity compared with the young group. The rate of increase in leg V̇o2 was, however, similar in the two groups as a result of higher ( P < 0.05) arteriovenous O2 difference in the older group. Potentiation of cGMP signaling did not affect the rate of increase in blood flow or V̇o2 in either group. Exercise training augmented ( P < 0.05) the increase in leg vascular conductance and blood flow during the onset of moderate-intensity exercise in both groups without altering V̇o2. These findings suggest that an age-related reduction in the initial vascular response to low- and moderate-intensity knee-extensor exercise is not limiting for V̇o2 in older individuals. A lower blood flow response in aging does not appear to be a result of reduced cGMP signaling.
Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule
Authors: Wu Peng , Gao Zhong-Xiuzi , Su Xiao-Tong , Ellison David H. , Hadchouel Juliette , Teulon Jacques , Wang Wen-Hui
Published: April 2018

With-no-lysine kinase 4 (WNK4) and kidney-specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring tertiapin-Q (TPNQ; ROMK inhibitor)-sensitive K+ currents with whole cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS- WNK1−/− and WNK4−/− mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited. Moreover, WNK4−/− mice were hypokalemic, while KS- WNK1−/− mice had normal plasma K+ levels. High K+ (HK) intake significantly increased TPNQ-sensitive K+ currents in DCT2/CNT of WT and WNK4−/− mice but not in KS- WNK1−/− mice. However, TPNQ-sensitive K+ currents in the cortical collecting duct (CCD) were normal not only under control conditions but also significantly increased in response to HK in KS- WNK1−/− mice. This suggests that the deletion of KS-WNK1-induced inhibition of ROMK occurs only in the DCT2/CNT. Renal clearance study further demonstrated that the deletion of KS-WNK1 did not affect the renal ability of K+ excretion under control conditions and during increasing K+ intake. Also, HK intake did not cause hyperkalemia in KS- WNK1−/− mice. We conclude that KS-WNK1 but not WNK4 is required for HK intake-induced stimulation of ROMK activity in DCT2/CNT. However, KS-WNK1 is not essential for HK-induced stimulation of ROMK in the CCD, and the lack of KS-WNK1 does not affect net renal K+ excretion.
Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage
Authors: Jönsson Sofia , Melville Jacqueline M. , Becirovic-Agic Mediha , Hultström Michael
Published: April 2018

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.
Renoprotective impact of estrogen receptor-α and its splice variants in female mice with type 1 diabetes
Authors: Irsik Debra L. , Romero-Aleshire Melissa J. , Chavez Erin M. , Fallet Rachel W. , Brooks Heddwen L. , Carmines Pamela K. , Lane Pascale H.
Published: April 2018

Estrogen has been implicated in the regulation of growth and immune function in the kidney, which expresses the full-length estrogen receptor-α (ERα66), its ERα splice variants, and estrogen receptor-β (ERβ). Thus, we hypothesized that these splice variants may inhibit the glomerular enlargement that occurs early in type 1 diabetes (T1D). T1D was induced by streptozotocin (STZ) injection in 8- to 12-wk-old female mice lacking ERα66 (ERα66KO) or all ERα variants (αERKO), and their wild-type (WT) littermates. Basal renal ERα36 protein expression was reduced in the ERα66KO model and was downregulated by T1D in WT mice. T1D did not alter ERα46 or ERβ in WT-STZ; however, ERα46 was decreased modestly in ERα66KO mice. Renal hypertrophy was evident in all diabetic mice. F4/80-positive immunostaining was reduced in ERα66KO compared with WT and αERKO mice but was higher in STZ than in Control mice across all genotypes. Glomerular area was greater in WT and αERKO than in ERα66KO mice, with T1D-induced glomerular enlargement apparent in WT-STZ and αERKO-STZ, but not in ERα66KO-STZ mice. Proteinuria and hyperfiltration were evident in ERα66KO-STZ and αERKO-STZ, but not in WT-STZ mice. These data indicate that ERα splice variants may exert an inhibitory influence on glomerular enlargement and macrophage infiltration during T1D; however, effects of splice variants are masked in the presence of the full-length ERα66, suggesting that ERα66 acts in opposition to its splice variants to influence these parameters. In contrast, hyperfiltration and proteinuria in T1D are attenuated via an ERα66-dependent mechanism that is unaffected by splice variant status.
Choosing a foveal goal recruits the saccadic system during smooth pursuit
Authors: Heinen Stephen J. , Badler Jeremy B. , Watamaniuk Scott N. J.
Published: April 2018

Models of smooth pursuit eye movements stabilize an object’s retinal image, yet pursuit is peppered with small, destabilizing “catch-up” saccades. Catch-up saccades might help follow a small, spot stimulus used in most pursuit experiments, since fewer of them occur with large stimuli. However, they can return when a large stimulus has a small central feature. It may be that a central feature on a large object automatically recruits the saccadic system. Alternatively, a cognitive choice is made that the feature is the pursuit goal, and the saccadic system is then recruited to pursue it. Observers pursued a 5-dot stimulus composed of a central dot surrounded by four peripheral dots arranged as a diamond. An attention task specified the pursuit goal as either the central element, or the diamond gestalt. Fewer catch-up saccades occurred with the Gestalt goal than with the central goal, although the additional saccades with the central goal neither enhanced nor impeded pursuit. Furthermore, removing the central element from the diamond goal further reduced catch-up saccade frequency, indicating that the central element automatically triggered some saccades. Higher saccade frequency was not simply due to narrowly focused attention, since attending a small peripheral diamond during pursuit elicited fewer saccades than attending the diamond positioned foveally. The results suggest some saccades are automatically elicited by a small central element, but when it is chosen as the pursuit goal the saccadic system is further recruited to pursue it.

NEW & NOTEWORTHY Smooth-pursuit eye movements stabilize retinal image motion to prevent blur. Curiously, smooth pursuit is frequently supplemented by small catchup saccades that could reduce image clarity. Catchup saccades might only be needed to pursue small laboratory stimuli, as they are infrequent during large object pursuit. Yet large objects with central features revive them. Here, we show that voluntarily selecting a feature as the pursuit goal elicits saccades that do not help pursuit.
Pulsed infrared releases Ca2+from the endoplasmic reticulum of cultured spiral ganglion neurons
Authors: Barrett John N. , Rincon Samantha , Singh Jayanti , Matthewman Cristina , Pasos Julio , Barrett Ellen F. , Rajguru Suhrud M.
Published: April 2018

Inner ear spiral ganglion neurons were cultured from day 4 postnatal mice and loaded with a fluorescent Ca2+indicator (fluo-4, -5F, or -5N). Pulses of infrared radiation (IR; 1,863 nm, 200 µs, 200–250 Hz for 2–5 s, delivered via an optical fiber) produced a rapid, transient temperature increase of 6–12°C (above a baseline of 24–30°C). These IR pulse trains evoked transient increases in both nuclear and cytosolic Ca2+concentration ([Ca2+]) of 0.20–1.4 µM, with a simultaneous reduction of [Ca2+] in regions containing endoplasmic reticulum (ER). IR-induced increases in cytosolic [Ca2+] continued in medium containing no added Ca2+(±Ca2+buffers) and low [Na+], indicating that the [Ca2+] increase was mediated by release from intracellular stores. Consistent with this hypothesis, the IR-induced [Ca2+] response was prolonged and eventually blocked by inhibition of ER Ca2+-ATPase with cyclopiazonic acid, and was also inhibited by a high concentration of ryanodine and by inhibitors of inositol (1,4,5)-trisphosphate (IP3)-mediated Ca2+release (xestospongin C and 2-aminoethoxydiphenyl borate). The thermal sensitivity of the response suggested involvement of warmth-sensitive transient receptor potential (TRP) channels. The IR-induced [Ca2+] increase was inhibited by TRPV4 inhibitors (HC-067047 and GSK-2193874), and immunostaining of spiral ganglion cultures demonstrated the presence of TRPV4 and TRPM2 that colocalized with ER marker GRP78. These results suggest that the temperature sensitivity of IR-induced [Ca2+] elevations is conferred by TRP channels on ER membranes, which facilitate Ca2+efflux into the cytosol and thereby contribute to Ca2+-induced Ca2+-release via IP3and ryanodine receptors.

NEW & NOTEWORTHY Infrared radiation-induced photothermal effects release Ca2+from the endoplasmic reticulum of primary spiral ganglion neurons. This Ca2+release is mediated by activation of transient receptor potential (TRPV4) channels and involves amplification by Ca2+-induced Ca2+-release. The neurons immunostained for warmth-sensitive channels, TRPV4 and TRPM2, which colocalize with endoplasmic reticulum. Pulsed infrared radiation provides a novel experimental tool for releasing intracellular Ca2+, studying Ca2+regulatory mechanisms, and influencing neuronal excitability.
Neuromuscular changes of the aged human hamstrings
Authors: Kirk Eric A. , Gilmore Kevin J. , Rice Charles L.
Published: April 2018

Despite the life-long importance for posture and locomotion, neuromuscular properties of the hamstrings muscle have not been explored with adult aging. The purpose of this study was to assess and compare age-related effects on contractile function, spinal motor neuron output expressed as motor unit (MU) discharge rates in the hamstrings of 11 young (26 ± 4 yr) and 10 old (80 ± 5 yr) men. Maximal voluntary isometric contractions (MVC), stimulated contractile properties, and surface and intramuscular electromyography (EMG) from submaximal to MVC were recorded in the biceps femoris (BF) and semimembranosus-semitendinosus (SS) muscles. MVC torque was ~50% less in the old with both age groups attaining ≥93% mean voluntary activation. Evoked twitches in the old were ~50% lower in amplitude and >150% longer in duration compared with those in the young. At successive voluntary contractions of 25, 50, and 100% MVC, MU discharge rates were up to 45% lower in old, with no differences in relative submaximal surface EMG between age groups. Furthermore, the old had significantly lower MU discharge rates in the SS at all contraction intensities compared with the BF muscle. Men in their 8th to 10th decades of life demonstrate substantially lower strength and MU discharge rates in this functionally important large lower limb muscle group, with greater age-related effect on discharge rates in the medial hamstrings. These findings, compared with those in other muscles studied, highlight that the neuromuscular properties of limb muscles, and indeed within functionally similar portions of a muscle group, are not all affected equally by the aging process.

NEW & NOTEWORTHY In the hamstrings, we found that both contractile function and motor unit discharge rates across the range of voluntary intensities were lower in the old. The differences in discharge rates due to age were greater in the medial hamstrings muscle group compared with the lateral hamstrings. Compared with previous studies, these results highlight that not all muscles are affected equally by aging and there may be compartmental differences within functionally similar muscles.
Predictability, force, and (anti)resonance in complex object control
Authors: Maurice Pauline , Hogan Neville , Sternad Dagmar
Published: April 2018

Manipulation of complex objects as in tool use is ubiquitous and has given humans an evolutionary advantage. This study examined the strategies humans choose when manipulating an object with underactuated internal dynamics, such as a cup of coffee. The dynamics of the object renders the temporal evolution complex, possibly even chaotic, and difficult to predict. A cart-and-pendulum model, loosely mimicking coffee sloshing in a cup, was implemented in a virtual environment with a haptic interface. Participants rhythmically manipulated the virtual cup containing a rolling ball; they could choose the oscillation frequency, whereas the amplitude was prescribed. Three hypotheses were tested: 1) humans decrease interaction forces between hand and object; 2) humans increase the predictability of the object dynamics; and 3) humans exploit the resonances of the coupled object-hand system. Analysis revealed that humans chose either a high-frequency strategy with antiphase cup-and-ball movements or a low-frequency strategy with in-phase cup-and-ball movements. Counter to hypothesis 1, they did not decrease interaction force; instead, they increased the predictability of the interaction dynamics, quantified by mutual information, supporting hypothesis 2. To address hypothesis 3, frequency analysis of the coupled hand-object system revealed two resonance frequencies separated by an antiresonance frequency. The low-frequency strategy exploited one resonance, whereas the high-frequency strategy afforded more choice, consistent with the frequency response of the coupled system; both strategies avoided the antiresonance. Hence, humans did not prioritize small interaction forces but rather strategies that rendered interactions predictable. These findings highlight that physical interactions with complex objects pose control challenges not present in unconstrained movements.

NEW & NOTEWORTHY Daily actions involve manipulation of complex nonrigid objects, which present a challenge since humans have no direct control of the whole object. We used a virtual-reality experiment and simulations of a cart-and-pendulum system coupled to hand movements with impedance to analyze the manipulation of this underactuated object. We showed that participants developed strategies that increased the predictability of the object behavior by exploiting the resonance structure of the object but did not minimize the hand-object interaction force.