bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of the interfacial and electrical properties of atomic-layer-deposited Hf0.5Al0.5O/Si gate stacks using Al2O3 passivation layer with various thickness
Authors: Gao Juan , He Gang , Wang Die , Liang Shuang
Published: December 2018

The interfacial properties and electrical characteristics of atomic layer deposited Hf0.5Al0.5O/Si with different Al2O3 barrier layer thicknesses have been investigated. X-ray photoelectron spectroscopy measurements have shown that a 1-nm-thick Al2O3 buffer layer can effectively suppress the silicate formation and improve interfacial properties. Accordingly, the sample with a 1-nm-thick Al2O3 layer exhibits improved electrical properties, including the lowest density of oxide charge of 3.16 × 1010 cm−2, an interface charge density of 0.82 × 1011 cm−2 eV−1, and an oxide trapped charge density of 0.79 × 1011 cm−2. The reduced leakage current at an applied substrate voltage of 1 V is 3.28 × 10−6 A/cm2. Furthermore, the carrier transportation mechanism of Al/Hf0.5Al0.5O/Al2O3/Si/Al MOS device has been researched systematically. Through the analysis, it could be found that for all samples, thermionic emission and Poole–Frenkel emission are dominant mechanisms of carrier transport under a low electric field region, as well as Fowler–Nordheim tunneling is the main carrier transport mechanism at a high electric field region.
Controlling surface chemical states for selective patterning of CoFeB
Authors: Altieri Nicholas D. , Chen Jack Kun-Chieh , Chang Jane P.
Published: December 2018

Controlling the surface chemical states of CoFeB thin films was employed to create a chemical contrast between the modified surface and the underlying intermetallic thin film, thereby enabling a selective etching process. The oxidation states of Co and Fe were tailored by reacting the CoFeB surface to chlorine or oxygen plasmas. This modified surface resulted in an enhanced etch rate as well as selectivity in an etchant such as H2 plasma or an organic vapor such as formic acid. Hydrogen plasma was found to be effective in removing metal chlorides and restoring the magnetic properties of CoFeB. For a halogen-free process, the formic acid vapor was found to be most effective in removing oxidized CoFeB. To realize atomic layer etch, a cyclical process was developed with alternating cycles of oxygen plasma with a −100 V substrate bias and formic acid vapor, resulting in a controlled etch rate at 1.8 nm/cycle and extremely high selectivity to the underlying intermetallic CoFeB.
A silencer incorporated within the thickness of the edge of the door for increasing sound transmission loss
Authors: Sakamoto Shuichi , Koseki Shota , Chinda Mizuki , Abe Shota
Published: December 2018

The present study focuses on a silencer built within the thick portion of a door edge and reports on the results of evaluating silencers by determining sound transmission loss via theoretical analysis and experiments on three types of silencers. The theoretical analysis involved determining the calculated values of sound transmission loss obtained using the transfer matrix method. The change in cross-sectional shape was analyzed by elemental division of the transfer matrix. Using the above, simulations were performed with respect to the optimum shape of the silencer. These theoretical analyses were then compared with the measurement results. Furthermore, the study includes the results of an experiment that attempted to restrain the dip in sound transmission loss by adding a non-woven fabric to the opening of the silencer. In a side branch silencer with an increasing shape wherein the longitudinal cross-section is a linear or an exponential function, the peak of the transmission loss was shifted to the lower frequency side when compared with that in the case of a rectangular side branch silencer. Furthermore, in comparisons between the two, the sound attenuation peak frequency was lower in the case of the exponential shape. The resonance of the side branch was suppressed by adding a non-woven fabric to the opening of the side branch silencer. As a result, the peak and dip of sound attenuation were alleviated, and the sound attenuation characteristics could be adjusted.
The microRNA miR-7a-5p ameliorates ischemic brain damage by repressing α-synuclein
Authors: Kim TaeHee , Mehta Suresh L. , Morris-Blanco Kahlilia C. , Chokkalla Anil K. , Chelluboina Bharath , Lopez Mary , Sullivan Ruth , Kim Hung Tae , Cook Thomas D. , Kim Joo Yong , Kim HwuiWon , Kim Chanul , Vemuganti Raghu
Published: December 2018

Rapid intervention with an miR-7 mimic may protect the brain in patients who have had a stroke.
A Single Adaptive Mutation in Sodium Taurocholate Cotransporting Polypeptide Induced by Hepadnaviruses Determines Virus Species Specificity
Authors: Takeuchi Junko S. , Fukano Kento , Iwamoto Masashi , Tsukuda Senko , Suzuki Ryosuke , Aizaki Hideki , Muramatsu Masamichi , Wakita Takaji , Sureau Camille , Watashi Koichi
Published: December 2018

HBV and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary arms race between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidence supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species specificity.
Epstein-Barr Virus Induces Expression of the LPAM-1 Integrin in B CellsIn VitroandIn Vivo
Authors: Delecluse Susanne , Tsai Ming-Han , Shumilov Anatoliy , Bencun Maja , Arrow Sebastian , Beshirova Aisha , Cottignies-Calamarte Andréa , Lasitschka Felix , Bulut Olcay Cem , Münz Christian , Zeier Martin , Behrends Uta , Delecluse Henri-Jacques
Published: December 2018

EBV causes tumors in multiple organs, particularly in the oro- and nasopharyngeal area but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.
HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses
Authors: Amelio Patrizia , Portevin Damien , Hella Jerry , Reither Klaus , Kamwela Lujeko , Lweno Omar , Tumbo Anneth , Geoffrey Linda , Ohmiti Khalid , Ding Song , Pantaleo Giuseppe , Daubenberger Claudia , Perreau Matthieu
Published: December 2018

Mycobacterium tuberculosis
and human immunodeficiency virus (HIV) infections are coendemic in several regions of the world, and
M. tuberculosis
/HIV-coinfected individuals are more susceptible to progression to tuberculosis disease. We therefore hypothesized that HIV infection would potentially impair
M. tuberculosis
-specific protective immunity in individuals suffering from latent tuberculosis infection (LTBI) or active pulmonary tuberculosis (PTB). In this study, we demonstrated that
M. tuberculosis
/HIV-coinfected individuals have fewer circulating
M. tuberculosis
-specific CD4 T cells and that those that remained were functionally impaired in both LTBI and PTB settings. In addition, we showed that HIV infection significantly interferes with
M. tuberculosis
-induced systemic proinflammatory cytokine/chemokine responses. Taken together, these data suggest that HIV infection impairs functionally favorable
M. tuberculosis
-specific immunity.
Disseminated cryptococcal infection initially presenting as cryptococcal cellulitis in an HIV-negative patient on long-term steroids
Authors: Kerr Colm , Stack William A , Sadlier Corinna , Jackson Arthur
Published: December 2018

Cryptococcosis is an invasive fungal infection caused by encapsulated yeasts of theCryptococcusspecies. Inoculation usually occurs by inhalation through the respiratory tract, where it can then spread haematogenously to various sites, such as the central nervous system or the skin, in susceptible patients. We present the case of a 68-year-old male patient on long-term steroids who presented with a right upper limb cellulitis not responding to antibiotics. This was subsequently diagnosed as cryptococcal cellulitis on an urgent skin biopsy. Wound swabs and blood cultures, which were initially negative, were repeated and confirmed the presence of disseminated cryptococcal disease. The patient’s neighbours kept racing pigeons and this was hypothesised as a potential source of infection.
Propensity-matched analysis of minimally invasive approach versus sternotomy for mitral valve surgery
Authors: Grant Stuart W , Hickey Graeme L , Modi Paul , Hunter Steven , Akowuah Enoch , Zacharias Joseph
Published: December 2018

Objective

The objective of this multicentre study was to compare short-term and midterm outcomes between sternotomy and minimally invasive approaches for mitral valve surgery.

Methods

Data for all mitral valve procedures with or without concomitant tricuspid atrial fibrillation surgery were analysed from three UK hospitals between January 2008 and December 2016. To account for selection bias between minimally invasive approach and sternotomy, one-to-one propensity score calliper matching without replacement was performed. The main outcome measure was midterm reintervention free survival that was summarised by the Kaplan-Meier estimator and compared between treatment arms using the stratified log-rank test.

Results

A total of 2404 procedures (1757 sternotomy and 647 minimally invasive) were performed during the study period. Propensity score matching resulted in 639 matched pairs with improved balance postmatching in all 31 covariates (absolute standardised mean differences <10%). Despite longer procedural times patients who underwent minimally invasive surgery had a lower need for transfusion (20.5%vs14.4%, p=0.005) and reduced median postoperative length of stay (7 vs 6 days, p<0.001). There were no statistically significant differences in the rates of in-hospital mortality or postoperative stroke. Reintervention-free survival at 8 years was estimated as 86.1% in the minimally invasive group and 84.1% in the sternotomy group (p=0.40).

Conclusions

Minimally invasive surgery is associated with excellent short-term outcomes and comparable midterm outcomes for patients undergoing mitral valve surgery. A minimally invasive approach should be considered for all patients who require mitral valve intervention and should be the standard against which transcatheter mitral techniques are compared.
Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis
Authors: Moore John J , Massey Jennifer C , Ford Carole D , Khoo Melissa L , Zaunders John J , Hendrawan Kevin , Barnett Yael , Barnett Michael H , Kyle Kain A , Zivadinov Robert , Ma Kris C , Milliken Sam T , Sutton Ian J , Ma David D F
Published: December 2018

Background

Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.

Methods

This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.

Outcomes

The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.

Results

Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12–66). The median Expanded Disability Status Scores (EDSS) was 6 (2–7) and patients had failed a median of 4 (2–7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+T regulatory cells, immunosuppressive CD56hinatural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.

Conclusions

The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.

Trial registration number

ACTRN12613000339752.
Women’s occupational exposure to polycyclic aromatic hydrocarbons and risk of breast cancer
Authors: Lee Derrick G , Burstyn Igor , Lai Agnes S , Grundy Anne , Friesen Melissa C , Aronson Kristan J , Spinelli John J
Published: December 2018

Objective

To estimate the association between occupational polycyclic aromatic hydrocarbon (PAH) exposure and female breast cancer.

Methods

Lifetime work histories for 1130 cases and 1169 controls from British Columbia and Ontario (Canada) were assessed for PAH exposure using a job-exposure matrix based on compliance measurements obtained during US Occupational Safety and Health Administration workplace safety inspections.

Results

Exposure to any level of PAHs was associated with an increased risk of breast cancer (OR=1.32, 95% CI: 1.10 to 1.59), as was duration at high PAH exposure (for >7.4 years: OR=1.45, 95% CI: 1.10 to 1.91; ptrend=0.01), compared with women who were never exposed. Increased risk of breast cancer was most strongly associated with prolonged duration at high occupational PAH exposure among women with a family history of breast cancer (for >7.4 years: OR=2.79, 95% CI: 1.25 to 6.24; ptrend<0.01).

Conclusions

Our study suggests that prolonged occupational exposure to PAH may increase breast cancer risk, especially among women with a family history of breast cancer.
An improved SFLA for flexible job shop scheduling problem considering energy consumption
Authors: Zhang Xiaoxing , Ji Zhicheng , Wang Yan
Published: December 2018

In this paper, a multi-objective flexible job shop scheduling problem (MOFJSP) was studied systematically. A novel energy-saving scheduling model was established based on considering makespan and total energy consumption simultaneously. Different from previous studies, four types of energy consumption were considered in this model, including processing energy, idle energy, transport energy, and turn-on/off energy. In addition, a turn-off strategy is adopted for energy-saving. A modified shuffled frog-leaping algorithm (SFLA) was applied to solve this model. Moreover, operators of multi-point crossover and neighborhood search were both employed to obtain optimal solutions. Experiments were conducted to verify the performance of the SFLA compared with a non-dominated sorting genetic algorithm with blood variation (BVNSGA-II). The results show that this algorithm and strategy are very effective.
Dynamical Analysis of a Phytoplankton–Zooplankton System with Harvesting Term and Holling III Functional Response
Authors: Jiang Zhichao , Zhang Wenzhi , Zhang Jing , Zhang Tongqian
Published: December 2018

A toxin-producing phytoplankton and zooplankton system is investigated. Considering that zooplankton can be harvested for food in some bodies of water, the harvesting term is introduced to zooplankton population. Firstly, from the ordinary differential equation (ODE) system, we obtain the global asymptotic stability of equilibrium and optimal capture problem. Secondly, based on the ODE system, the diffusion term is introduced and the global asymptotic stability of the steady state solution is obtained. As a result, the diffusion cannot affect the global asymptotic stability of equilibrium, and Turing instability cannot occur. Once again, a delayed differential equation (DDE) system is put forward. The global asymptotic stability of boundary equilibrium and the existence of local Hopf bifurcation at positive equilibrium are discussed. Furthermore, it is proved that there exists at least one positive periodic solution as delay varies in some region by using the global Hopf result of Wu for functional differential equations. Lastly, some numerical simulations are carried out for supporting the theoretical analyses and the positive impacts of harvesting effort, and the release rate of toxin is given. The unstable interval of the positive equilibrium becomes smaller and smaller with the increase of harvesting effort or the release rate of toxin.
Noncommutative inspired wormholes admitting conformal motion involving minimal coupling
Authors: Zubair M. , Waheed Saira , Mustafa G. , Ur Rehman Hamood
Published: December 2018

In this paper, we explore the existence of wormhole solutions exhibiting spherical symmetry in a modified gravity namely [Formula: see text] theory by involving some aspects of noncommutative geometry. For this purpose, we consider the anisotropic matter contents along with the well-known Gaussian and Lorentizian distributions of string theory. For the sake of simplicity in analytic discussions, we take a specific form of [Formula: see text] function given by [Formula: see text]. For both these noncommutative distributions, we get exact solutions in terms of exponential and hypergeometric functions. By taking some suitable choice of free parameters, we investigate different interesting aspects of these wormhole solutions graphically. We also explored the stability of these wormhole models using equilibrium condition. It can be concluded that the obtained solutions are stable and physically viable satisfying the wormhole existence criteria. Lastly, we discuss the constraints for positivity of the active gravitational mass for both these distributions.
Fisher-discriminative regularized latent sparse transfer model
Authors: Gou Xu , Lu Wei , Wang Yi , Yan Binyu , Xin Mulin
Published: December 2018

Top performing algorithms are trained on massive amounts of labeled data. Alternatively, domain adaptation (DA) provides an attractive way to address the few labeled tasks when the labeled data from a different but related domain are available. Motivated by Fisher criterion, we present the novel discriminative regularization term on the latent subspace which incorporates the latent sparse domain transfer (LSDT) model in a unified framework. The key underlying idea is to make samples from one class closer and farther away from different class samples. However, it is nontrivial to design the efficient optimization algorithm. Instead, we construct a convex surrogate relaxation optimization constraint to ease this issue by alternating direction method of multipliers (ADMM) algorithm. Subsequently, we generalize our model in the reproduced kernel Hilbert space (RKHS) for tracking the nonlinear domain shift. Empirical studies demonstrate the performance improvement on the benchmark vision dataset Caltech-4DA.
The PCL Theorem
Authors: Bushkov Victor , Dziuma Dmytro , Fatourou Panagiota , Guerraoui Rachid
Published: December 2018

We establish a theorem called the PCL theorem, which states that it is impossible to design a transactional memory algorithm that ensures (1)
parallelism
, i.e., transactions do not need to synchronize unless they access the same application objects, (2) very little
consistency
, i.e., a consistency condition, called
weak adaptive consistency
, introduced here and that is weaker than snapshot isolation, processor consistency, and any other consistency condition stronger than them (such as opacity, serializability, causal serializability, etc.), and (3) very little
liveness
, i.e., which transactions eventually commit if they run solo.
Deterministic Edge Connectivity in Near-Linear Time
Authors: Kawarabayashi Ken-Ichi , Thorup Mikkel
Published: December 2018

We present a deterministic algorithm that computes the edge-connectivity of a graph in near-linear time. This is for a simple undirected unweighted graph
G
with
n
vertices and
m
edges. This is the first
o
(
mn
) time deterministic algorithm for the problem. Our algorithm is easily extended to find a concrete minimum edge-cut. In fact, we can construct the classic cactus representation of all minimum cuts in near-linear time.

The previous fastest deterministic algorithm by Gabow from STOC '91 took Õ(
m
+λ
2
n
), where λ is the edge connectivity, but λ can be as big as
n
−1. Karger presented a randomized near-linear time Monte Carlo algorithm for the minimum cut problem at STOC’96, but the returned cut is only minimum with high probability.

Our main technical contribution is a near-linear time algorithm that contracts vertex sets of a simple input graph
G
with minimum degree Δ, producing a multigraph Ḡ with Õ(
m
/Δ) edges, which preserves all minimum cuts of
G
with at least two vertices on each side.

In our deterministic near-linear time algorithm, we will decompose the problem via low-conductance cuts found using PageRank a la Brin and Page (1998), as analyzed by Andersson, Chung, and Lang at FOCS’06. Normally, such algorithms for low-conductance cuts are randomized Monte Carlo algorithms, because they rely on guessing a good start vertex. However, in our case, we have so much structure that no guessing is needed.
Scaling Exponential Backoff
Authors: Bender Michael A. , Fineman Jeremy T. , Gilbert Seth , Young Maxwell
Published: December 2018

Randomized exponential backoff is a widely deployed technique for coordinating access to a shared resource. A good backoff protocol should, arguably, satisfy three natural properties: (1) it should provide constant throughput, wasting as little time as possible; (2) it should require few failed access attempts, minimizing the amount of wasted effort; and (3) it should be robust, continuing to work efficiently even if some of the access attempts fail for spurious reasons. Unfortunately, exponential backoff has some well-known limitations in two of these areas: it can suffer subconstant throughput under bursty traffic, and it is not robust to adversarial disruption.

The goal of this article is to “fix” exponential backoff by making it scalable, particularly focusing on the case where processes arrive in an online, worst-case fashion. We present a relatively simple backoff protocol, R
e
-B
ackoff
, that has, at its heart, a version of exponential backoff. It guarantees expected constant throughput with dynamic process arrivals and requires only an expected polylogarithmic number of access attempts per process.

R
e
-B
ackoff
is also robust to periods where the shared resource is unavailable for a period of time. If it is unavailable for
D
time slots, R
e
-B
ackoff
provides the following guarantees. For
n
packets, the expected number of access attempts for successfully sending a packet is
O
(log
2
(
n
+
D
)). For the case of an infinite number of packets, we provide a similar result in terms of the maximum number of processes that are ever in the system concurrently.
NEURA
ghe
Authors: Meloni Paolo , Capotondi Alessandro , Deriu Gianfranco , Brian Michele , Conti Francesco , Rossi Davide , Raffo Luigi , Benini Luca
Published: December 2018

Deep convolutional neural networks (CNNs) obtain outstanding results in tasks that require human-level understanding of data, like image or speech recognition. However, their computational load is significant, motivating the development of CNN-specialized accelerators. This work presents NEURA
ghe
, a flexible and efficient hardware/software solution for the acceleration of CNNs on Zynq SoCs. NEURA
ghe
leverages the synergistic usage of Zynq ARM cores and of a powerful and flexible Convolution-Specific Processor deployed on the reconfigurable logic. The Convolution-Specific Processor embeds both a convolution engine and a programmable soft core, releasing the ARM processors from most of the supervision duties and allowing the accelerator to be controlled by software at an ultra-fine granularity. This methodology opens the way for cooperative heterogeneous computing: While the accelerator takes care of the bulk of the CNN workload, the ARM cores can seamlessly execute hard-to-accelerate parts of the computational graph, taking advantage of the NEON vector engines to further speed up computation. Through the companion NeuDNN SW stack, NEURA
ghe
supports end-to-end CNN-based classification with a peak performance of 169GOps/s, and an energy efficiency of 17GOps/W. Thanks to our heterogeneous computing model, our platform improves upon the state-of-the-art, achieving a frame rate of 5.5 frames per second (fps) on the end-to-end execution of VGG-16 and 6.6fps on ResNet-18.
Lack of urea transporters, UT-A1 and UT-A3, increases nitric oxide accumulation to dampen medullary sodium reabsorption through ENaC
Authors: Rogers Richard T. , Sun Michael A. , Yue Qiang , Bao Hui-Fang , Sands Jeff M. , Blount Mitsi A. , Eaton Douglas C.
Published: December 2018

Although the role of urea in urine concentration is known, the effect of urea handling by the urea transporters (UTs), UT-A1 and UT-A3, on sodium balance remains elusive. Serum and urinary sodium concentration is similar between wild-type mice (WT) and UT-A3 null (UT-A3 KO) mice; however, mice lacking both UT-A1 and UT-A3 (UT-A1/A3 KO) have significantly lower serum sodium and higher urinary sodium. Protein expression of renal sodium transporters is unchanged among all three genotypes. WT, UT-A3 KO, and UT-A1/A3 KO acutely respond to hydrochlorothiazide and furosemide; however, UT-A1/A3 KO fail to show a diuretic or natriuretic response following amiloride administration, indicating that baseline epithelial Na+channel (ENaC) activity is impaired. UT-A1/A3 KO have more ENaC at the apical membrane than WT mice, and single-channel analysis of ENaC in split-open inner medullary collecting duct (IMCD) isolated in saline shows that ENaC channel density and open probability is higher in UT-A1/A3 KO than WT. UT-A1/A3 KO excrete more urinary nitric oxide (NO), a paracrine inhibitor of ENaC, and inner medullary nitric oxide synthase 1 mRNA expression is ~40-fold higher than WT. Because endogenous NO is unstable, ENaC activity was reassessed in split-open IMCD with the NO donor PAPA NONOate [1-propanamine-3-(2-hydroxy-2-nitroso-1-propylhydrazine)], and ENaC activity was almost abolished in UT-A1/A3 KO. In summary, loss of both UT-A1 and UT-A3 (but not UT-A3 alone) causes elevated medullary NO production and salt wasting. NO inhibition of ENaC, despite elevated apical accumulation of ENaC in UT-A1/A3 KO IMCD, appears to be the main contributor to natriuresis in UT-A1/A3 KO mice.
Unraveling reno-protective effects of SGLT2 inhibition in human proximal tubular cells
Authors: Pirklbauer Markus , Schupart Ramona , Fuchs Lisa , Staudinger Petra , Corazza Ulrike , Sallaberger Sebastian , Leierer Johannes , Mayer Gert , Schramek Herbert
Published: December 2018

Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. Because the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-β1 and downregulated by either of the two SGLT2i in HK-2 and RPTEC/TERT1 (renal proximal tubular epithelial cells/telomerase reverse transcriptase 1) cells. Extracellular matrix organization showed the highest significance in pathway enrichment analysis. Differential gene expression of three annotated genes of interest within this pathway was verified on mRNA level in both cell lines. Whereas TGF-β1 induced mRNA expression of thrombospondin 1 (THBS1; 4.3-fold), tenascin C (TNC; 8-fold), and platelet-derived growth factor subunit B (PDGF-B; 4.2-fold), SGLT2i downregulated basal mRNA expression of THBS1 (0.2-fold), TNC (0.5 fold), and PDGF-B (0.6-fold). Administration of SGLT2i in the presence of TGF-β1 resulted in a significant inhibition of TGF-β1-induced THBS1 and TNC mRNA expression and TGF-β1-induced THBS1, TNC, and PDGF-BB protein expression. We conclude that SGLT2i block basal and TGF-β1-induced expression of key mediators of renal fibrosis and kidney disease progression in two independent human PT cell lines.
Effort matching between arms depends on relative limb geometry and personal control
Authors: Logan Lindsey M. , Semrau Jennifer A. , Cluff Tyler , Scott Stephen H. , Dukelow Sean P.
Published: December 2018

Proprioception encompasses our sense of position and movement of our limbs, as well as the effort with which we engage in voluntary actions. Historically, sense of effort has been linked to centrally generated signals that elicit voluntary movements. We were interested in determining the effect of differences in limb geometry and personal control on sense of effort. In experiment 1, subjects exerted either extension or flexion torques to resist a torque applied by a robot exoskeleton to their reference elbow. They attempted to match this torque by exerting an equal effort torque (in a congruent direction with the reference arm) with their opposite (matching) arm in different limb positions (±15°). Subjects produced greater matching torque when their matching arm exerted effort toward the mirrored position of the reference (e.g., reference/matching arms at 90°/105° elbow flexion) vs. away (e.g., 90°/75° flexion). In experiment 2, a larger angular difference between arms (30°) resulted in a larger discrepancy in matched torques. Furthermore, in both experiments 1 and 2, subjects tended to overestimate the reference arm torque. This motivated a third experiment to determine whether providing more personal control might influence perceived effort and reduce the overestimation of the reference torques that we observed ( experiments 3a and 3b). Overestimation of the matched torques decreased significantly when subjects self-selected the reference torque that they were matching. Collectively, our data suggest that perceived effort between arms can be influenced by signals relating to the relative geometry of the limbs and the personal control of motor output during action.

NEW & NOTEWORTHY This work highlights how limb geometry influences our sense of effort during voluntary motor actions. It also suggests that loss of personal control during motor actions leads to an increase in perceived effort.
Activin A in Mammalian Physiology
Authors: Bloise Enrrico , Ciarmela Pasquapina , Dela Cruz Cynthia , Luisi Stefano , Petraglia Felice , Reis Fernando M.
Published: December 2018

Activins are dimeric glycoproteins belonging to the transforming growth factor beta superfamily and resulting from the assembly of two beta subunits, which may also be combined with alpha subunits to form inhibins. Activins were discovered in 1986 following the isolation of inhibins from porcine follicular fluid, and were characterized as ovarian hormones that stimulate follicle stimulating hormone (FSH) release by the pituitary gland. In particular, activin A was shown to be the isoform of greater physiological importance in humans. The current understanding of activin A surpasses the reproductive system and allows its classification as a hormone, a growth factor, and a cytokine. In more than 30 yr of intense research, activin A was localized in female and male reproductive organs but also in other organs and systems as diverse as the brain, liver, lung, bone, and gut. Moreover, its roles include embryonic differentiation, trophoblast invasion of the uterine wall in early pregnancy, and fetal/neonate brain protection in hypoxic conditions. It is now recognized that activin A overexpression may be either cytostatic or mitogenic, depending on the cell type, with important implications for tumor biology. Activin A also regulates bone formation and regeneration, enhances joint inflammation in rheumatoid arthritis, and triggers pathogenic mechanisms in the respiratory system. In this 30-yr review, we analyze the evidence for physiological roles of activin A and the potential use of activin agonists and antagonists as therapeutic agents.
A Comparative Study on Rock Properties in Splitting and Compressive Dynamic Tests
Authors: Wu Nan , Zhu Zhende , Zhou Yaojun , Gao Shihu
Published: December 2018

The dynamic properties of rock in splitting (tensile) and compressive tests are the focus of rock dynamic mechanics research. In this study, a split Hopkinson pressure bar (SHPB) apparatus was used to assess the comparability and strain rate effect of rock samples under two kinds of load conditions. With an increase in impact velocity under compression and splitting (tensile) tests, the strain rate of the samples increased continuously. The rock properties and strain rate in the two kinds of samples exhibited clear similarities: the dimensionless stress‐strain curves of the rock samples were similar under the same strain rates. The peak strength and elastic modulus of the two kinds of samples increased with an increase in the strain rate. The number of cracks increased from intergranular to transgranular failure. The rack initiation value of the two kinds of samples was close at the same strain rate and declined with an increase in the strain rate as evidenced by a power function.
Antioxidative and Anti‐Inflammatory Effects of Water Extract of Acrostichum aureum Linn. against Ethanol‐Induced Gastric Ulcer in Rats
Authors: Wu Xue , Huang Qionghui , Xu Nan , Cai Jian , Luo Dandan , Zhang Qian , Su Ziren , Gao Changjun , Liu Yuhong
Published: December 2018

Acrostichum aureum Linn., a medicinal pteridophyte growing in mangrove forests and coastal regions of tropical and subtropical areas worldwide, has been proved to possess various biological effects. However, the protective effect of Acrostichum aureum Linn. against gastric ulcer still remains unidentified. Therefore, the gastroprotective effect of the water extract of Acrostichum aureum Linn. (WEAC) was investigated in ethanol‐induced gastric injury model. According to our results, pretreatment with WEAC (100, 200, and 400 mg/kg) could dramatically decrease the ulcer areas and ameliorate the pathological damage induced by alcohol in rat’s gastric tissues. In addition, WEAC administration prevented the stomach from oxidative damage via markedly increasing the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and decreasing the malondialdehyde (MDA). Besides, WEAC pretreatment alleviated inflammatory infiltration by reducing the secretion of proinflammatory cytokines including tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) as well as decreasing the protein expressions of phosphorylation of IκBα and p65. Taken together, WEAC exerted potential therapeutic efficacy for gastric ulceration, and this may be involved in the suppression of oxidative stress and inflammatory response.
Model-Based Testing Applied to Software Components of Satellite Simulators
Authors: Silva Paulo Diego Barbosa da , Ambrosio Ana Maria , Villani Emilia
Published: December 2018

Operational simulators have a fundamental role in space programs. During a satellite operation, these simulators are essential for validating critical manoeuvres, testing new on-board software versions, and supporting the diagnosis of anomalies. With the purpose of reusing the operational simulators, the Brazilian National Institute for Space Research has proposed a new standard for the specification of the components that must be integrated in their in-house developed simulators. The new standard describes the behaviour of satellite subsystems using cause-effect tables that relate telecommands, electrical switches, equipment working states, energy consumption, telemetries, and operating modes of the subsystem. Using this new standard as input, this work proposes an approach that merges model-based testing and model checking to verify the correct implementation of new components in the satellite simulator. The verification approach consists of extracting state machines from the cause-effect tables and used it to automatically derive a test case suite. In order to validate the proposal, we applied it to three different satellite subsystems and assessed the results obtained from the test campaigns. In all the three cases, the proposed approach identified errors in the simulator components that were not initially detected by the traditional testing approach used at the Brazilian National Institute for Space Research.
Routes to Multiple Equilibria for Mass‐Action Kinetic Systems
Authors: Alonso Antonio A. , Otero-Muras Irene , Pájaro Manuel
Published: December 2018

In this work we explore two potential mechanisms inducing multiple equilibria for weakly reversible networks with mass‐action kinetics. The study is performed on a class of polynomial dynamic systems that, under some mild assumptions, are able to accommodate in their state‐space form weakly reversible mass‐action kinetic networks. The contribution is twofold. We provide an explicit representation of the set of all positive equilibria attained by the system class in terms of a set of (positive parameter dependent) algebraic relations. With this in hand, we prove that deficiency‐one networks can only admit multiple equilibria via folding of the equilibrium manifold, whereas a bifurcation leading to multiple branches is only possible in networks with deficiencies larger than one. Interestingly, some kinetic networks within this latter class are capable of sustaining multiple equilibria for any reaction simplex, as we illustrate with one example.
Digital Anatomy to Improve Screw Insertion Techniques for Plate-Screw Fixation of the Pubic Body
Authors: Li Wenlong , Zhao Futing , Sun Zhaoyun , Wang Xing , Gao Shenglong , Xu Bo , Mu Weidong
Published: December 2018

Objectives. This study aims to investigate screw insertion sites on the pubic body and the safe screw insertion parameters of a plate-screw fixation system based on the premise of avoiding damage to the inguinal canal and disruption of the rectus abdominis at the pubic symphysis and pubic crest. Research Methods. Excluding cases with poor image quality, tumors, malformations, and fractures, the data of 80 healthy adults (40 males and 40 females aged from 21 to 83 years old, with an average age of 51.65 years) undergoing a computed tomography (CT) scan of the pelvis between January and June of 2017 were collected from Shandong Provincial Hospital. The CT scans were imported to Mimics® software to reconstruct three-dimensional pelvic models. A 3.5 mm pelvic reconstruction plate was placed starting at the outer edge of the pubic tubercle and along the pelvic brim. The two innermost screw insertion sites were marked. The safe range for the screw insertion sites was then determined. The screw insertion plane was selected to measure the safe screw insertion parameters. The length of the screw, the direction of insertion, and intersex differences were then explored via statistical analyses. Results. The medial inclination angles (MIAs) of the screw insertion plane for males and females were 30.42±7.95° and 32.88±10.65°, respectively, with no statistically significant differences. For the medial screw, the maximum anterior inclination angle (MAIA), the maximum screw length, and the maximum posterior inclination angle (MPIA) were 46.51±4.01°, 12.40±9.53 mm, and 11.78±10.22° on average, respectively, with no significant differences by gender (P>0.05). For the lateral screw, the MAIA was 10.35±9.46° and showed no gender differences (P>0.05), but the male group had a greater MPIA (male 11.80±11.00° vs. female 6.23±7.91°, P<0.05) and maximum screw length (male 55.71±6.36 mm vs. female 48.68±8.65, P<0.001). For the tangential screw, the maximum screw length, MIA, and anterior/posterior inclination angle (APIA) were 52.19±8.33 mm, 31.65±9.42°, and 7.53±10.18°, respectively, with no significant differences in the angles by gender (both P>0.05), although the screw length in the male group was significantly longer than that in the female group. Conclusions. Insertion of two screws into the pubic body through a plate from the lateral side of the pubic tubercle is safe and can maintain the origin of the rectus abdominis and the integrity of the inguinal canal compared to traditional plate-screw fixation. Considering that the pubic body is thinner on the lateral side, we suggest a more medial inclination angle for the lateral screw.
Generalized Fractional-Order Bernoulli Functions via Riemann-Liouville Operator and Their Applications in the Evaluation of Dirichlet Series
Authors: Sanchez-Ortiz Jorge
Published: December 2018

In this work, we define a new class of functions of the Bernoulli type using the Riemann-Liouville fractional integral operator and derive a generating function for these class generalized functions. Then, these functions are employed to derive formulas for certain Dirichlet series.
Prevalence of Attention Deficit Hyperactivity Disorder Symptoms in Children Who Were Treated at Emergency Service due to Unintentional Injury
Authors: İz Mehmet , Çeri Veysi
Published: December 2018

Aim. Attention Deficit Hyperactivity Disorder (ADHD) is a developmental disorder characterized by severe inattention, hyperactivity, and impulsivity. This research aims to determine the frequency of ADHD symptoms in children who were treated in emergency paediatric services due to unintentional injuries. Method. This study was carried out with children who were treated due to unintentional injuries in an Emergency Department. ADHD symptoms were evaluated using the DSM-IV-based Screening and Assessment Scale for Behavioural Disorders in Children and Adolescents. Results. The study sample consisted of 89 girls (40.1%) and 133 boys (59.9%)—a total of 222 children. The participants ranged from 5 to 18 years of age, and the mean age was found to be 11.5±3 years. According to medical evaluations, the most common diagnosis for the unintentional injuries was soft tissue trauma (41.9%). The mean ADHD and ODD (Oppositional Defiant Disorder) scores of our study sample were, respectively, 19.9±12 and 7.7±5.7. The prevalence of children with possible ADHD was as high as 81.6% (179) and, for ODD, was 62.6% (139), according to cut-off values. Conclusion. Our results pointed out very high levels of ADHD and ODD symptoms among children who were treated at emergency services for accidental injuries. Appropriately screening for ADHD in children with accidental injuries and referring them to child psychiatry units may prevent later accidents and injuries.
A Hybrid Fuzzy Wavelet Neural Network Model with Self‐Adapted Fuzzy c‐Means Clustering and Genetic Algorithm for Water Quality Prediction in Rivers
Authors: Huang Mingzhi , Tian Di , Liu Hongbin , Zhang Chao , Yi Xiaohui , Cai Jiannan , Ruan Jujun , Zhang Tao , Kong Shaofei , Ying Guangguo
Published: December 2018

Water quality prediction is the basis of water environmental planning, evaluation, and management. In this work, a novel intelligent prediction model based on the fuzzy wavelet neural network (FWNN) including the neural network (NN), the fuzzy logic (FL), the wavelet transform (WT), and the genetic algorithm (GA) was proposed to simulate the nonlinearity of water quality parameters and water quality predictions. A self‐adapted fuzzy c‐means clustering was used to determine the number of fuzzy rules. A hybrid learning algorithm based on a genetic algorithm and gradient descent algorithm was employed to optimize the network parameters. Comparisons were made between the proposed FWNN model and the fuzzy neural network (FNN), the wavelet neural network (WNN), and the neural network (ANN). The results indicate that the FWNN made effective use of the self‐adaptability of NN, the uncertainty capacity of FL, and the partial analysis ability of WT, so it could handle the fluctuation and the nonseasonal time series data of water quality, while exhibiting higher estimation accuracy and better robustness and achieving better performances for predicting water quality with high determination coefficients R2 over 0.90. The FWNN is feasible and reliable for simulating and predicting water quality in river.
Using the Spleen as anIn VivoSystemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy withα-PD-L1
Authors: Markel Justin E. , Noore Jabeen , Emery Eric J. , Bobnar Harley J. , Kleinerman Eugenie S. , Lindsey Brock A.
Published: December 2018

Indications for immunotherapies are still unclear, and there is a great need for real-time patient immune status monitoring. In this study, we confirmed that the local and systemic immune profiles of an orthotopic osteosarcoma model with or without luciferase transfection were statistically equivalent. Next, we used flow cytometry to describe systemic immune cell populations influenced by osteosarcoma disease progression. When compared to vehicle-inoculated sham mice, it was found that tumor-bearing mice had significant immunophenotype disturbances at approximately 11 weeks after inoculation (at which time 90% of primary tumor-bearing mice have fulminant pulmonary metastases). Percent populations of natural killer cells and T regulatory cells were increased in the spleens of tumor-bearing mice (p<0.0083) compared to shams. Additionally, T lymphocytes from spleens of tumor-bearing mice showed increased Tim-3/PD-1 exhaustion status (p<0.0083). There were also increases in the percent populations of myeloid cells and overall M1/M2 macrophage marker expression on tumor-bearing mice spleens versus controls (p<0.00714). Finally, treatment with 20 μgα-PD-L1 decreased T-cell exhaustion back to sham status, with a corresponding increase in CTLA-4 expression on cytotoxic T cells in the majority of mice tested. Checkpoint inhibition also increased splenic monocyte maturation and returned macrophage M1/M2 marker expression back to sham status. These data suggest that cancer induces systemic immune dysregulation and that these changes may be elucidated and utilized for treatment purposes by sampling the systemic immune environment via the spleen. In addition, treatment with the checkpoint inhibitorα-PD-L1 may neutralize but not overcome the systemic immunological changes induced by a progressing malignancy.