Miracle-dz/UniFAR-FTUs huggingface dataset:
Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors

The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the ζ chain of the T cell receptor. After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth.
Analysis of plant phosphatidylcholines by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The use of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) for the quantitative determination of phospholipid (PL) molecular species has been problematic, due primarily to the formation of multiple signals (corresponding to the molecular ion and other adducts) for some classes of PL. For example, analysis of phosphatidylcholine (PC) yielded signals that corresponded to protonated and sodiated molecules in the MALDI spectrum. The resulting spectral overlap among various molecular species (e.g. [PC(16:0/18:2) + Na] and [PC(18:2/18:3)]) made it impossible to ascertain their relative amounts using this technique. Other spectral ambiguities existed among different structural isomers, such as PC(18:1/18:1) and PC(18:0/18:2). We determined that molecular species could be resolved by MALDI-TOFMS by first removing the polar head (e.g. phosphocholine) from the phospholipid to effect production of only the sodiated molecules of the corresponding diacylglycerols (DAGs). Analysis of the resulting spectrum allowed unequivocal determination of the molecular species profile of PC from potato tuber and soybean. Estimation of fatty acid composition based on the molecular species determined by MALDI-TOFMS analysis agreed with that from GC-FID analysis. Post-source decay (PSD) was used to resolve standard isomers of PC (e.g. 18:1/18:1 vs. 18:0/18:2). Our results indicated that PSD is a useful approach for resolving structural isomers of PL molecular species.
A Fatty Acid Messenger Is Responsible for Inducing Dispersion in Microbial Biofilms

ABSTRACT It is well established that in nature, bacteria are found primarily as residents of surface-associated communities called biofilms. These structures form in a sequential process initiated by attachment of cells to a surface, followed by the formation of matrix-enmeshed microcolonies, and culminating in dispersion of the bacteria from the mature biofilm. In the present study, we have demonstrated that, during growth, Pseudomonas aeruginosa produces an organic compound we have identified as cis-2-decenoic acid, which is capable of inducing the dispersion of established biofilms and of inhibiting biofilm development. When added exogenously to P. aeruginosa PAO1 biofilms at a native concentration of 2.5 nM, cis-2-decenoic acid was shown to induce the dispersion of biofilm microcolonies. This molecule was also shown to induce dispersion of biofilms, formed by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Streptococcus pyogenes, Bacillus subtilis, Staphylococcus aureus, and the yeast Candida albicans. Active at nanomolar concentrations, cis-2-decenoic acid appears to be functionally and structurally related to the class of short-chain fatty acid signaling molecules such as diffusible signal factor, which act as cell-to-cell communication molecules in bacteria and fungi.
Two Related RNA-editing Proteins Target the Same Sites in Mitochondria of Arabidopsis thaliana*

Background: Pentatricopeptide repeat (PPR) proteins act at specific RNA-editing sites in plant mitochondria. Results: Two related PPR proteins with only five repeat units differentially influence RNA editing in pollen and leaves. Conclusion: Two PPR proteins target the same two sites in RNA editing. Significance: This is the first report on overlapping specificities of PPR proteins in RNA editing. The facilitators for specific cytosine-to-uridine RNA-editing events in plant mitochondria and plastids are pentatricopeptide repeat (PPR)-containing proteins with specific additional C-terminal domains. Here we report the related PPR proteins mitochondrial editing factor 8 (MEF8) and MEF8S with only five such repeats each to be both involved in RNA editing at the same two sites in mitochondria of Arabidopsis thaliana. Mutants of MEF8 show diminished editing in leaves but not in pollen, whereas mutants of the related protein MEF8S show reduced RNA editing in pollen but not in leaves. Overexpressed MEF8 or MEF8S both increase editing at the two target sites in a mef8 mutant. Double mutants of MEF8 and MEF8S are not viable although both identified target sites are in mRNAs for nonessential proteins. This suggests that MEF8 and MEF8S may have other essential functions beyond these two editing sites in complex I mRNAs.
STIM2 protein mediates distinct store‐dependent and store‐independent modes of CRAC channel activation

STIM1 and CRACM1 (or Orai1) are essential molecular components mediating store‐oper‐ated Ca2+ entry (SOCE) and Ca2+ release‐activated Ca2+ (CRAC) currents. Although STIM1 acts as a luminal Ca2+ sensor in the endoplasmic reticulum (ER), the function of STIM2 remains unclear. Here we reveal that STIM2 has two distinct modes of activating CRAC channels: a store‐operated mode that is activated through depletion of ER Ca2+ stores by inositol 1,4,5‐trisphosphate (InsP3) and store‐independent activation that is mediated by cell dialysis during whole‐cell perfusion. Both modes are regulated by calmodulin (CaM). The store‐operated mode is transient in intact cells, possibly reflecting recruitment of CaM, whereas loss of CaM in perfused cells accounts for the persistence of the store‐independent mode. The inhibition by CaM can be reversed by 2‐aminoethoxydiphenyl borate (2‐APB), resulting in rapid, store‐independent activation of CRAC channels. The aminoglycoside antibiotic G418 is a highly specific and potent inhibitor of STIM2‐dependent CRAC channel activation. The results reveal a novel bimodal control of CRAC channels by STIM2, the store dependence and CaM regulation, which indicates that the STIM2/CRACM1 complex may be under the control of both luminal and cytoplasmic Ca2+ levels. —Parvez S. , Beck, A. , Peinelt, C. , Soboloff, J., Lis, A. , Monteilh‐Zoller, M. , Gill, D. L. , Fleig, A. , Penner R. STIM2 protein mediates distinct store‐dependent and store‐independent modes of CRAC channel activation. FASEB J. 22, 752–761 (2008)
Evaluation of the accuracy of transfer learning on sentiment analysis for Indonesian tweets

Sentiment analysis is an automatic process of understanding, extracting and processing textual data to obtain the sentiment information. From machine learning point of view, the sentiment analysis is a supervised learning problem whose training and predicting data come from a similar domain. When domain changes, the machine learning model must be rebuilt from scratch using new training data. New training data requires manual labeling process which is very costly and time-consuming. Therefore, it would be more effective and efficient using transfer learning which uses the training data from an already available domain to deal with the estimating data on different domains. In this paper, we evaluate the accuracy of the transfer learning on sentiment analysis for Indonesian tweets. Our simulations show that the accuracy of the transfer learning is still lower than that of the supervised learning. Moreover, the bi-gram features can improve the accuracy of the transfer learning.
Durometry for the assessment of skin disease in systemic sclerosis.

OBJECTIVE To examine the validity of a durometer to objectively measure skin hardness in systemic sclerosis (SSc), and to compare digital durometry with the modified Rodnan skin score (MRSS) and ultrasonography. METHODS Patients with SSc and healthy controls underwent durometry measurements in 3 assessments: a Latin square experiment to establish durometry's intra- and interobserver reliability compared with skin scoring (5 SSc, 1 control); a longitudinal cohort to assess sensitivity to change in skin hardness (13 SSc, 5 controls); and an ultrasound cohort to evaluate correlation between durometry, ultrasound-measured skin thickness, and clinical skin scoring (30 SSc, 12 controls). RESULTS Intraobserver reproducibility was higher for durometry than for clinical skin scoring (intraclass correlation coefficient [ICC] 0.97 versus 0.85), whereas interobserver reproducibility was similar (0.75 versus 0.73). Interobserver reproducibility of durometry was good for all body areas (ICC 0.61-0.85), but for skin scoring it was moderate in the legs (0.51) and poor in the abdomen (0.08), feet (0.09), and fingers (0.27). Durometry scores correlated with clinical skin scores (Latin square: r = 0.44, P = 0.03; longitudinal cohort: r = 0.81, P < 0.001) and ultrasound-measured skin thickness (hands: r = 0.58, forearms: r = 0.63, upper arms: r = 0.40; P < or = 0.001 for all). Uninvolved skin in patients with SSc was harder than skin from controls (mean +/- SD 23 +/- 7 durometer units [DU] versus 19 +/- 6 DU; P < 0.0001). Finally, there was a strong correlation between change in MRSS and change in durometry score (r = 0.77, P = 0.002). CONCLUSION Durometer-measured skin hardness correlates well with MRSS and ultrasound-measured skin thickness, provides greater reliability than MRSS, and is sensitive to changes in skin hardness over time. Durometry should be considered for use in clinical therapeutic SSc trials.
The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy. A Southwest oncology group study

Elevated serum levels of carcinoembryonic antigen (CEA) were found in 70% of 141 patients with advanced gastrointestinal (GI) cancers. Serial CEA measurements were performed on 70 patients before and during chemotherapy. The majority were treated with 5‐FU and Methyl‐CCNU (33 patients), 5‐FU (19 patients), or 5‐FU and mitomycin‐C (8 patients). In 49 patients with colorectal carcinoma who had elevated serum CEA prior to chemotherapy, 18 had objective partial tumor remission, 16/18 (89%) showed definite decrease in CEA level, one had no change, and one had an increase CEA titer. Thirty‐one patients had either stable disease (10 patients) or increasing disease (21 patients) while on chemotherapy. Of these patients four showed decrease in CEA, eight had no change, and 19 had increase in CEA levels as compared to pretreatment value. The survival of patients with a decrease in CEA during chemotherapy was statistically significant (p = .03) as compared to survival of those with no change or increasing CEA levels. In 21 patients with other GI cancers, the correlation between the clinical response and change in CEA level observed was not as definite as in patients with colorectal carcinoma.
Antislip Readhesion Control Based on Speed-Sensorless Vector Control and Disturbance Observer for Electric Commuter Train—Series 205-5000 of the East Japan Railway Company

The improvement of adhesion characteristics is important in electric commuter train. The electric commuter train has both a slip phenomenon and a slide phenomenon. Slip-and-slide phenomena degrade the comfortable riding performance of electric commuter train. We have already proposed an antislip/ antislide readhesion control system based on disturbance observer and sensorless vector control. The effectiveness of the proposed method has been confirmed by the experiment and the numerical simulation using the tested bogie system of electric commuter train. Then, we apply the proposed method to the actual electric commuter train of series 205-5000 of the East Japan Railway Company. In the experimental results of series 205-5000, this paper demonstrates that the proposed antislip/slide readhesion control system has the desired driving wheel torque response. Moreover, this paper discusses the evaluation method of readhesion control test results.
Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation

The cilium serves as a cellular antenna by coordinating upstream environmental cues with numerous downstream signaling processes that are indispensable for the function of the cell. This role is supported by the revelation that defects of the cilium underlie an emerging class of human disorders, termed “ciliopathies. ” Although mounting interest in the cilium has demonstrated the essential role that the organelle plays in vertebrate development, homeostasis, and disease pathogenesis, the mechanisms regulating cilia morphology and function remain unclear. Here, we show that the target-of-rapamycin (TOR) growth pathway modulates cilia size and function during zebrafish development. Knockdown of tuberous sclerosis complex 1a (tsc1a), which encodes an upstream inhibitor of TOR complex 1 (Torc1), increases cilia length. In contrast, treatment of embryos with rapamycin, an inhibitor of Torc1, shortens cilia length. Overexpression of ribosomal protein S6 kinase 1 (S6k1), which encodes a downstream substrate of Torc1, lengthens cilia. Furthermore, we provide evidence that TOR-mediated cilia assembly is evolutionarily conserved and that protein synthesis is essential for this regulation. Finally, we demonstrate that TOR signaling and cilia length are pivotal for a variety of downstream ciliary functions, such as cilia motility, fluid flow generation, and the establishment of left-right body asymmetry. Our findings reveal a unique role for the TOR pathway in regulating cilia size through protein synthesis and suggest that appropriate and defined lengths are necessary for proper function of the cilium.
Blastocyst transfer: a useful tool for reduction of high-order multiple gestations in a human assisted reproduction program.

OBJECTIVE We evaluated the efficacy of blastocyst transfer in decreasing the incidence of high-order multiple gestations after in vitro fertilization. STUDY DESIGN We conducted a retrospective analysis of 218 patients who were undergoing in vitro fertilization and by our criteria of three 8-cell embryos on day 3 could receive either a day 3 transfer of cleaved embryos or a day 5 transfer of blastocysts. Ongoing pregnancy rates, implantation rates (determined by the total number of visualized gestational sacs), and multiple pregnancy rates were compared between the 2 groups. RESULTS Respective day 3 and day 5 ongoing pregnancy rates (61% and 51%) and implantation rates (35% and 33%) were not significantly different. There were 9 triplet or higher gestations in the day 3 group and 0 in the day 5 group. CONCLUSION Blastocyst transfer can be used to reduce the number of embryos transferred and the resultant incidence of high-order multiple pregnancies while maintaining high pregnancy rates.
Optimization of ultrasound contrast agents with computational models to improve selection of ligands and binding strength

Diagnosis of cardiovascular disease is currently limited by the testing modality. Serum tests for biomarkers can provide quantification of severity but lack the ability to localize the source of the cardiovascular disease, while imaging technology such as angiography and ultrasound can only determine areas of reduced flow but not the severity of tissue ischemia. Targeted imaging with ultrasound contrast agents offers the ability to locally image as well as determine the degree of ischemia by utilizing agents that will cause the contrast agent to home to the affected tissue. Ultrasound molecular imaging via targeted microbubbles (MB) is currently limited by its sensitivity to molecular markers of disease relative to other techniques (e.g., radiolabeling). We hypothesize that computational modeling may provide a useful first approach to maximize microbubble binding by defining key parameters governing adhesion. Adhesive dynamics (AD) was used to simulate the fluid dynamic and stochastic molecular binding of microbubbles to inflamed endothelial cells. Sialyl LewisX (sLex), P‐selectin aptamer (PSA), and ICAM‐1 antibody (abICAM) were modeled as the targeting receptors on the microbubble surface in both single‐ and dual‐targeted arrangements. Microbubble properties (radius [Rc], kinetics [kf, kr], and densities of targeting receptors) and the physical environment (shear rate and target ligand densities) were modeled. The kinetics for sLex and PSA were measured with surface plasmon resonance. Rc, shear rate, and densities of sLex, PSA, or abICAM were varied independently to assess model sensitivity. Firm adhesion was defined as MB velocity <2% of the free stream velocity. AD simulations revealed an optimal microbubble radius of 1–2 µm and thresholds for $k_{{\rm f}}^{{\rm in}} $ (>102 s−1) and $k_{{\rm r}}^{{\rm o}} $ (<10−3 s−1) for firm adhesion in a multi‐targeted system. State diagrams for multi‐targeted microbubbles suggest sLex and abICAM microbubbles may require 10‐fold more ligand to achieve firm adhesion at higher shear rates than sLex and PSA microbubbles. The AD model gives useful insight into the key parameters for stable microbubble binding, and may allow flexible, prospective design, and optimization of microbubbles to enhance clinical translation of ultrasound molecular imaging. Biotechnol. Bioeng. 2010;107: 854–864. © 2010 Wiley Periodicals, Inc.
The Gas Vesicle Gene (gvp) Cluster of the Cyanobacterium Pseudanabaena sp. Strain PCC 6901

A gene cluster located downstream from gvpA in the cyanobacterium Pseudanabaena sp. strain PCC 6901 has been cloned and sequenced. The three genes, orfl, gvpN and gvpj, are consecutive with no intergenic region. In contrast to GvpN and Gvpj, which share high similarity at the amino acid level with their counterparts in other cyanobacteria and halophilic archaea, Orfl is only 29% identical to the C-terminal part of GvpC from Anabaena flos-aquae and its sequence organization is reminiscent of the halophilic archaeal GvpC.
Indexing for Moving Objects in Multi-Floor Indoor Spaces That Supports Complex Semantic Queries

With the emergence of various types of indoor positioning technologies (e.g., radio-frequency identification, Wi-Fi, and iBeacon), how to rapidly retrieve indoor cells and moving objects has become a key factor that limits those indoor applications. Euclidean distance-based indexing techniques for outdoor moving objects cannot be used in indoor spaces due to the existence of indoor obstructions (e.g., walls). In addition, currently, the indexing of indoor moving objects is mainly based on space-related query and less frequently on semantic query. To address these two issues, the present study proposes a multi-floor adjacency cell and semantic-based index (MACSI). By integrating the indoor cellular space with the semantic space, the MACSI subdivides open cells (e.g., hallways and lobbies) using space syntax and optimizes the adjacency distances between three-dimensionally connected cells (e.g., elevators and stairs) based on the caloric cost that extends single floor indoor space to three dimensional indoor space. Moreover, based on the needs of semantic query, this study also proposes a multi-granularity indoor semantic hierarchy tree and establishes semantic trajectories. Extensive simulation and real-data experiments show that—compared with the indoor trajectories delta tree (ITD-tree) and the semantic-based index (SI)—the MACSI produces more reliable query results with significantly higher semantic query and update efficiencies; has superior semantic expansion capability; and supports multi-granularity complex semantic queries.
Sensitivity analysis on electrical parameters for Permanent Magnet Synchronous Machine manufacturing tolerances in EV and HEV

Production processes of Permanent Magnet Synchronous Machines suffer from manufacturing tolerances because of assembly imperfections. This causes undesired deviations in the machine's performance and behavior. In particular, the equivalent circuit parameters of the machine are affected. Therefore, the validity of the electrical parameters of a reference machine is doubtful for sample machines. In this work, a sensitivity analysis is done in order to investigate the influence of design variables (e.g. rotor outer radius) on the electrical parameters. The aim is to show the importance of paying an attention to the parameters' deviations resulting from tolerances, to identify how the parameter deviations trend is, and which geometrical parameters have the most significant impact on the machine parameters. The study is done for an 18kW permanent magnet synchronous machine by changing the design variables in the tolerance band. Analysis results show that a mathematical model, that describes the deviations of electrical parameters, can be extracted.
Toxin-induced RhoA Activity Mediates CCL1-triggered Signal Transducers and Activators of Transcription Protein Signaling*

Background: Rho GTPases are involved in STAT-dependent transcription. However, the connecting signaling pathways are unknown. Results: Activated RhoA induces STAT3 phosphorylation via ROCK, JNK, CCL1 synthesis, and secretion. Conclusion: Auto/paracrine cytokine signaling is a link between RhoA and STAT3. Significance: The knowledge about the connection between RhoA and STAT signaling is crucial for understanding several diseases, especially cancer. RhoA is reportedly involved in signal transducers and activators of transcription (STAT)-dependent transcription. However, the pathway connecting the GTPase and STAT signaling has not been characterized. Here, we made use of bacterial toxins, which directly activate Rho GTPases to analyze this pathway. Cytotoxic necrotizing factors (CNFs) are produced by pathogenic Escherichia coli strains and by Yersinia pseudotuberculosis. They activate small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. We show that RhoA activation leads to phosphorylation and activation of STAT3 and identify signal proteins involved in this pathway. RhoA-dependent STAT3 stimulation requires ROCK and Jun kinase activation as well as AP1-induced protein synthesis. The secretion of one or more factors activates the JAK-STAT pathway in an auto/paracrine manner. We identify CCL1/I-309 as an essential cytokine, which is produced and secreted upon RhoA activation and which is able to activate STAT3-dependent signaling pathways.