bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse large B-cell lymphomas
Authors: Pascual Marién , Mena-Varas María , Robles Eloy Francisco , Garcia-Barchino Maria-Jose , Panizo Carlos , Hervas-Stubbs Sandra , Alignani Diego , Sagardoy Ainara , Martinez-Ferrandis Jose Ignacio , Bunting Karen L. , Meier Stephen , Sagaert Xavier , Bagnara Davide , Guruceaga Elizabeth , Blanco Oscar , Celay Jon , Martínez-Baztan Alvaro , Casares Noelia , Lasarte Juan José , MacCarthy Thomas , Melnick Ari , Martinez-Climent Jose Angel , Roa Sergio 
Published: April 2019

Abstract
Refractory or relapsed diffuse large B-cell lymphoma (DLBCL) often associates with the activated B-cell-like (ABC) subtype and genetic alterations that drive constitutive NF-κB activation and impair B-cell terminal differentiation. Here, we show that DNA damage response by p53 is a central mechanism suppressing the pathogenic cooperation of IKK2ca-enforced canonical NF-κB and impaired differentiation resulting from Blimp1 loss in ABC-DLBCL lymphomagenesis. We provide evidences that the interplay between these genetic alterations and the tumor microenvironment select for additional molecular addictions that promote lymphoma progression, including aberrant coexpression of FOXP1 and the B-cell mutagenic enzyme activation-induced deaminase, and immune evasion through major histocompatibility complex class II downregulation, PD-L1 upregulation, and T-cell exhaustion. Consistently, PD-1 blockade cooperated with anti-CD20-mediated B-cell cytotoxicity, promoting extended T-cell reactivation and antitumor specificity that improved long-term overall survival in mice. Our data support a pathogenic cooperation among NF-κB-driven prosurvival, genetic instability, and immune evasion mechanisms in DLBCL and provide preclinical proof of concept for including PD-1/PD-L1 blockade in combinatorial immunotherapy for ABC-DLBCL.
CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p
Authors: Wang Lu , Yang Guang , Zhao Danfeng , Wang Jiaqi , Bai Yang , Peng Qiang , Wang Hongzhi , Fang Ruizhe , Chen Guang , Wang Zhichao , Wang Keliang , Li Guangbin , Yang Yinhui , Wang Ziqi , Guo Pengyu , Peng Li , Hou Dayong , Xu Wanhai 
Published: April 2019

Abstract

Background
Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells.

Methods
The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined.

Results
CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103+ CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103+ exosomes were increased in blood samples from CCRCC patients with lung metastasis.

Conclusions
CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103+ acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103+ exosomes as a potential metastatic diagnostic biomarker.

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Attack detection in water distribution systems using machine learning
Authors: Ramotsoela Daniel T. , Hancke Gerhard P. , Abu-Mahfouz Adnan M. 
Published: April 2019

Abstract
The threat to critical water system infrastructure has increased in recent years as is evident from the increasing number of reported attacks against these systems. Preventative security mechanisms are often not enough to keep attackers out so a second layer of security in the form of intrusion detection is paramount in order to limit the damage of successful attacks. In this paper several traditional anomaly detection techniques are evaluated in the context of attack detection in water distribution systems. These algorithms were centrally trained on the entire feature space and compared to multi-stage detection
techniques that were designed to isolate both local and global anomalies. A novel ensemble technique that combines density-based and parametric algorithms was also developed and tested in the application environment. The traditional techniques had comparable results to the multi-stage systems and when used in conjunction with a local anomaly detector the performances of these algorithms were greatly improved. The developed ensemble technique also had promising results outperforming the density-based techniques and having comparable results to the parametric algorithms.
Seismic attribute enhancement of weak and discontinuous gas hydrate bottom-simulating reflectors in the Pegasus Basin, New Zealand
Authors: Bedle Heather 
Published: April 2019

Gas hydrates in the oceanic subsurface are often difficult to image with reflection seismic data, particularly when the strata run parallel to the seafloor and in regions that lack the presence of a bottom-simulating reflector (BSR). To address and understand these imaging complications, rock-physics modeling and seismic attribute analysis are performed on modern 2D lines in the Pegasus Basin in New Zealand, where the BSR is not continuously imaged. Based on rock-physics and seismic analyses, several seismic attribute methods identify weak BSR reflections, with the far-angle stack data being particularly effective. Rock modeling results demonstrate that far-offset seismic data are critical in improving the imaging and interpretation of the base of the gas hydrate stability zone. The rock-physics modeling results are applied to the Pegasus 2009 2D data set that reveals a very weak seismic reflection at the base of the hydrates in the far-angle stack. This often-discontinuous reflection is significantly weaker in amplitude than typical BSRs associated with hydrates. These weak far-angle stack BSRs often do not appear clearly in full stack data, the most commonly interpreted seismic data type. Additional amplitude variation with angle (AVA) attribute analyses provide insight into identifying the presence of gas hydrates in regions lacking a strong BSR. Although dozens of seismic attributes were investigated for their ability to reveal weak reflections at the base of the gas hydrate stability zone, those that enhance class 2 AVA anomalies were most effective, particularly the seismic fluid factor attribute.
Cultural adaptation of cognitive–behavioural therapy
Authors: Naeem Farooq , Phiri Peter , Rathod Shanaya , Ayub Muhammad 
Published: April 2019

SUMMARYThe study of cultural factors in the application of psychotherapy across cultures – ethnopsychotherapy – is an emerging field. It has been argued that Western cultural values underpin cognitive–behavioural therapy (CBT) as they do other modern psychosocial interventions developed in the West. Therefore, attempts have been made to culturally adapt CBT for ethnic minority patients in the West and local populations outside the West. Some frameworks have been proposed based on therapists’ individual experiences, but this article describes a framework that evolved from a series of qualitative studies to culturally adapt CBT and that was field tested in randomised controlled trials. We describe the process of adaptation, details of methods used and the areas that need to be focused on to adapt CBT to a given culture. Further research is required to move the field forward, but cultural adaptation alone cannot improve outcomes. Access to evidence-based psychosocial interventions, including CBT, needs to be improved for culturally adapted interventions to achieve their full potential.LEARNING OBJECTIVESAfter reading this article you will be able to:
•recognise the link between cultural factors and the need to adapt psychosocial interventions•identify the necessary steps to culturally adapt CBT•understand the modifications required to deliver therapy to individuals from diverse cultural backgrounds.
Mathematical Approach to Differentiate Spontaneous and Induced Evolution to Drug Resistance During Cancer Treatment
Authors: Greene James M. , Gevertz Jana L. , Sontag Eduardo D. 
Published: April 2019

Purpose Drug resistance is a major impediment to the success of cancer treatment. Resistance is typically thought to arise from random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that progression to drug resistance need not occur randomly, but instead may be induced by the treatment itself via either genetic changes or epigenetic alterations. This relatively novel notion of resistance complicates the already challenging task of designing effective treatment protocols. Materials and Methods To better understand resistance, we have developed a mathematical modeling framework that incorporates both spontaneous and drug-induced resistance. Results Our model demonstrates that the ability of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. We have also proven that the induction parameter in our model is theoretically identifiable and propose an in vitro protocol that could be used to determine a treatment’s propensity to induce resistance.
Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting
Authors: Bidaud-Meynard Aurélien , Bossard Florian , Schnúr Andrea , Fukuda Ryosuke , Veit Guido , Xu Haijin , Lukacs Gergely L. 
Published: April 2019

ABSTRACT
Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia and can be impaired in human diseases. Maintenance of apical polarity in the face of CFTR non-polarized delivery and inefficient apical retention of mutant CFTRs lacking PDZ-domain protein (NHERF1, also known as SLC9A3R1) interaction, remains enigmatic. Here, we show that basolateral CFTR delivery originates from biosynthetic (∼35%) and endocytic (∼65%) recycling missorting. Basolateral channels are retrieved via basolateral-to-apical transcytosis (hereafter denoted apical transcytosis), enhancing CFTR apical expression by two-fold and suppressing its degradation. In airway epithelia, CFTR transcytosis is microtubule-dependent but independent of Myo5B, Rab11 proteins and NHERF1 binding to its C-terminal DTRL motif. Increased basolateral delivery due to compromised apical recycling and accelerated internalization upon impaired NHERF1–CFTR association is largely counterbalanced by efficient CFTR basolateral internalization and apical transcytosis. Thus, transcytosis represents a previously unrecognized, but indispensable, mechanism for maintaining CFTR apical polarity that acts by attenuating its constitutive and mutation-induced basolateral missorting.
Enhanced Visible-Light-Driven H2 Production via UiO-66 Nanospheres Attached to Flower-Shaped ZnIn2S4 Microspheres
Authors: Jiang Jifei , Zhu Qiong , Guo Yu , Cheng Lin , Lou Yongbing , Chen Jinxi 
Published: April 2019

Abstract
Photocatalytic hydrogen production is an effective strategy for meeting energy challenges. Here, a composite for photocatalytic hydrogen production via introduction of UiO-66 nanospheres into flower-shaped ZnIn2S4 microspheres (ZIS/U6) is described. The optimum composite with 20 mg UiO-66 loading displayed the high photocatalytic rate of 1860.9 µmol g−1 h−1 with an apparent quantum efficiency of 1.4% at 420 nm under visible-light irradiation, which is nearly 3 times higher than that of ZnIn2S4. The improved photocatalytic H2 rate mainly benefited from effective electron transfer between ZnIn2S4 and UiO-66. Additionally, we tried to introduce UiO-66-NH2 and UiO-66-(SH)2 with excellent visible light absorption into ZnIn2S4 to obtain composites. Surprisingly, they did not exhibit better photocatalytic hydrogen production rates. Combined with the electrochemical test results, it was found that they had completely different electron transfer paths from ZIS/U6. Therefore, a different photocatalytic mechanism was proposed and further verified by transient photocurrent.
Extraction and purification of RNA from human carious dentine: an approach to enable bacterial gene expression studies
Authors: Bezerra Daniela da Silva , Neves Beatriz Gonçalves , Guedes Sarah Florindo de Figueiredo , Regis Wanessa Fernandes Matias , Stipp Rafael Nobrega , Rodrigues Lidiany Karla Azevedo 
Published: April 2019

Background: RNA isolation from bacteria within dentine caries lesions could be difficult due to reduced amount of collectable biomass and high mRNA instability. Attempting to overcome this challenge we describe one protocol developed to extract and purify total RNA from dentine lesions. Objective: customize a bacterial RNA extraction and purification method from human carious dentine. Methods: quantity and purity of extracted RNA were measured with a microvolume UV-VIS spectrophotometer, RNA integrity was assessed by standard denaturing agarose gel electrophoresis and images were captured under ultraviolet light with camera and analyzed. DNase treatment removed genomic DNA and an additional step of purification was carried out in silica spin column. Results: final yield (ng/μl) was 67.01 ± 22.33, absorbance ratio A260/A280 = 2.0 ± 0.07 and RNA integrity were obtained. The purified samples were reversely transcribed and the expression of atpD and fabM gene from Streptococcus mutans analyzed by quantitative real-time PCR. Conclusion: the extraction methodology developed produced high-quality RNA from dentine microbiota for transcriptional analysis.
The study of protein recruitment to laser-induced DNA lesions can be distorted by photoconversion of the DNA binding dye Hoechst
Authors: Hurst Verena , Gasser Susan M. 
Published: April 2019

A commonly used approach for assessing DNA repair factor recruitment in mammalian cells is to induce DNA damage with a laser in the UV or near UV range and follow the local increase of GFP-tagged proteins at the site of damage. Often these measurements are performed in the presence of the blue DNA dye Hoechst, which is used as a photosensitizer. However, a light-induced switch of Hoechst from a blue-light to a green-light emitter will give a false positive signal at the site of damage. Thus, photoconversion signals must be subtracted from the overall green-light emission to determine true recruitment. Here we demonstrate the photoconversion effect and suggest control experiments to exclude false-positive results.
Search Among Queues Under Quality Differentiation
Authors: Yang Luyi , Debo Laurens G. , Gupta Varun 
Published: April 2019

Customers looking for service providers often face search frictions and have to trade off quality and availability. To understand customers’ search behavior when they are confronted with a large collection of vertically differentiated, congested service providers, we build a model in which arriving customers conduct a costly sequential search to resolve uncertainty about service providers’ quality and queue length and select one to join by optimal stopping rules. Customers search, in part, because of variations in waiting time across service providers, which, in turn, is determined by the search behavior of customers. Thus, an equilibrium emerges. We characterize customers’ equilibrium search/join behavior in a mean field model as the number of service providers grows large. We find that reducing either the search cost or customer arrival rate may increase the average waiting time in the system as customers substitute toward high-quality service providers. Moreover, with lower search costs, the improved quality obtained by customers may not make up for the prolonged wait, therefore degrading the average search reward and, more importantly, decreasing customer welfare; when customers search, their welfare can even be lower than if they are not allowed to search at all. This paper was accepted by Gad Allon, operations management.
Zonificación forestal bajo el concepto de Áreas de Respuesta Homogénea en el centro de México
Authors: Reyes Cárdenas Oscar , Flores Garnica José Germán , Treviño Garza Eduardo Javier , Aguirre Calderón Oscar Alberto , Cárdenas Tristán Abraham 
Published: April 2019

El aprovechamiento racional de los recursos naturales hace necesario identificar y analizar su condición espaciotemporal; existen diversas técnicas para generar información al respecto basadas en el manejo de información dentro del Sistema de Información Geográfica (SIG). Por ello, el objetivo del presente trabajo fue determinar Áreas de Respuesta Homogénea (ARH) que identifiquen superficies forestales, con condiciones ambientales similares, mediante el empleo de la técnica del álgebra de mapas. Para lograr lo anterior, se utilizó como variable principal el tipo de vegetación (6 clases) y fue complementada con variables físicas del territorio, tales como exposición (5 clases), altitud (7 intervalos) y tipo de suelo (8 clases). Para determinar las ARH se generaron expresiones a partir de la combinación de las clases mencionadas. En total se desarrollaron 2 016 combinaciones. Con el propósito de realizar la validación de los resultados se utilizaron los datos registrados en los conglomerados del Inventario Nacional Forestal y Suelos 2004-2007. Como resultado de este estudio se obtuvieron mapas por cada tipo de vegetación, en los cuales se presentan las cinco combinaciones a partir de las que se obtuvieron las mayores superficies. Con la finalidad de determinar la confiabilidad de los resultados se generó una matriz de confusión y se calculó el índice Kappa. A partir de los resultados conseguidos, se considera que, con la combinación de las cuatro variables empleadas en el estudio, es posible determinar superficies forestales, por lo que pueden ser empleadas en la definición de éstas.
Kombination unterschiedlicher Modellierungsansätze für die betriebsbegleitende Simulation industrieller Prozesse
Authors: Bergs Christoph , Heizmann Michael 
Published: April 2019

Zusammenfassung
Die Kombination von unterschiedlichen Modellierungsansätzen wird schon seit längerer Zeit betrachtet – vor allem um sogenannte Grey-Box-Modelle zu erstellen. Im Rahmen der Digitalisierung von Produktionen entstehen jedoch bedingt durch eine größere Datenbasis neue Möglichkeiten im Bereich der Modellbildung. Dieser Beitrag befasst sich daher mit einem Konzept, Modelle unterschiedlicher Produktlebenszyklusphasen sowie unterschiedlichen Typs miteinander zu kombinieren. Diese Modellkombination soll einen Mehrwert für den Betreiber darstellen, indem dieser detaillierte Simulationsmodelle während des Betriebs als Entscheidungsunterstützung verwenden kann. Zunächst werden die unterschiedlichen Modellierungsansätze sowie deren Kombination eingeführt. Daraufhin wird ein Konzept für das Training und die Betriebsphase der Modelle beschrieben. Abschließend wird das Potential des Ansatzes am Beispiel der thermischen Zustandsüberwachung einer Asynchronmaschine dargestellt.
Comparative study of back propagation artificial neural networks and logistic regression model in predicting poor prognosis after acute ischemic stroke
Authors: Liang Yaru , Li Qiguang , Chen Peisong , Xu Lingqing , Li Jiehua 
Published: April 2019

Abstract

Objective
To investigate the predictive value of clinical variables on the poor prognosis at 90-day follow-up from acute stroke onset, and compare the diagnostic performance between back propagation artificial neural networks (BP ANNs) and Logistic regression (LR) models in predicting the prognosis.

Methods
We studied the association between clinical variables and the functional recovery of 435 acute ischemic stroke patients. The patients were divided into 2 groups according to modified Rankin Scale scores evaluated on the 90th day after stroke onset. Both BP ANNs and LR models were established for predicting the poor outcome and their diagnostic performance were compared by receiver operating curve.

Results
Age, free fatty acid, homocysteine and alkaline phosphatase were closely related with the poor outcome in acute ischemic stroke patients and finally enrolled in models. The accuracy, sensitivity and specificity of BP ANNs were 80.15%, 75.64% and 82.07% respectively. For the LR model, the accuracy, sensitivity and specificity was 70.61%, 88.46% and 63.04% respectively. The area under the ROC curve of the BP ANNs and LR model was 0.881and 0.809.

Conclusions
Both BP ANNs and LR model were promising for the prediction of poor outcome by combining age, free fatty acid, homocysteine and alkaline phosphatase. However, BP ANNs model showed better performance than LR model in predicting the prognosis.
Gang Rivalry and Crime: A Differential Game Approach
Authors: Faria João Ricardo , Mixon Franklin G. , Upadhyaya Ashish , Upadhyaya Kamal P. 
Published: April 2019

AbstractThis study contributes to the modern literature on the economics of crime by proposing and solving two models of a differential game that considers the dynamic strategic behavior of two gangs engaged in a territorial conflict. The police force acts as the leader in the game. In the first model, each gang is concerned solely by the actions of the other, thus leading to an equilibrium wherein the greater one gang’s criminal activity, the greater the rival gang’s criminal activity. In the second model both gangs account primarily for police activities aimed at maintaining law and order, thus leading to an equilibrium wherein the gangs respond directly to the law enforcement activities of the police force. Exploratory analyses employing gang-related crime and police activities in Los Angeles provide empirical support for the main features of both models of the differential game, such as how gang rivalry fuels criminal activity and how the role of police is crucial in reducing gang-related crime.
Funktionen, Konstellationen und Mittel der Wiedergabe – Ein dreidimensionales textpragmatisches Modell
Authors: Steinseifer Martin 
Published: April 2019

AbstractStarting out from examples of citing in scientific texts and based on the critical assessment of linguistic accounts, the paper argues for a domain specific pragmatic account of (speech) representation in texts. It introduces a new three-dimensional model that identifies different kinds of representation drawing on the linguisticmeansof presenting the speech of others, the specificfunctionsin narrative, reporting, and argumentative texts, and the varying communicativeconstellations – i. e. whether literal, oral, or mental, original or imagined sources are (re-)presented. By focusing on the different functions and constellations in domains like science, journalism and literature the model can serve as a framework for future comparative investigations of (speech) representation.