bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
Authors: Oeckl Patrick , Weydt Patrick , Steinacker Petra , Anderl-Straub Sarah , Nordin Frida , Volk Alexander E , Diehl-Schmid Janine , Andersen Peter M , Kornhuber Johannes , Danek Adrian , Fassbender Klaus , Fliessbach Klaus ,   German Consortium for Frontotemporal Lobar Degeneration, Jahn Holger , Lauer Martin , Müller Kathrin , Knehr Antje , Prudlo Johannes , Schneider Anja , Thal Dietmar R , Yilmazer-Hanke Deniz , Weishaupt Jochen H , Ludolph Albert C , Otto Markus 
Published: September 2018

ObjectiveTo investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.MethodsThe neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.ResultsCSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (−80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).ConclusionOur data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.
Colored collapse models from the non-interferometric perspective
Authors: Carlesso Matteo , Ferialdi Luca , Bassi Angelo 
Published: September 2018

Abstract

Models of spontaneous wave function collapse describe the quantum-to-classical transition by assuming a progressive breakdown of the superposition principle when the mass of the system increases, providing a well-defined phenomenology in terms of a non-linearly and stochastically modified Schrödinger equation, which can be tested experimentally. The most popular of such models is the continuous spontaneous localization (CSL) model: in its original version, the collapse is driven by a white noise, and more recently, generalizations in terms of colored noises, which are more realistic, have been formulated. We will analyze how current non-interferometric tests bound the model, depending on the spectrum of the noise. We will find that low frequency purely mechanical experiments provide the most stable and strongest bounds.

Graphical abstract
A Stochastic Inventory Model for a Random Yield Supply Chain with Wholesale-Price and Shortage Penalty Contracts
Authors: Sato Kimitoshi , Yagi Kyoko , Shimazaki Masahito 
Published: September 2018

This paper analyzes an infinite horizon, single-product, continuous-time inventory model with supply and demand risks to evaluate the impact of coordinating a production policy between a distributor and a supplier. We consider a wholesale-price contract and a shortage penalty contract as a coordination mechanisms in an inventory replenishment system. The demand process is described by a Brownian motion with drift, and this inventory model can be formulated as an impulse control problem with uncertain replenishment quantities. We show that under some assumptions, there exist optimal ordering and production policies. We also provide some numerical examples to investigate the effect of these coordination mechanisms on the expected costs and the optimal policies. The computational experiments reveal that (i) the production quantity in decentralized case is higher than that in the centralized case, (ii) the centralized approach strategy results in the lower joint total cost as compared with independent decision approaches, and (iii) the shortage penalty contract has a beneficial effect on the total cost to the entire supply chain in decentralized system.
Packet Aggregation Real-Time Scheduling for Large-Scale WIA-PA Industrial Wireless Sensor Networks
Authors: Jin Xi , Guan Nan , Xia Changqing , Wang Jintao , Zeng Peng 
Published: September 2018

The IEC standard WIA-PA is a communication protocol for industrial wireless sensor networks. Its special features, including a hierarchical topology, hybrid centralized-distributed management and packet aggregation make it suitable for large-scale industrial wireless sensor networks. Industrial systems place large real-time requirements on wireless sensor networks. However, the WIA-PA standard does not specify the transmission methods, which are vital to the real-time performance of wireless networks, and little work has been done to address this problem.
In this article, we propose a real-time aggregation scheduling method for WIA-PA networks. First, to satisfy the real-time constraints on dataflows, we propose a method that combines the real-time theory with the classical bin-packing method to aggregate original packets into the minimum number of aggregated packets. The simulation results indicate that our method outperforms the traditional bin-packing method, aggregating up to 35% fewer packets, and improves the real-time performance by up to 10%. Second, to make it possible to solve the scheduling problem of WIA-PA networks using the classical scheduling algorithms, we transform the ragged time slots of WIA-PA networks to a universal model. In the simulation, a large number of WIA-PA networks are randomly generated to evaluate the performances of several real-time scheduling algorithms. By comparing the results, we obtain that the earliest deadline first real-time scheduling algorithm is the preferred method for WIA-PA networks.
Divergent Biological Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer
Authors: Seiler Roland , Gibb Ewan A. , Wang Natalie Q. , Oo Htoo Zarni , Lam Hung-Ming , van Kessel Kim E. , Voskuilen Charlotte S. , Winters Brian , Erho Nicholas , Takhar Mandeep M. , Douglas James , Vakar-Lopez Funda , Crabb Simon J. , van Rhijn Bas W.G. , Fransen van de Putte Elisabeth E. , Zwarthoff Ellen C. , Thalmann George N. , Davicioni Elai , Boormans Joost L. , Dall'Era Marc , van der Heijden Michiel S. , Wright Jonathan L. , Black Peter C. 
Published: September 2018

Abstract

Purpose:
After cisplatin-based neoadjuvant chemotherapy (NAC), 60% of patients with muscle-invasive bladder cancer (MIBC) still have residual invasive disease at radical cystectomy. The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied.

Experimental Design:
Radical cystectomy samples were available for gene expression analysis from 133 patients with residual invasive disease after cisplatin-based NAC, of whom 116 had matched pre-NAC samples. Unsupervised consensus clustering (CC) was performed and the consensus clusters were investigated for their biological and clinical characteristics. Hematoxylin & Eosin and IHC on tissue microarrays were used to confirm tissue sampling and gene expression analysis.

Results:
Established molecular subtyping models proved to be inconsistent in their classification of the post-NAC samples. Unsupervised CC revealed four distinct consensus clusters. The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal and a luminal phenotype, respectively, and were similar to the corresponding established pretreatment molecular subtypes. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecule expression, but lacked both basal and luminal markers. The CC4-Scar–like subtype expressed genes associated with wound healing/scarring, although the proportion of tumor cell content in this subtype did not differ from the other subtypes. Patients with CC4-Scar–like tumors had the most favorable prognosis.

Conclusions:
This study expands our knowledge on MIBC not responding to cisplatin by suggesting molecular subtypes to understand the biology of these tumors. Although these molecular subtypes imply consequences for adjuvant treatments, this ultimately needs to be tested in clinical trials.
Sorafenib and Carfilzomib Synergistically Inhibit the Proliferation, Survival, and Metastasis of Hepatocellular Carcinoma
Authors: Jiang Chao , Xu Rui , Li Xiao-Xing , Zhou Yu-Feng , Xu Xiao-Yi , Yang Yang , Wang Hui-Yun , Zheng X.F. Steven 
Published: September 2018

Abstract
Hepatocellular carcinoma (HCC) is one of the most common and deadly human cancers. The 5-year survival rate is very low. Unfortunately, there are few efficacious therapeutic options. Until recently, Sorafenib has been the only available systemic drug for advanced HCC. However, it has very limited survival benefits, and new therapies are urgently needed. In this study, we investigated the anti-HCC activity of carfilzomib, a second-generation, irreversible proteasome inhibitor, as a single agent and in combination with sorafenib. In vitro, we found that carfilzomib has moderate anticancer activity toward liver cancer cells, but strongly enhances the ability of sorafenib to suppress HCC cell growth, proliferation, migration, invasion, and survival. Remarkably, the drug combination exhibits even more potent antitumor activity when tested in animal tumor models. Mechanistically, the combined treatment activates caspase-dependent and endoplasmic reticulum stress/CHOP-mediated apoptotic pathways, and suppresses epithelial–mesenchymal transition. In conclusion, our results demonstrate that the combination of carfilzomib and sorafenib has synergistic antitumor activities against HCC, providing a potential therapeutic strategy to improve the mortality and morbidity of HCC patients.
The Aged Microenvironment Influences the Tumorigenic Potential of Malignant Prostate Epithelial Cells
Authors: Bianchi-Frias Daniella , Damodarasamy Mamatha , Hernandez Susana A. , Gil da Costa Rui M. , Vakar-Lopez Funda , Coleman Ilsa M. , Reed May J. , Nelson Peter S. 
Published: September 2018

Abstract

The incidence of prostate cancer is directly linked to age, but age-associated changes that facilitate prostate cancer development and progression are poorly understood. This study investigated age-related changes in the prostate microenvironment for their influence on prostate cancer behavior. Prostate cancer cells implanted orthotopically into the prostate demonstrated accelerated tumor growth in aged compared with young mice. Metastatic lesions following intravenous injection were also more numerous in aged mice. Tumors from young and aged mice showed no significant differences concerning their proliferation index, apoptosis, or angiogenesis. However, analysis of tumor-infiltrating immune cells by IHC and RNA sequencing (RNA-seq) revealed elevated numbers of macrophages in prostates from aged mice, which are quickly polarized towards a phenotype resembling protumorigenic tumor-associated macrophages upon tumor cell engraftment. Older patients with prostate cancer (&gt;60 years old) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset displayed higher expression of macrophage markers (CD163 and VSIG4) which associated with higher rates of biochemical relapse. Remodeling of the collagenous extracellular matrix (ECM) was associated with prostate cancer growth and invasion in the aged microenvironment. Moreover, the collagen matrix extracted from aged mice enhanced the invasiveness and proliferation of prostate cancer cells in vitro. Together, these results demonstrate that the aged prostatic microenvironment can regulate the growth and metastasis of malignant prostate cells, highlighting the role of resident macrophages and their polarization towards a protumorigenic phenotype, along with remodeling of the ECM.

Implications:
These findings demonstrate the importance of age-associated tumor microenvironment alterations in regulating key aspects of prostate cancer progression.
Differential Expression of Cancer-Associated Fibroblast-Related Proteins in Ductal Carcinoma in situ According to Molecular Subtype and Stromal Histology
Authors: Lee Ji Hee  , Kim Hye Min , Koo Ja Seung 
Published: September 2018

<b><i>Objective:</i></b> The purpose of this study is to investigate the expression of cancer-associated fibroblast (CAF)-related proteins and their implication in ductal carcinoma in situ (DCIS). <b><i>Methods:</i></b> We constructed a tissue microarray of 223 cases of DCIS and examined immunohistochemical staining for the 7 CAF-related proteins. We classified DCIS into luminal type, human epidermal growth factor receptor-2 (HER-2) type, and triple negative breast cancer (TNBC) according to the immunohistochemical results for estrogen receptor, progesterone receptor, and HER-2. We also classified DCIS into desmoplastic, normal-like, and inflammatory type according to stromal histology. <b><i>Results:</i></b> There were significant differences in the expression of S100A4, podoplanin, prolyl 4-hydroxylase subunit alpha 3, NG2, and PDGFRα in stromal cells of DCIS when classified according to molecular subtype. The expression rate of all CAF-related proteins in stromal cells was higher in the HER-2 type and TNBC than in the luminal type (<i>p</i> &#x3c; 0.001). When classified according to stromal subtype, there were significant differences in the expression of all CAF-related proteins in stromal cells, with the inflammatory stromal type showing higher expression of CAF-related proteins than other stromal types. <b><i>Conclusion:</i></b> The expression of CAF-related proteins in stromal cells of DCIS varies according to molecular subtype and stromal type.
Exercise-Stress Echocardiography and Effort Intolerance in Asymptomatic/Minimally Symptomatic Patients With Degenerative Mitral Regurgitation Combined Invasive–Noninvasive Hemodynamic Monitoring
Authors: Utsunomiya Hiroto , Hidaka Takayuki , Susawa Hitoshi , Izumi Kanako , Harada Yu , Kinoshita Mirai , Itakura Kiho , Masada Kenji , Kihara Yasuki 
Published: September 2018

Background

Effort intolerance, measured objectively by reduced peak oxygen consumption (V

o
2

), has been considered as an important prognosticator in degenerative mitral regurgitation (MR). However, its mechanism is unknown.

Methods and Results

In 25 asymptomatic/minimally symptomatic patients with grade III+ or greater degenerative MR undergoing semisupine invasive exercise testing, Doppler estimates and invasive measurement of systolic (SPAP) and mean pulmonary artery pressure (MPAP) and cardiac output (CO) were simultaneously obtained. Echocardiographic estimates of SPAP, MPAP, and CO correlated well with invasive measurement at peak exercise (bias, SPAP, −0.7±7.4 mm Hg; MPAP, 1.2±6.3 mm Hg; CO, 0.2±2.5 L/min). Heart rate reserve (β, 3.997; 95% CI, 2.704–5.290 per 41.5% increase;
P
<0.001), MPAP/CO slope (β, −3.846; 95% CI, −5.926 to −1.766 per 4.85 mm Hg/L per minute increase;
P
=0.001), and tricuspid annular plane systolic excursion/SPAP slope (β, 4.094; 95% CI, 2.252–5.936 per 0.22 mm/mm Hg increase;
P
=0.003) were associated with peak V

o
2

even after adjustment for increase in MR vena contracta during exercise and peak SPAP. The MPAP/CO slope of 4.13 had a sensitivity and a specificity for predicting effort intolerance (%predicted peak V

o
2

<70%) of 57% and 91%, respectively, whereas the tricuspid annular plane systolic excursion/SPAP slope of 0.25 had a respective sensitivity and specificity of 86% and 82%.

Conclusions
The agreement between echocardiographic and invasive measures of pulmonary artery pressures and CO during exercise is acceptable. In patients with degenerative MR, effort intolerance is predominantly because of chronotropic incompetence, abnormal pulmonary vascular reserve, and limited right ventricular contractile reserve and not simply because of exercise-induced MR or pulmonary hypertension.
Atrial Dysfunction in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Zghaib Tarek , Bourfiss Mimount , van der Heijden Jeroen F. , Loh Peter , Hauer Richard N. , Tandri Harikrishna , Calkins Hugh , Nazarian Saman , te Riele Anneline S.J.M. , Zimmerman Stefan L. , Velthuis Birgitta K. 
Published: September 2018

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that is predominantly known to affect the ventricles. Evidence for atrial involvement remains limited. Therefore, we aimed to characterize atrial involvement in ARVC using functional cardiac magnetic resonance, define the extent of atrial size and function variation attributable to ventricular variables, and identify cardiac magnetic resonance–based predictors of atrial arrhythmias (AA) in ARVC.

Methods and Results:

We analyzed cine cardiac magnetic resonance images of 66 definite ARVC patients without a history of AA or severe heart failure and 24 healthy controls. Using tissue tracking, we evaluated phasic biatrial volumes, ejection fractions (EFs), peak longitudinal strain, and strain rates (SRs). The primary outcome was the occurrence of AA during 6.8 years [3.0–10.8 years] of follow-up. Compared with controls, ARVC patients had higher biatrial volumes, reduced right atrial (RA) conduit function (passive EF [RAEF
passive
] and peak early-diastolic SR), reduced RA and left atrial (LA) reservoir function (peak systolic SR), and reduced RA and LA pump function (peak late-diastolic SR;
P
<0.05). Using multivariable analysis, predictors of increased risk of AA during follow-up were higher atrial volumes (RAV
min
and LAV
min
), decreased LA reservoir function (total LAEF and LA peak longitudinal strain), and decreased RA conduit function (passive RAEF and RA early-diastolic SR).

Conclusions:
Compared with controls, patients with ARVC were found to have enlarged atria with decreased function on functional cardiac magnetic resonance examination. RA and LA parameters predict incident AA after adjusting for clinical and ventricular characteristics which suggests atrial involvement in ARVC.
Multilateral Investment Court: The Gap Between the EU and China
Authors: Ning Hongling , Qi Tong 
Published: September 2018

Abstract
The EU has now shifted from ad hoc investment arbitration to an envisaged Multilateral Investment Court. Its essential character is expected to be a two-instance standing court system, together with a random allocation of cases. This judicialized court system could address China’s preference of correctness as to ISDS system to some extent, subject to the competence of judges, while at the same time it raises new problems and new concerns. Firstly, would the envisaged standing court, in the context of enhancing the regulatory powers of states, still be qualified as a neutral forum to strike the appropriate balance between the protection of investors’ right and preservation of states’ regulatory powers? Secondly, would the judicialized court system be effective and flexible enough to suit the current nature of ISDS? Thirdly, would the envisaged two-tier court system be put into efficient operation so as not to become a de facto bar to access of justice? In fact, a judicialized system has its pros and cons, and thus its successful establishment and operation would be subject to more detailed rules.
Validation of the GPM Version-5 Surface Rainfall Products over Great Britain and Ireland
Authors: Watters Daniel , Battaglia Alessandro , Mroz Kamil , Tridon Frédéric 
Published: September 2018

Abstract
Instantaneous surface rain rate estimates from the Global Precipitation Measurement (GPM) mission’s Dual-Frequency Precipitation Radar (DPR) and combined DPR and multifrequency microwave imager (CMB) version-5 products are compared to those from the Met Office Radarnet 4 system’s Great Britain and Ireland (GBI) radar composite product. The spaceborne and ground-based rainfall products are collocated spatially and temporally and compared at 5- and 25-km resolutions over GBI during a 3-yr period (from May 2014 to April 2017). The comparison results are evaluated as a function of both the intensity and variability of precipitation within the DPR field of view and are stratified spatially and seasonally. CMB and DPR products underestimate rain rates with respect to the Radarnet product by 21% and 31%, respectively, when considering 25-km resolution data taken within 75 km of a ground-based radar. Large variability in the discrepancies between spaceborne and ground-based rain rate estimates is the result of limitations of both systems and random errors in the collocation of their measurements. The Radarnet retrieval is affected by issues with measuring the vertical extent of precipitation at far ranges, while the GPM system struggles in properly quantifying orographic precipitation. Part of the underestimation by the GPM products appears to be a consequence of an erroneous DPR clutter identification in the presence of low freezing levels. Both products are susceptible to seasonal variations in performance and decreases in precision with increased levels of heterogeneity within the instruments’ field of view.
A Numerical Study of Coastal-Trapped Waves in Jervis Bay, Australia
Authors: Liao Fanglou , Wang Xiao Hua 
Published: September 2018

AbstractCoastal-trapped waves (CTWs) in Jervis Bay were investigated using a Jervis Bay Ocean Model (JBOM), based on the Princeton Ocean Model. Under the typical temperature stratification in Jervis Bay in summer, the first three modes of external CTWs can scatter into the bay. The wind stress inside Jervis Bay can generate CTWs, and the wind stress on the adjacent shelf can also generate CTWs in the bay by oscillations at the bay's opening, which are associated with temperature fluctuations there. The actual subinertial CTWs in Jervis Bay are a result of the interference of these CTWs. The amplitudes of the first three CTW modes were calculated from the observed sea level data. Three numerical experiments were designed to identify the major forcing for the observed subinertial temperature oscillations in Jervis Bay during an observational program in the summer of 1988/89. It was found that the local wind stress was the major contributor to the observed oscillations.