Miracle-dz/UniFAR-FTUs huggingface dataset:
The Catalytic Activity of the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 3 Is Required To Sustain CD4+ CD8+ Thymocyte Survival

ABSTRACT Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family whose function is largely unknown. Given the central role of MAPKs in T cell development, we hypothesized that ERK3 may regulate thymocyte development. Here we have shown that ERK3 deficiency leads to a 50% reduction in CD4+ CD8+ (DP) thymocyte number. Analysis of hematopoietic chimeras revealed that the reduction in DP thymocytes is intrinsic to hematopoietic cells. We found that early thymic progenitors seed the Erk3−/− thymus and can properly differentiate and proliferate to generate DP thymocytes. However, ERK3 deficiency results in a decrease in the DP thymocyte half-life, associated with a higher level of apoptosis. As a consequence, ERK3-deficient DP thymocytes are impaired in their ability to make successful secondary T cell receptor alpha (TCRα) gene rearrangement. Introduction of an already rearranged TCR transgene restores thymic cell number. We further show that knock-in of a catalytically inactive allele of Erk3 fails to rescue the loss of DP thymocytes. Our results uncover a unique role for ERK3, dependent on its kinase activity, during T cell development and show that this atypical MAPK is essential to sustain DP survival during RAG-mediated rearrangements.
A bio-inspired adaptive end-to-end network multi-path routing to achieve load-balance

Load-balance is one of the most important problems in the multipath routing. To this point, this paper proposed a new bio-inspired adaptive multipath routing (BAMR) protocol based on a mathematic biology model ARAS, which is inspired by the host Escherichia coli cells to regulate its metabolic synthesis to keep the high cell growth rate. The BAMR take the routing decision to imitate the adaptive behavior of biological systems. Firstly, BAMR integrates the round trip delay and the available bandwidth of path for calculating a new bio-inspired routing-decision metric, i.e., the path fitness, which can be equivalently regarded as the growth rate of cell volume. Then the fitness of each path is applied to the ARAS model to calculate its packet delivery gain, respectively, which is equivalent to the concentration of each nutrient in the bacterial cell. Finally, the source node chooses the path with the highest packet delivery gain for each packet. Through the proposed routing protocol, the source node can efficiently distributes traffic among multiple paths, and allocates more traffic to a less loaded path within the path capacity.
Topology of Mammalian Isoprenylcysteine Carboxyl Methyltransferase Determined in Live Cells with a Fluorescent Probe

ABSTRACT Isoprenylcysteine carboxyl methyltransferase (Icmt) is a highly conserved enzyme that methyl esterifies the α carboxyl group of prenylated proteins including Ras and related GTPases. Methyl esterification neutralizes the negative charge of the prenylcysteine and thereby increases membrane affinity. Icmt is an integral membrane protein restricted to the endoplasmic reticulum (ER). The Saccharomyces cerevisiae ortholog, Ste14p, traverses the ER membrane six times. We used a novel fluorescent reporter to map the topology of human Icmt in living cells. Our results indicate that Icmt traverses the ER membrane eight times, with both N and C termini disposed toward the cytosol and with a helix-turn-helix structure comprising transmembrane (TM) segments 7 and 8. Several conserved amino acids that map to cytoplasmic portions of the enzyme are critical for full enzymatic activity. Mammalian Icmt has an N-terminal extension consisting of two TM segments not found in Ste14p and therefore likely to be regulatory. Icmt is a target for anticancer drug discovery, and these data may facilitate efforts to develop small-molecule inhibitors.
Adaptive Inverse Perspective Mapping for lane map generation with SLAM

This paper proposes an adaptive Inverse Perspective Mapping (IPM) algorithm to obtain accurate bird's-eye view images from the sequential images of forward looking cameras. These images are often distorted by the motion of the vehicle; even a small motion can cause a substantial effect on bird's-eye view images. In this paper, we propose an adaptive model for the IPM to accurately transform camera images to bird's-eye view images by using motion information. Using motion derived from the monocular visual simultaneous localization and mapping (SLAM), experimental result shows that the proposed approaches can provide stable bird's-eye view images, even with large motion during the drive.
Development of a wearable HCI controller through sEMG & IMU sensor fusion

This paper studies a novel wearable human-computer interface that allows a user to interact with computer-based applications through the fusion of sEMG and IMU sensors. The proposed system is able to detect human motion intention, specifically, the gestures of the wrist and hand. It then translates the gestures and transmits it as command signals for computer-based applications. The novelty of the proposed system is the training-free control scheme to decode sEMG signals into target motions. The classified gestures could be identified by two sEMG sensors mounted on a forearm. One IMU sensor is used to calculate the real-time arm configuration. This can be a command signal for a cursor position in a computer-based application through the proposed projection method. Our method also comprises the drift compensation algorithm which makes our system more robust in prolonged operation. It also makes a user feel more comfortable. For evaluating the applicability of the proposed method, we developed a presentation controller that allows the user to control the mouse cursor, and three distinctive commands using wrist and hand gestures. The proposed system is validated by experiments with six subjects.
Integrated visual analytics workflow with GeoTime and nSpace VAST 2010 mini challenge 1 award: Outstanding Analysis and Accuracy

This paper is a case study focusing on the analytical process performed by three junior analysts using the nSpace/GeoTime tools to investigate arms dealing activities from various text records. Our integrated visual analytic applications created an environment that supported systematic use of analytical methods and helped junior analysts achieve the results that won an award for ‘Outstanding Analysis and Accuracy’.
Taber's Cyclopedic Medical Dictionary

Taber's 22 bring meanings to life! In hand, online, or on your mobile device-anywhere and everywhere, Taber's 22 is the all-in-one, go-to source in the classroom, clinical, and beyond. Under the editorial direction of Donald Venes, MD, MSJ, a team of expert consulting editors and consultants, representing nearly every health care profession, ensures that the content reflects the most current healthcare information. A wealth of resources puts the language of nursing, medicine and the healthcare professions at your fingertips.Features: Web, mobile, and print platforms-ensure access in any setting; crossword puzzles, flashcards, and listen-and-learn activities - meet the needs of visual, kinesthetic, and auditory learners; over 30,000 audio pronunciations - build speaking confidence; must-know, rarely memorized information; Appendices for normal reference laboratory values and prefixes, suffices, and combining forms, as well as abbreviations, symbols, and units of measurement, documentation system definitions, and complementary and alternative medicine; full-color illustrations of anatomy and physiology, and photographs of diseases and disorders; translations of common healthcare terms and phrases in English, French, and Spanish. The tools for success: Patient Care Statements summarize assessment, treatment, and patient teaching requirements; Caution/Safety Statements set in red bars with an easy-to find icon highlight information critical to safe patient care; Nursing-focused appendices include all NANDA-approved diagnoses organized alphabetically and by diseases/disorders, NIC intervention labels and definitions, and NOC outcome labels and definitions. This is the state-of-the-art in healthcare and medicine. This is the brand-new Taber'sPlus, the online center for interactive, multimedia learning activities and healthcare resources. New: over 100 videos linked directly to entries; over 8,000 brand-new entries, over 65,000 in all; over 500 new, full-color illustrations, over 1,200 in all; and, over 1,500 new audio pronunciations, nearly 32,000 in all.
BaobabView: Interactive construction and analysis of decision trees

We present a system for the interactive construction and analysis of decision trees that enables domain experts to bring in domain specific knowledge. We identify different user tasks and corresponding requirements, and develop a system incorporating a tight integration of visualization, interaction and algorithmic support. Domain experts are supported in growing, pruning, optimizing and analysing decision trees. Furthermore, we present a scalable decision tree visualization optimized for exploration. We show the effectiveness of our approach by applying the methods to two use cases. The first case illustrates the advantages of interactive construction, the second case demonstrates the effectiveness of analysis of decision trees and exploration of the structure of the data.
Relative Bioavailability of an Emulsion Formulation for Omega‐3‐Acid Ethyl Esters Compared to the Commercially Available Formulation: A Randomized, Parallel‐Group, Single‐Dose Study Followed by Repeat Dosing in Healthy Volunteers

LOVAZA (omega‐3‐acid ethyl esters; eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]), with diet, lowers very high triglycerides (≥500 mg/dL) in adults. This study evaluated whether an emulsion formulation (LEM) increases the bioavailability of EPA/DHA compared to the reference formulation (RF) in healthy volunteers. Following relative bioavailability assessment, LEM, RF, and placebo were dosed for 2 weeks. Exposure measurements included plasma‐free and total fatty acid (EPA/DHA) concentrations and phospholipid and red blood cell (RBC) incorporation. Following single doses, the dose‐normalized EPA plasma‐corrected AUCs were 14‐fold (total) and 12‐fold (free) higher and DHA plasma‐corrected AUCs were 10‐fold (total) and 13‐fold (free) higher for LEM compared to RF. EPA and DHA incorporation into phospholipids increased for all active treatments; the increase was dose dependent for EPA. An 8‐fold increase over baseline was observed in EPA incorporation for LEM (4‐capsule dose) compared to a 4‐fold increase for RF 4 g. DHA incorporation increased to a lesser degree, and RBC incorporation also increased. Pharmacodynamic evaluations revealed slight decreases (−8% to −25%) in the mean fasting triglyceride concentrations in all groups, including placebo, compared to baseline. Following a high‐fat meal, no consistent treatment‐related effect on the triglyceride profiles was observed. Study treatments were safe and tolerated. In conclusion, LEM improves the oral bioavailability of EPA and DHA.
Softly, softly, the way forward? A qualitative study of the first year of implementing clinical governance in primary care

The aim of this study was to explore the views of Primary Care Organisation (PCO) clinical governance leads on the implementation and development of clinical governance within primary care in the south west region. A grounded theory study using focus groups, research interviews and negotiated feedback reports was designed for use in the primary care setting. The subjects were a purposeful sample of 16 PCG-level clinical governance leads. Four main categories emerged from the data. These included: (1) defining clinical governance; (2) the process of implementing clinical governance; (3) positive aspects of clinical governance; and (4) concerns about delivering clinical governance. At the time of collecting the data (approximately 1 year after the introduction of clinical governance), there was evidence of a culture in primary care where clinicians valued efforts to improve the quality of patient care and enjoyed their own involvement in decision-making at a grass-roots level. However, whilst the concept of clinical governance was received with enthusiasm, the delivery of clinical governance faced challenges. These challenges included the paucity of ear-marked funding, the speed of implementation, the volume of work, and the impact on the clinical governance lead's relationships at home and at work and on his/her emotional wellbeing.
Nuclear Receptors TR2 and TR4 Recruit Multiple Epigenetic Transcriptional Corepressors That Associate Specifically with the Embryonic β-Type Globin Promoters in Differentiated Adult Erythroid Cells

ABSTRACT Nuclear receptors TR2 and TR4 (TR2/TR4) were previously shown to bind in vitro to direct repeat elements in the mouse and human embryonic and fetal β-type globin gene promoters and to play critical roles in the silencing of these genes. By chromatin immunoprecipitation (ChIP) we show that, in adult erythroid cells, TR2/TR4 bind to the embryonic β-type globin promoters but not to the adult β-globin promoter. We purified protein complexes containing biotin-tagged TR2/TR4 from adult erythroid cells and identified DNMT1, NuRD, and LSD1/CoREST repressor complexes, as well as HDAC3 and TIF1β, all known to confer epigenetic gene silencing, as potential corepressors of TR2/TR4. Coimmunoprecipitation assays of endogenous abundance proteins indicated that TR2/TR4 complexes consist of at least four distinct molecular species. In ChIP assays we found that, in undifferentiated murine adult erythroid cells, many of these corepressors associate with both the embryonic and the adult β-type globin promoters but, upon terminal differentiation, they specifically dissociate only from the adult β-globin promoter concomitant with its activation but remain bound to the silenced embryonic globin gene promoters. These data suggest that TR2/TR4 recruit an array of transcriptional corepressors to elicit adult stage-specific silencing of the embryonic β-type globin genes through coordinated epigenetic chromatin modifications.
H3K4 Trimethylation by Set1 Promotes Efficient Termination by the Nrd1-Nab3-Sen1 Pathway

ABSTRACT In Saccharomyces cerevisiae, the Nrd1-Nab3-Sen1 pathway mediates the termination of snoRNAs and cryptic unstable transcripts (CUTs). Both Nrd1 and the Set1 histone H3K4 methyltransferase complex interact with RNA polymerase II (Pol II) during early elongation, leading us to test whether these two processes are functionally linked. The deletion of SET1 exacerbates the growth rate and termination defects of nrd1 mutants. Set1 is important for the appropriate recruitment of Nrd1. Additionally, Set1 modulates histone acetylation levels in the promoter-proximal region via the Rpd3L deacetylase and NuA3 acetyltransferase complexes, both of which contain PHD finger proteins that bind methylated H3K4. Increased levels of histone acetylation reduce the efficiency of Nrd1-dependent termination. We speculate that Set1 promotes proper early termination by the Nrd1-Nab3-Sen1 complex by affecting the kinetics of Pol II transcription in early elongation.
BID Binds to Replication Protein A and Stimulates ATR Function following Replicative Stress

ABSTRACT Proapoptotic BH3-interacting death domain agonist (BID) regulates apoptosis and the DNA damage response. Following replicative stress, BID associates with proteins of the DNA damage sensor complex, including replication protein A (RPA), ataxia telangiectasia and Rad3 related (ATR), and ATR-interacting protein (ATRIP), and facilitates an efficient DNA damage response. We have found that BID stimulates the association of RPA with components of the DNA damage sensor complex through interaction with the basic cleft of the N-terminal domain of the RPA70 subunit. Disruption of the BID-RPA interaction impairs the association of ATR-ATRIP with chromatin as well as ATR function, as measured by CHK1 activation and recovery of DNA replication following hydroxyurea (HU). We further demonstrate that the association of BID with RPA stimulates the association of ATR-ATRIP to the DNA damage sensor complex. We propose a model in which BID associates with RPA and stimulates the recruitment and/or stabilization of ATR-ATRIP to the DNA damage sensor complex.
Integration of Elf-4 into Stem/Progenitor and Erythroid Regulatory Networks through Locus-Wide Chromatin Studies Coupled with In Vivo Functional Validation

ABSTRACT The ETS transcription factor Elf-4 is an important regulator of hematopoietic stem cell (HSC) and T cell homeostasis. To gain insights into the transcriptional circuitry within which Elf-4 operates, we used comparative sequence analysis coupled with chromatin immunoprecipitation (ChIP) with microarray technology (ChIP-chip) assays for specific chromatin marks to identify three promoters and two enhancers active in hematopoietic and endothelial cell lines. Comprehensive functional validation of each of these regulatory regions in transgenic mouse embryos identified a tissue-specific enhancer (−10E) that displayed activity in fetal liver, dorsal aorta, vitelline vessels, yolk sac, and heart. Integration of a ChIP-sequencing (ChIP-Seq) data set for 10 key stem cell transcription factors showed Pu.1, Fli-1, and Erg were bound to the −10E element, and mutation of three highly conserved ETS sites within the enhancer abolished its activity. Finally, the transcriptional repressor Gfi1b was found to bind to and repress one of the Elf-4 promoters (−30P), and we show that this repression of Elf-4 is important for the maturation of primary fetal liver erythroid cells. Taken together, our results provide a comprehensive overview of the transcriptional control of Elf-4 within the hematopoietic system and, thus, integrate Elf-4 into the wider transcriptional regulatory networks that govern hematopoietic development.
Characterization of Critical Domains within the Tumor Suppressor CASZ1 Required for Transcriptional Regulation and Growth Suppression

ABSTRACT CASZ1 is a zinc finger (ZF) transcription factor that is critical for controlling the normal differentiation of subtypes of neural and cardiac muscle cells. In neuroblastoma tumors, loss of CASZ1 is associated with poor prognosis and restoration of CASZ1 function suppresses neuroblastoma tumorigenicity. However, the key domains by which CASZ1 transcription controls developmental processes and neuroblastoma tumorigenicity have yet to be elucidated. In this study, we show that loss of any one of ZF1 to ZF4 resulted in a 58 to 79% loss in transcriptional activity, as measured by induction of tyrosine hydroxylase promoter-luciferase activity, compared to that of wild-type (WT) CASZ1b. Mutation of ZF5 or deletion of the C-terminal sequence of amino acids (aa) 728 to 1166 (a truncation of 38% of the protein) does not significantly alter transcriptional function. A series of N-terminal truncations reveals a critical transcriptional activation domain at aa 31 to 185 and a nuclear localization signal at aa 23 to 29. Soft agar colony formation assays and xenograft studies show that WT CASZ1b is more active in suppressing neuroblastoma growth than CASZ1b with a ZF4 mutation or a deletion of aa 31 to 185. This study identifies key domains needed for CASZ1b to regulate gene transcription. Furthermore, we establish a link between loss of CASZ1b transcriptional activity and attenuation of CASZ1b-mediated inhibition of neuroblastoma growth and tumorigenicity.
Clarifying the Behavioral Economics of Social Anxiety Disorder

Social anxiety disorder is associated with lower interpersonal warmth, possibly explaining its associated interpersonal impairment. Across two samples, we attempted to replicate previous findings that the disorder’s constraint of interpersonal warmth can be detected via behavioral economic tasks. We also tested the test–retest stability of task indices. Results indicated that factors associated with social anxiety disorder (and not the disorder itself), such as the severity of social anxiety and more extreme interpersonal problems, lead to less generous behavior on the economic task examined. Results were clearest regarding fine-grained indices derived from latent trajectories. Unexpectedly, the combination of generalized anxiety disorder and higher depression also restricted generosity. Two of three indices showed acceptable test–retest stability. Maladaptive giving behavior may be a treatment target to improve interpersonal functioning in psychiatric disorders; therefore, future work should more precisely characterize behavioral economic tasks, including basic psychometric work (i.e., tests of reliability and validity).
The outcome with aggressive treatment in severe head injuries: Part II: Acute and chronic barbiturate administration in the management of head injury

J" In a series of 100 consecutive patients with severe head injuries, uncontrolled intracranial hypertension, which was defined as occurring when intracranial pressure (ICP) exceeded 40 mm Hg for 15 minutes or more, occurred in 25 patients. This was despite high-dose dexamethasone, hyperventilation, normothermia, appropriate surgical evacuation, and cerebrospinal fluid drainage when possible. Persistently elevated ICP occurred in 19 patients with diffuse brain injury, and in six patients uncontrolled intracranial hypertension followed evacuation of a surgical mass. All of these patients received intravenous barbiturates to control the ICP. At the time of initial barbiturate administration, 11 of the 25 had bilaterally unreactive pupils and 12 were decerebrate. The initial pentobarbital loading dose (3 to 5 mg/kg) effectively reduced the ICP in 76% of the patients. Prolonged pentobarbital treatment with blood barbiturate levels from 2.5 to 3.5 mg% was associated with normalization of the ICP (ICP less than 15 mm Hg) in 13 patients. In those patients responding to barbiturates, the daily mannitol requirement was reduced from 4.5 to 0.5 gm/kg/day (p < 0.01). In six nonresponders to barbiturates, mannitol requirements increased to 5.9 gm/kg/day; five of these died and one remains vegetative. Ten of the 19 barbiturate responders have returned to a productive life, two remain moderately disabled, two are severely disabled, one is vegetative, and four are dead. The high rate of good quality survival in this series of severely brain-injured patients indicates that barbiturates are useful in the treatment of uncontrolled intracranial hypertension and that a broader investigation of the clinical application of barbiturates is indicated.
Performance analysis of microcellular mobile communication systems

The performance of microcellular mobile communication systems such as the handover priority system, the overlaying macrocell system, and handover priority with overlaying macrocell system are evaluated and compared to that of the standard microcellular system by using spectrum efficiency, grade of service, and total efficiency as evaluation criteria. The total efficiency is composed of spectrum efficiency, blocking probability, and forced termination probability, and represents the comprehensive performance of the systems. Computational results suggest that high efficiency can be achieved by applying the overlaying macrocell system when the offered traffic is low and the handover priority system when it is high. Also the combined system, i.e., handover priority with overlaying macrocell system, is expected to have higher efficiency over the wide range of the offered traffic. <<ETX>>