bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale Restructuring of Polymer Materials to Produce Single Polymer Composites and Miscible Blends
Authors: Tonelli Alan E.
Published: June 2019

I summarize work conducted in our laboratories over the past 30 years using small host molecules to restructure polymer materials at the nanometer level. Certain small molecules, such as the cyclic starches cyclodextrins (CDs) and urea (U) can form non-covalent crystalline inclusion compounds (ICs) with a range of guest molecules, including many polymers. In polymer-CD- and -U-ICs, guest polymer chains reside in narrow channels created by the host molecule crystals, where they are separated and highly extended. When the host crystalline lattice is carefully removed, the guest polymer chains coalesce into a bulk sample with an organization that is distinct from that normally produced from its melt or from solution. Amorphous regions of such coalesced polymer samples have a greater density, likely with less chain entanglement and more chain alignment. As a consequence, after cooling from their melts, coalesced amorphous polymers show glass-transition temperatures (Tgs) that are elevated above those of samples prepared from their solutions or melts. Upon cooling from their melts, coalesced samples of crystallizable polymers show dramatically-increased abilities to crystallize more rapidly and much closer to their melting temperatures (Tms). These unique behaviors of polymers coalesced from their CD- and U-ICs are unexpectedly resistant to extended annealing above their Tgs and Tms. Taking advantage of this behavior permits us to create polymer materials with unique and improved properties. Among these are amorphous polymers with elevated Tgs and semi-crystalline polymers with finer more uniform morphologies. Improved mechanical properties can be achieved through self-nucleation with small amounts of the same polymer made rapidly crystallizable through coalescence from its CD- or U-IC. This can lead to single polymer composites with as-received polymer matrices and self-nucleated reinforcements. Through simultaneous formation and subsequent coalescence from their common CD–ICs, stable well-mixed blends can be achieved between any two or more polymers, despite their inherent immiscibilities. Such coalesced and well-mixed blends are also resistant to phase segregation when heated for extensive periods well above their Tgs and Tms.
Noncompetitive Chromogenic Lateral-Flow Immunoassay for Simultaneous Detection of Microcystins and Nodularin
Authors: Akter Sultana , Kustila Teemu , Leivo Janne , Muralitharan Gangatharan , Vehniäinen Markus , Lamminmäki Urpo
Published: June 2019

Cyanobacterial blooms cause local and global health issues by contaminating surface waters. Microcystins and nodularins are cyclic cyanobacterial peptide toxins comprising numerous natural variants. Most of them are potent hepatotoxins, tumor promoters, and at least microcystin-LR is possibly carcinogenic. In drinking water, the World Health Organization (WHO) recommended the provisional guideline value of 1 µg/L for microcystin-LR. For water used for recreational activity, the guidance values for microcystin concentration varies mostly between 4–25 µg/L in different countries. Current immunoassays or lateral flow strips for microcystin/nodularin are based on indirect competitive method, which are generally more prone to sample interference and sometimes hard to interpret compared to two-site immunoassays. Simple, sensitive, and easy to interpret user-friendly methods for first line screening of microcystin/nodularin near water sources are needed for assessment of water quality and safety. We describe the development of a two-site sandwich format lateral-flow assay for the rapid detection of microcystins and nodularin-R. A unique antibody fragment capable of broadly recognizing immunocomplexes consisting of a capture antibody bound to microcystins/nodularin-R was used to develop the simple lateral flow immunoassay. The assay can visually detect the major hepatotoxins (microcystin-LR, -dmLR, -RR, -dmRR, -YR, -LY, -LF -LW, and nodularin-R) at and below the concentration of 4 µg/L. The signal is directly proportional to the concentration of the respective toxin, and the use of alkaline phosphatase activity offers a cost efficient alternative by eliminating the need of toxin conjugates or other labeling system. The easy to interpret assay has the potential to serve as a microcystins/nodularin screening tool for those involved in water quality monitoring such as municipal authorities, researchers, as well as general public concerned of bathing water quality.
Electrophysiological Responses to Emotional Facial Expressions Following a Mild Traumatic Brain Injury
Authors: Drapeau Joanie , Gosselin Nathalie , Peretz Isabelle , McKerral Michelle
Published: June 2019

The present study aimed to measure neural information processing underlying emotional recognition from facial expressions in adults having sustained a mild traumatic brain injury (mTBI) as compared to healthy individuals. We thus measured early (N1, N170) and later (N2) event-related potential (ERP) components during presentation of fearful, neutral, and happy facial expressions in 10 adults with mTBI and 11 control participants. Findings indicated significant differences between groups, irrespective of emotional expression, in the early attentional stage (N1), which was altered in mTBI. The two groups showed similar perceptual integration of facial features (N170), with greater amplitude for fearful facial expressions in the right hemisphere. At a higher-level emotional discrimination stage (N2), both groups demonstrated preferential processing for fear as compared to happiness and neutrality. These findings suggest a reduced early selective attentional processing following mTBI, but no impact on the perceptual and higher-level cognitive processes stages. This study contributes to further improving our comprehension of attentional versus emotional recognition following a mild TBI.
Imagery-Mediated Verbal Learning Depends on Vividness–Familiarity Interactions: The Possible Role of Dualistic Resting State Network Activity Interference
Authors: Lefebvre Etienne , D’Angiulli Amedeo
Published: June 2019

Using secondary database analysis, we tested whether the (implicit) familiarity of eliciting noun-cues and the (explicit) vividness of corresponding imagery exerted additive or interactive influences on verbal learning, as measured by the probability of incidental noun recall and image latency times (RTs). Noun-cues with incongruent levels of vividness and familiarity (high/low; low/high, respectively) at encoding were subsequently associated at retrieval with the lowest recall probabilities, while noun-cues related with congruent levels (high/high; low/low) were associated with higher recall probabilities. RTs in the high vividness and high familiarity grouping were significantly faster than all other subsets (low/low, low/high, high/low) which did not significantly differ among each other. The findings contradict: (1) associative theories predicting positive monotonic relationships between memory strength and learning; and (2) non-monotonic plasticity hypothesis (NMPH), aiming at generalizing the non-monotonic relationship between a neuron’s excitation level and its synaptic strength to broad neural networks. We propose a dualistic neuropsychological model of memory consolidation that mimics the global activity in two large resting-state networks (RSNs), the default mode network (DMN) and the task-positive-network (TPN). Based on this model, we suggest that incongruence and congruence between vividness and familiarity reflect, respectively, competition and synergy between DMN and TPN activity. We argue that competition or synergy between these RSNs at the time of stimulus encoding disproportionately influences long term semantic memory consolidation in healthy controls. These findings could assist in developing neurophenomenological markers of core memory deficits currently hypothesized to be shared across multiple psychopathological conditions.
Uncovering Dynamic Brain Reconfiguration in MEG Working Memory n-Back Task Using Topological Data Analysis
Authors: Duman Ali Nabi , Tatar Ahmet Emin , Pirim Harun
Published: June 2019

The increasing availability of high temporal resolution neuroimaging data has increased the efforts to understand the dynamics of neural functions. Until recently, there are few studies on generative models supporting classification and prediction of neural systems compared to the description of the architecture. However, the requirement of collapsing data spatially and temporally in the state-of-the art methods to analyze functional magnetic resonance imaging (fMRI), electroencephalogram (EEG) and magnetoencephalography (MEG) data cause loss of important information. In this study, we addressed this issue using a topological data analysis (TDA) method, called Mapper, which visualizes evolving patterns of brain activity as a mathematical graph. Accordingly, we analyzed preprocessed MEG data of 83 subjects from Human Connectome Project (HCP) collected during working memory n-back task. We examined variation in the dynamics of the brain states with the Mapper graphs, and to determine how this variation relates to measures such as response time and performance. The application of the Mapper method to MEG data detected a novel neuroimaging marker that explained the performance of the participants along with the ground truth of response time. In addition, TDA enabled us to distinguish two task-positive brain activations during 0-back and 2-back tasks, which is hard to detect with the other pipelines that require collapsing the data in the spatial and temporal domain. Further, the Mapper graphs of the individuals also revealed one large group in the middle of the stimulus detecting the high engagement in the brain with fine temporal resolution, which could contribute to increase spatiotemporal resolution by merging different imaging modalities. Hence, our work provides another evidence to the effectiveness of the TDA methods for extracting subtle dynamic properties of high temporal resolution MEG data without the temporal and spatial collapse.
RNF128 Promotes Invasion and Metastasis Via the EGFR/MAPK/MMP-2 Pathway in Esophageal Squamous Cell Carcinoma
Authors: Gao Jing , Wang Yang , Yang Jie , Zhang Weixia , Meng Kun , Sun Yue , Li Yangjia , He Qing-Yu
Published: June 2019

Background: The prognosis of esophageal squamous cell carcinoma (ESCC) is generally poor, and the identification of molecular markers related to the regulation of ESCC invasion and migration is important. Methods and Results: In this study, we report that ring finger protein-128 (RNF128) enhances the invasiveness and motility of ESCC cells by using transwell assays and Western blotting. A xenograft nude mouse model showed that RNF128 promotes the metastasis of ESCC cells in the lung. A signal pathway analysis identified the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/matrix matalloproteinases 2 (MMP-2) cascade as a mediator of RNF128-induced enhancement of ESCC progression. Inhibition experiments using inhibitors of EGFR, ERK kinase (MEK)/extracellular-signal-regulated-kinase (ERK), and MMP-2 reversed this progression. Co-immunoprecipitation demonstrated that RNF128 promotes the activation of the EGFR/ERK/MMP-2 pathway by interacting with p53 and p53 interacting with EGFR. Conclusion: Our results establish the functional role of RNF128 in driving the invasion and metastasis of ESCC through the EGFR/MAPK/MMP-2 pathway, implicating its potential as a candidate therapeutic target and prognostic biomarker for ESCC.
PTEN Hamartoma Tumor Syndrome: A Clinical Overview
Authors: Pilarski Robert
Published: June 2019

The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a grouping of related genetic disorders that has been linked to germline mutations in the PTEN gene. These disorders include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease, and autism spectrum disorders associated with macrocephaly. The majority of the clinical information available on PHTS, however, is related to individuals diagnosed with CS. There is still much to be learned about this disorder, since diagnostic criteria for CS were only established in 1996, before the identification of the PTEN gene, and were based primarily on features seen in cases reported in the existing literature. More recently, however, data from several large series of patients have shown that a number of the clinical features associated with PTEN mutations are either more or less common than previously reported. In addition, we now know that only about 30–35% of patients meeting clinical diagnostic criteria for Cowden syndrome actually have a detectable PTEN mutation. Thus, our understanding of PTEN-related diseases and their management has evolved significantly over time. The United States National Comprehensive Cancer Network (NCCN) has produced and regularly updates practice guidelines which include clinical diagnostic criteria as well as guidelines for PTEN testing and management of patients with mutations. This review will summarize the overall literature on PHTS as well as recent findings which are broadening our understanding of this set of disorders.
Uveal Versus Cutaneous Melanoma; Same Origin, Very Distinct Tumor Types
Authors: van der Kooij Monique K. , Speetjens Frank M. , van der Burg Sjoerd H. , Kapiteijn Ellen
Published: June 2019

Here, we critically evaluated the knowledge on cutaneous melanoma (CM) and uveal melanoma (UM). Both cancer types derive from melanocytes that share the same embryonic origin and display the same cellular function. Despite their common origin, both CM and UM display extreme differences in their genetic alterations and biological behavior. We discuss the differences in genetic alterations, metastatic routes, tumor biology, and tumor-host interactions in the context of their clinical responses to targeted- and immunotherapy.
11C-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma
Authors: Vyakaranam Achyut Ram , Crona Joakim , Norlén Olov , Hellman Per , Sundin Anders
Published: June 2019

Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing 11C-hydroxy-ephedrine (11C-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. 11C-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of 11C-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor 11C-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R2 = 0.22, p = 0.016). 11C-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor 11C-HED uptake were not helpful for tumor characterization.
10-Year Locoregional Control with Postoperative External Beam Radiotherapy in Patients with Locally Advanced High-Risk Non-Anaplastic Thyroid Carcinoma De Novo or at Relapse, a Propensity Score Analysis
Authors: Servagi Vernat Stéphanie , Khalifa Jonathan , Sun Xu-Shan , Kammerer Emmanuel , Blais Eivind , Faivre Jean-Christophe , Sio Terence , Pan Jianji , Qiu Hao , Bar-Sela Gil , Simon Jean-Marc , Salleron Julia , Thariat Juliette
Published: June 2019

(1) Background: To assess the role of postoperative external beam radiotherapy (pEBRT) on locoregional failure (LRF) for patients with locally advanced high-risk non-anaplastic thyroid carcinoma (naTC) at primary event or relapse. (2) Methods: Between 1995 and 2015, postoperative naTC patients with a theoretical indication for EBRT were included based on criteria that were common to American-British-French current guidelines, i.e., pT3-4, pN+, gross or microscopic residual disease. Inverse probability of treatment weighting (IPTW) after multiple imputation was used to reduce selection biases. (3) Results: Of 254 naTC patients, 216 patients underwent pEBRT (106 de novo, 110 at relapse, median dose 60 Gy) and 38 underwent surgery only. pEBRT patients had more gross residual disease, a major prognostic factor (p = 0.027) but less perineural invasion (p = 0.008) or lymphovascular emboli (p = 0.009). pEBRT patients more frequently underwent radioiodine therapy (p = 0.026). The 10-year cumulative incidence of LRF was 56% (95% CI, 32–74%) in operated patients, and 23% (95% CI, 17–30%) in pEBRT patients. After IPTW method, pEBRT reduced the risk of LRF (hazard ratio 0.30; 95% CI [0.18–0.49], p < 0.001), but had no impact on OS. In the pEBRT group, non-Intensity Modulated RadioTherapy (IMRT) plans and interruption of the radiotherapy were associated with poorer survival, while extended versus limited field strategy and dose were not. (4) Conclusions: In naTC patients who have pT3-4, pN+ disease or R1-2 resection, pEBRT improved LRF. Limited-field IMRT is preferred.
Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy
Authors: Elmallah Mohammed I. Y. , Micheau Olivier
Published: June 2019

One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. At the chromatin level, gene expression is tightly controlled by DNA methyl transferases, histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyl-binding proteins. In particular, the expression level and function of several tumor suppressor genes, or oncogenes such as c-Myc, p53 or TRAIL, have been found to be regulated by acetylation. For example, HATs are a group of enzymes, which are responsible for the acetylation of histone proteins, resulting in chromatin relaxation and transcriptional activation, whereas HDACs by deacetylating histones lead to chromatin compaction and the subsequent transcriptional repression of tumor suppressor genes. Direct acetylation of suppressor genes or oncogenes can affect their stability or function. Histone deacetylase inhibitors (HDACi) have thus been developed as a promising therapeutic target in oncology. While these inhibitors display anticancer properties in preclinical models, and despite the fact that some of them have been approved by the FDA, HDACi still have limited therapeutic efficacy in clinical terms. Nonetheless, combined with a wide range of structurally and functionally diverse chemical compounds or immune therapies, HDACi have been reported to work in synergy to induce tumor regression. In this review, the role of HDACs in cancer etiology and recent advances in the development of HDACi will be presented and put into perspective as potential drugs synergizing with TRAIL’s pro-apoptotic potential.
Gold Nanorod-Assisted Photothermal Therapy Decreases Bleeding during Breast Cancer Surgery in Dogs and Cats
Authors: Ali Moustafa R. K. , Farghali Haithem A. M. , Wu Yue , El-Sayed Ivan , Osman Ahmed H. , Selim Salah A. , El-Sayed Mostafa A.
Published: June 2019

For localized tumors, gold nanorod (AuNR)-assisted plasmonic photothermal therapy (PPTT) is a potentially effective alternative to traditional surgery, in which AuNRs absorb near-infrared light and convert it to heat in order to kill cancer cells. However, for large tumors (volume ≥ 20 cm3), an uneven distribution of AuNRs might cause inhomogeneity of the heat distribution inside the tumor. Surgery is frequently recommended for removing large tumors, but it is associated with a high risk of cancer recurrence and metastasis. Here, we applied PPTT before surgery, which showed improved treatment for large tumors. We divided the animals (eight cats/dogs) into two groups: Group I (control), where three cases were solely treated with surgery, laser, or AuNRs alone, resulting in recurrence and metastasis; and Group II, where animals were treated with PPTT before surgery. In Group II, four out of the five cases had tumor regression without any recurrence or metastasis. Interestingly, we observed that applying PPTT before surgery displayed reduced bleeding during tumor removal, supported by histopathology that showed altered blood vessels. In conclusion, our study showed that applying AuNR-assisted PPTT (AuNRs-PPTT) before surgery could significantly affect blood vessels inside the tumor, leading to a decreased amount of bleeding during surgery, which can potentially decrease the risk of metastasis and blood loss during surgery.
Myoferlin Contributes to the Metastatic Phenotype of Pancreatic Cancer Cells by Enhancing Their Migratory Capacity through the Control of Oxidative Phosphorylation
Authors: Rademaker Gilles , Costanza Brunella , Anania Sandy , Agirman Ferman , Maloujahmoum Naïma , Di Valentin Emmanuel , Goval Jean Jacques , Bellahcène Akeila , Castronovo Vincenzo , Peulen Olivier
Published: June 2019

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies with an overall survival of 5% and is the second cause of death by cancer, mainly linked to its high metastatic aggressiveness. Accordingly, understanding the mechanisms sustaining the PDAC metastatic phenotype remains a priority. In this study, we generated and used a murine in vivo model to select clones from the human Panc-1 PDAC cell line that exhibit a high propensity to seed and metastasize into the liver. We showed that myoferlin, a protein previously reported to be overexpressed in PDAC, is significantly involved in the migratory abilities of the selected cells. We first report that highly metastatic Panc-1 clones expressed a significantly higher myoferlin level than the corresponding low metastatic ones. Using scratch wound and Boyden’s chamber assays, we show that cells expressing a high myoferlin level have higher migratory potential than cells characterized by a low myoferlin abundance. Moreover, we demonstrate that myoferlin silencing leads to a migration decrease associated with a reduction of mitochondrial respiration. Since mitochondrial oxidative phosphorylation has been shown to be implicated in the tumor progression and dissemination, our data identify myoferlin as a valid potential therapeutic target in PDAC.
Porosity Design of Shaped Zeolites for Improved Catalyst Lifetime in the Methanol-to-Hydrocarbons Reaction
Authors: Bingre Rogéria , Li Renna , Wang Qiang , Nguyen Patrick , Onfroy Thomas , Louis Benoît
Published: June 2019

Additional porosity, such as meso- and macropores, was introduced in zeolite extrudates with the intention intuit of improving the effective diffusivity of the catalysts. The samples were characterized in depth by nitrogen adsorption-desorption, mercury intrusion porosimetry, ammonia temperature programmed desorption and adsorption of pyridine followed by infrared spectroscopy. The results revealed no significant change in the acidity but an increase of the pore volume. According to significant improvement in the effective diffusivity, the samples were tested in the methanol-to-hydrocarbons reaction. The catalytic stability was greatly enhanced with an increase in the pore volume, demonstrating a relation between effective diffusivity and resistance to deactivation by coke formation. Further experiments also revealed a higher toluene adsorption capacity and a raise in the breakthrough time over the most porous samples due to better accessibility of toluene molecules into the active sites of the zeolite.
Novel Combi-lipase Systems for Fatty Acid Ethyl Esters Production
Authors: Toro Esteban C. , Rodríguez Diego F. , Morales Nelson , García Lina M. , Godoy César A.
Published: June 2019

Most Combi-lipases (CL) are based on mixtures of different lipases immobilized on different supports. The increased CL efficiency has been attributed solely to the complementary selectivity of lipases. However, the role of the immobilization support in CL or in co-immobilized systems (coCL) and the application of kinetic models to account CL composition effects, have not been assessed. In this work, commercial lipases from Thermomyces lunuginosus (TLL), Candida antarctica (CALB) and Rhizomocur miehei (RML) and supports as Lewatit®VPOC1600 (LW) and Purolite®ECR1604 (PU), were combined to produce new CL systems for the production of fatty acid ethyl esters (EE) which are the main component of ethylic biodiesel: Co-immobilization slightly altered palm olein EE yields with regard to that of equivalent CL systems, e.g., the best coCL of TLL and CALB in LW (89.5%) and the respective CL (81.8%). The support did affect CL behavior: (i) The best coCL of TLL and RML on LW produced 80.0% EE while on PU 76.4%; (ii) CL based on mixtures of the same enzyme, but immobilized on different supports (semiCL) show complementarity: The best TLL semiCL produced 86.1% EE while its constituents (LW) and (PU) produced individually 78.2 and 70.3%, respectively. The proposed model accounts adequately the EE production properties for CL systems based on TLL, CALB and LW. This work expands the tools to obtain new CL systems for EE production.
Investigation of C1 + C1 Coupling Reactions in Cobalt-Catalyzed Fischer-Tropsch Synthesis by a Combined DFT and Kinetic Isotope Study
Authors: Qi Yanying , Yang Jia , Holmen Anders , Chen De
Published: June 2019

Understanding the chain growth mechanism is of vital importance for the development of catalysts with enhanced selectivity towards long-chain products in cobalt-catalyzed Fischer-Tropsch synthesis. Herein, we discriminate various C1 + C1 coupling reactions by theoretical calculations and kinetic isotope experiments. CHx(x=0−3), CO, HCO, COH, and HCOH are considered as the chain growth monomer respectively, and 24 possible coupling reactions are first investigated by theoretical calculations. Eight possible C1 + C1 coupling reactions are suggested to be energetically favorable because of the relative low reaction barriers. Moreover, five pathways are excluded where the C1 monomers show low thermodynamic stability. Effective chain propagation rates are calculated by deconvoluting from reaction rates of products, and an inverse kinetic isotope effect of the C1 + C1 coupling reaction is observed. The theoretical kinetic isotope effect of CO + CH2 is inverse, which is consistent with the experimental observation. Thus, the CO + CH2 pathway, owing to the relatively lower barrier, the high thermodynamic stability, and the inverse kinetic isotope effect, is suggested to be a favorable pathway.
Development of Personalized Therapeutic Strategies by Targeting Actionable Vulnerabilities in Metastatic and Chemotherapy-Resistant Breast Cancer PDXs
Authors: Punzi Simona , Meliksetian Marine , Riva Laura , Marocchi Federica , Pruneri Giancarlo , Criscitiello Carmen , Orsi Franco , Spaggiari Lorenzo , Casiraghi Monica , Della Vigna Paolo , Luzi Lucilla , Curigliano Giuseppe , Pelicci Pier Giuseppe , Lanfrancone Luisa
Published: June 2019

Human breast cancer is characterized by a high degree of inter-patients heterogeneity in terms of histology, genomic alterations, gene expression patterns, and metastatic behavior, which deeply influences individual prognosis and treatment response. The main cause of mortality in breast cancer is the therapy-resistant metastatic disease, which sets the priority for novel treatment strategies for these patients. In the present study, we demonstrate that Patient Derived Xenografts (PDXs) that were obtained from metastatic and therapy-resistant breast cancer samples recapitulate the wide spectrum of the disease in terms of histologic subtypes and mutational profiles, as evaluated by whole exome sequencing. We have integrated genomic and transcriptomic data to identify oncogenic and actionable pathways in each PDX. By taking advantage of primary short-term in vitro cultures from PDX tumors, we showed their resistance to standard chemotherapy (Paclitaxel), as seen in the patients. Moreover, we selected targeting drugs and analyzed PDX sensitivity to single agents or to combination of targeted and standard therapy on the basis of PDX-specific genomic or transcriptomic alterations. Our data demonstrate that PDXs represent a suitable model to test new targeting drugs or drug combinations and to prioritize personalized therapeutic regimens for pre-clinal and clinical tests.
C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro
Authors: Li Xinyue , Hu Xiaopeng , Tian Geng G. , Cheng Ping , Li Zezhong , Zhu Mingyan , Zhou Huchen , Wu Ji
Published: June 2019

Postnatal female germline stem cells (FGSCs) are a type of germline stem cell with self-renewal ability and the capacity of differentiation toward oocyte. The proliferation, differentiation, and apoptosis of FGSCs have been researched in recent years, but autophagy in FGSCs has not been explored. This study investigated the effects of the small-molecule compound 89 (C89) on FGSCs and the underlying molecular mechanism in vitro. Cytometry, Cell Counting Kit-8 (CCK8), and 5-ethynyl-2’-deoxyuridine (EdU) assay showed that the number, viability, and proliferation of FGSCs were significantly reduced in C89-treated groups (0.5, 1, and 2 µM) compared with controls. C89 had no impact on FGSC apoptosis or differentiation. However, C89 treatment induced the expression of light chain 3 beta II (LC3BII) and reduced the expression of sequestosome-1 (SQSTM1) in FGSCs, indicating that C89 induced FGSC autophagy. To investigate the mechanism of C89-induced FGSC autophagy, RNA-seq technology was used to compare the transcriptome differences between C89-treated FGSCs and controls. Bioinformatics analysis of the sequencing data indicated a potential involvement of the phosphatidylinositol 3 kinase and kinase Akt (PI3K-Akt) pathway in the effects of C89′s induction of autophagy in FGSCs. Western blot confirmed that levels of p-PI3K and p-Akt were significantly reduced in the C89- or LY294002 (PI3K inhibitor)-treated groups compared with controls. Moreover, we found cooperative functions of C89 and LY294002 in inducing FGSC autophagy through suppressing the PI3K-Akt pathway. Taken together, this research demonstrates that C89 can reduce the number, viability, and proliferation of FGSCs by inducing autophagy. Furthermore, C89 induced FGSC autophagy by inhibiting the activity of PI3K and Akt. The PI3K-Akt pathway may be a target to regulate FGSC proliferation and death.
The Cell Wall Hydrolytic NlpC/P60 Endopeptidases in Mycobacterial Cytokinesis: A Structural Perspective
Authors: Squeglia Flavia , Moreira Miguel , Ruggiero Alessia , Berisio Rita
Published: June 2019

In preparation for division, bacteria replicate their DNA and segregate the newly formed chromosomes. A division septum then assembles between the chromosomes, and the mother cell splits into two identical daughters due to septum degradation. A major constituent of bacterial septa and of the whole cell wall is peptidoglycan (PGN), an essential cell wall polymer, formed by glycan chains of β−(1-4)-linked-N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), cross-linked by short peptide stems. Depending on the amino acid located at the third position of the peptide stem, PGN is classified as either Lys-type or meso-diaminopimelic acid (DAP)-type. Hydrolytic enzymes play a crucial role in the degradation of bacterial septa to split the cell wall material shared by adjacent daughter cells to promote their separation. In mycobacteria, a key PGN hydrolase, belonging to the NlpC/P60 endopeptidase family and denoted as RipA, is responsible for the degradation of septa, as the deletion of the gene encoding for this enzyme generates abnormal bacteria with multiple septa. This review provides an update of structural and functional data highlighting the central role of RipA in mycobacterial cytokinesis and the fine regulation of its catalytic activity, which involves multiple molecular partners.
Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver
Authors: Kinast Volker , Leber Stefan L. , Brown Richard J. P. , Vieyres Gabrielle , Behrendt Patrick , Eßbach Constanze , Strnad Pavel , Vondran Florian W. R. , Cornberg Markus , Wex Cora , Pietschmann Thomas , Haybaeck Johannes , Todt Daniel , Steinmann Eike
Published: June 2019

Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.
Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?
Authors: Yoshikawa Fabio Seiti Yamada , Teixeira Franciane Mouradian Emidio , Sato Maria Notomi , Oliveira Luanda Mara da Silva
Published: June 2019

Extracellular vesicles (EVs) are released by various cells and recently have attracted attention because they constitute a refined system of cell–cell communication. EVs deliver a diverse array of biomolecules including messenger RNAs (mRNAs), microRNAs (miRNAs), proteins and lipids, and they can be used as potential biomarkers in normal and pathological conditions. The cargo of EVs is a snapshot of the donor cell profile; thus, in viral infections, EVs produced by infected cells could be a central player in disease pathogenesis. In this context, miRNAs incorporated into EVs can affect the immune recognition of viruses and promote or restrict their replication in target cells. In this review, we provide an updated overview of the roles played by EV-delivered miRNAs in viral infections and discuss the potential consequences for the host response. The full understanding of the functions of EVs and miRNAs can turn into useful biomarkers for infection detection and monitoring and/or uncover potential therapeutic targets.
How Will the Emerging Plurality of Lives Change How We Conceive of and Relate to Life?
Authors: Persson Erik , Abbott Jessica , Balkenius Christian , Cabak Redei Anna , Čápová Klara Anna , Dravins Dainis , Dunér David , Gunneflo Markus , Hedlund Maria , Johansson Mats , Melin Anders , Persson Petter
Published: June 2019

The project “A Plurality of Lives” was funded and hosted by the Pufendorf Institute for Advanced Studies at Lund University, Sweden. The aim of the project was to better understand how a second origin of life, either in the form of a discovery of extraterrestrial life, life developed in a laboratory, or machines equipped with abilities previously only ascribed to living beings, will change how we understand and relate to life. Because of the inherently interdisciplinary nature of the project aim, the project took an interdisciplinary approach with a research group made up of 12 senior researchers representing 12 different disciplines. The project resulted in a joint volume, an international symposium, several new projects, and a network of researchers in the field, all continuing to communicate about and advance the aim of the project.
Investigations on Forming Ether Coated Iron Nanoparticle Materials by First-Principle Calculations and Molecular Dynamic Simulations
Authors: Sun Junlei , Hui Shixuan , Liu Pingan , Sun Ruochen , Wang Mengjun
Published: June 2019

The mechanism of coating effects between ether molecules and iron (Fe) nanoparticles was generally estimated using first-principle calculations and molecular dynamic (MD) simulations coupling with Fe (110) crystal layers and sphere models. In the present work, the optimized adsorption site and its energy were confirmed. The single sphere model in MD simulations was studied for typical adsorption behaviors, and the double sphere model was built to be more focused on the gap impact between two particles. In those obtained results, it is demonstrated that ether molecules were prone to be adsorbed on the long bridge site of the Fe (110) crystal while comparing with other potential sites. Although the coating was not completely uniform at early stages, the formation of ether layer ended up being equilibrated finally. Accompanied with charge transfer, those coated ether molecules exerted much binding force on the shell Fe atoms. Additionally, when free ether molecules were close to the gap between two nanoparticles, they were found to come under double adsorption effects. Although this effect might not be sufficient to keep them adsorbed, the movement of these ether molecules were hindered to some extent.
Topological Phase Transition in a One-Dimensional Elastic String System
Authors: Tsai Ya-Wen , Wang Yao-Ting , Luan Pi-Gang , Yen Ta-Jen
Published: June 2019

We show that topological interface mode can emerge in a one-dimensional elastic string system which consists of two periodic strings with different band topologies. To verify their topological features, Zak-phase of each band is calculated and reveals the condition of topological phase transition accordingly. Apart from that, the transmittance spectrum illustrates that topological interface mode arises when two topologically distinct structures are connected. The vibration profile further exhibits the non-trivial interface mode in the domain wall between two periodic string composites.
Electro-Optical Switching of Dual-Frequency Nematic Liquid Crystals: Regimes of Thin and Thick Cells
Authors: Melnyk Olha , Garbovskiy Yuriy , Bueno-Baques Dario , Glushchenko Anatoliy
Published: June 2019

Conventional display applications of liquid crystals utilize thin layers of mesogenic materials, typically less than 10 µm. However, emerging non-display applications will require thicker, i.e., greater than 100 µm, layers of liquid crystals. Although electro-optical performance of relatively thin liquid crystal cells is well-documented, little is known about the properties of thicker liquid crystal layers. In this paper, the electro-optical response of dual-frequency nematic liquid crystals is studied using a broad range (2–200 µm) of the cell thickness. Two regimes of electro-optical switching of dual-frequency nematics are observed and analyzed.
Structural Insights into the Two-Step Spin-Crossover Compound Fe(3,4-dimethyl-pyridine)2[Ag(CN)2]2
Authors: Rodríguez-Velamazán José Alberto , Kitase Kosuke , Palacios Elías , Castro Miguel , Fernández-Blanco Ángel , Burriel Ramón , Kitazawa Takafumi
Published: June 2019

The crystal structure of the polymeric spin crossover compound Fe(3,4-dimethyl-pyridine)2[Ag(CN)2]2 has been solved and its temperature dependence followed by means of single-crystal and powder X-ray diffraction. This compound presents a two-step spin transition with relatively abrupt steps centred at ca. 170 K and 145 K and a plateau at around 155 K. The origin of the two-step transition is discussed in light of these structural studies. The observations are compatible with a mostly disordered state between the two steps, consisting of mixing of high-spin and low-spin species, while weak substructure reflections in the mixed phase could indicate some degree of long-range order of the high-spin and low-spin sites.
Application of Second Law Analysis in Heat Exchanger Systems
Authors: Ashrafizadeh Seyed Ali
Published: June 2019

In recent decades, the second law of thermodynamics has been commonly applied in analyzing heat exchangers. Many researchers believe that the minimization of entropy generation or exergy losses can be considered as an objective function in designing heat exchangers. Some other researchers, however, not only reject the entropy generation minimization (EGM) philosophy, but also believe that entropy generation maximization is a real objective function in designing heat exchangers. Using driving forces and irreversibility relations, this study sought to get these two views closer to each other. Exergy loss relations were developed by sink–source modeling along the heat exchangers. In this case, two types of heat exchangers are introduced, known as “process” and “utility” heat exchangers. In order to propose an appropriate procedure, exergy losses were examined based on variables and degrees of freedom, and they were different in each category. The results showed that “EGM” philosophy could be applied only to utility heat exchangers. A mathematical model was also developed to calculate exergy losses and investigate the effects of various parameters. Moreover, the validity of the model was evaluated by some experimental data using a double-pipe heat exchanger. Both the process and utility heat exchangers were simulated during the experiments. After verifying the model, some case studies were conducted. The final results indicated that there was not a real minimum point for exergy losses (or entropy generation) with respect to the operational variables. However, a logic minimum point could be found for utility heat exchangers with regard to the constraints.
Navigating Black Identity Development: The Power of Interactive Multicultural Read Alouds with Elementary-Aged Children
Authors: Piper Rebekah E.
Published: June 2019

Racial identity development in young children is influenced by interactions with teachers and curriculum in schools. This article, using the framework of critical race theory, critical literacy, and critical pedagogy, explores how three elementary-aged Black children view their own identity development. Specifically, observing how children interact with Movement-Oriented Civil Rights-Themed Children’s Literature (MO-CRiTLit) in the context of a non-traditional summer literacy program, Freedom Schools, to influence their Black identity. Professional development and preservice teacher preparation are needed to support teachers as they navigate through learning about pedagogical practices that increase student engagement.
Look How Far We Haven’t Come: The Possible Implications of Current Educational Context and Practices for Young Black Males by Amanda VandeHei Carter
Authors: Carter Amanda VandeHei
Published: June 2019

Data that are derived from high stakes testing in the United States have created rhetoric of fear and criticism around our public K–12 educational system. Stakeholders often blame these low-test scores on the school, administration, or teachers. Due to the way that this data is shared with the general public Different from this narrative, within many schools, high stakes testing data are reported in an aggregated fashion, usually by students’ race. While the general public may be pointing their finger at schools, administrators, or teachers for poorly achieving students, these folks can quickly shift the blame to certain populations of students who are not performing well on standardized tests. Teachers spend time sorting and labeling children into groups and categories in an effort to “fix the problem”. While sometimes well intended, the planning, instruction, and assessment of daily and weekly instruction is focused on an end result of getting particular groups of students to score better on standardized tests. This article provides the counter narrative to this conversation and it strives to tell the story of a student who has fallen victim to standardized unauthentic curriculum. Multiple case study was the methodology used for this research. Consistent with this methodology, the data were gathered through one-on-one interviews, classroom observations, and small group discussions. Hardiman’s model of White Identity Development (WID) and Freebody and Luke’s four resources model were the conceptual frameworks that were used to guide the study. The findings shared in this article represent the data collected from one participant in this multiple case study.
“…4542 Miles from Home…”: Repositioning English Language Learners as Power Brokers and Teachers as Learners in the Study Abroad Context
Authors: Fasching-Varner Kenneth J. , Stone Michaela P. , Mora Mella Roberto , Olave Henríquez Francisco , Yacoman Palma Macarena
Published: June 2019

This article provides an empirical context for the role that bi/multi-lingual children and families may play in supporting pre-service and in-service educators engaging difference through a literacy and language situated study abroad internship in Chile. Drawing on data over a 15-year longitudinal study of the program, the authors examine how students and parents navigate serving the role of teacher, whereas the teacher participants navigate a new role as a learner in a context where they, many for the first time, experience being language and cultural minorities.
Experiencing Anti-Immigrant Policies on Both Sides of the U.S./Mexico Borderland: A Comparative Study of Mexican and Iranian Families
Authors: Candel Sandra L. , Fayazpour Shahla
Published: June 2019

The experiences of Mexican and Iranian immigrant families are often unheard and unpacked. The purpose of this qualitative study is to examine how race, ethnicity, and national identity are at the core of the sociopolitical and economic issues that Latino and Iranian families undergo in the United States. Using critical race theory as a framework, this research analyzed the ways in which Mexican immigrant families who were deported, and Iranian-immigrant families living in the United States, have been differently affected by post 9/11 anti-immigrant policies and by zero tolerance policies enacted by the Trump administration. The research question guiding this study was: How do U.S. anti-immigrant policies affect Iranian and Mexican immigrant families and their children’s futures? Our findings uncovered that both groups were negatively affected, however, in different ways. Iranian immigrant parents worried about their socioeconomic status in the United States and their children’s future. They also feared that their relatives might not be able to visit them due to the U.S. Muslim Travel Ban placed on people from seven Muslim-majority countries, including Iran. On the other hand, Mexican immigrants who lived in the United States undocumented were deported to Mexico. However, after deportation, and responding to the threat of the Trump administration to deport millions more, the Mexican government provided dual citizenship to U.S.-born children of Mexican returnees to facilitate their access to government services, including education. All people and place names are pseudonyms.