bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent chromosomal rearrangements ofROS1,FRKandIL6activating JAK/STAT pathway in inflammatory hepatocellular adenomas
Authors: Bayard Quentin , Caruso Stefano , Couchy Gabrielle , Rebouissou Sandra , Bioulac Sage Paulette , Balabaud Charles , Paradis Valerie , Sturm Nathalie , de Muret Anne , Guettier Catherine , Bonsang Benjamin , Copie Christiane , Letouzé Eric , Calderaro Julien , Imbeaud Sandrine , Nault Jean-Charles , Zucman-Rossi Jessica
Published: January 2020

Background

Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumours characterised by an activation of the janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway caused by oncogenic activating mutations. However, a subset of IHCA lacks of identified mutation explaining the inflammatory phenotype.

Methods

657 hepatocellular adenomas developed in 504 patients were analysed for gene expression of 17 genes and for mutations in seven genes by sequencing. 22 non-mutated IHCAs were analysed by whole-exome and/or RNA sequencing.

Results

We identified 296 IHCA (45%), 81% of them were mutated in eitherIL6ST(61%),FRK(8%),STAT3(5%),GNAS(3%) orJAK1(2%). Among non-mutated IHCA, RNA sequencing identified recurrent chromosome rearrangement involvingROS1, FRKorIL6genes.ROS1fusions were identified in 8 IHCA, involving C-terminal part of genes highly expressed in the liver (PLG,RBP4,APOB) fused with exon 33–35 to 43 ofROS1including the tyrosine kinase domain. In two cases a truncatedROS1transcript from exon 36 to 43 was identified.ROS1rearrangements were validated by fluorescence in situ hybridisation (FISH) and led toROS1overexpression. Among the 5 IHCA withFRKrearrangements, 5 different partners were identified (MIA3,MIA2,LMO7,PLEKHA5, SEC16B) fused to a common region inFRKthat included exon 3–8. No overexpression ofFRKtranscript was detected but the predicted chimeric proteins lacked the auto-inhibitory SH2–SH3 domains. In two IHCA, we identified truncated 3’UTR ofIL6associated with overexpression of the transcript.

Conclusion

Recurrent chromosomal alterations involvingROS1,FRKorIL6genes lead to activation of the JAK/STAT pathway in IHCAs.
Response spectrum-based seismic response of bridge embankments
Authors: Carvajal Juan-Carlos , Finn William D. Liam , Ventura Carlos Estuardo
Published: January 2020

A single degree of freedom model is presented for calculating the free-field seismic response of bridge embankments due to horizontal ground shaking using equivalent linear analysis and a design response spectrum. The shear wave velocity profile, base flexibility, 2D shape, and damping ratio of the embankment are accounted for in the model. A step-by-step procedure is presented for calculating the effective cyclic shear strain of the embankment, equivalent homogeneous shear modulus and damping ratio, fundamental period of vibration, peak crest acceleration, peak shear stress profile, peak shear strain profile, equivalent linear shear modulus profile, and peak relative displacement profile. Model calibration and verification of the proposed procedure is carried out with linear, equivalent linear, and nonlinear finite element analysis for embankments with fundamental periods of vibration between 0.1 and 1.0 s. The proposed model is simple, rational, and suitable for practical implementation using spreadsheets for a preliminary design phase of bridge embankments.
A similarity of quantum phase transition and quench dynamics in the Dicke model beyond the thermodynamic limit
Authors: Shen Lituo , Shi Zhicheng , Yang Zhenbiao , Wu Huaizhi , Zhong Zhirong , Zheng Shibiao
Published: January 2020

We study the quantum phase transition in the Dicke model beyond the thermodynamic limit. With the Kibble–Zurek mechanism and adiabatic dynamics, we find that the residual energy is inversely proportional to the number of qubits, indicating that more qubits can obtain more energies from the oscillator as the number of qubits increases. Finally, we put forward a promising experiment device to realize this system.
Magnetically influenced dielectric and electrical transport of inorganic–organic polymer-based hybrid nanocomposites
Authors: Nath Debajyoti , Mandal S. K.
Published: January 2020

Polymer-based hybrid nanocomposites of [Formula: see text]-([Formula: see text]) poly(vinylidene fluoride) (PVDF) ([Formula: see text], 0.6 and 0.7) have been prepared through low-cost chemical reaction process. The improvement of dielectric properties in polymer-based hybrid [Formula: see text]–PVDF nanocomposites can be utilized to make a suitable memory storage device. Surface modified [Formula: see text] (LFO) nanoparticles are well distributed inside the polymer resulting in improved dielectric constant and reduced dielectric loss. The study of complex and modulus impedance spectroscopy (IS) shows some interesting results for an influence of grain and grain boundary effects of electrical conductivity attributing the non-Debye type phenomena. The change of relaxation frequency with an applied magnetic field is ascribing the spin-dependent mechanism of electrical transport at grain boundaries (GBs). The fitting of Nyquist plot attributes the magnetic domain wall containing GB’s pinning center in the system. The higher concentration of filler LFO nanoparticles shows maximum values of dielectric constant assigning the Maxwell–Wagner–Sillars (MWS) polarization. The current study is focused towards the query to learn the complete study of magnetic field dependence electrical and dielectric properties in a system holding an excessive potential for a capable candidate for industrial applications.
Stochastic Resonance in Strongly Coupled Duffing and Van der pol Oscillators Under Trichotomous Noise and Bearing Fault Diagnosis
Authors: Zhang Gang , Wu Xia , Zhang Tianqi
Published: January 2020

Weak signal detection is an important topic, which has been widely studied in various fields. Different from other signal processing methods, stochastic resonance (SR) can utilize noise to enhance the characteristic frequency. Inspired by the unique advantage of SR, the strongly coupled Duffing and Van der pol SR system (SCD-VSR) is investigated. The simulation results show that the relationship between the output average signal–noise ratio increase (MSNRI) and different jump values of trichotomous noise presents different odd symmetrical distribution. It is also found that a double SR phenomenon could be observed when the damping coefficient of Van der pol system is small. Moreover, as the damping coefficient of the Duffing system increases, the output response would become gradually smooth. In addition,a smaller damping force coupling coefficient combined with a large restoring force coupling coefficient would achieve better system response. In the case of detecting an analog signal, MSNRI of SCD-VSR is larger than that of both classical bistable SR system (CBSR) and coupled Duffing SR system (CDSR). In addition, the experiments suggest that SCD-VSR could obtain a higher MSNRI and better detection effect, which implies the performance is superior to CBSR and CDSR.
Malware Detection Using Optimized Activation-Based Deep Belief Network: An Application on Internet of Things
Authors: Sagar G. V. R.
Published: January 2020

Number of malware detection models has been proposed recently, which still poses major limitations in terms of detection rate. Hence, to overcome this, this paper introduces a new malware detection model with three stages: Feature Extraction, Feature selection and Classification. In feature extraction phase, the Term Frequency-Inverse Document Frequency (TF-IDF) and Information gain (IG) features are extracted. More importantly, the IG feature is subjected with the Holoentropy evaluation. Following the feature extraction phase feature selection is performed using Principle Component Analysis (PCA). Finally, to do the classification process, Deep Belief Network (DBN) is used with optimized activation function. To work out this optimization scenario, this paper intends to propose a new hybrid algorithm that combines the concept of Lion Algorithm (LA) and Glowworm Swarm Algorithm (GSO). The performance of proposed Lion Updated GSO (LU-GSO) is compared over other conventional models with respect to various evaluation measures and proves the betterments over others. Through the performance analysis, it was observed that the proposed model attains high accuracy, which is 10.21%, 10.04%, 9.18% and 6.42% better than LA, GSO, GWO and PSO, respectively.
Evaluation of Research Trends in Knowledge Management: A Hybrid Analysis through Burst Detection and Text Clustering
Authors: Sohrabi Babak , Vanani Iman Raeesi , Jalali Seyed Mohammad Jafar , Abedin Ehsan
Published: January 2020

This paper aims to analyze the content of validated journal articles related to Knowledge Management (KM) in more than 18,000 papers of the Web of Science (WoS) database and then provide the most recent specific trends in KM field using text mining and burst detection to help researchers invest in the most challenging and fruitful areas of KM research domain. The method for finding the recent trend of KM includes the following steps: Conducting searches and collecting the publication data from WoS; using a hybrid analysis through burst detection and text clustering; also enriching and analyzing the results in order to achieve an overall perspective about the KM position and the popularity among researchers. This study could be valuable for researchers and KM specialists as well as managers as they may study the history of a subject by getting the structure of its scientific productions, so as to purposefully plan and determine the research priorities in KM.
Macroporous 3D MXene architecture for solar-driven interfacial water evaporation
Authors: Ju Maomao , Yang Yawei , Zhao Jianqiu , Yin Xingtian , Wu Yutao , Que Wenxiu
Published: January 2020

Interfacial water evaporation through solar heating with photothermal materials is a promising strategy for seawater desalination and wastewater purification. Tightly packed 2D membranes with high reflection losses and limited vapor escape channels result in a low evaporation rate. In this work, 3D MXene architecture was fabricated by dropping the delaminated Ti3C2 ([Formula: see text]-Ti3C2) nanosheets onto the carbonized melamine foam (CMF) framework. Owing to the macroporous 3D architecture, more effective broadband solar absorption and vapor escaping were achieved. As a result, the 3D CMF@[Formula: see text]-Ti3C2-based evaporator delivers a water evaporation rate of 1.60[Formula: see text]kg/m2[Formula: see text][Formula: see text][Formula: see text]h with a solar-to-vapor conversion efficiency of up to 84.6%.
The Reliability of Enterprise Applications
Authors: Sha Sanjay
Published: January 2020

Enterprise reliability is a discipline that ensures applications will deliver the required business functionality in a consistent, predictable, and cost-effective manner without compromising core aspects such as availability, performance, and maintainability. This article describes a core set of principles and engineering methodologies that enterprises can apply to help them navigate the complex environment of enterprise reliability and deliver highly reliable and cost-efficient applications.
Investigating fibrosis and inflammation in an ex vivo NASH murine model
Authors: Gore Emilia , Bigaeva Emilia , Oldenburger Anouk , Jansen Yvette J. M. , Schuppan Detlef , Boersema Miriam , Rippmann Jörg F. , Broermann Andre , Olinga Peter
Published: January 2020

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, characterized by excess fat accumulation (steatosis). Nonalcoholic steatohepatitis (NASH) develops in 15–20% of NAFLD patients and frequently progresses to liver fibrosis and cirrhosis. We aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices (PCLS). NASH was induced in C57Bl/6 mice on an amylin and choline-deficient l-amino acid-defined (CDAA) diet. PCLS were prepared from steatohepatitic (sPCLS) and control (cPCLS) livers and cultured for 48 h with LPS, TGFβ1, or elafibranor. Additionally, C57Bl/6 mice were placed on CDAA diet for 12 wk to receive elafibranor or vehicle from weeks 7 to 12. Effects were assessed by transcriptome analysis and procollagen Iα1 protein production. The diets induced features of human NASH. Upon culture, all PCLS showed an increased gene expression of fibrosis- and inflammation-related markers but decreased lipid metabolism markers. LPS and TGFβ1 affected sPCLS more pronouncedly than cPCLS. TGFβ1 increased procollagen Iα1 solely in cPCLS. Elafibranor ameliorated fibrosis and inflammation in vivo but not ex vivo, where it only increased the expression of genes modulated by PPARα. sPCLS culture induced inflammation-, fibrosis-, and lipid metabolism-related transcripts, explained by spontaneous activation. sPCLS remained responsive to proinflammatory and profibrotic stimuli on gene expression. We consider that PCLS represent a useful tool to reproducibly study NASH progression. sPCLS can be used to evaluate potential treatments for NASH, as demonstrated in our elafibranor study, and serves as a model to bridge results from rodent studies to the human system.

NEW & NOTEWORTHY This study showed that nonalcoholic steatohepatitis can be studied ex vivo in precision-cut liver slices obtained from murine diet-induced fatty livers. Liver slices develop a spontaneous inflammatory and fibrogenic response during culture that can be augmented with specific modulators. Additionally, the model can be used to test the efficacy of pharmaceutical compounds (as shown in this investigation with elafibranor) and could be a tool for preclinical assessment of potential therapies.
Loss of circadian geneBmal1in the collecting duct lowers blood pressure in male, but not female, mice
Authors: Zhang Dingguo , Jin Chunhua , Obi Ijeoma E. , Rhoads Megan K. , Soliman Reham H. , Sedaka Randee S. , Allan J. Miller , Tao Binli , Speed Joshua S. , Pollock Jennifer S. , Pollock David M.
Published: January 2020

Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor Bmal1. A high-salt diet induces a phase shift in Bmal1 expression in the renal inner medulla that is dependent on endothelin type B (ETB) receptors. Furthermore, ETBreceptor-mediated natriuresis is sex dependent. Therefore, experiments tested the hypothesis that collecting duct Bmal1 regulates blood pressure in a sex-dependent manner. We generated a mouse model that lacks Bmal1 expression in the collecting duct, where ETBreceptor abundance is highest. Male, but not female, collecting duct Bmal1 knockout (CDBmal1KO) mice had significantly lower 24-h mean arterial pressure (MAP) than flox controls (105 ± 2 vs. 112 ± 3 mmHg for male mice and 106 ± 1 vs. 108 ± 1 mmHg for female mice, by telemetry). After 6 days on a high-salt (4% NaCl) diet, MAP remained significantly lower in male CDBmal1KO mice than in male flox control mice (107 ± 2 vs. 113 ± 1 mmHg), with no significant differences between genotypes in female mice (108 ± 2 vs. 109 ± 1 mmHg). ETBreceptor blockade for another 6 days increased MAP similarly in both male and female CDBmal1KO and flox control mice. However, MAP remained lower in male CDBmal1KO mice than in male flox control mice (124 ± 2 vs. 130 ± 2 mmHg). No significant differences were observed between female CDBmal1KO and flox mice during ETBblockade (130 ± 2 vs. 127 ± 2 mmHg). There were no significant genotype differences in amplitude or phase of MAP in either sex. These data suggest that collecting duct Bmal1 has no role in circadian MAP but plays an important role in overall blood pressure in male, but not female, mice.
The expression level of class III phosphatidylinositol-3 kinase controls the degree of compensatory nephron hypertrophy
Authors: Liu Ting , Dai Caihong , Xu Jinxian , Li Shude , Chen Jian-Kang
Published: January 2020

Excessive compensatory nephron hypertrophy (CNH) has been implicated in setting the stage for progressive nephron damage. Lack of a class III phosphatidylinositol 3-kinase (Pik3c3) inhibitor suitable for using in animals and lack of a Pik3c3-deficient animal model preclude the possibility of conclusively defining a role for Pik3c3 in CNH in previous studies. Here, we report that insertion of an Frt-flanked PGK-Neo cassette into intron 19 of the mouse Pik3c3 gene resulted in a hypomorphic allele. This allowed us to create a unique mouse model and provide the first definitive genetic evidence demonstrating whether Pik3c3 is essential for the regulation of CNH. Our results indicate that homozygous Pik3c3 hypomorphic ( Pik3c3Hypo/Hypo) mice express significantly low levels of Pik3c3 than heterozygous Pik3c3 hypomorphic ( Pik3c3Hypo/WT) littermates, which already express a lower level of Pik3c3 than wild-type ( Pik3c3WT/WT) littermates. Interestingly, after unilateral nephrectomy (UNX), Pik3c3Hypo/Hypo mice develop a significantly lower degree of CNH than Pik3c3WT/WT mice and Pik3c3Hypo/WT mice, as revealed by measurement of kidney weight, kidney-to-body weight ratio, renal protein-to-DNA ratio, and morphometric analysis of proximal tubular and glomerular size. Mechanistically, UNX-induced mammalian target of rapamycin complex 1 (mTORC1) signaling to phosphorylation of ribosomal protein S6 (rpS6) in the remaining kidney was markedly inhibited in Pik3c3 hypomorphic mice. In conclusion, the present study reports a Pik3c3 hypomorphic mouse model and provides the first definitive evidence that Pik3c3 controls the degree of compensatory nephron hypertrophy. In addition, our signaling data provide the first definitive in vivo proof that Pik3c3 functions upstream of the mTORC1-S6 kinase 1-rpS6 pathway in the regulation of compensatory nephron hypertrophy.
Cosmc-dependent mucin-typeO-linked glycosylation is essential for podocyte function
Authors: Stotter Brian R. , Talbot Brianna E. , Capen Diane E. , Artelt Nadine , Zeng Junwei , Matsumoto Yasuyuki , Endlich Nicole , Cummings Richard D. , Schlondorff Johannes S.
Published: January 2020

Mucin-type O-linked glycosylation, a posttranslational modification affecting the stability and biophysical characteristics of proteins, requires C1GalT1 (T synthase) and its obligate, X-linked chaperone Cosmc. Hypomorphic C1GalT1 mutations cause renal failure via not yet established mechanisms. We hypothesize that impaired Cosmc-dependent O-glycosylation in podocytes is sufficient to cause disease. Podocyte-specific Cosmc knockout mice were generated and phenotyped to test this hypothesis. Female heterozygous mice displaying mosaic inactivation of Cosmc in podocytes due to random X-linked inactivation were also examined. Mice with podocyte-specific Cosmc deletion develop profound albuminuria, foot process effacement, glomerular sclerosis, progressive renal failure, and impaired survival. Glomerular transcriptome analysis reveals early changes in cell adhesion, extracellular matrix organization, and chemokine-mediated signaling pathways, coupled with podocyte loss. Expression of the O-glycoprotein podoplanin was lost, while Tn antigen, representing immature O-glycans, was most abundantly found on podocalyxin. In contrast to hemizygous male and homozygous female animals, heterozygous female mosaic animals developed only mild albuminuria, focal foot process effacement, and nonprogressive kidney disease. Ultrastructurally, Cosmc-deficient podocytes formed Tn antigen-positive foot processes interdigitating with those of normal podocytes but not with other Cosmc-deficient cells. This suggests a cell nonautonomous mechanism for mucin-type O-glycoproteins in maintaining podocyte function. In summary, our findings demonstrated an essential and likely cell nonautonomous role for mucin-type O-glycosylation for podocyte function.
Enhancing kidney DDAH-1 expression by adenovirus delivery reduces ADMA and ameliorates diabetic nephropathy
Authors: Wetzel Michael D. , Gao Ting , Stanley Kristen , Cooper Timothy K. , Morris Sidney M. , Awad Alaa S.
Published: January 2020

Endothelial dysfunction, characterized by reduced bioavailability of nitric oxide and increased oxidative stress, is a hallmark characteristic in diabetes and diabetic nephropathy (DN). High levels of asymmetric dimethylarginine (ADMA) are observed in several diseases including DN and are a strong prognostic marker for cardiovascular events in patients with diabetes and end-stage renal disease. ADMA, an endogenous endothelial nitric oxide synthase (NOS3) inhibitor, is selectively metabolized by dimethylarginine dimethylaminohydrolase (DDAH). Low DDAH levels have been associated with cardiac and renal dysfunction, but its effects on DN are unknown. We hypothesized that enhanced renal DDAH-1 expression would improve DN by reducing ADMA and restoring NOS3 levels. DBA/2J mice injected with multiple low doses of vehicle or streptozotocin were subsequently injected intrarenally with adenovirus expressing DDAH-1 (Ad-h-DDAH-1) or vector control [Ad-green fluorescent protein (GFP)], and mice were followed for 6 wk. Diabetes was associated with increased kidney ADMA and reduced kidney DDAH activity and DDAH-1 expression but had no effect on kidney DDAH-2 expression. Ad-GFP-treated diabetic mice showed significant increases in albuminuria, histological changes, glomerular macrophage recruitment, inflammatory cytokine and fibrotic markers, kidney ADMA levels, and urinary thiobarbituric acid reactive substances excretion as an indicator of oxidative stress, along with a significant reduction in kidney DDAH activity and kidney NOS3 mRNA compared with normal mice. In contrast, Ad-h-DDAH-1 treatment of diabetic mice reversed these effects. These data indicate, for the first time, that DDAH-1 mediates renal tissue protection in DN via the ADMA-NOS3-interaction. Enhanced renal DDAH-1 activity could be a novel therapeutic tool for treating patients with diabetes.
Effect of Preoperative Nutritional Risk Screening on Postoperative Recovery in Patients with Laparoscopic-Assisted Radical Resection for Colorectal Cancer
Authors: Wang Xiaolong , Wu Jianlin , Lei Sen , Tian Feng , Cao Ce , Shi Guangfeng
Published: January 2020

Background and Objectives. This study investigated the effect of preoperative nutrition on the recovery and prognosis of colorectal cancer patients after laparoscopic radical resection. Methods and Study Design. A retrospective analysis was conducted on 120 colorectal cancer patients between January 2015 and August 2017. Patients were divided into two groups: those without nutritional risk (NRS 2002<3) and those with nutritional risk (NRS 2002≥3). The impacts of preoperative nutritional status on postoperative complications and short-term outcomes were analyzed. Finally, univariate and multivariate logistic regression analyses were used to study risk factors associated with postoperative complications. Results. There were statistically significant differences in BMI, albumin, total cholesterol, and lymphocyte count between patients from the two groups (all P<0.05). There was no difference in the incidence rate of postoperative complications between the two groups, but there was a statistically significant difference in the total number of complications (P<0.05). There were no significant differences between the two groups regarding abdominal drainage volume, exhaust (flatus) time, hospitalization cost, morbidity, or 60 d readmission rate (all P>0.05). However, patients with nutritional risk had higher postoperative blood transfusion volumes, albumin infusions, weight difference before and after surgery, and postoperative hospital stays than the nonnutritional risk group (all P<0.05). Smoking, diabetes, and preoperative nutritional risk were the risk factors by the univariate and multivariate logistic regression analyses. Conclusions. The postoperative complication rate was increased, and the short-term efficacy was decreased in the preoperative nutritional risk group compared with those without nutritional risk.
Predicting the Viscosity of Petroleum Emulsions Using Gene Expression Programming (GEP) and Response Surface Methodology (RSM)
Authors: Umar Abubakar A. , Saaid Ismail M. , Sulaimon Aliyu A. , Pilus Rashidah M.
Published: January 2020

This paper summarizes an investigation of certain operating parameters on the viscosity of petroleum emulsions. The production of crude oil is accompanied by emulsified water production, which comes along with various challenges like corroding the transport systems and catalysts poisoning during petroleum refining in the downstream. Several process variables are believed to affect the ease with which emulsified water can be separated from emulsions. Some of the issues have not been extensively examined in the literature. The simplicity with which water is separated from petroleum changes with age (after formation) of the emulsion; notwithstanding, this subject has not been investigated broadly in literature. This study tries to assess the correlation between aging time, water cut, crude oil viscosity, water viscosity and amount of solids and viscosity of petroleum emulsions. To achieve that, a response surface methodology (RSM) based on Box-Behnken design (BBD) was used to design the experiment. Synthetic emulsions were prepared from an Offshore Malaysian Crude oil based on the DoE design and were aged for 7 days. The emulsions viscosities were measured at 60-degree Celsius using an electromagnetic viscometer (EV100). The broad pressure and temperature range of the HPHT viscometer permit the imitation of acute conditions under which such emulsions may form. The data obtained from the RSM analysis was used to develop a prediction model using gene expression programming (GEP). It was discovered that the viscosity of water has no effect on the viscosities of the studied emulsions, as does the water cut and amount of solids. The most significant factor that affects emulsion viscosity is the aging time, with the emulsion becoming more viscous over time. This is believed to be imminent because of variations in the interfacial film structure. This is followed by the amount of solids, also believed to be as a result of increasing coverage at the interface of the water droplets, limiting the movements of the dispersed droplets (reduced coalescence), thereby increasing the viscosity of the emulsions.
The Shrinking of Beijing and the Rising of Xiong’an: Optimize Population Migration in terms of Transport Service
Authors: Lin Hongzhi
Published: January 2020

The population of Beijing has already come to its loading capacity. The China central government plans to build an ideal city named Xiong’an nearby Beijing. The city is expected to work as a carrying hub for noncapital functions of Beijing. The central government does not rush to build before a deliberated urban planning is accomplished. For sustainable development, a difficulty faced by urban planners is that the maximum number of people can be migrated from Beijing to Xiong’an with constraint on level of transport service. This paper developed a specialized bilevel programming model where the upper level is to ensure a predetermined transport service level regarding to population migration, while the lower level is feedback equilibrium between trip generation and traffic assignment. To be more specific, trip is generated by the gravity model, and traffic is assigned by the user equilibrium model. It is well known that the bilevel programming problem is tough and challenging. A try-and-error algorithm is designed for the upper-level model, and a method of successive average (MSA) is developed for the lower-level model. The effectiveness of the model and algorithm is validated by an experimental study using the current transport network between Beijing and Xiong’an. It shows that the methods can be very useful to identify the maximum population migration subject to level of transport service.
Identification of Weakly Pitch-Shifted Voice Based on Convolutional Neural Network
Authors: Ye Yongchao , Lao Lingjie , Yan Diqun , Wang Rangding
Published: January 2020

Pitch shifting is a common voice editing technique in which the original pitch of a digital voice is raised or lowered. It is likely to be abused by the malicious attacker to conceal his/her true identity. Existing forensic detection methods are no longer effective for weakly pitch-shifted voice. In this paper, we proposed a convolutional neural network (CNN) to detect not only strongly pitch-shifted voice but also weakly pitch-shifted voice of which the shifting factor is less than ±4 semitones. Specifically, linear frequency cepstral coefficients (LFCC) computed from power spectrums are considered and their dynamic coefficients are extracted as the discriminative features. And the CNN model is carefully designed with particular attention to the input feature map, the activation function and the network topology. We evaluated the algorithm on voices from two datasets with three pitch shifting software. Extensive results show that the algorithm achieves high detection rates for both binary and multiple classifications.
Transplantation Site Affects the Outcomes of Adipose-Derived Stem Cell-Based Therapy for Retinal Degeneration
Authors: Hu Chengyu , La Huanzhi , Wei Xuancheng , Zhou Yue , Ou Qingjian , Chen Zhiyang , Zhu Xiaoman , Xu Jing-Ying , Jin Caixia , Gao Furong , Wang Juan , Zhang Jingfa , Zhang Jieping , Lu Lixia , Xu Guo-Tong , Tian Haibin
Published: January 2020

Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane- (ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.
Targeting Tumor Neoangiogenesis via Targeted Adenoviral Vector to Achieve Effective Cancer Gene Therapy for Disseminated Neoplastic Disease
Authors: Lee Myungeun , Lu Zhi Hong , Li Jie , Kashentseva Elena A. , Dmitriev Igor P. , Mendonca Samir A. , Curiel David T.
Published: January 2020

The application of cancer gene therapy has heretofore been restricted to local, or locoregional, neoplastic disease contexts. This is owing to the lack of gene transfer vectors, which embody the requisite target cell selectivity in vivo required for metastatic disease applications. To this end, we have explored novel vector engineering paradigms to adapt adenovirus for this purpose. Our novel strategy exploits three distinct targeting modalities that operate in functional synergy. Transcriptional targeting is achieved via the hROBO4 promoter, which restricts transgene expression to proliferative vascular endothelium. Viral binding is modified by incorporation of an RGD4C peptide in the HI loop of the fiber knob for recognition of cellular integrins. Liver sequestration is mitigated by ablation of factor X binding to the major capsid protein hexon by a serotype swap approach. The combination of these technologies into the context of a single-vector agent represents a highly original approach. Studies in a murine model of disseminated cancer validated the in vivo target cell selectivity of our vector agent. Of note, clear gains in therapeutic index accrued these vector modifications. Whereas there is universal recognition of the value of vector targeting, very few reports have validated its direct utility in the context of cancer gene therapy. In this regard, our article validates the direct gains that may accrue these methods in the stringent delivery context of disseminated neoplastic disease. Efforts to improve vector targeting thus represent a critical direction to fully realize the promise of cancer gene therapy.
Assessment of Chronological Volume Changes in Radial Forearm Free Flaps for Tongue Cancer
Authors: Kim Min-Su , Oh Kyoung Ho , Cho Jae-Gu , Baek Seung-Kuk , Woo Jeong-Soo , Jung Kwang-Yoon , Kwon Soon Young
Published: January 2020

Objective: The radial forearm free flap (RFFF) is a commonly used free flap for tongue cancer. Postoperative changes in the volume of free flap are known to influence the functional restoration of the resected tongue. This study aimed to estimate chronological volume changes in RFFFs for tongue cancer and to determine the clinical factors affecting these changes. Methods: Clinical data for 19 patients who underwent RFFF reconstruction for tongue cancer between May 2004 and September 2013 were retrospectively reviewed. The flap volume was measured 3, 6, 12, 24, and 36 months after surgery using CT and the Picture Archiving and Communication System software. Results: Relative to volumes at 3 months, median flap volumes decreased to 98.55, 70.16, 62.86, and 58.84% at 6, 12, 24, and 36 months, respectively. None of the evaluated parameters were correlated with volume changes. Conclusions: Over time, the volume of RFFF in the tongue decreased. Considering this, free flap reconstruction should be carried out in tongue cancer surgery.
Endoscopic Treatment of Obesity: From Past to Future
Authors: Štimac Davor , Klobučar Majanović Sanja , Belančić Andrej
Published: January 2020

Background: Conventional approaches in the management of obesity offer only a limited potential for sustained weight loss. Moreover, bariatric surgery, although momentarily being the most effective weight-loss treatment, has some serious pitfalls, such as significant morbidity rate, high substantial costs and limited patient applicability. Hence, there is a substantial need for endoscopic approaches to obesity. Summary: The aim of this article is to provide a historical overview of bariatric endoscopy in the management of obesity; moreover to selectively review and evaluate the currently available endoscopic weight-loss techniques and devices, and third to identify new directions and future prospects in this rapidly advancing field. Key Messages: Bariatric endoscopy procedures efficiently replicate some of the anatomical features and the physiological effects of the traditional weight-loss surgical approaches, while at the same time being more applicable, entirely reversible, less-invasive, safer and more cost effective. Endoscopic modalities in the treatment of obesity can be categorized into the following: restrictive procedures, malabsorptive procedures, gastric function/emptying regulation, gastric aspiration, and so on. To conclude, it is of high importance to constantly evaluate the long-term efficacy and safety of new endoscopic weight-loss techniques and devices, based on evidence-based medicine principles.
Evolution and Revolution of Hepatitis C Management: From Non-A, Non-B Hepatitis Toward Global Elimination
Authors: Basyte-Bacevice Viktorija , Kupcinskas Juozas
Published: January 2020

Discovery of hepatitis C in 1989 allowed basic research to identify critical components of hepatitis C virus (HCV) structure and life cycle. Interferon (IFN)-α was introduced as first treatment for chronic hepatitis C and later was enhanced by pegylation, addition of ribavirin, and resulted in improved sustained virologic response. Better understanding of HCV structure, enzymes, and lifecycle led to the discovery of direct-acting antivirals and IFN-free era. Successful HCV therapy created a rare possibility of global disease eradication, which is now a major goal internationally. However, hepatitis C remains a major public health challenge, and more resources are needed to reach global elimination.
Recognition and Initial Management of Fulminant Myocarditis
Authors: Kociol Robb D. , Cooper Leslie T. , Fang James C. , Moslehi Javid J. , Pang Peter S. , Sabe Marwa A. , Shah Ravi V. , Sims Daniel B. , Thiene Gaetano , Vardeny Orly ,   On behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology
Published: January 2020

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.
Wintertime Wood Smoke, Traffic Particle Pollution, and Preeclampsia
Authors: Assibey-Mensah Vanessa , Glantz J. Christopher , Hopke Philip K. , Jusko Todd A. , Thevenet-Morrison Kelly , Chalupa David , Rich David Q.
Published: January 2020

Previous studies have reported associations between ambient fine particle concentrations and preeclampsia; however, the impact of particulate pollution on early- and late-onset preeclampsia is understudied. Furthermore, few studies have examined the association between source-specific particles such as markers of traffic pollution or wood combustion on adverse pregnancy outcomes. Electronic medical records and birth certificate data were linked with land-use regression models in Monroe County, New York for 2009 to 2013 to predict monthly pollutant concentrations for each pregnancy until the date of clinical diagnosis during winter (November–April) for 16 116 births. Up to 30% of ambient wintertime fine particle concentrations in Monroe County, New York is from wood combustion. Multivariable logistic regression was used to separately estimate the odds of preeclampsia (all, early-, and late-onset) associated with each interquartile range increase in fine particles, traffic pollution, and woodsmoke concentrations during each gestational month, adjusting for maternal characteristics, birth hospital, temperature, and relative humidity. Each 3.64 µg/m
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increase in fine particle concentration was associated with an increased odds of early-onset preeclampsia during the first (odds ratio, 1.35 [95% CI, 1.08–1.68]), second (odds ratio, 1.51 [95% CI, 1.23–1.86]), and third (odds ratio, 1.25 [95% CI, 1.06–1.46]) gestational months. Increases in traffic pollution and woodsmoke during the first gestational month were also associated with increased odds of early-onset preeclampsia. Increased odds of late-onset preeclampsia were not observed. Our findings suggest that exposure to wintertime particulate pollution may have the greatest effect on maternal cardiovascular health during early pregnancy.
Deterring Wartime Atrocities: Hard Lessons from the Yugoslav Tribunal
Authors: McAllister Jacqueline R.
Published: January 2020

Advocates of wartime international criminal tribunals (ICTs) hope that such tribunals can deter combatant atrocities against civilians. Yet, more than twenty-five years after the establishment of the first wartime ICT—the International Criminal Tribunal for the former Yugoslavia (ICTY)—wartime ICTs’ role in deterring such violence remains a matter of debate. Insights from criminology, as well as research on civil conflicts and international legal compliance, suggest that ICTs are most likely to deter government and rebel forces from committing atrocities against civilians when all three of the following conditions are present: (1) ICT officials have secured sufficient prosecutorial support, (2) combatant groups rely on support from liberal constituencies, and (3) combatant groups have centralized structures. Case studies of the ICTY's impact on fourteen combatant groups from the Yugoslav conflicts—combined with hundreds of field interviews with war veterans and others—confirm this prediction. The ICTY's record thus sheds important light on how and when contemporary wartime ICTs—including the International Criminal Court—might succeed in deterring combatant atrocities against civilians.
Search for Face Identity or Expression: Set Size Effects in Developmental Prosopagnosia
Authors: Djouab Sara , Albonico Andrea , Yeung Shanna C. , Malaspina Manuela , Mogard Anna , Wahlberg Rachel , Corrow Sherryse L. , Barton Jason J. S.
Published: January 2020

The set size effect during visual search indexes the effects of processing load and thus the efficiency of perceptual mechanisms. Our goal was to investigate whether individuals with developmental prosopagnosia show increased set size effects when searching faces for face identity and how this compares to search for face expression. We tested 29 healthy individuals and 13 individuals with developmental prosopagnosia. Participants were shown sets of three to seven faces to judge whether the identities or expressions of the faces were the same across all stimuli or if one differed. The set size effect was the slope of the linear regression between the number of faces in the array and the response time. Accuracy was similar in both controls and prosopagnosic participants. Developmental prosopagnosic participants displayed increased set size effects in face identity search but not in expression search. Single-participant analyses reveal that 11 developmental prosopagnosic participants showed a putative classical dissociation, with impairments in identity but not expression search. Signal detection theory analysis showed that identity set size effects were highly reliable in discriminating prosopagnosic participants from controls. Finally, the set size ratios of same to different trials were consistent with the predictions of self-terminated serial search models for control participants and prosopagnosic participants engaged in expression search but deviated from those predictions for identity search by the prosopagnosic cohort. We conclude that the face set size effect reveals a highly prevalent and selective perceptual inefficiency for processing face identity in developmental prosopagnosia.
Valence-dependent Disruption in Processing of Facial Expressions of Emotion in Early Visual Cortex—A Transcranial Magnetic Stimulation Study
Authors: Guo Kun , Calver Lauren , Soornack Yoshi , Bourke Patrick
Published: January 2020

Our visual inputs are often entangled with affective meanings in natural vision, implying the existence of extensive interaction between visual and emotional processing. However, little is known about the neural mechanism underlying such interaction. This exploratory transcranial magnetic stimulation (TMS) study examined the possible involvement of the early visual cortex (EVC, Area V1/V2/V3) in perceiving facial expressions of different emotional valences. Across three experiments, single-pulse TMS was delivered at different time windows (50–150 msec) after a brief 10-msec onset of face images, and participants reported the visibility and perceived emotional valence of faces. Interestingly, earlier TMS at ∼90 msec only reduced the face visibility irrespective of displayed expressions, but later TMS at ∼120 msec selectively disrupted the recognition of negative facial expressions, indicating the involvement of EVC in the processing of negative expressions at a later time window, possibly beyond the initial processing of fed-forward facial structure information. The observed TMS effect was further modulated by individuals' anxiety level. TMS at ∼110–120 msec disrupted the recognition of anger significantly more for those scoring relatively low in trait anxiety than the high scorers, suggesting that cognitive bias influences the processing of facial expressions in EVC. Taken together, it seems that EVC is involved in structural encoding of (at least) negative facial emotional valence, such as fear and anger, possibly under modulation from higher cortical areas.
The Art of the Bedchamber and Jin Ping Mei
Authors: McMahon Keith
Published: January 2020

The ‘art of the bedchamber’ texts occupy a key place in pre-modern Chinese sexual culture, sharing that place with an even larger body of texts of later origin, the sexually explicit novels and stories of the Ming (1368-1644) and Qing (1644-1911) dynasties, and Jin Ping Mei (The plum in the golden vase) in particular. The two genres – the texts of the bedchamber arts and Ming and Qing erotic fiction – have key commonalities, especially in the governing theme that not only must a man please a woman in sex, but that she is sexually formidable, and that he must be masterful in order to please her. Both genres center on the man’s relations with multiple women. But they differ because what appears as the art of sex in Ming and Qing fiction drastically reinvents the contents and spirit of the classic art of the bedchamber, which promotes sex as the harmonizing of yin and yang for the sake of nourishing health and longevity. Sex is measured and temperate, neither rushed nor violent. The art of sex in Ming and Qing fiction instead focuses on ways in which characters make themselves sexually powerful, usually by means of drugs and/or the use of special techniques, including those that absorb vital essences from their partners. Besides detailing these points, the article will analyze specific traces of the art of the bedchamber in Jin Ping Mei, such as the practices of kissing and absorbing saliva, the adoption of positions of intercourse, and the use of sexual devices, chemicals, and aphrodisiacs.