gebhart/patrepeval huggingface dataset:
Intertwined canonical and non-canonical initiation in dual promoters are pervasive and differentially regulate Polymerase II transcription (2018)

The diversity and complexity of transcription start site (TSS) selection reflects variation of preinitiation complexes, divergent function of promoter-binding proteins and underlies not only transcriptional dynamics but may also impact on post-transcriptional fates of RNAs. The majority of metazoan genes are transcribed by RNA polymerase II from a canonical initiation motif having an YR dinucleotide at their TSSs. In contrast, translation machinery-associated genes carry promoters with polypyrimidine initiator (known as 5′-TOP or TCT) with cytosine replacing the R nucleotide. The functional significance of start site choice in promoter architectures is little understood. To get insight into the developmental regulation of start site selection we profiled 5′ ends of transcripts during zebrafish embryogenesis. We uncovered a novel class of dual-initiation (DI) promoters utilized by thousands of genes. In DI promoters non-canonical YC-initiation representing 5′-TOP/TCT initiators is intertwined with canonical YR-initiation. During maternal to zygotic transition, the two initiation types are divergently used in hundreds of DI promoters, demonstrating that the two initiation systems are distinctly regulated. We show via the example of snoRNA host genes and translation interference experiments that dual-initiation from shared promoters can lead to divergent spatio-temporal expression dynamics generating distinct sets of RNAs with different post-transcriptional fates. Thus utilization of DI promoters in large number of genes suggests two transcription initiation mechanisms targeting these promoters. DI promoters are conserved within human and fruit fly and reflect an evolutionary conserved mechanism for switching transcription initiation to adapt to the changing developmental context. Thus, our findings highlight a novel level of complexity of core promoter regulation in metazoans and broaden the scope for identification and characterization of alternative RNA products generated at shared core promoters.
Differential Association of Receptor-Gβγ Complexes with β-Arrestin2 Determines Recycling Bias and Potential for Tolerance of Delta Opioid Receptor Agonists (2012)

Opioid tendency to generate analgesic tolerance has been previously linked to biased internalization. Here, we assessed an alternative possibility; whether tolerance of delta opioid receptor agonists (DORs) could be related to agonist-specific recycling. A first series of experiments revealed that DOR internalization by DPDPE and SNC-80 was similar, but only DPDPE induced recycling. We then established that the non-recycling agonist SNC-80 generated acute analgesic tolerance that was absent in mice treated with DPDPE. Furthermore, both agonists stabilized different conformations, whose distinct interaction with Gβγ subunits led to different modalities of β-arrestin2 (βarr2) recruitment. In particular, bioluminescence resonance energy transfer (BRET) assays revealed that sustained activation by SNC-80 drew the receptor C terminus in close proximity of the N-terminal domain of Gγ2, causing βarr2 to interact with receptors and Gβγ subunits. DPDPE moved the receptor C-tail away from the Gβγ dimer, resulting in βarr2 recruitment to the receptor but not in the vicinity of Gγ2. These differences were associated with stable DOR-βarr2 association, poor recycling, and marked desensitization following exposure to SNC-80, while DPDPE promoted transient receptor interaction with βarr2 and effective recycling, which conferred protection from desensitization. Together, these data indicate that DORs may adopt ligand-specific conformations whose distinct recycling properties determine the extent of desensitization and are predictive of analgesic tolerance. Based on these findings, we propose that the development of functionally selective DOR ligands that favor recycling could constitute a valid strategy for the production of longer acting opioid analgesics.
Constructing a landmark identification system for Geo-tagged photographs based on Web data analysis (2009)

In this research, we propose a method to automatically generate a landmark identification system for geo-tagged photographs, based on analysis of various data collected from the Web. The method first conducts Web analysis based on three major procedures: (1) Automatic extraction of points-of-interest (POIs) based on geographical clustering of geo-tagged images, (2) Retrieval of landmark candidates for each extracted POI from search results of map search API, and (3) Collection and feature extraction of Web images of the landmark candidates. The system then identifies the landmark which appears in the query geo-tagged photograph, by comparing the location and content-based features of the query with the information accumulated by the previous procedures. Experimental results show that the proposed method is capable to construct a highly accurate landmark identification system by leveraging Web information.
Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma (2005)

The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment, surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEGF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing.
Biotin, pantothenic acid and vitamin E in the British household food supply. (1982)

Intakes of biotin, pantothenic acid and vitamin E in Britain were calculated by applying values from the 4th edition of McCance and Widdowson's The composition of foods or other published values to the amounts of food recorded in the National Food Survey of 1979. National average intakes were found to be biotin distributions could also be made to the intake of the B vitamins by alcoholic drinking and confectionery. Comparison of intakes with suggested recommended intakes values were rather low while for pantothenic acid the recommendations were met.
Thread-Level Parallelization and Optimization of NWChem for the Intel MIC Architecture (2014)

In the multicore era it was possible to exploit the increase in on-chip parallelism by simply running multiple MPI processes per chip. Unfortunately, manycore processors' greatly increased thread- and data-level parallelism coupled with a reduced memory capacity demand an altogether different approach. In this paper we explore augmenting two NWChem modules, triples correction of the CCSD(T) and Fock matrix construction, with OpenMP in order that they might run efficiently on future manycore architectures. As the next NERSC machine will be a self-hosted Intel MIC (Xeon Phi) based supercomputer, we leverage an existing MIC testbed at NERSC to evaluate our experiments. In order to proxy the fact that future MIC machines will not have a host processor, we run all of our experiments in tt native mode. We found that while straightforward application of OpenMP to the deep loop nests associated with the tensor contractions of CCSD(T) was sufficient in attaining high performance, significant effort was required to safely and efficiently thread the TEXAS integral package when constructing the Fock matrix. Ultimately, our new MPI OpenMP hybrid implementations attain up to 65x better performance for the triples part of the CCSD(T) due in large part to the fact that the limited on-card memory limits the existing MPI implementation to a single process per card. Additionally, we obtain up to 1.6x better performance on Fock matrix constructions when compared with the best MPI implementations running multiple processes per card.
Lineage tracing of genome-edited alleles reveals high fidelity axolotl limb regeneration (2017)

Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs. This allowed us, for the first time, to assess the contributions of multiple low frequency cell lineages to the regenerating limb at once. Our comparisons reveal that regenerated limbs are high fidelity replicas of the originals even after repeated amputations.
Predicting the Polarity Strength of Adjectives Using WordNet (2009)

A key element of any sentiment analysis system is the ability to assign a polarity strength value to words appearing within the documents. In this paper we present a novel approach to polarity strength assignment. The approach is knowledge based in that it uses WordNet to build an adjective graph which is used to measure semantic distance between words of known polarity (reference or seed words) and the target word, which is then used to assign a polarity to the target word. We extend previous work in this area by using a small training data set to learn an optimal predictor of polarity strength and to dampen polarity assigned to non-polar adjectives. We also extend the coverage of previous approaches by exploring additional lexical relations not studied previously. The method has been evaluated on a validation set and shows excellent potential in reducing the assignment of spurious polarity and accurately predicting polarity values for polar adjectives.
The EGFR Pathway Regulates BCRP Expression in NSCLC Cells: Role of Erlotinib (2014)

While multidrug resistance (MDR) in cancer is well established, little is known about the cellular pathways regulating the expression and trafficking of the MDR efflux transporter like BCRP (ABCG2). Here we evaluated the role of signalling downstream of EGFR on BCRP expression and sub-cellular localization using lung cancer cells harboring BCRP but expressing various EGFR and Ras activating mutations; A549 (K-Ras-G12S), H292 wild-type EGFR and Ras, and H1650 (EGFR-DelE747-A750). Immunocytochemistry and immunofluorescence studies demonstrated that BCRP was predominantly intracellular but its expression was found also on the plasma membrane in A549 and H1650 cells with activated Ras and EGFR. Remarkably, EGFR inhibition by erlotinib at IC₅₀ concentrations induced a differential timedependent alteration in BCRP gene and protein expression. In H1650 cells, erlotinib enhanced both the total and plasma membrane degradation of BCRP by ubiquitination within 6-24 hours, whereas BCRP expression regained the original basal levels after 48 hours. In erlotinib treated H292 cells, BCRP levels decreased at 24 hours until 72 hours, whereas in A549 cells erlotinib initially reduced BCRP expression but then induced its accumulation on the plasma membrane at 72 hours. We further found that the PI3K/Akt inhibitor LY294002 down-regulated BCRP expression, hence showing that the Akt pathway is involved in the regulation of BCRP expression but not in its localization in these lung cancer cell lines. Finally, the selective BCRP transport inhibitor Ko143 did not increase erlotinib sensitivity, but did decrease the transport activity of BCRP in A549 and H1650 cells as it induced the accumulation of its transport substrate topotecan. In conclusion, our results suggest that the EGFR and Akt pathways are involved in regulation of BCRP expression, trafficking and drug transport activity. These findings warrant future studies on the pharmacologic modulation of these pathways to enhance the efficacy of anticancer combinations of erlotinib with drugs that are BCRP transport substrates.
Left Atrial Rhythm (1968)

Various criteria have been proposed for the diagnosis of left atrial rhythm (LAR) in previous experimental and electrocardiographic studies. Differentiation from A-V junctional rhythms remains ill-defined. In order to assess the left atrial (LA) P wave and to define LAR, the P wave and loop were studied by direct LA pacing in 11 patients undergoing diagnostic transseptal left heart catheterization. Experimental LAR produced changes in P-wave configuration and polarity. These changes were most obvious in lead V 1 and indicated reversal of the sequence and direction of activation with left atrial preceding right atrial depolarization. A typical "dome and dart" P wave occurred in two studies. P-wave configuration in leads I and V 6 was highly variable; frequent orientation of the LA P vector within the transitional zone of the horizontal electrical axis was thought to be responsible. The LA P loop showed reversal of the direction of inscription of the initial forces, indicating a change in the pattern of atrial depolarization. Stimulation of the appendage produced left-to-right spread of atrial depolarization, whereas activation of the main body was directed primarily anteriorly. Impulse formation in the right side of the posterior wall was usually directed from right to left. When the postero-inferior area was activated, the anterior P vector became directed superiorly, and resembled that of coronary sinus rhythm (CSR) in the frontal plane. This study indicates that the P wave in lead V 1 is most important in the diagnosis of LAR; inversion of the P wave in lead V 6 is not essential. LAR can usually be differentiated from CSR, since in the horizontal plane, activation of the LA main body is more anteriorly directed than the spatial P vector of CSR.
Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study (2021)

This grade is used to predict prognosis of patients undergoing resection of HCC.
The exercise-inducible bile acid receptor Tgr5 improves skeletal muscle function in mice (2018)

TGR5 (also known as G protein-coupled bile acid receptor 1, GPBAR1) is a G protein-coupled bile acid receptor that is expressed in many diverse tissues. TGR5 is involved in various metabolic processes, including glucose metabolism and energy expenditure; however, TGR5's function in skeletal muscle is not fully understood. Using both gain- and loss-of-function mouse models, we demonstrate here that Tgr5 activation promotes muscle cell differentiation and muscle hypertrophy. Both young and old transgenic mice with muscle-specific Tgr5 expression exhibited increased muscle strength. Moreover, we found that Tgr5 expression is increased by the unfolded protein response (UPR), which is an adaptive response required for maintenance of endoplasmic reticulum (ER) homeostasis. Both ER stress response element (ERSE)- and unfolded protein response element (UPRE)-like sites are present in the 5' upstream region of the <i>Tgr5</i> gene promoter and are essential for <i>Tgr5</i> expression by Atf6α (activating transcription factor 6α), a well known UPR-activated transcriptional regulator. We observed that in the skeletal muscle of mice, exercise-induced UPR increases <i>Tgr5</i> expression, an effect that was abrogated in <i>Atf6</i>α KO mice, indicating that Atf6α is essential for this response. These findings indicate that the bile acid receptor Tgr5 contributes to improved muscle function and provide an additional explanation for the beneficial effects of exercise on skeletal muscle activity.
Roles of the transforming growth factor β1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: Results of an immunohistochemical study (1997)

Background In the United States, pulmonary adenocarcinomas have recently replaced squamous cell carcinomas as the most frequent type of lung cancer encountered. The incidence of a pulmonary adenocarcinoma continued to increase worldwide. Method To determine the roles of the transforming growth factor-β1 (TGF-β1), and TGF-β type I receptor (TβR-I), and the TGF-β type II receptor (TβR-II) in the progression of a pulmonary adenocarcinoma, their respective expressions have been immunohistologically studied in specimens from 120 pulmonary adenocarcinoma patients. Result: The overall prognosis was significantly poorer for patients showing positive TGF-β1, TβR-I, TβR-II expressions than for patients who were negative to all three immunostainings (P < 0.01). Our multivariate analysis also revealed that a positive TGF-β1 response significantly affect prognosis (P < 0.05). Conclusions TGF-β1, TβR-I, and TβR-II play important roles in tumor progression, and a positive TGF-β1 expression can serve as a pulmonary adenocarcinoma marker. TβR-I and TβR-II expressions are necessary for TGF-β signal transduction. J. Surg. Oncol. 64:262–267, 1997 © 1997 Wiley-Liss, Inc.
FreeCam: A Hybrid Camera System for Interactive Free-Viewpoint Video (2011)

We describe FreeCam - a system capable of generating live free-viewpoint video by simulating the output of a virtual camera moving through a dynamic scene. The FreeCam sensing hardware consists of a small number of static color video cameras and state-of-the-art Kinect depth sensors, and the FreeCam software uses a number of advanced GPU processing and rendering techniques to seamlessly merge the input streams, providing a pleasant user experience. A system such as FreeCam is critical for applications such as telepresence, 3D video-conferencing and interactive 3D TV. FreeCam may also be used to produce multi-view video, which is critical to drive newgeneration autostereoscopic lenticular 3D displays.
SAT-298 Integrative Single-Cell Transcriptomic and Epigenomic Landscape of Mouse Anterior Pituitary Cell Types (2020)

Abstract The pituitary gland is a critical regulator of the neuroendocrine system. To further our understanding of the classification, cellular heterogeneity, and regulatory landscape of pituitary cell types, we performed and computationally integrated single cell (SC)/single nucleus (SN) resolution experiments capturing RNA expression, chromatin accessibility, and DNA methylation state from mouse dissociated whole pituitaries. Both SC and SN transcriptome analysis and promoter accessibility identified the five classical hormone-producing cell types (somatotropes, gonadotropes (GT), lactotropes, thyrotropes, and corticotropes). GT cells distinctively expressed transcripts for Cga, Fshb, Lhb, Nr5a1, and Gnrhr in SC RNA-seq and SN RNA-seq. This was matched in SN ATAC-seq with GTs specifically showing open chromatin at the promoter regions for the same genes. Similarly, the other classically defined anterior pituitary cells displayed transcript expression and chromatin accessibility patterns characteristic of their own cell type. This integrated analysis identified additional cell-types, such as a stem cell cluster expressing transcripts for Sox2, Sox9, Mia, and Rbpms, and a broadly accessible chromatin state. In addition, we performed bulk ATAC-seq in the LβT2b gonadotrope-like cell line. While the FSHB promoter region was closed in the cell line, we identified a region upstream of Fshb that became accessible by the synergistic actions of GnRH and activin A, and that corresponded to a conserved region identified by a polycystic ovary syndrome (PCOS) single nucleotide polymorphism (SNP). Although this locus appears closed in deep sequencing bulk ATAC-seq of dissociated mouse pituitary cells, SN ATAC-seq of the same preparation showed that this site was specifically open in mouse GT, but closed in 14 other pituitary cell type clusters. This discrepancy highlighted the detection limit of a bulk ATAC-seq experiment in a subpopulation, as GT represented ~5% of this dissociated anterior pituitary sample. These results identified this locus as a candidate for explaining the dual dependence of Fshb expression on GnRH and activin/TGFβ signaling, and potential new evidence for upstream regulation of Fshb. The pituitary epigenetic landscape provides a resource for improved cell type identification and for the investigation of the regulatory mechanisms driving cell-to-cell heterogeneity. Additional authors not listed due to abstract submission restrictions: N. Seenarine, M. Amper, N. Jain (ISMMS).
Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease (2016)

These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.
Analysis and Design of Iterative Learning Control Strategies for UPS Inverters (2007)

In this paper, two iterative-learning-based control methods for uninterruptible power system (UPS) inverters, viz., direct iterative learning controller (direct ILC) and hybrid iterative learning controller (hybrid ILC), are proposed. In both methods, a zero-phase filter that is designed in the frequency domain is applied in order to provide compensation for the resonant peak in the system model to ensure error convergence. Furthermore, a "forgetting factor" is introduced in both control algorithms to increase the robustness of the scheme against measurement noise, initialization error, and/or variation of system dynamics due to any parameter drift. In the direct ILC method, ILC is combined with the feedforward of the reference to improve dynamic performance. This method is shown to be capable of achieving very high steady-state performance although its dynamic response was not very good. In the hybrid ILC method, ILC is combined with a proportional-derivative controller aside from the reference feedforward to improve the dynamic response further. Experimental results show that both proposed controllers can achieve very low total harmonic distortion and fast error convergence under different loads while using only one sensor. The proposed direct ILC is an effective solution for UPS products where high-quality steady-state output voltage is more important than fast dynamic response, while hybrid ILC can result in excellent steady-state performance with a more improved dynamic response than direct ILC