bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies
Authors: Lopes Ana , Martins Eva , Silva Renata , Pinto Madalena , Remião Fernando , Sousa Emília , Fernandes Carla
Published: March 2018

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1–8, studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (−) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1–8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (−) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.
Preliminary Characterization and Bioactivities of Some Impatiens L. Water-Soluble Polysaccharides
Authors: Szewczyk Katarzyna , Heise Esther , Piwowarski Jakub
Published: March 2018

Preliminary characterization and bioactivity of water-soluble polysaccharides from four Impatiens species—I. glandulifera Royle, I. parviflora DC., I. balsamina L., and I. noli-tangere L.—were investigated. The yields of polysaccharides range widely from 1.97% for I. parviflora roots to 18.63% for I. balsamina aerial parts. SEC (Size exclusion chromatography) chromatograms show that all samples contained a low molecular weight part that consisted of components of similar molecular weight. The aerial parts and roots of I. balsamina, and I. glandulifera aerial parts had considerable amounts of high molecular weight components up to 2.3 MDa. The sugar composition analysis revealed that Impatiens polysaccharides consisted primarily of galactose, arabinose, rhamnose, mannose, xylose, and glucose. All polysaccharide fractions, except for I. parviflora roots, also contain galacturonic acid. Moreover, in vitro bioactivity of obtained polysaccharides were evaluated. The antioxidant activity was evaluated on the basis of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethyl-benzthia-6-sulfonic acid) (ABTS) radical scavenging assays. The highest antioxidant activity was obtained for I. balsamina aerial parts and I. parviflora roots. Among the tested fractions, only the polysaccharides from I. glandulifera aerial parts were able to significantly decrease the production of IL-8 by 32.7 ± 10.5%. The results suggest that Impatiens species can be considered as a new source of antioxidants.
Synthesis of O-Amino Sugars and Nucleosides
Authors: Chen Na , Xie Juan
Published: March 2018

Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks based on nucleosides and sugars is in high demand for the generation of novel oligonucleotide mimics and glycoconjugates for biomedical applications. Recently, aminooxyl-functionalized compounds have attracted increasing research interest because of their easy derivatization through oxime ligation or N-oxyamide formation reactions. Various biological applications have been reported for O-amino carbohydrate- and nucleoside-derived compounds. Here, we report our efforts in the design and synthesis of glyco-, glycosyl, nucleoside- and nucleo-aminooxy acid derivatives from readily available sugars and amino acids, and their use for the generation of N-oxyamide-linked oligosaccharides, glycopeptides, glycolipids, oligonucleosides and nucleopeptides as novel glycoconjugates or oligonucleotide mimics. Delicate and key points in the synthesis will be emphasized.
The GF-3 SAR Data Processor
Authors: Han Bing , Ding Chibiao , Zhong Lihua , Liu Jiayin , Qiu Xiaolan , Hu Yuxin , Lei Bin
Published: March 2018

The Gaofen-3 (GF-3) data processor was developed as a workstation-based GF-3 synthetic aperture radar (SAR) data processing system. The processor consists of two vital subsystems of the GF-3 ground segment, which are referred to as data ingesting subsystem (DIS) and product generation subsystem (PGS). The primary purpose of DIS is to record and catalogue GF-3 raw data with a transferring format, and PGS is to produce slant range or geocoded imagery from the signal data. This paper presents a brief introduction of the GF-3 data processor, including descriptions of the system architecture, the processing algorithms and its output format.
On the Deployment and Noise Filtering of Vehicular Radar Application for Detection Enhancement in Roads and Tunnels
Authors: Kim Young-Duk , Son Guk-Jin , Song Chan-Ho , Kim Hee-Kang
Published: March 2018

Recently, radar technology has attracted attention for the realization of an intelligent transportation system (ITS) to monitor, track, and manage vehicle traffic on the roads as well as adaptive cruise control (ACC) and automatic emergency braking (AEB) for driving assistance of vehicles. However, when radar is installed on roads or in tunnels, the detection performance is significantly dependent on the deployment conditions and environment around the radar. In particular, in the case of tunnels, the detection accuracy for a moving vehicle drops sharply owing to the diffuse reflection of radio frequency (RF) signals. In this paper, we propose an optimal deployment condition based on height and tilt angle as well as a noise-filtering scheme for RF signals so that the performance of vehicle detection can be robust against external conditions on roads and in tunnels. To this end, first, we gather and analyze the misrecognition patterns of the radar by tracking a number of randomly selected vehicles on real roads. In order to overcome the limitations, we implement a novel road watch module (RWM) that is easily integrated into a conventional radar system such as Delphi ESR. The proposed system is able to perform real-time distributed data processing of the target vehicles by providing independent queues for each object of information that is incoming from the radar RF. Based on experiments with real roads and tunnels, the proposed scheme shows better performance than the conventional method with respect to the detection accuracy and delay time. The implemented system also provides a user-friendly interface to monitor and manage all traffic on roads and in tunnels. This will accelerate the popularization of future ITS services.
Research into Kinect/Inertial Measurement Units Based on Indoor Robots
Authors: Li Huixia , Wen Xi , Guo Hang , Yu Min
Published: March 2018

As indoor mobile navigation suffers from low positioning accuracy and accumulation error, we carried out research into an integrated location system for a robot based on Kinect and an Inertial Measurement Unit (IMU). In this paper, the close-range stereo images are used to calculate the attitude information and the translation amount of the adjacent positions of the robot by means of the absolute orientation algorithm, for improving the calculation accuracy of the robot’s movement. Relying on the Kinect visual measurement and the strap-down IMU devices, we also use Kalman filtering to obtain the errors of the position and attitude outputs, in order to seek the optimal estimation and correct the errors. Experimental results show that the proposed method is able to improve the positioning accuracy and stability of the indoor mobile robot.
Detection of Volatile Compounds Emitted from Nasal Secretions and Serum: Towards Non-Invasive Identification of Diseased Cattle Biomarkers
Authors: Maurer Devin , Koziel Jacek , Engelken Terry , Cooper Vickie , Funk Jenna
Published: March 2018

Non-invasive diagnostics and finding biomarkers of disease in humans have been a very active research area. Some of the analytical technologies used for finding biomarkers of human disease are finding their use in livestock. Non-invasive sample collection from diseased cattle using breath and headspace of fecal samples have been reported. In this work, we explore the use of volatile organic compounds (VOCs) emitted from bovine nasal secretions and serum for finding biomarkers for bovine respiratory disease (BRD). One hundred nasal swabs and 100 serum samples (n = 50 for both ‘sick’ and ‘healthy’) were collected at the time of treatment for suspected BRD. Solid-phase microextraction (SPME) was used to collect headspace samples that were analyzed using gas chromatography-mass spectrometry (GC-MS). It was possible to separate sick cattle using non-invasive analyses of nasal swabs and also serum samples by analyzing and comparing volatiles emitted from each group of samples. Four volatile compounds were found to be statistically significantly different between ‘sick’ and ‘normal’ cattle nasal swabs samples. Five volatile compounds were found to be significantly different between ‘sick’ and ‘normal’ cattle serum samples, with phenol being the common marker. Future studies are warranted to improve the extraction efficiency targeting VOCs preliminarily identified in this study. These findings bring us closer to the long-term goal of real-time, animal-side detection and separation of sick cattle.
Melioidosis in Singapore: Clinical, Veterinary, and Environmental Perspectives
Authors: Sim Siew , Ong Catherine , Gan Yunn , Wang Dongling , Koh Victor , Tan Yian , Wong Michelle , Chew Janet , Ling Sian , Tan Brian , Ye Agnes , Bay Patrick , Wong Wai , Fernandez Charlene , Xie Shangzhe , Jayarajah Praveena , Tahar Tasha , Oh Pei , Luz Sonja , Chien Jaime , Tan Thuan , Chai Louis , Fisher Dale , Liu Yichun , Loh Jimmy , Tan Gladys
Published: March 2018

Melioidosis is a notifiable infectious disease registered with the Ministry of Health (MOH) and Agri-Food & Veterinary Authority (AVA), Singapore. From a clinical perspective, increased awareness of the disease has led to early detection and treatment initiation, thus resulting in decreasing mortality rates in recent years. However, the disease still poses a threat to local pet, zoo and farm animals, where early diagnosis is a challenge. The lack of routine environmental surveillance studies also makes prevention of the disease in animals difficult. To date, there have been no reports that provide a complete picture of how the disease impacts the local human and animal populations in Singapore. Information on the distribution of Burkholderia pseudomallei in the environment is also lacking. The aim of this review is to provide a comprehensive overview of both published and unpublished clinical, veterinary and environmental studies on melioidosis in Singapore to achieve better awareness and management of the disease.
Hepatitis B At-Birth Dose Vaccine: An Urgent Call for Implementation in Ghana
Authors: Awuku Yaw , Yeboah-Afihene Mary
Published: March 2018

Globally, approximately two billion people are infected with the Hepatitis B virus with attributable death estimated at about half a million people annually across the globe. Chronic hepatitis B infection is also an important public health problem in Ghana. The main mode of transmission in endemic regions is the perinatal route. Mother-to-child transmission can be reduced by antiviral therapy especially in the last trimester and adherence to the national immunization schedule. The World Health Organization recommends to add the birth dose vaccine to the current expanded program on immunization (EPI) in all countries but especially for endemic regions. The evidence for the efficacy of the birth dose HBV vaccine is overwhelming and there is an urgent need for its introduction into the current EPI schedule in Ghana.
Knockdown of Urothelial Carcinoma-Associated 1 Suppressed Cell Growth and Migration Through Regulating miR-301a and CXCR4 in Osteosarcoma MHCC97 Cells
Authors: Zhu Genglong , Liu Xialei , Su Yonghui , Kong Fangen , Hong Xiaopeng , Lin Zhidong
Published: March 2018

Liver cancer is one of the most common malignancies in the world and a leading cause of cancer-related mortality. Accumulating evidence has highlighted the critical role of long noncoding RNAs (lncRNAs) in various cancers. The present study aimed to explore the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in cell growth and migration in MHCC97 cells and its underlying mechanism. First, we assessed the expression of UCA1 in MHCC97 and three other cell lines by RT-qPCR. Then the expression of UCA1, miR-301a, and CXCR4 in MHCC97 cells was altered by transient transfection. The effects of UCA1 and miR-301 on cell viability, migration, invasion, and apoptosis were assessed. The results revealed that UCA1 expression was relatively higher in MHCC97 cells than in MG63, hFOB1.19, and OS-732 cells. Knockdown of UCA1 reduced cell viability, inhibited migration and invasion, and promoted cell apoptosis. However, the effect of UCA1 knockdown on cell growth and migration was blocked by miR-301a overexpression, whose expression was regulated by UCA1. We also found that miR-301a positively regulated CXCR4 expression. CXCR4 inhibition reversed the effect of miR-301a overexpression on cell growth and migration. Moreover, miR-301a activated the Wnt/β-catenin and NF-κB pathways via regulating CXCR4. The present study demonstrated that UCA1 inhibition exerted an antigrowth and antimigration role in MHCC97 cells through regulating miR-301a and CXCR4 expression.
Adjuvant Chemotherapy Following Surgical Resection Improves Survival in Patients With Early Stage Small Cell Lung Cancer
Authors: Yao Yuanshan , Zhou Yinjie , Yang Zhenhua , Huang Hongbo , Shen Haibo
Published: March 2018

The purpose of this study was to determine the effects of resection coupled with standard chemotherapy on the survival prognosis of patients with early stage small cell lung carcinoma (SCLC). Patients (n = 110) with mediastinal lymph node-negative SCLC were enrolled
in this study. The baseline clinical data of patients with surgery were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were measured by Kaplan‐Meier and log-rank test analyses. Ninety-eight patients received mediastinoscopy biopsy, and pulmonary
lobectomy or sublobar resection, and 67 patients underwent adjuvant chemotherapy after pulmonary lobectomy. Adjuvant chemotherapy after surgical intervention was associated with longer OS (median OS: 42.14 vs. 33.53 months, p = 0.01) and PFS (median PFS: 25.20 vs. 13.48
months, p = 0.000) compared to resection alone for all patients. Adjuvant chemotherapy was associated with improvement of survival for N1 patients with stage II (median OS: 36.42 vs. 26.68 months, p = 0.021). The median PFS was 19.02 m (16.08, 21.96)
and 13.25 m (10.19, 16.30) (p = 0.031), respectively, for patients of N1 stage who received chemotherapy and those who did not. Cox regression analysis demonstrated that age, TNM stage (N stage, not T stage), and chemotherapy were independent risk factors that might affect
overall survival in patients with mediastinal lymph node-negative SCLC. These findings suggest that the application of adjuvant chemotherapy following pulmonary lobectomy is associated with improvements of survival prognoses for patients with SCLC. The combination of surgical intervention
with conventional therapy should be taken into consideration as a prospective multidisciplinary regimen for early stage SCLC.
miR-148b Functions as a Tumor Suppressor by Targeting Endoplasmic Reticulum Metallo Protease 1 in Human Endometrial Cancer Cells
Authors: Qu Jinfeng , Zhang Lei , Li Lanyu , Su Yujie
Published: March 2018

This study investigated the tumor-suppressive role of miR-148b in regulating endoplasmic reticulum metalloprotease 1 (ERMP1) expression and the oxidative stress response in endometrial cancer cells. Human endometrial cancer RL95-2 cells were used and transfected with miR-148b mimic,
miR-148b inhibitor, or their scrambled negative control. Thereafter, the transfection efficiency was determined by RT-qPCR, and cell proliferation was assessed by MTT assay. The dual-luciferase reporter assay, Western blot, and RT-qPCR were conducted to determine the target gene of miR-148b.
ERMP1 is a putative target of miR-148b, and thereby the overexpression and downregulation of ERMP1 on the proliferation of RL95-2 cells were assessed. Next, the expressions of hypoxia-inducible factor 1 (HIF-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed by Western
blot. Intracellular reactive oxygen species (ROS) was determined using dichlorofluorescin diacetate (DCFDA). Results showed that differential expression of miR-148b or ERMP1 was observed in normal endometrial tissues and endometrial cancerous tissues. Enhanced expression of miR-148b effectively
inhibited proliferation of RL95-2 cells. ERMP1 was the target of miR-148b. ERMP1 silencing obviously suppressed proliferation of RL95-2 cells. Thus, miR-148b repressed cell proliferation, likely through downregulating ERMP1. Furthermore, it was observed that miR-148b significantly decreased
expression of HIF-1 and Nrf2 by downregulating ERMP1. The intracellular ROS level was enhanced by miR-148b via downregulating ERMP1. To conclude, our results suggested that miR-148b suppressed cell proliferation and regulated the oxidative stress response in human endometrial cancer RL95-2
cells by inhibiting ERMP1.
Emphatic fingerspelling as code-mixing in American Sign Language
Authors: Montemurro Kathryn , Brentari Diane
Published: March 2018

In this paper, we propose a view of fingerspelling in American Sign Language (ASL) not only as cross-modal lexical borrowing (Padden & Gunsauls 2003), but also as code-mixing. Using corpus data from public online video sources, we show that fingerspelling can be utilized for pragmatic and sentential purposes aside from the more generally cited uses (e.g. personal names, technical terms, gaps in the lexicon). Namely, it may be used to put emphasis on a particular word, generally in focus constructions. This motivation for fingerspelling is used with items which have a well-attested lexical alternative. In these cases, fingerspelling is not necessary but rather driven by its function in the discourse.
A key for the determination of European species of Eosentomon Berlese, 1909 (Protura, Eosentomata, Eosentomidae)
Authors: Shrubovych Julia , Bernard Ernest C.
Published: March 2018

European species ofEosentomonare examined. A taxonomic key to identification of 61Eosentomonspecies is provided based on body chaetotaxy, shape, and position of sensilla on the foretarsus and shape of sensilla on the maxillary palps. Biogeographically, 13 of the known EuropeanEosentomonspecies are known only from their type localities.
Dynamiques de campagne et choix des candidats
Authors: Vitiello Thomas , Cautrès Bruno , Martigny Vincent , Strudel Sylvie , Krouwel André
Published: March 2018

En s’appuyant sur un corpus de données collectées grâce au Système d’Aide au Vote (SAV) de La Boussole présidentielle, cet article analyse les dynamiques de la campagne de la primaire de la droite et du centre. Dans un contexte de polarisation des candidats lors de l’élection, François Fillon est apparu aux électeurs de la primaire comme un compromis entre les centristes réunis autour d’Alain Juppé et les soutiens de Nicolas Sarkozy, jugés plus radicaux. En outre, ce sont moins les enjeux programmatiques soulevés par le vainqueur que son image et sa présidentialité qui ont permis sa désignation, soulignant ainsi l’importance des dynamiques de campagne dans un scrutin de primaires.
Des voix (vraiment) pas comme les autres ?
Authors: Moualek Jérémie
Published: March 2018

En France, les élections de 2017 ont mis en lumière un phénomène considéré longtemps comme marginal par la sociologie électorale : le vote « blanc et nul ». L’objet de cet article est de déconstruire quelques-unes des prénotions liées à ce geste et d’en proposer une lecture nouvelle. Ainsi, l’auteur l’aborde non pas seulement comme une réponse à une offre politique déterminée mais, aussi, comme une pratique aux usages et investissements pluriels. Le tout, en montrant combien ces votes témoignent surtout de rapports socialement différenciés au politique, voire à la démocratie représentative.
Les classes populaires aussi quittent Bruxelles. Une analyse de la périurbanisation des populations à bas revenus
Authors: De Laet Sarah
Published: March 2018

Les déménagements depuis le territoire de la Région de Bruxelles-Capitale vers les communes périurbaines de Flandre ou de Wallonie sont classiquement étudiés sous l’angle des classes moyennes. Pourtant, aujourd’hui, 30 % des personnes quittant la Région pour s’installer ailleurs en Belgique, sont issues des classes populaires. Les classes populaires urbaines font face à une double pression, sociale d’une part avec la déstructuration du modèle salarial, les pénuries d’emplois et l’insécurité économique ; spatiale d’autre part, notamment du fait de l’augmentation des coûts du logement en ville. Face à ces pressions, certains ménages des classes populaires optent pour un déménagement hors de la Région de Bruxelles-Capitale. À la suite de travaux qui ont attiré l’attention sur de tels processus de « périurbanisation modeste », notamment en France, cet article s’intéresse à l’importance de ce phénomène dans le cas bruxellois. Il met également en évidence les espaces de destination des ménages populaires qui quittent les quartiers populaires centraux bruxellois. Du point de vue de ces derniers, ces départs vers des communes de périphérie proche ou vers d’autres villes opèrent une forme de tri socio-spatial dont les implications sont importantes pour ces espaces de départ.
“The cinema needs the individual, and migrants need the cinema to re-emerge as an individual.” Interview with Andrea Segre
Authors: De Gourcy Constance
Published: March 2018

For several decades, migratory issues have become an important subject for contemporary societies whose cinema has played a major role. As a source and research tool, the cinema helps us understand the history of migration and underlines the way in which society deals with alterity through the mobilisation of the foreigner. The interview with Andrea Segre, famous director and scriptwriter of internationally acclaimed documentaries and films, highlights the capacity of the cinema to open up news worlds – and not only to reflect existing ones. In these worlds, differences between people not so much an obstacle but the foundation of our common humanity.
WOUND HEALING ACTIVITY OF SHEEP’S BLADDER EXTRACELLULAR MATRIX IN DIABETIC RATS
Authors: Zihayat Bahare , Khodadadi Arash , Torabi Molook , Mehdipour Mohammad , Basiri Mohsen , Asadi-Shekarri Majid
Published: March 2018

Diabetic ulcers (DUs) are a chronic, non-healing diabetes complication that leads to high hospital expenses and, in extreme cases, to amputation. Peripheral vascular diseases, diabetic neuropathy, abnormal cellular and cytokine activity are among the major factors that hinder diabetic wound healing. DUs represent an important challenge in the development of new and efficient wound dressings. The extracellular matrix (ECM) has been effectively used as a scaffold for constructive remodeling of multiple tissues in animal and human. Sheep’s urinary bladder matrix was evaluated for its wound healing activity in streptozotocin-induced diabetic rats using excision model. In this experiment, 48 male Sprague dawley rats weighing 220–250[Formula: see text]g were divided into four equal groups of control, vaseline, diabetics + (10[Formula: see text]mg/wound) and [Formula: see text] (50[Formula: see text]mg/wound). Diabetes was induced by intraperitoneal injection of streptozotocin (45[Formula: see text]mg/kg B.W) solved in 0.05[Formula: see text]M citrate buffer. Seven days after confirming diabetes statue, skin wounds were created on the back of each rat. Rate of wound healing and histological assay using hematoxylin and Eosin staining (H&E) were used for evaluation of the wound healing in different groups. ECM treated animals exhibited significant improvement in both wound area and rate of wound healing when compared to controls ([Formula: see text]). The ECM treated wounds were found to epithelize faster as compared to controls. The sheep’s ECM promotes significant wound healing in male diabetic rats and further studies on this activity in animal models and humans are suggested.
Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function
Authors: Sage Peter T. , Schildberg Frank A. , Sobel Raymond A. , Kuchroo Vijay K. , Freeman Gordon J. , Sharpe Arlene H.
Published: March 2018

The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type–specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type–specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells. PD-1 is highly expressed on effector populations, including T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells, which reside in germinal centers. We also show that DC PD-L1 is essential for limiting Tfh and Tfr cell differentiation. In addition, we find that PD-1 suppresses Tfh cell differentiation and help for Ig class switching, even in the presence of wild-type Tfr cells. Our work points to critical roles for PD-L1 expressed on DCs in mediating PD-1 functions.
B Cell–Intrinsic mTORC1 Promotes Germinal Center–Defining Transcription Factor Gene Expression, Somatic Hypermutation, and Memory B Cell Generation in Humoral Immunity
Authors: Raybuck Ariel L. , Cho Sung Hoon , Li Jingxin , Rogers Meredith C. , Lee Keunwook , Williams Christopher L. , Shlomchik Mark , Thomas James W. , Chen Jin , Williams John V. , Boothby Mark R.
Published: March 2018

B lymphocytes migrate among varied microenvironmental niches during diversification, selection, and conversion to memory or Ab-secreting plasma cells. Aspects of the nutrient milieu differ within these lymphoid microenvironments and can influence signaling molecules such as the mechanistic target of rapamycin (mTOR). However, much remains to be elucidated as to the B cell–intrinsic functions of nutrient-sensing signal transducers that modulate B cell differentiation or Ab affinity. We now show that the amino acid–sensing mTOR complex 1 (mTORC1) is vital for induction of Bcl6—a key transcriptional regulator of the germinal center (GC) fate—in activated B lymphocytes. Accordingly, disruption of mTORC1 after B cell development and activation led to reduced populations of Ag-specific memory B cells as well as plasma cells and GC B cells. In addition, induction of the germ line transcript that guides activation-induced deaminase in selection of the IgG1 H chain region during class switching required mTORC1. Expression of the somatic mutator activation-induced deaminase was reduced by a lack of mTORC1 in B cells, whereas point mutation frequencies in Ag-specific GC-phenotype B cells were only halved. These effects culminated in a B cell–intrinsic defect that impacted an antiviral Ab response and drastically impaired generation of high-affinity IgG1. Collectively, these data establish that mTORC1 governs critical B cell–intrinsic mechanisms essential for establishment of GC differentiation and effective Ab production.
Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma
Authors: Lozano Ester , Díaz Tania , Mena Mari-Pau , Suñe Guillermo , Calvo Xavier , Calderón Marcos , Pérez-Amill Lorena , Rodríguez Vanina , Pérez-Galán Patricia , Roué Gaël , Cibeira M. Teresa , Rosiñol Laura , Isola Ignacio , Rodríguez-Lobato Luis-Gerardo , Martin-Antonio Beatriz , Bladé Joan , Fernández de Larrea Carlos
Published: March 2018

Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j (LILRB1), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape. To gain insight into the molecular mechanisms underlying CD85j functions, we next enforced expression of CD85j in human myeloma cell lines by lentiviral transduction. Interestingly, gene expression profiling of CD85j-overexpressing cells revealed a set of downregulated genes with crucial functions in MM pathogenesis. Furthermore, in vitro functional assays demonstrated that CD85j overexpression increased susceptibility to T cell– and NK-mediated killing. Consistently, ligation of CD85j decreased the number of PCs from individuals with MGUS but not from patients with MM. In conclusion, downregulation of inhibitory immune checkpoints on malignant PCs may provide a novel mechanism of immune escape associated with myeloma pathogenesis.
Contribution of Adipose-Derived Factor D/Adipsin to Complement Alternative Pathway Activation: Lessons from Lipodystrophy
Authors: Wu Xiaobo , Hutson Irina , Akk Antonina M. , Mascharak Smita , Pham Christine T. N. , Hourcade Dennis E. , Brown Rebecca , Atkinson John P. , Harris Charles A.
Published: March 2018

Factor D (FD) is an essential component of the complement alternative pathway (AP). It is an attractive pharmaceutical target because it is an AP-specific protease circulating in blood. Most components of the complement activation pathways are produced by the liver, but FD is highly expressed by adipose tissue. Two critical questions are: 1) to what degree does adipose tissue contribute to circulating FD levels and 2) what quantity of FD is sufficient to maintain a functional AP? To address these issues, we studied a novel mouse strain with complete lipodystrophy (LD), the fld mouse with partial LD, an FD-deficient mouse, and samples from lipodystrophic patients. FD was undetectable in the serum of LD mice, which also showed minimal AP function. Reconstitution with purified FD, serum mixing experiments, and studies of partial LD mice all demonstrated that a low level of serum FD is sufficient for normal AP activity in the mouse system. This conclusion was further supported by experiments in which wild-type adipose precursors were transplanted into LD mice. Our results indicate that almost all FD in mouse serum is derived from adipose tissue. In contrast, FD levels were reduced ∼50% in the sera of patients with congenital generalized LD. Our studies further demonstrate that a relatively small amount of serum FD is sufficient to facilitate significant time-dependent AP activity in humans and in mice. Furthermore, this observation highlights the potential importance of obtaining nearly complete inhibition of FD in treating alternative complement activation in various autoimmune and inflammatory human diseases.
Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments
Authors: Gao Yunhuan , Wang Tiantian , Li Yuanyuan , Zhang Yuan , Yang Rongcun
Published: March 2018

Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBPβ play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBPβ isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBPβ isoform liver-enriched inhibitory protein promoted the activation of C/EBPβ and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. Additionally, lnc-chop also promoted the enrichment of H3K4me3 on the promoter region of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2. These findings suggest an important role of lnc-chop in controlling immunosuppressive function of MDSCs in the tumor environment.
How Frequent does Bow and Arrow Sign Locate Ileocecal Valve during Colonoscopy?
Authors: Akere Adegboyega , Edries Tejan Ahmad
Published: March 2018

Aim: Two major ways to locate the ileocecal valve (ICV) are to look for a thickening or bulge on the ileocecal fold, and the other is the “bow and arrow” method or the “appendix trick”. The aim of this study was to determine the accuracy of “bow and arrow” method to locate the ICV during colonoscopy. Patients and Methods: Colonoscopy was performed with the patients in the left lateral position. After cecal intubation had been confirmed, the appendiceal opening was identified, with the curve serving as the bow, an imaginary arrow was placed across the curve toward the appendix lumen. The tip of the imaginary arrow was then followed to confirm if it correlated to the location of the ICV. Results: The “bow and arrow” accurately located the ICV in 105 (76.6%) patients, but failed in 32 (23.4%) patients. The mean age (56.2 ± 13.1 years) of the patients in whom the “bow and arrow” located the ICV was lower than that (62.7 ± 0.9 years) of the patients in whom it failed to locate the ICV. Males, 58 (71.6%) had positive “bow and arrow”, while this was observed in 47 (83.9%) females. It correctly located the ICV in 73 (53.3%) of those with thin‑lip ICV, 20 (14.6%) of those with volcanic type, and 12 (8.8%) of those with double bulge ICV. Conclusion: The bow and arrow sign could not locate the ICV in all cases in our practice and so where it failed, alternative method should be employed to locate the ICV.
Endoscopic Ultrasound-Guided Choledochoduodenostomy for Biliary Drainage in Patients with Lower End Common Bile Duct Block: A Single-Center Experience
Authors: Singla Vikas , Prajapati Ritesh , Anikhindi Shrihari Anil , Kumar Mandhir , Kumar Ashish , Sharma Praveen , Bansal Naresh , Arora Anil
Published: March 2018

Objective: Endoscopic ultrasound (EUS)-guided biliary drainage is evolving as an alternative technique in patients with failed endoscopic retrograde cholangiopancreatography. The objective of this study was to find out the outcome of EUS-guided choledochoduodenostomy in patients with malignant mid and lower end biliary obstruction with inaccessible papilla presenting at our center. Methods: The present study was a single-center prospective observational study. Data of all the patients who underwent choledochoduodensotomy from January 2014 to December 2015 were recorded. Outcome measures were technical success and clinical success. Technical success was defined as successful placement of stent in the biliary system; clinical success was defined as 50% reduction in bilirubin at 2 weeks. Complications during the procedure and follow-up were recorded. Results: A total of 10 patients underwent EUS-guided choledochoduodenostomy. Cause of biliary obstruction was pancreatic cancer in eight patients, two patients had carcinoma gallbladder with mid-common bile duct (CBD) block due to compression by metastatic lymph nodes, and one patient had ampullary carcinoma. Mean bilirubin value was 16.4 mg/dL (±3.2 mg/dL). Technical and clinical success were 100% and 90%, respectively. No immediate procedure-related complication was noticed. Two patients had stent migration during the follow-up. Conclusion: EUS-guided choledochoduodenostomy is an effective and safe alternative for rescuing biliary drainage in patients with mid and lower end malignant CBD block with inaccessible papilla.
Beyond Realism and Antirealism ---At Last?
Authors: Rouse Joseph
Published: March 2018

This paper recapitulates my four primary lines of argument that what is wrong with scientific realism is not realist answers to questions to which various anti-realists give different answers, but instead assumptions shared by realists and anti-realists in framing the question. Each strategy incorporates its predecessors as a consequence. A first, minimalist challenge, taken over from Arthur Fine and Michael Williams, rejects the assumption that the sciences have a general aim or goal. A second consideration is that realists and antirealists undertake a mistaken, substantive commitment to a separation between mind and world, which allows them to frame the issue in terms of how epistemic “access” to the world is mediated. A third strategy for dissolving the realism question challenges its underlying commitment to the independence of meaning and truth, a strategy pursued in different ways by Donald Davidson, Robert Brandom, John McDowell, John Haugeland, and myself. The fourth and most encompassing strategy shows that realists and antirealists are thereby committed to an objectionably antinaturalist conception of scientific understanding, in conflict with what the sciences themselves have to say about our own conceptual capacities.
The Relevance of Evidence from the History of Science in the Contemporary Realism/Anti-realism Debate
Authors: Wray K. Brad
Published: March 2018

It is widely assumed that it is the anti-realist who stakes his case on evidence from the history of science. I argue that (i) realists have failed to recognize the need to collect evidence from the history of science to support their methodological claims, and (ii) anti-realists do not rely on evidence from the history of science to the extent that many suggest.
What is Scientific Realism?
Authors: Chakravartty Anjan , Van Fraassen Bas C.
Published: March 2018

Decades of debate about scientific realism notwithstanding, we find ourselves bemused by what different philosophers appear to think it is, exactly. Does it require any sort of belief in relation to scientific theories and, if so, what sort? Is it rather typified by a certain understanding of the rationality of such beliefs? In the following dialogue we explore these questions in hopes of clarifying some convictions about what scientific realism is, and what it could or should be. En route, we encounter some profoundly divergent conceptions of the nature of science and of philosophy.
Realism for realistic people
Authors: Chang Hasok
Published: March 2018

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Gravitational Waves and Scientific Realism
Authors: Collins Harry
Published: March 2018

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Theoretical practices that work: those that mimic Nature’s own
Authors: Cartwright Nancy
Published: March 2018

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Engaging philosophically with the history of science: two challenges for scientific realism
Authors: Arabatzis Theodore
Published: March 2018

I raise two challenges for scientific realists. The first is a pessimistic meta-induction (PMI), but not of the more common type, which focuses on rejected theories and abandoned entities. Rather, the PMI I have in mind departs from conceptual change, which is ubiquitous in science. Scientific concepts change over time, often to a degree that is difficult to square with the stability of their referents, a sine qua non for realists. The second challenge is to make sense of successful scientific practice that was centered on entities that have turned out to be fictitious
A Fond Farewell to "Approximate Truth"?
Authors: Stanford P. Kyle
Published: March 2018

Most commonly, the scientific realism debate is seen as dividing those who do and do not think that the striking empirical and practical successes of at least our best scientific theories indicate with high probability that those theories are ‘approximately true’. But I want to suggest that this characterization of the debate has far outlived its usefulness. Not only does it obscure the central differences between two profoundly different types of contemporary scientific realist, but even more importantly it serves to disguise the most substantial points of actual disagreement between these two kinds of realists and those who instead think the historical record of scientific inquiry itself reveals that such realism is untenable in either form.
Tolstoy’s argument: realism and the history of science
Authors: Psillos Stathis
Published: March 2018

In his intervention to the ‘bankruptcy of science debate’, which raged in Paris in the turn of the twentieth century, Leo Tolstoy was one of the first to use the past record of science as a weapon against current science. It is not inductive. It does not conclude that all current scientific theories will be abandoned; nor that most of them will be abandoned; not even that it is more likely than not that all or most of them will be abandoned. Its conclusion is modest: some of presently accepted theories will have the fate of those past theories that once dominated the scene but subsequently were abandoned.
Scientific Realism and the History of Chemistry
Authors: Hendry Robin
Published: March 2018

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Feyerabendian Pragmatism
Authors: Foss Jeff
Published: March 2018

In the not-too-distant future the scientific realism debate will be absorbed into the far more ancient-and-venerable, old-and-unqualified, realism debate. The first efficient mover of this absorption will be the fact that scientific ontology is a growing and very mixed bag, including not just rocks, plants, animals, and stars, but the Higgs boson, the Big Bang, evolutionary pressures, teenage anxieties, economic growth, social trends, countries, industrial toxins, and hedge funds. Trying to hedge off these ever-stranger newcomers by such moves as castling the debate within well- (or best-) established, mature (two decades old? five?), basic physics is to submit to a biased umpire, with a narrow strike-zone, to get to an arbitrary first base.
Functional Capacity and Self-Esteem of People With Cerebral Palsy
Authors: Espín-Tello Sandra Martina , Dickinson Heather Olivia , Bueno-Lozano Manuel , Jiménez-Bernadó María Teresa , Caballero-Navarro Ana Luisa
Published: March 2018

OBJECTIVE. We assessed whether functional capacity predicts self-esteem in people with cerebral palsy (CP).

METHOD. We conducted a cross-sectional observational study of 108 people with CP, ages 16–65 yr, who were residents of Spain. Self-esteem was captured using the Rosenberg Self-Esteem Scale (RSES), and functional capacity using the Barthel Index (BI). Sociodemographic characteristics were recorded. The relationship between the RSES score and the BI score was analyzed using linear regression.

RESULTS. RSES scores increased significantly as BI scores increased (regression coefficient = 0.047, 95% confidence interval [0.017, 0.078], p = .003). People with a higher level of education, active employment, and independent living arrangements tended to have better functional capacity and higher self-esteem.

CONCLUSION. Greater functional capacity predicted higher self-esteem; this effect is probably partly mediated by education, employment, and living arrangements.
ENSINO AO PROEJA POR MEIO DE AULAS PRÁTICAS: MINICURSO “FATORES QUE AFETAM A FOTOSSÍNTESE”.
Authors: Freitas Samylla Tassia Ferreira de , Sousa Leticia Ferreira de , Rodrigues Agna Rita dos Santos , Oliveira Sandra Mara Santos Lemos de , Santos Luiz Carlos Ramos dos
Published: March 2018

A Educação de Jovens e Adultos permite a democratização do ensino, contribuindo para que trabalhadores, muito tempo fora da escola, tenham acesso à educação. Nessa perspectiva, as aulas práticas são vistas como uma opção viável para experimentar as teorias vistas em sala de aula, dar maior significado ao processo de ensino-aprendizagem, considerando o conhecimento prévio que esses alunos trazem consigo. Para tanto, o minicurso “Fatores que Afetam a Fotossíntese” foi ofertado aos alunos do PROEJA Administração durante o estágio supervisionado. Esses alunos tiveram, pela primeira vez, o acesso ao laboratório, bem como aos seus equipamentos, aprendendo, após a ministração de aula teórica, a manuseá-los e a realizar experimentos, garantindo que o conteúdo da teoria fosse observado na prática, valorizando o trabalho em equipe e a contextualização com suas realidades.
AGROTÓXICOS: UMA PROPOSTA INTERDISCIPLINAR NO ENSINO MÉDIO EM UMA ESCOLA DO CAMPO NO DISTRITO DE IPEZAL/MS
Authors: Soares Stela De Almeida , Vinholi Júnior Airton José
Published: March 2018

Este estudo teve como objetivo a realização de um diagnóstico do processo de ensino e de aprendizagem, tendo como eixo norteador o tema Agrotóxico. A partir desta temática, foram propostas aulas que abordaram conteúdos elencados nos componentes curriculares de história, geografia, biologia, química e língua portuguesa, visando oferecer aos estudantes e professores sugestões de aulas interdisciplinares. Inicialmente, foi realizado um diagnóstico dos conhecimentos prévios que os estudantes têm sobre os agrotóxicos. As demais etapas do projeto foram estruturadas após a análise desses conhecimentos de estudantes do ensino médio em uma escola localizada no distrito de Ipezal, munícipio de Angélica, Mato Grosso do Sul (MS). A referida escola é considerada do campo e possui o eixo temático Terra, Vida e Trabalho (TVT), porém nunca abordou o tema Agrotóxico no âmbito da pesquisa acadêmica entre a comunidade interna. Ademais, os estudantes convivem com o agronegócio intenso na região, uma vez que o município concentra lavouras ao redor e também seis usinas de álcool e açúcar em seu entorno. Por conta de tais fatores, foi realizado o diagnóstico para que, posteriormente, pudessem ser oferecidas sugestões de aplicação de metodologias didáticas que viessem a atender os interesses e os conhecimentos prévios dos estudantes. O trabalho alcançou pontos positivos, principalmente no que se refere aos danos causados por agrotóxicos na população, pois de acordo com as respostas dos estudantes, todos podem ser prejudicados quanto à saúde.
EVASÃO ESCOLAR NA EDUCAÇÃO DE JOVENS E ADULTOS: UM OLHAR A PARTIR DO COLÉGIO ESTADUAL NORMAL PROFESSOR CÉSAR AUGUSTO CEVA EM IPAMERI – GO
Authors: Batalha Rafaela Vieira , Silva Cleber Cezar da
Published: March 2018

O trabalho tem por objetivo fazer um breve contexto histórico da Educação de Jovens e Adultos (EJA) focando no processo de evasão e desistência escolar. Para tanto utiliza-se o método histórico documental e abordagem qualiquantitativa para demonstrar a constituição deste campo tanto nacionalmente quanto regionalmente, chegando até o Colégio Estadual Normal Professor César Augusto Ceva (CENCAC) em Ipameri-Goiás. O estudo de caso é realizado através de dados quantitativos que descortinam a realidade que se estende a várias instituições de ensino nacionais: os altos índices de evasão escolar. Avaliam-se então os fatores intraescolares e extraescolares que levam a esta alta incidência de abandono da sala de aula, tentando descobrir quais são os fatores que geram esta realidade.    Palavras-chave: Educação de Jovens e Adultos. Evasão Escolar. História da Educação.