bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of T Cell Activities Mediated by Human TCRs and CARs That Use the Same Recognition Domains
Authors: Harris Daniel T. , Hager Marlies V. , Smith Sheena N. , Cai Qi , Stone Jennifer D. , Kruger Philipp , Lever Melissa , Dushek Omer , Schmitt Thomas M. , Greenberg Philip D. , Kranz David M. 
Published: December 2017

Abstract
Adoptive T cell therapies have achieved significant clinical responses, especially in hematopoietic cancers. Two types of receptor systems have been used to redirect the activity of T cells, normal heterodimeric TCRs or synthetic chimeric Ag receptors (CARs). TCRs recognize peptide-HLA complexes whereas CARs typically use an Ab-derived single-chain fragments variable that recognizes cancer-associated cell-surface Ags. Although both receptors mediate diverse effector functions, a quantitative comparison of the sensitivity and signaling capacity of TCRs and CARs has been limited due to their differences in affinities and ligands. In this study we describe their direct comparison by using TCRs that could be formatted either as conventional αβ heterodimers, or as single-chain fragments variable constructs linked to CD3ζ and CD28 signaling domains or to CD3ζ alone. Two high-affinity TCRs (KD values of ∼50 and 250 nM) against MART1/HLA-A2 or WT1/HLA-A2 were used, allowing MART1 or WT1 peptide titrations to easily assess the impact of Ag density. Although CARs were expressed at higher surface levels than TCRs, they were 10–100-fold less sensitive, even in the absence of the CD8 coreceptor. Mathematical modeling demonstrated that lower CAR sensitivity could be attributed to less efficient signaling kinetics. Furthermore, reduced cytokine secretion observed at high Ag density for both TCRs and CARs suggested a role for negative regulators in both systems. Interestingly, at high Ag density, CARs also mediated greater maximal release of some cytokines, such as IL-2 and IL-6. These results have implications for the next-generation design of receptors used in adoptive T cell therapies.
Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress
Authors: Zhang Shusong , Zhang Xinwei , Wang Ke , Xu Xi , Li Mingyang , Zhang Jun , Zhang Yan , Hao Jie , Sun Xiuyuan , Chen Yingyu , Liu Xiaohui , Chang Yingjun , Jin Rong , Wu Hounan , Ge Qing 
Published: December 2017

Abstract
Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4+ recent thymic emigrants (RTEs), and mature naive T cells in the periphery. The results demonstrate that RTEs and naive T cells had reduced mitochondrial content and mitochondrial reactive oxygen species when compared with SP thymocytes. This downregulation of mitochondria requires T cell egress from the thymus and occurs early after young T cells enter the circulation. Autophagic clearance of mitochondria, but not mitochondria biogenesis or fission/fusion, contributes to mitochondrial downregulation in RTEs. The enhanced apoptosis signal-regulating kinase 1/MAPKs and reduced mechanistic target of rapamycin activities in RTEs relative to SP thymocytes may be involved in this mitochondrial reduction. These results indicate that the gain of metabolic quiescence is one of the important maturation processes during SP–RTE transition. Together with functional maturation, it promotes the survival and full responsiveness to activating stimuli in young T cells.
The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells
Authors: Göpfert Christiane , Andreas Nico , Weber Franziska , Häfner Norman , Yakovleva Tatiana , Gaestel Matthias , Kamradt Thomas , Drube Sebastian 
Published: December 2017

Abstract
IL-33 is an IL-1 cytokine superfamily member. Binding of IL-33 to the IL-33R induces activation of the canonical NF-κB signaling and activation of MAPKs. In bone marrow–derived dendritic cells, IL-33 induces the production of IL-6, IL-13, and TNF-α. However, the signaling pathways resulting in IL-33–induced effector functions of dendritic cells are unknown. In this article, we show that the IL-33–induced cytokine production is only partly dependent on p65. Thereby, p65 mediates the production of IL-6, but not of IL-13, whereas the p38–Mapk-activated protein kinases 2/3 (MK2/3) signaling module mediates the IL-13, but not the IL-6, production. In addition, GM-CSF, which is critical for the differentiation and proliferation of bone marrow–derived dendritic cells, potentiates the p65-dependent IL-6 and the p38-MK2/3–dependent IL-13 production. Furthermore, we found that effective TNF-α production is only induced in the presence of GM-CSF and IL-33 via the p38-MK2/3 signaling module. Taken together, we found that the p38-MK2/3 signaling module is essential to mediate IL-33–induced cytokine production in dendritic cells.
Extracellular Lactate: A Novel Measure of T Cell Proliferation
Authors: Grist James T. , Jarvis Lorna B. , Georgieva Zoya , Thompson Sara , Kaur Sandhu Harpreet , Burling Keith , Clarke Ashley , Jackson Sarah , Wills Mark , Gallagher Ferdia A. , Jones Joanne L. 
Published: December 2017

Abstract
Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i.e., [3H]thymidine incorporation and the use of cell proliferation dyes). Furthermore, we demonstrate the usefulness of measuring lactate as a read-out in conventional suppression assays and high-throughput peptide-screening assays. Extracellular lactate was stably produced over 7 d, and results were reproducibly performed over several freeze–thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable, and easy-to-implement research tool for measuring T cell responses and cellular metabolic changes in vitro.
EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production
Authors: Guo Muyao , Price Madeline J. , Patterson Dillon G. , Barwick Benjamin G. , Haines Robert R. , Kania Anna K. , Bradley John E. , Randall Troy D. , Boss Jeremy M. , Scharer Christopher D. 
Published: December 2017

Abstract
Epigenetic remodeling is required during B cell differentiation. However, little is known about the direct functions of epigenetic enzymes in Ab-secreting cells (ASC) in vivo. In this study, we examined ASC differentiation independent of T cell help and germinal center reactions using mice with inducible or B cell–specific deletions of Ezh2. Following stimulation with influenza virus or LPS, Ezh2-deficient ASC poorly proliferated and inappropriately maintained expression of inflammatory pathways, B cell–lineage transcription factors, and Blimp-1–repressed genes, leading to fewer and less functional ASC. In the absence of EZH2, genes that normally gained histone H3 lysine 27 trimethylation were dysregulated and exhibited increased chromatin accessibility. Furthermore, EZH2 was also required for maximal Ab secretion by ASC, in part due to reduced mitochondrial respiration, impaired glucose metabolism, and poor expression of the unfolded-protein response pathway. Together, these data demonstrate that EZH2 is essential in facilitating epigenetic changes that regulate ASC fate, function, and metabolism.
OCCULT HEPATITIS B VIRUS INFECTION AND ASSOCIATED GENOTYPES AMONG HBSAG-NEGATIVE SUBJECTS IN BURKINA FASO
Authors: DIARRA Birama , YONLI Albert Théophane , SORGHO Pegdwendé Abel , COMPAORE Tegwinde Rebecca , Obiri -Yeboah Dorcas , OUATTARA Abdoul Karim , Lassina Traore , ZONGO Wendpagnangdé Arsène , Soubeiga Serge Théophile , Pietra Virginio , Nagalo Bolni-Marius , Djigma Wendkuuni Florencia , Tao Issoufou , Sanogo Rokia , SIMPORE Jacques 
Published: December 2017

Background: Occult Hepatitis B virus infection (OBI), is characterized by the absence of detectable HBsAg in the blood of a person assumed to be healthy. It remains a potential transmission threat and risk to HBV chronic infection. The purpose of this study was to determine the OBI prevalence among HBsAg negative subjects and to characterize associated genotypes.Methods: Blood samples of 219 HBsAg-negative subjects tested by ELISA were collected. HBV DNA was investigated in all samples. Viral loads were determined using quantitative real-time PCR. All samples were screened for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome was sequenced. The database was analyzed using the SPSS and Epi info softwares. Phylogenetic analysis was performed using the BioEdit and MEGA softwares.Results: Of the 219 samples, 20.1 % were anti-HBc positive, 1.8 % HBeAg and 22.8 % were anti-HBe positive. Fifty-six 56 (25.6 %) of the samples had a detectable HBV DNA and viral loads ranging from 4 IU/mL to 13.6 106 IU/mL. Sixteen of them (16/56) had a viral load < 200 IU/mL, resulting in an OBI prevalence of 7.3 % (16/219) in our study. The remaining 40 subjects had viral loads ˃ 200 IU/mL, resulting in a “false OBI” prevalence of 18.3% (40/219). HBV genotype E was predominant followed by the quasi-sub-genotype A3. A single "false OBI" strain had the characteristic mutation G145R. Other mutations were observed and all located in the major hydrophilic region (MHR) of the S gene.Conclusion: The study reported a prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in Burkina Faso. It further provides information on the existence of “false OBI “. This study has found mutations in the major hydrophilic region (MHR) of the pre-S/S gene of HBV. Key words: HBV, OBI, Genotypes, Real-time PCR, Sequencing
Insulin Syringe: A Gimmick in Pediatric Dentistry
Authors: Singh Chanchal , Kour Gurpreet , Masih Updesh , Srivastava Manvi , Yadav Priti 
Published: December 2017

ABSTRACTAimThe management of pain and anxiety in dentistry encompasses a number of procedural issues, including the delivery of anesthetic solution. One of the most important ways to manage the behavior of children is pain control. Trypanophobia is very common among dental patients and the most important goal of guidelines on behavior guidance for pediatric dental patient is to ease fear and anxiety in dental procedures in children. For the stated reasons, the purpose of the present study was to record child's pain sensation both objectively and subjectively while receiving dental local anesthesia using conventional syringes and diabetic needles.Materials and methodsTwenty children of age group 6 to 12 years undergoing routine dental procedures participated in the study. Every child acted as one's own control, while receiving treatment on the opposite side of the same arch. Each patient was randomly assigned to receive the injection either with conventional syringe or diabetic needle for the first visit, while the injection with the other needle was administered during the second visit. Rating scales were used for objective and subjective evaluations.ResultsStatistical analysis of the measurements were made using Wilcoxon signed U test and Mann—Whitney U test which showed the mean sound, eye, motor (SEM) score difference using insulin syringe. The outcome was statistically significant when compared using the mean ranks between male and female patients with that of control group.ConclusionIt can be concluded that diabetic syringes exhibit clinical advantage and its use in pediatric dentistry for local anesthetics (LA) infiltration can prove beneficial.How to cite this articleKour G, Masih U, Singh C, Srivastava M, Yadav P, Kushwah J. Insulin Syringe: A Gimmick in Pediatric Dentistry. Int J Clin Pediatr Dent 2017;10(4):319-323.
Comparative Study on Two Variants of Laghupanchamula (A Compound Ayurvedic Formulation) for Important Groups of Phytochemicals and Antioxidant Activity
Authors: Ghildiyal Shivani , Joshi Apurva , Joshi Vinod K 
Published: December 2017

ABSTRACT

Introduction
Laghupanchamula is a compound formulation prepared by combinations of roots of five herbs. Two variants of Laghupanchamula have been described in Ayurvedic classics where beside four common herbs fifth one is either Gokshura (Tribulus terrestris L.) or Eranda (Ricinus communis L.). The objective of the study is to make comparison between two variants of Laghupanchmula with respect to important group of phytochemicals and antioxidant activity to corroborate the science behind their therapeutic utility.

Materials and methods
Standard methods have been followed for quantitative determination of total quantity of phenols, tannins, flavonoids, and flavonols, and in vitro antioxidant activity in variants of Laghupanchmula formulations. Qualitative high-performance liquid chromatography (HPLC) analysis has also been performed to establish presence/absence of important chemical constituents in formulations.

Results
Additional quantity of phenols, tannins, flavonoids, and flavonols has been observed in Laghupanchamula variant containing Eranda than the variant containing Gokshura. Greater antioxidant activity has also been found in formulation containing Eranda. The HPLC analysis revealed the presence of shikimic acid, gallic acid, catechin in both formulations, but rutin has been found only in formulation containing Eranda.

Conclusion
From the results of experiments it has been observed that the formulation containing Eranda has more antioxidant activity as it contains more quantities of phenol, tannins, flavonoids, and flavonols than the formulation containing Gokshura.

How to cite this article
Ghildiyal S, Joshi A, Joshi VK. Comparative Study on Two Variants of Laghupanchamula (A Compound Ayurvedic Formulation) for Important Groups of Phytochemicals and Antioxidant Activity. J Drug Res Ayurvedic Sci 2017;2(3):157-163.
Pharmacological Profile of Tithonia diversifolia (Hemsl.) A.Gray: A Comprehensive Review
Authors: Upadhyay Sachchida N , Kawlni Lalrinpuia 
Published: December 2017

ABSTRACT

Aim
This review aims to provide an up-to-date overview of pharmacological studies of Tithonia diversifolia (Hemsl.) A.Gray. Moreover, the focus of this review is the possible exploitation of this species to treat different diseases and to suggest future investigations.

Background
Tithonia diversifolia (Hemsl.) A.Gray is an important medicinal plant whose leaf is the major organ used alone or in combination with other plants for the treatment of a wide variety of ailments. This plant has been a subject of research interest because of its various indigenous medicinal uses in many countries.

Results
Different pharmacological studies on T. deversifolia show that it possesses antibacterial, antioxidant, anti-inflammatory, antinociception, analgesic, antidiarrheal, antimalarial, antihyperglycemic, and cancer chemopreventive activities due to the presence of different active constituents.

Conclusion
Tithonia diversifolia (Hemsl.) A.Gray extracts and their active constituents should be subjected to detailed mechanistic studies to fully understand the mode of action of the active constituents.

Clinical significance
Till date, there is no scientific literature/data regarding clinical trials of this plant except preclinical studies on different laboratory animals.

How to cite this article
Kawlni L, Bora M, Upadhyay SN, Hazra J. Pharmacological Profile of Tithonia diversifolia (Hemsl.) A.Gray: A Comprehensive Review. J Drug Res Ayurvedic Sci 2017;2(3):183-187.
Suspended Sediment Dynamics in the Macrotidal Seine Estuary (France): 2. Numerical Modeling of Sediment Fluxes and Budgets Under Typical Hydrological and Meteorological Conditions
Authors: Schulz E. , Grasso F. , Le Hir P. , Verney R. , Thouvenin B. 
Published: December 2017

AbstractUnderstanding the sediment dynamics in an estuary is important for its morphodynamic and ecological assessment as well as, in case of an anthropogenically controlled system, for its maintenance. However, the quantification of sediment fluxes and budgets is extremely difficult from in‐situ data and requires thoroughly validated numerical models. In the study presented here, sediment fluxes and budgets in the lower Seine Estuary were quantified and investigated from seasonal to annual time scales with respect to realistic hydro‐ and meteorological conditions. A realistic three‐dimensional process‐based hydro‐ and sediment‐dynamic model was used to quantify mud and sand fluxes through characteristic estuarine cross‐sections. In addition to a reference experiment with typical forcing, three experiments were carried out and analyzed, each differing from the reference experiment in either river discharge or wind and waves so that the effects of these forcings could be separated. Hydro‐ and meteorological conditions affect the sediment fluxes and budgets in different ways and at different locations. Single storm events induce strong erosion in the lower estuary and can have a significant effect on the sediment fluxes offshore of the Seine Estuary mouth, with the flux direction depending on the wind direction. Spring tides cause significant up‐estuary fluxes at the mouth. A high river discharge drives barotropic down‐estuary fluxes at the upper cross‐sections, but baroclinic up‐estuary fluxes at the mouth and offshore so that the lower estuary gains sediment during wet years. This behavior is likely to be observed worldwide in estuaries affected by density gradients and turbidity maximum dynamics.
Regime‐Dependent Differences in Surface Freshwater Exchange Estimates Over the Ocean
Authors: Wong Sun , Behrangi Ali 
Published: December 2017

AbstractDifferences in gridded precipitation (P), surface evaporation (E), and the resultant surface freshwater exchange (P − E) among different products over the ocean are diagnosed as functions of moisture advection (Qadvt) and moisture tendency by dynamical convergence (Qcnvg). Compared to the GPCP product, the TRMM3B42 product captures higher frequency of precipitation with larger extreme precipitation rates in regimes of deep convection and more light rain detections in regimes of frequent occurrence of boundary layer clouds. Discrepancies in E depend on moisture flux divergence, with the OAFlux product having the largest E in regimes of divergence. Discrepancies in mean P − E in deep convective regimes are highly influenced by differences in precipitation, with the TRMM3B42 product yielding P − E histograms closer to those inferred from the reanalysis moisture flux convergence. In nonconvergent regimes, observation‐based P − E histograms skew toward positive values while the inferred reanalysis histograms are symmetric about the means.
Magnetospheric Multiscale Observations of Electron Scale Magnetic Peak
Authors: Yao S. T. , Shi Q. Q. , Guo R. L. , Yao Z. H. , Tian A. M. , Degeling A. W. , Sun W. J. , Liu J. , Wang X. G. , Zong Q. G. , Zhang H. , Pu Z. Y. , Wang L. H. , Fu S. Y. , Xiao C. J. , Russell C. T. , Giles B. L. , Feng Y. Y. , Xiao T. , Bai S. C. , Shen X. C. , Zhao L. L. , Liu H. 
Published: December 2017

AbstractThe sudden enhancements of magnetic strength, named magnetic peaks (MPs), are often observed in the magnetosheath of magnetized planets. They are usually identified as flux ropes (FRs) or magnetic mirror mode structures. Previous studies of MPs are mostly on the magnetohydrodynamics (MHD) scale. In this study, an electron scale MP is reported in the Earth magnetosheath. We present a typical case with a scale of ~7 electron gyroradii and a duration of ~0.18 s. A strong magnetic disturbance and associated electrical current are detected. Electron vortex is found perpendicular to the magnetic field line and is self‐consist with the peak. We use multipoint spacecraft techniques to determine the propagation velocity of the MP structure and find that the magnetic peak does propagate relative to the plasma (ion) flow. This is very different from the magnetic mirror mode that does not propagate relative to the plasma flow. Furthermore, we developed an efficient method that can effectively distinguish “magnetic bottle like” and “FRs like” structures. The MP presented in this study is identified as magnetic bottle like type. The mechanism to generate the electron scale magnetic bottle like structure is still unclear, suggesting that new theory needs to be developed to understand such small‐scale phenomena.
Variation of Jupiter's Aurora Observed by Hisaki/EXCEED: 3. Volcanic Control of Jupiter's Aurora
Authors: Tao Chihiro , Kimura Tomoki , Tsuchiya Fuminori , Muirakami Go , Yoshioka Kazuo , Yamazaki Atsushi , Badman Sarah V. , Misawa Hiroaki , Kita Hajime , Kasaba Yasumasa , Yoshikawa Ichiro , Fujimoto Masaki 
Published: December 2017

AbstractTemporal variation of Jupiter's northern aurora during enhanced Io volcanic activity was detected using the EXCEED spectrometer on board the Hisaki Earth‐orbiting planetary space telescope. It was found that in association with reported Io volcanic events in early 2015, auroral power and estimated field‐aligned currents were enhanced during day of year 40–120. Furthermore, the far ultraviolet color ratio decreased during the event, indicating a decrease of auroral electron mean energy and total acceleration by <30%. During the episode of enhanced Io volcanic activity, Jupiter's magnetosphere contains more source current via increased suprathermal plasma density by up to 42%; therefore, it would have required correspondingly less electron acceleration to maintain the enhanced field‐aligned current and corotation enforcement current. Sporadic large enhancements in auroral emission detected more frequently during the active period could have been contributed by nonadiabatic magnetospheric energization.
Contribution of Deformation to Sea Ice Mass Balance: A Case Study From an N‐ICE2015 Storm
Authors: Itkin Polona , Spreen Gunnar , Hvidegaard Sine Munk , Skourup Henriette , Wilkinson Jeremy , Gerland Sebastian , Granskog Mats A. 
Published: December 2017

AbstractThe fastest and most efficient process of gaining sea ice volume is through the mechanical redistribution of mass as a consequence of deformation events. During the ice growth season divergent motion produces leads where new ice grows thermodynamically, while convergent motion fractures the ice and either piles the resultant ice blocks into ridges or rafts one floe under the other. Here we present an exceptionally detailed airborne data set from a 9 km2 area of first year and second year ice in the Transpolar Drift north of Svalbard that allowed us to estimate the redistribution of mass from an observed deformation event. To achieve this level of detail we analyzed changes in sea ice freeboard acquired from two airborne laser scanner surveys just before and right after a deformation event brought on by a passing low‐pressure system. A linear regression model based on divergence during this storm can explain 64% of freeboard variability. Over the survey region we estimated that about 1.3% of level sea ice volume was pressed together into deformed ice and the new ice formed in leads in a week after the deformation event would increase the sea ice volume by 0.5%. As the region is impacted by about 15 storms each winter, a simple linear extrapolation would result in about 7% volume increase and 20% deformed ice fraction at the end of the season.