bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmented 3D venous navigation for neuroendovascular procedures
Authors: Blanc Raphaël , Fahed Robert , Roux Pascal , Smajda Stanislas , Ciccio Gabriele , Desilles Jean-Philippe , Redjem Hocine , Mazighi Mikael , Baharvahdat Humain , Piotin Michel
Published: October 2017

Background

Endovascular venous access is increasingly used for the treatment of many cerebrovascular diseases. The quality of venous roadmapping through arterial injection can be problematic because of contrast media dilution, slow flow velocity, and unilateral opacification of the venous system.

Objective

To describe our experience with the VesselNavigator (Philips Healthcare, Best, The Netherlands) in performing live 3D roadmapping for intracranial venous procedures.

Material and methods

Live 3D roadmapping is an image-processing technique that allows dynamic roadmapping of vessels with immediate adaptation to the C-arm movements without the need for contrast injection. For this purpose, 3D MR venography is overlaid on live fluoroscopy images after semiautomatic coregistration. The technique was applied to cases of idiopathic venous stenosis and arteriovenous fistula.

Results

The process of coregistration was performed by the principal operator in <5 min, just before the treatment. The accuracy was controlled peroperatively and was judged satisfactory. Three illustrative cases demonstrate the use of this software for venous navigation and pressure measurement (case 1), venous stenting (case 2), and transvenous embolization of a carotid-cavernous fistula (case 3).

Conclusion

Our preliminary experience suggests that it is a feasible and safe technique for intracranial venous navigation and procedures. The potential lowering of overall radiation dose and contrast media use needs to be verified with further studies.
Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review
Authors: Navarro-Compán Victoria , Plasencia-Rodríguez Chamaida , de Miguel Eugenio , Diaz del Campo Petra , Balsa Alejandro , Gratacós Jordi
Published: October 2017

Objectives

First, to investigate if switching biological disease-modifying antirheumatic drugs (bDMARDs) after the failure to prior bDMARD is efficacious in patients with axial spondyloarthritis (axSpA). Second, to evaluate the influence on this efficacy of (1) the reason to discontinue prior tumour necrosis factor inhibitor (TNFi), (2) changing the type of TNFi and (3) changing the target.

Methods

A systematic literature review until January 2017 was performed using Medline, EMBASE and Cochrane databases. Longitudinal studies assessing clinical response after switching bDMARDs in patients with axSpA were analysed.

Results

In total, 9 studies out of 1862 retrieved citations were included. Overall, the level of evidence was poor. In these studies, all patients received a TNFi as first bDMARD, 1956 patients switched to a second bDMARD (97% TNFi and 3% interleukin-17 inhibitors (IL-17i)) and 170 to a third bDMARD (all TNFi). Clinical response (Bath Ankylosing Spondylitis Disease Activity Index 50) after a second TNFi was achieved by 25%–56% of patients compared with 50%–72% after the first TNFi. Also, 47% of patients switching to IL-17i after a TNFi responded (Assessment of SpondyloArthritis international Society 40) compared with 66% in those who received IL-17i as first line. The response after switching was not influenced by the reason to discontinue, type of prior TNFi or changing the target.

Conclusions

In patients with axSpA, switching to a second bDMARD (a TNFi or IL-17i) after prior TNFi is efficacious. Nevertheless, the clinical response is lower than the observed in patients naive to bDMARD. So far, the reason to discontinue prior bDMARD or the type of bDMARD has not been identified as predictor of response. Published evidence for switching to a third bDMARD is lacking.
High prevalence of high-risk HPV genotypes other than 16 and 18 in cervical cancers of Curaçao: implications for choice of prophylactic HPV vaccine
Authors: Hooi Desiree J , Lissenberg-Witte Birgit I , de Koning Maurits N C , Pinedo Herbert M , Kenter Gemma G , Meijer Chris JLM , Quint Wim G
Published: October 2017

Background

Curaçao is a Dutch-Caribbean Island located in a high-risk area for cervical cancer.

Prior to introduction of a prophylactic human papillomavirus (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required.

Objective

To investigate the prevalence of HPV genotypes in invasive cervical cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in Curaçao.

Methods

Paraffin-embedded blocks of 104 cervical cancers (89 squamous, 15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the presence of HPV. Sections were stained by H&E for histopathological evaluation, and DNA was extracted using proteinase K. HPV genotypes were detected using Short PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) .

Results

HPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.

The three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%), covering 58.7%.

HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was 85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1.

Conclusions

Our study, the largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV-type 16 and 18 in cervical cancer is lower compared with the world population but no differences in prevalence of these two HPV types are seen in precancerous lesions.

When considering HPV vaccination in Curaçao, the relatively high contribution of non-HPV 16/18 genotypes in ICC should be taken into account.
The avian embryo as a model for fetal alcohol spectrum disorder
Authors: Flentke George R. , Smith Susan M.
Published: October 2017

Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chicken (Gallus gallus domesticus) is a powerful embryological research model, and was possibly the first in which the teratogenicity of alcohol was demonstrated. Pharmacologically relevant exposure to alcohol in the range of 20–70 mmol/L (20–80 mg/egg) disrupt the growth of chicken embryos, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models. The avian embryo’s direct accessibility has enabled novel insights into the teratogenic mechanisms of alcohol. These include the contribution of IGF1 signaling to growth suppression, the altered flow dynamics that reshape valvuloseptal morphogenesis and mediate its cardiac teratogenicity, and the suppression of Wnt and Shh signals thereby disrupting the migration, expansion, and survival of the neural crest, and underlie its characteristic craniofacial deficits. The genetic diversity within commercial avian strains has enabled the identification of unique loci, such as ribosome biogenesis, that modify vulnerability to alcohol. This venerable research model is equally relevant for the future, as the application of technological advances including CRISPR, optogenetics, and biophotonics to the embryo’s ready accessibility creates a unique model in which investigators can manipulate and monitor the embryo in real-time to investigate the effect of alcohol on cell fate.
Sampling effects on the effectiveness of ecological indicators in detecting fishery-induced community changes
Authors: Zhang Chongliang , Chen Yong , Xu Binduo , Xue Ying , Ren Yiping
Published: October 2017

Effective ecological indicators (EI) should reflect changes to ecosystem status in a timely manner to guide fisheries management; however, the robustness of EIs in the face of sampling uncertainty is not well understood and sampling errors may result in delayed or even unhelpful actions for management. In this study, we use a size-spectrum model to evaluate the effectiveness of EIs in detecting fishery-induced ecosystem changes given various levels of sampling uncertainty. We demonstrate that there is a time-lag that exists between changes in fishing pressure and EI response. The selectivity of survey gears can strongly determine the level of EI responses within certain size ranges. EIs may lose statistical power once sampling errors exceed a certain level, implying that several decades of monitoring data may be needed to be sure of detecting even a large change. Multivariate methods can strengthen the statistical powers of EIs, but only when the level of sampling noises is low. This study suggests the need for considering the impact of sampling uncertainty on the use of EIs in fisheries management.
Temperature-dependent consumption of spiders by little brown bats (Myotis lucifugus), but not northern long-eared bats (Myotis septentrionalis), in northern Canada
Authors: Kaupas L.A. , Barclay R.M.R.
Published: October 2017

Intraspecific variation in diet has been observed in many species, including the geographically widespread little brown bat (Myotis lucifugus (Le Conte, 1831)). Spider consumption by M. lucifugus is more common in northern regions of their distribution, possibly due to reduced availability of aerial prey during low temperatures. However, in previously studied northern regions, M. lucifugus was the only bat species captured. The purpose of our study was to examine whether there is overlap in the diet and morphology of M. lucifugus and the northern long-eared bat (Myotis septentrionalis (Trouessart, 1897)), a species that commonly gleans prey, in the Northwest Territories, Canada. There were significant differences in the dietary composition and wing morphology of the two species, suggesting partitioning of resources. Both species consumed spiders, although unlike M. septentrionalis, the probability of M. lucifugus consuming spiders was significantly greater at low temperatures. Myotis lucifugus demonstrated a different pattern of spider consumption than in other northern regions where it consumes spiders throughout the summer, suggesting the possibility of resource competition where M. lucifugus overlaps with M. septentrionalis. Further research is needed to determine whether arthropods are seasonally limiting at high latitudes and to examine how these species capture nonaerial prey, including spiders.
Bifurcation of Quasiperiodic Orbit in a 3D Piecewise Linear Map
Authors: Patra Mahashweta , Banerjee Soumitro
Published: October 2017

Earlier investigations have demonstrated how a quasiperiodic orbit in a three-dimensional smooth map can bifurcate into a quasiperiodic orbit with two disjoint loops or into a quasiperiodic orbit of double the length in the shape of a Möbius strip. Using a three-dimensional piecewise smooth (PWS) normal form map, we show that in a piecewise smooth system, in addition to the mechanisms reported earlier, new pathways of creation of tori with multiple loops may result from border collision bifurcations. We also illustrate the occurrence of multiple attractor bifurcations due to the interplay between the stable and the unstable manifolds. Two techniques of analyzing bifurcations of ergodic tori are available in literature: the second Poincaré section method and the Lyapunov bundle method. We have shown that these methods can explain the period-doubling and double covering bifurcations in PWS systems, but fail in some cases — especially those which result from nonsmoothness of the system. We have shown that torus bifurcations due to border collision can be explained by change in eigenvalues of the unstable fixed points.
Chaos in Fractional Order Cubic Chua System and Synchronization
Authors: Odibat Zaid , Corson Nathalie , Aziz-Alaoui M. A. , Alsaedi Ahmed
Published: October 2017

This paper deals with fractional order Chua system with cubic nonlinearity (cubic Chua system), which is a modification of Chua system. The aim is, first, to study the chaotic behavior in fractional order cubic Chua system. We found that chaos indeed exists in the fractional version of this system. The necessary condition for exhibiting chaotic attractors similar to its integer order counterpart is presented. This condition is used to distinguish for which parameters and orders the system generates double scroll chaotic attractors. The synchronization problem between two coupled chaotic fractional order cubic Chua systems is then addressed. An adaptive feedback control scheme for the synchronization with suitable feedback nonlinear controller applied to the response system is presented. Numerical simulations are performed to verify the theoretical analysis.
Nonlinear interaction between electromagnetic and gravitational waves: An appraisal
Authors: Barreto W. , de Oliveira H. P. , Rodrigues E. L.
Published: October 2017

Wave propagation of field disturbances is ubiquitous. The electromagnetic and gravitational are cousin theories in which the corresponding waves play a relevant role to understand several related physical aspects. It has been established that small electromagnetic waves can generate gravitational waves and vice versa when scattered by a charged black hole. In the realm of cylindrical spacetimes, we present here a simple nonlinear effect of the conversion of electromagnetic to gravitational waves reflected by the amount of mass extracted from them.
SMALL-WORLD AND SCALE-FREE PROPERTIES OF FRACTAL NETWORKS MODELED ON n-DIMENSIONAL SIERPINSKI PYRAMID
Authors: ZENG CHENG , ZHOU MENG
Published: October 2017

In this paper, we construct evolving networks based on the construction of the [Formula: see text]-dimensional Sierpinski pyramid by the self-similar structure. We show that such networks have scale-free and small-world effects.
Hurst Estimation of Scale Invariant Processes with Stationary Increments and Piecewise Linear Drift
Authors: Modarresi N. , Rezakhah S.
Published: October 2017

The characteristic feature of the discrete scale invariant (DSI) processes is the invariance of their finite dimensional distributions by dilation for certain scaling factor. DSI process with piecewise linear drift and stationary increments inside prescribed scale intervals is introduced and studied. To identify the structure of the process, first, we determine the scale intervals, their linear drifts and eliminate them. Then, a new method for the estimation of the Hurst parameter of such DSI processes is presented and applied to some period of the Dow Jones indices. This method is based on fixed number equally spaced samples inside successive scale intervals. We also present some efficient method for estimating Hurst parameter of self-similar processes with stationary increments. We compare the performance of this method with the celebrated FA, DFA and DMA on the simulated data of fractional Brownian motion (fBm).
INTERSEGMENTAL COORDINATION IN LOWER EXTREMITIES AND MULTI-SEGMENTAL SPINE DURING DIFFERENT ACTIVITIES OF DAILY LIVING
Authors: GUO DAIQI , KUAI SHENGZHENG , ZHOU WENYU , GUAN XINYU , LIAO ZHENHUA , LIU WEIQIANG , WANG DAPING
Published: October 2017

Background: Human movement consists of numerous degrees of freedom (DOF). How the nervous system (NS) computes the appropriate command to coordinate these DOFs to finish specific tasks is still hotly debated. One common way to simplify the redundant DOFs is to coordinate multiple DOFs by combining them into units or synergies. The present study aimed to investigate the kinematic complexity of five activities of daily living (ADLs) and to detect the amount of kinematic synergy during every ADL and the relationship of the motion pattern between these ADLs. Method: Twenty-six able-bodied male individuals performed level walking, stair climbing, trunk bending, ipsilateral pick-up and contralateral pick-up in sequence. The segmental excursion of the thorax, upper lumbar, lower lumbar, pelvis, thigh and shank was calculated. Principal component analysis (PCA) was applied to determine the motion pattern of every ADL. Result: In the sagittal plane, trunk bending, ipsilateral pick-up and contralateral pick-up could be simplified by using one principal component (PC) with more than 95% variance accounted for (VAF). In addition, the motion pattern of every PC was similar among the three ADLs. Moreover, the angles between the vectors representing the first PC of the three ADLs were all less than 10[Formula: see text]. Level walking and stair climbing needed at least two PCs to reach 95% VAF. In addition, the motion pattern was different between the two ADLs. Moreover, the angle between the first PC of the two ADLs was around 90[Formula: see text]. In the coronal plane, the five ADLs except contralateral pick-up arrived at 90% VAF with two PCs. The motion pattern and the angle between the first PC both demonstrated larger differences among the five ADLs. Conclusion: Two PCs were essential to represent level walking and stair climbing, indicating a complex control strategy used by the NS. Trunk bending, ipsilateral pick-up and contralateral pick-up could be described with one PC in the sagittal plane, showing a strong coupling and simple motion pattern. In addition, the motion pattern varied considerably among these ADLs. The outcomes of this study can help clinicians to select suitable ADLs for the patients with various joint or disc diseases and to conduct corresponding functional test and rehabilitation.
Analysis of the First Modal Shape Using Two Case Studies
Authors: de Macêdo Wahrhaftig Alexandre
Published: October 2017

Eigenvector analysis can be performed to determine the shapes of the undamped free vibration modes of a system. Eigenvector analysis involves solving the generalized eigenvalue problem, which considers the stiffness and mass matrix of a structure. For a geometric nonlinear study, both parts of the total stiffness matrix are required. As modal analysis depends on the stiffness, the effect of its reduction on the modal shape of vibration of the structure must be determined. Case studies were evaluated using the finite element method, considering and neglecting the geometric portion of the stiffness matrix. Mathematic functions were applied for comparison.
MergeTree
Authors: Viitanen Timo , Koskela Matias , Jääskeläinen Pekka , Kultala Heikki , Takala Jarmo
Published: October 2017

Ray tracing is a computationally intensive rendering technique traditionally used in offline high-quality rendering. Powerful hardware accelerators have been recently developed that put real-time ray tracing even in the reach of mobile devices. However, rendering animated scenes remains difficult, as updating the acceleration trees for each frame is a memory-intensive process. This article proposes MergeTree, the first hardware architecture for
Hierarchical Linear Bounding Volume Hierarchy
(HLBVH) construction, designed to minimize memory traffic. For evaluation, the hardware constructor is synthesized on a 28nm process technology. Compared to a state-of-the-art binned surface area heuristic sweep (SAH) builder, the present work speeds up construction by a factor of 5, reduces build energy by a factor of 3.2, and memory traffic by a factor of 3. A software HLBVH builder on a graphics processing unit (GPU) requires 3.3 times more memory traffic. To take tree quality into account, a rendering accelerator is modeled alongside the builder. Given the use of a toplevel build to improve tree quality, the proposed builder reduces system energy per frame by an average 41% with primary rays and 13% with diffuse rays. In large ( > 500K triangles) scenes, the difference is more pronounced, 62% and 35%, respectively.
Towards ubiquitous indoor spatial awareness on a worldwide scale
Authors: Elhamshary Moustafa , Youssef Moustafa
Published: October 2017

While a remarkable effort has been put in developing indoor spatial awareness systems, they are still isolated efforts that are tailored to specific deployments. A truly ubiquitous indoor spatial awareness system is envisioned to be deployed on a large scale worldwide, with minimum overhead, and to work with the heterogeneous IoT devices. Such a system will enable a wide set of new applications including worldwide seamless direction finding between indoor locations, anywhere anytime health monitoring, enhanced first responders' safety, and providing richer context for indoor mobile computing applications.

In this paper, we describe our vision and work towards achieving ubiquitous indoor spatial awareness systems as well as the open challenges that need to be addressed to materialize this dream.
LRU Cache under Stationary Requests
Authors: Jiang Bo , Nain Philippe , Towsley Don
Published: October 2017

In this paper we extend an approximation first proposed by Fagin [4] for the LRU cache under the independence reference model to systems where requests for different contents form independent stationary and ergodic processes. We show that this approximation becomes exact as the number of contents goes to infinity while maintaining the fraction of the contents that can populate the cache to be constant. Last, we provide results on the rate of convergence.
Distributed Optimization via Local Computation Algorithms
Authors: London Palma , Chen Niangjun , Vardi Shai , Wierman Adam
Published: October 2017

We propose a new approach for distributed optimization based on an emerging area of theoretical computer science -- local computation algorithms. The approach is fundamentally different from existing methodologies and provides a number of benefits, such as robustness to link failure and adaptivity in dynamic settings. Specifically, we develop an algorithm, LOCO, that given a convex optimization problem P with n variables and a "sparse" linear constraint matrix with m constraints, provably finds a solution as good as that of the best online algorithm for P using only O(log(n+m)) messages with high probability. The approach is not iterative and communication is restricted to a localized neighborhood. In addition to analytic results, we show numerically that the performance improvements over classical approaches for distributed optimization are significant, e.g., it uses orders of magnitude less communication than ADMM.
Battery Swapping Assignment for Electric Vehicles
Authors: You Pengcheng , Sun Youxian , Pang John , Low Steven , Chen Minghua
Published: October 2017

This paper formulates a multi-period optimal station assignment problem for electric vehicle (EV) battery swapping that takes into account both temporal and spatial couplings. The goal is to reduce the total EV cost and station congestion due to temporary shortage in supply of available batteries. We show that the problem is reducible to the minimum weight perfect bipartite matching problem. This leads to an efficient solution based on the Hungarian algorithm. Numerical results suggest that the proposed solution provides a significant improvement over a greedy heuristic that assigns EVs to nearest stations.
Load-side Frequency Regulation with Limited Control Coverage
Authors: Pang John Z.F. , Guo Linqi , Low Steven H.
Published: October 2017

Increasing renewable energy increases uncertainty in energy systems. As a consequence, generator-side control for frequency regulation, impacted by the slow reaction of generators to meet urgent needs, may no longer suffice. With increasing integration of smart appliances which are able to sense, communicate and control, load-side control can help alleviate the aforementioned problem as it reacts fast and helps to localize disturbances. However, almost all existing methods for optimal load-side control require full information control coverage in the system. Framing the problem as an optimization problem and applying saddle-point dynamics, we obtain a control law that rebalances power and asymptotically stabilizes frequency after a disturbance. We generalize previous work to design a controller which only requires partial control coverage over all nodes, yet still achieves secondary frequency control. We verify these results via simulation.
A Dynamic Game Analysis and Design of Infrastructure Network Protection and Recovery
Authors: Chen Juntao , Touati Corinne , Zhu Quanyan
Published: October 2017

Infrastructure networks are vulnerable to both cyber and physical attacks. Building a secure and resilient networked system is essential for providing reliable and dependable services. To this end, we establish a two-player three-stage game framework to capture the dynamics in the infrastructure protection and recovery phases. Specifically, the goal of the infrastructure network designer is to keep the network connected before and after the attack, while the adversary aims to disconnect the network by compromising a set of links. With costs for creating and removing links, the two players aim to maximize their utilities while minimizing the costs. In this paper, we use the concept of subgame perfect equilibrium (SPE) to characterize the optimal strategies of the network defender and attacker. We derive the SPE explicitly in terms of system parameters. Finally, we use a case study of UAV-enabled communication networks for disaster recovery to corroborate the obtained analytical results.
NF-κB-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells
Authors: Su Jiahui , Liu Xiyang , Xu Chuanming , Lu Xiaohan , Wang Fei , Fang Hui , Lu Aihua , Qiu Qixiang , Li Chunling , Yang Tianxin
Published: October 2017

(Pro)renin receptor (PRR), a component of the renin-angiotensin system, has emerged as a new regulator of collecting duct function. The present study was designed to investigate the role of PRR in high salt-induced apoptosis in cultured mouse inner medullary collecting duct cells, mIMCD-K2 cells. Exposure to high NaCl at 550 mosM/kgH2O increased PRR protein abundance, as did exposure to mannitol, sodium gluconate, or choline chloride. This was accompanied by upregulation of the abundance of phosphorylated NF-κB p65 protein. NF-κB inhibition with QNZ, caffeic acid phenethyl ester, or small interfering RNA (siRNA)-mediated silencing of NF-κB p65 attenuated high-NaCl-induced PRR upregulation. Exposure to high salt for 24 h induced apoptosis, as assessed by immunoblotting and immunocytochemistry analysis of cleaved caspase-3 and flow cytometry analysis of the number of apoptotic cells. High-NaCl-induced apoptosis was attenuated by a PRR decoy inhibitor, PRO20, or siRNA-mediated silencing of NF-κB p65. These results show that induction of PRR expression by exposure to high NaCl occurs through activation of NF-κB, thus contributing to cell apoptosis.
Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer
Authors: Bader Jackie E. , Enos Reilly T. , Velázquez Kandy T. , Carson Meredith S. , Nagarkatti Mitzi , Nagarkatti Prakash S. , Chatzistamou Ioulia , Davis J. Mark , Carson James A. , Robinson Cory M. , Murphy E. Angela
Published: October 2017

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 μl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFβ, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC.

NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.
Neutrophil elastase increases airway ceramide levels via upregulation of serine palmitoyltransferase
Authors: Karandashova Sophia , Kummarapurugu Apparao B. , Zheng Shuo , Chalfant Charles E. , Voynow Judith A.
Published: October 2017

Altered sphingolipid metabolism is associated with increased inflammation; however, the impact of inflammatory mediators, including neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. Using a well-characterized mouse model of NE oropharyngeal aspiration, we investigated a potential link between NE-induced airway inflammation and increased synthesis of various classes of sphingolipids, including ceramide species. Sphingolipids in bronchoalveolar lavage fluids (BAL) were identified and quantified using reverse-phase high-performance liquid chromatography/electrospray ionization tandem mass spectrometry analysis. BAL total and differential cell counts, CXCL1/keratinocyte chemoattractant (KC) protein levels, and high-mobility group box 1 (HMGB1) protein levels were determined. NE exposure increased BAL long-chain ceramides, total cell and neutrophil counts, and upregulated KC and HMGB1. The mRNA and protein levels of serine palmitoyltransferase (SPT) long-chain subunits 1 and 2, the multimeric enzyme responsible for the first, rate-limiting step of de novo ceramide generation, were determined by qRT-PCR and Western analyses, respectively. NE increased lung SPT long-chain subunit 2 (SPTLC2) protein levels but not SPTLC1 and had no effect on mRNA for either subunit. To assess whether de novo ceramide synthesis was required for NE-induced inflammation, myriocin, a SPT inhibitor, or a vehicle control was administered intraperitoneally 2 h before NE administration. Myriocin decreased BAL d18:1/22:0 and d18:1/24:1 ceramide, KC, and HMGB1 induced by NE exposure. These results support a feed-forward cycle of NE-generated ceramide and ceramide-driven cytokine signaling that may be a potential target for intervention in lung disease typified by chronic neutrophilic inflammation.
Attenuation of accelerated renal cystogenesis in Pkd1 mice by renin-angiotensin system blockade
Authors: Fitzgibbon Wayne R. , Dang Yujing , Bunni Marlene A. , Baicu Catalin F. , Zile Michael R. , Mullick Adam E. , Saigusa Takamitsu
Published: October 2017

The intrarenal renin angiotensin system (RAS) is activated in polycystic kidney disease. We have recently shown in the Pkd1 mouse that Gen 2 antisense oligonucleotide (ASO), which suppresses angiotensinogen (Agt) synthesis, is efficacious in slowing kidney cyst formation compared with lisinopril. The aim of this current study was to determine 1) if unilateral nephrectomy accelerates cystogenesis in Pkd1 mice (as previously shown in cilia knockout mice) and 2) whether Agt ASO can slow the progression in this accelerated cystic mouse model. Adult Pkd1 conditional floxed allele mice expressing cre were administered tamoxifen, resulting in global knockout of Pkd1. Three weeks after tamoxifen injection, mice underwent left unilateral nephrectomy. Mice were then treated with Agt ASO (75 mg/kg per week) or aliskiren (20 mg/kg per day)+Agt ASO or control for 8 wk. Unilateral nephrectomy accelerated kidney cyst formation compared with nonnephrectomized mice. Both Agt ASO and Aliskiren+Agt ASO treatments significantly reduced plasma and urinary Agt levels. Blood pressure was lowest in Aliskiren+Agt ASO mice among all treatment groups, and the control group had the highest blood pressure. All mice developed significant kidney cysts at 8 wk after nephrectomy, but Agt ASO and Aliskiren+Agt ASO groups had fewer kidney cysts than controls. Renal pAkt, pS6 levels, and apoptosis were significantly suppressed in those receiving Agt ASO compared with controls. These results indicate that suppressing Agt using an ASO slowed the progression of accelerated cystic kidney disease induced by unilateral nephrectomy in Pkd1 mice by suppressing intrarenal RAS, mammalian target of rapamycin pathway, and cell proliferation.
Aging is associated with increased propensity for central apnea during NREM sleep
Authors: Chowdhuri Susmita , Pranathiageswaran Sukanya , Loomis-King Hillary , Salloum Anan , Badr M. Safwan
Published: October 2017

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (−2.6 ± 0.4 vs. −4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min−1·mmHg−1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep.

NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.
Multiple coupled resonances in the human vascular tree: refining the Westerhof model of the arterial system
Authors: Schumacher Gerhard , Kaden Jens J. , Trinkmann Frederik
Published: October 2017

The human arterial vascular tree can be described by multicompartment models using electrical components. First introduced in the 1960s by Noordergraaf and Westerhof, these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. Whereas the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta and brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-to-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values.

NEW & NOTEWORTHY We were able to find an individualized transfer function giving realistic pulse waveforms and blood pressures using a multicompartment model of the arterial system. Based on the hardware-built Westerhof approach, several simplifications initially introduced in the 1960s could be reversed using software simulation. Overall model quality was improved considerably, and multiple coupled resonances were identified as potential explanation for the formation of the aortic-to-radial transfer function, giving new impetus to the discussion of arterial pressure wave reflection.
A dual-axis rotation rule for updating the head direction cell reference frame during movement in three dimensions
Authors: Page Hector J. I. , Wilson Jonathan J. , Jeffery Kate J.
Published: October 2017

In the mammalian brain, allocentric (Earth-referenced) head direction, called azimuth, is encoded by head direction (HD) cells, which fire according to the facing direction of the animal’s head. On a horizontal surface, rotations of the head around the dorsoventral (D-V) axis, called yaw, correspond to changes in azimuth and elicit appropriate updating of the HD “compass” signal to enable large-scale navigation. However, if the animal moves through three-dimensional (3D) space then there is no longer a simple relationship between yaw rotations and azimuth changes, and so processing of 3D rotations is needed. Construction of a global 3D compass would require complex integration of 3D rotations, and also a large neuronal population, most neurons of which would be silent most of the time since animals rarely sample all available 3D orientations. We propose that, instead, the HD system treats the 3D space as a set of interrelated 2D surfaces. It could do this by updating activity according to both yaw rotations around the D-V axis and rotations of the D-V axis around the gravity-defined vertical axis. We present preliminary data to suggest that this rule operates when rats move between walls of opposing orientations. This dual-axis rule, which we show is straightforward to implement using the classic one-dimensional “attractor” architecture, allows consistent representation of azimuth even in volumetric space and thus may be a general feature of mammalian directional computations even for animals that swim or fly.

NEW & NOTEWORTHY Maintaining a sense of direction is complicated when moving in three-dimensional (3D) space. Head direction cells, which update the direction sense based on head rotations, may accommodate 3D movement by processing both rotations of the head around the axis of the animal’s body and rotations of the head/body around gravity. With modeling we show that this dual-axis rule works in principle, and we present preliminary data to support its operation in rats.
Lymphatic Endothelial Cell Plasticity in Development and Disease
Authors: Ma Wanshu , Oliver Guillermo
Published: October 2017

The lymphatic vasculature is crucial for maintaining tissue-fluid homeostasis, providing immune surveillance and mediating lipid absorption. The lymphatic vasculature is tightly associated with the blood vasculature, although it exhibits distinct morphological and functional features. Endothelial cells (ECs) lineage fate specification is determined during embryonic development; however, accumulating evidence suggests that differentiated ECs exhibit remarkable heterogeneity and plasticity. In this review, we provide an overview of the molecular mechanisms promoting lymphatic cell fate specification in the mammalian embryo. We also summarize available data suggesting that lymphatic EC fate is reprogrammable in normal and pathological settings. We further discuss the possible advantages of cell fate manipulation to treat certain disorders associated with lymphatic dysfunction.
Effects of Novel Nitric Oxide‐Releasing Molecules against Oxidative Stress on Retinal Pigmented Epithelial Cells
Authors: Pittalà Valeria , Fidilio Annamaria , Lazzara Francesca , Platania Chiara Bianca Maria , Salerno Loredana , Foresti Roberta , Drago Filippo , Bucolo Claudio
Published: October 2017

Oxidative stress is a hallmark of retinal degenerations such as age‐related macular degeneration and diabetic retinopathy. Enhancement of heme oxygenase‐1 (HO‐1) activity in the retina would exert beneficial effects by protecting cells from oxidative stress, therefore promoting cell survival. Because a crosstalk exists between nitric oxide (NO) and HO‐1 in promotion of cell survival under oxidative stress, we designed novel NO‐releasing molecules also capable to induce HO‐1. Starting from curcumin and caffeic acid phenethyl ester (CAPE), two known HO‐1 inducers, the molecules were chemically modified by acylation with 4‐bromo‐butanoyl chloride and 2‐chloro‐propanoyl chloride, respectively, and then treated in the dark with AgNO3 to obtain the nitrate derivatives VP10/12 and VP10/39. Human retinal pigment epithelial cells (ARPE‐19) subjected to H2O2‐mediated oxidative stress were treated with the described NO‐releasing compounds. VP10/39 showed significant (p < 0.05) antioxidant and protecting activity against oxidative damage, in comparison to VP10/12, which in turn showed at 100 μM concentration a slight but significant cell toxicity. Only VP10/39 significantly (p < 0.05) induced HO‐1 in ARPE‐19, most likely through covalent bond formation at Cys151 of the Keap1‐BTB domain, as revealed from molecular docking analysis. In conclusion, the present data indicate VP10/39 as a promising candidate to protect ARPE‐19 cells against oxidative stress.
Ethnopharmacological Uses, Phytochemistry, and Pharmacological Properties of Croton macrostachyus Hochst. Ex Delile: A Comprehensive Review
Authors: Maroyi Alfred
Published: October 2017

Croton macrostachyus is widely used as herbal medicine by the indigenous people of tropical Africa. The potential of C. macrostachyus as herbal medicine, the phytochemistry, and pharmacological properties of its parts used as herbal medicines are reviewed. The extensive literature survey revealed that C. macrostachyus is traditionally used to treat or manage at least 81 human and animal diseases and ailments. The species is used as herbal medicine for diseases and ailments such as abdominal pains, cancer, gastrointestinal disorders, malaria, pneumonia, sexually transmitted infections, skin infections, typhoid, and wounds and as ethnoveterinary medicine. Multiple classes of phytochemicals such as alkaloids, amino acids, anthraquinones, carbohydrates, cardiac glycosides, coumarins, essential oil, fatty acids, flavonoids, phenolic compounds, phlobatannins, polyphenols, phytosteroides, saponins, sterols, tannins, terpenoids, unsaturated sterol, vitamin C, and withanoides have been isolated from the species. Pharmacological studies on C. macrostachyus indicate that it has a wide range of pharmacological activities such as anthelmintic, antibacterial, antimycobacterial, antidiarrhoeal, antifungal, anticonvulsant and sedative, antidiabetic, anti‐inflammatory, antileishmanial, antioxidant, antiplasmodial, and larvicidal effects. Croton macrostachyus has potential as a possible source of a wide range of pharmaceutical products for the treatment of a wide range of both human and animal diseases and ailments.
Protective Effects of Ophiocordyceps lanpingensis on Glycerol-Induced Acute Renal Failure in Mice
Authors: Zhang Yanyan , Du Yaxi , Yu Hong , Zhou Yongchun , Ge Feng
Published: October 2017

Objective. Oxidative stress and immune response are associated with acute renal failure (ARF). Ophiocordyceps lanpingensis (OL) might be an antioxidant and immunopotentiator. In this study, we explored the protective effects of OL on glycerol-induced ARF. Methods. Male mice were randomly divided into four groups, specifically, glycerol-induced ARF model group, low-dose OL-treated group (1.0 g/kg/d), high-dose OL-treated group (2.0 g/kg/d), and control group. Renal conditions were evaluated using kidney index, serum creatinine (Cr), blood urea nitrogen (BUN), and histological analysis. Rhabdomyolysis was monitored using creatine kinase (CK) level. Oxidative stress was determined using kidney tissue glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Immune status was evaluated using immune organ indices and immunoglobulin G (IgG) level. Results. OL could relieve renal pathological injury and decrease the abnormal levels of kidney index, serum Cr, CK, BUN, and MDA, as well as increase the immune organ indices and the levels of IgG, GSH, and SOD. Treatment with a high dose of OL had more positive therapeutic effects on ARF than using a low dose of OL. Conclusion. OL could ameliorate renal dysfunction in glycerol-induced ARF in mice by inhibiting oxidative stress and enhancing immune response.
Gelatin Template Synthesis of Aluminum Oxide and/or Silicon Oxide Containing Micro/Mesopores Using the Proteic Sol-Gel Method
Authors: de Oliveira Amanda Sayure Kasuya , Paulista Adriana Perpetua Figueiredo , Alencar Ana Ellen Valentim de , Braga Tiago Pinheiro
Published: October 2017

Aluminum oxide and/or silicon oxide-based supports were synthesized by proteic sol-gel method. The characterization was performed through the analysis of TG, XRD, FTIR, SEM, and N2 physisorption. The XRD diffractograms showed an amorphous material profile. TG results indicate the total liberation of the organic and inorganic material in the calcination temperature used, occurring in different mass loss range. This piece of information was reaffirmed by the FTIR spectra, which presented characteristic bands of gelatin structure before calcinations which disappear in the spectrum of the solid after calcinations, indicating the loss of organic matter from gelatin after heat treatment. The spectra exhibited M-O stretching vibration at low wavenumbers after calcinations related to metal oxides. The acquired images by SEM suggest the obtaining of a highly porous material with very different characteristics depending on the composition of the support. The N2 isotherms indicate the presence of a micro/mesoporous oxide with interesting textural properties, particularly for the supports containing aluminum and silicon oxide. The ethanol dehydration results showed greater selectivity to diethyl ether compared to ethylene. From the reaction data, the following order of acid strength was obtained: 2Si-Al > Si-2Al > Si-Al > Al, which is related to the Si-Al ratio.