gebhart/patrepeval huggingface dataset:
Identification of the Critical Sequence Elements in the Cytoplasmic Domain of Leptin Receptor Isoforms Required for Janus Kinase/Signal Transducer and Activator of Transcription Activation by Receptor Heterodimers (2002)

Two predominant splice variants of the leptin receptor (LEPR) are coexpressed in leptin-responsive tissues: the long form, LEPRb, characterized as the signal-transducing receptor, and the signaling-defective short form, LEPRa. It is unknown whether heterodimers of these isoforms are capable of signal transduction via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. To address this question, chimeric receptors were constructed consisting of the transmembrane and intracellular parts of LEPRb and LEPRa fused with the extracellular domains of either the alpha- or beta-subunit of the IL-5 receptor. This strategy allows the directed heterodimerization of different LEPR cytoplasmic tails and excludes homodimerization. In COS-7 and HEPG2 cells, chimeric receptor heterodimers of LEPRa and LEPRb failed to activate the JAK/STAT pathway, whereas receptor dimers of LEPRb gave rise to the expected ligand-dependent activation of JAK2, phosphorylation of STAT3, and STAT3-dependent promoter activity. Markedly lower amounts of JAK2 were found to be associated with immunoprecipitated LEPRa chimeras than with LEPRb chimeras. Analysis of a series of deletion constructs indicated that a segment of 15 amino acids in addition to the 29 amino acids common to LEPRa and LEPRb was required for partial restoration of JAK/STAT activation. Site-directed mutagenesis of the critical sequence indicated that two hydrophobic residues (Leu896, Phe897) not present in LEPRa were indispensable for receptor signaling. These findings show that LEPRa/LEPRb heterodimers cannot activate STAT3 and identify sequence elements within the LEPR that are critical for the activation of JAK2 and STAT3.
Analysis of the apolipoprotein B3' hypervariable region in patients with essential hypertension. (1992)

1. The typing of the apolipoprotein B 3' hypervariable region was investigated in hypertensive and normotensive subjects using rapid typing of a variable number of tandemly repeated short DNA sequences (VNTR) by the polymerase chain reaction. 2. In the DNA samples of 89 normotensive and 99 hypertensive patients, 13 different-sized alleles were detected. The most frequent allele has 35 repeat units in both groups with frequencies of 0.624 and 0.596 in normotensive and hypertensive patients, respectively. Frequency distribution of 13 alleles was similar in both groups. 3. These results demonstrate no association between the apolipoprotein B gene polymorphism and essential hypertension.
Perineurioma (1986)

A unique benign peripheral nerve tumor, called a perineurioma, is described in this report. Light and electron microscopy and immunohistochemistry indicate that this tumor was derived from the perineurial cell. We discuss the ultrastructure, histogenesis, and management of this neoplasm. (Neurosurgery 19:134-138, 1986)
Effects of the multi‐kinase inhibitor midostaurin in combination with chemotherapy in models of acute myeloid leukaemia (2020)

Recently, several targeted agents have been developed for specific subsets of patients with acute myeloid leukaemia (AML), including midostaurin, the first FDA-approved FLT3 inhibitor for newly diagnosed patients with FLT3 mutations. However, in the initial Phase I/II clinical trials, some patients without FLT3 mutations had transient responses to midostaurin, suggesting that this multi-targeted kinase inhibitor might benefit AML patients more broadly. Here, we demonstrate submicromolar efficacy of midostaurin in vitro and efficacy in vivo against wild-type (wt) FLT3-expressing AML cell lines and primary cells, and we compare its effectiveness with that of other FLT3 inhibitors currently in clinical trials. Midostaurin was found to synergize with standard chemotherapeutic drugs and some targeted agents against AML cells without mutations in FLT3. The mechanism may involve, in part, the unique kinase profile of midostaurin that includes proteins implicated in AML transformation, such as SYK or KIT, or inhibition of ERK pathway or proviability signalling. Our findings support further investigation of midostaurin as a chemosensitizing agent in AML patients without FLT3 mutations.
Data from AXL Is a Potential Target for Therapeutic Intervention in Breast Cancer Progression (2023)

&lt;div&gt;Abstract&lt;p&gt;Protein kinases play important roles in tumor development and progression. A variety of members of this family of signal transduction enzymes serve as targets for therapeutic intervention in cancer. We have identified the receptor tyrosine kinase (RTK) AXL as a potential mediator of motility and invasivity of breast cancer cells. AXL is expressed in most highly invasive breast cancer cells, but not in breast cancer cells of low invasivity. Ectopic expression of AXL was sufficient to confer a highly invasive phenotype to weakly invasive MCF7 breast cancer cells. Experimental inhibition of AXL signaling by a dominant-negative AXL mutant, an antibody against the extracellular domain of AXL, or short hairpin RNA knockdown of AXL decreased motility and invasivity of highly invasive breast cancer cells. To selectively interfere with cancer cell properties defining the rate of disease progression, we identified 3-quinolinecarbonitrile compounds, which displayed potent inhibitory activity against AXL and showed strong interference with motility and invasivity of breast cancer cells. Our findings validated the RTK AXL as a critical element in the signaling network that governs motility and invasivity of breast cancer cells, and allowed the identification of experimental anti-AXL small molecular inhibitors that represent lead substances for the development of antimetastatic breast cancer therapy. [Cancer Res 2008;68(6):1905–15]&lt;/p&gt;&lt;/div&gt;
A Parametric Top-View Representation of Complex Road Scenes (2019)

In this paper, we address the problem of inferring the layout of complex road scenes given a single camera as input. To achieve that, we first propose a novel parameterized model of road layouts in a top-view representation, which is not only intuitive for human visualization but also provides an interpretable interface for higher-level decision making. Moreover, the design of our top-view scene model allows for efficient sampling and thus generation of large-scale simulated data, which we leverage to train a deep neural network to infer our scene model's parameters. Specifically, our proposed training procedure uses supervised domain-adaptation techniques to incorporate both simulated as well as manually annotated data. Finally, we design a Conditional Random Field (CRF) that enforces coherent predictions for a single frame and encourages temporal smoothness among video frames. Experiments on two public data sets show that: (1) Our parametric top-view model is representative enough to describe complex road scenes; (2) The proposed method outperforms baselines trained on manually-annotated or simulated data only, thus getting the best of both; (3) Our CRF is able to generate temporally smoothed while semantically meaningful results.
Guidance for Deploying GAA (2008)

This chapter contains sections titled: Integration with Application Servers Integration with OS Security Integration with Identity Management Systems Integration of GAA into Mobile Networks References
PRECLINICAL EVALUATION OF THE THORATEC HEARTMATE?? 111 LEFT VENTRICULAR ASSIST SYSTEM (2004)

Tamez, D; Gregoric, I D; Harms, K M; Dague, C; Radovancevic, B; Patel, V; Tuzun, E; Loree, H; Kindo, M; Bourque, K; Moore, S R; Byler, D L; Frazier, O H Author Information
Picosecond Pulse Generation by Edge Illumination of Si and InP Photoconductive Switches (1995)

Ultrafast electrical pulses are beginning to be used for performing broadband frequency domain characterization of circuits and for test and failure analysis of digital circuits.3 With frequency components in the terahertz regime, these pulses have been used for the characterization of transmission lines for high-speed interconnections on integrated circuits,1 and for measuring microwave S-parameters.2 Generation of ultrafast electrical pulses has been developed using pulsed lasers on semiconductors.4-6 Some of these techniques require special materials or geometries, which makes it difficult to use these methods as an analysis tool as in Ref. 2. However, edge illumination requires no special designs other than a coplanar transmission line.
Cost-effective RF interposer platform on low-resistivity Si enabling heterogeneous integration opportunities for beyond 5G (2022)

We present a highly-scaled packaging and system-integration RF interposer platform on low-resistivity Si (15-25 Ωcm). The heterogenous platform has been processed and characterized by measurements in the frequency range from 10 MHz to 110 GHz, revealing an interconnect insertion loss less than 0.3 dB/mm at 100 GHz and Q <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</inf> above 40 for integrated inductors. The excellent performance of the RF Si interposer enables high frequency interconnects between the ICs and the partial matching network in the package. The narrow pitch of the μbumps further enables flip-chip performance up to 500 GHz, allowing for heterogenous integration of multiple mm-wave ICs in different technologies, together with integrated high-Q passives, as well as antennas-in-package for RF to beyond-5G applications.
A Chromium Ethylidene Complex as a Potent Catalyst for Selective Ethylene Trimerization (2011)

Eins, zwei, drei …︁: Der Einkernkomplex [{η5-(tBu)2C4H2N}CrCl2(thf)] reagiert mit AlEt3 zu der zweikernigen Spezies [{[η5-(tBu)2C4H2N]CrEt}2(μ-Cl)2] (siehe Bild: Cr violett, Cl grün, C grau, H weiß). Der Komplex wirkt als Einkomponentenkatalysator für die selektive Trimerisierung von Ethylen; bei Zugabe größerer Mengen an aktivierendem AlEt3 kommt es zur Isomerisierung von 1-Hexen zu cis/trans-2-Hexen. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma (2014)

Grade IV glioblastoma is characterized by increased kinase activity of epidermal growth factor receptor (EGFR); however, EGFR kinase inhibitors have failed to improve survival in individuals with this cancer because resistance to these drugs often develops. We showed that tumor necrosis factor-α (TNFα) produced in the glioblastoma microenvironment activated atypical protein kinase C (aPKC), thereby producing resistance to EGFR kinase inhibitors. Additionally, we identified that aPKC was required both for paracrine TNFα-dependent activation of the transcription factor nuclear factor κB (NF-κB) and for tumor cell-intrinsic receptor tyrosine kinase signaling. Targeting aPKC decreased tumor growth in mouse models of glioblastoma, including models of EGFR kinase inhibitor-resistant glioblastoma. Furthermore, aPKC abundance and activity were increased in human glioblastoma tumor cells, and high aPKC abundance correlated with poor prognosis. Thus, targeting aPKC might provide an improved molecular approach for glioblastoma therapy.
Mutational screens highlight glycosylation as a modulator of CSF3R activity (2022)

Abstract The colony-stimulating factor 3 receptor (CSF3R) controls the growth of neutrophils, the most abundant type of white blood cell. In healthy neutrophils, signaling is dependent on CSF3R binding to its ligand CSF3. A single amino acid mutation in CSF3R, T618I, instead allows for constitutive, ligand-independent cell growth and leads to a rare type of cancer called chronic neutrophilic leukemia (CNL). We investigated why this threonine to isoleucine substitution is the predominant mutation in CNL and how it leads to uncontrolled neutrophil growth. Using protein domain mapping, we demonstrated that the single CSF3R domain containing residue 618 is sufficient for ligand-independent activity. We then applied an unbiased mutational screening strategy focused on this domain and found that activating mutations are enriched at sites normally occupied by asparagine, threonine, and serine residues – the three amino acids which are commonly glycosylated. We confirmed glycosylation at multiple CSF3R residues by mass spectrometry, including the presence of GalNAc and Gal-GalNAc glycans at wild-type threonine 618. Using the same approach applied to other cell surface receptors, we identified an activating mutation, S489F, in the interleukin-31 receptor alpha chain (IL-31Rα). Combined, these results suggest a role for glycosylated hotspot residues in regulating receptor signaling, mutation of which can lead to ligand-independent, uncontrolled activity.
Identification and Analysis of Precursors to Invasive Pancreatic Cancer (2012)

Precursor lesions of pancreatic cancer have been recognized about a century ago. The development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. Pancreatic intraepithelial neoplasia (PanIN) as microscopic precursor lesions can be distinguished from mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMN) that are cystic and can often be recognized on imaging. Since precursor lesions harbor the unique chance to treat a patient before a fatal pancreatic cancer can arise a molecular characterization is essential to understand the biology and to find diagnostic and therapeutic targets to fight this disease of near uniform lethality. In order to study precursor lesions on a molecular level a meticulous isolation of the neoplastic cells is inevitable. We present the salient histopathologic and molecular features of precursor lesions of pancreatic cancer as well as methods that have proved to be useful within experimental studies.
Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration (2021)

The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell surface of prostate cancer (PCa) cells influences cell-cell cohesion and dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)'s ability to digest components of the PSPN Complex in bone metastatic PCa cells using <i>in silico</i> analyses and in vitro experiments. Results demonstrated that in addition to the heparan sulfate proteoglycan, perlecan, all components of the PSPN Complex were degraded by MMP-7. To investigate the functional consequences of PSPN Complex cleavage, we developed a preformed microtumor model to examine initiation of cell dispersion after MMP-7 digestion. We found that while perlecan fully decorated with glycosaminoglycan limited dispersion of PCa microtumors, MMP-7 initiated rapid dyscohesion and migration even with perlecan present. Additionally, we found that a bioactive peptide (PLN4) found in perlecan domain IV in a region subject to digestion by MMP-7 further enhanced cell dispersion along with MMP-7. We found that digestion of the PSPN Complex with MMP-7 destabilized cell-cell junctions in microtumors evidenced by loss of co-registration of E-cadherin and F-actin. We conclude that MMP-7 plays a key functional role in PCa cell transition from a cohesive, indolent phenotype to a dyscohesive, migratory phenotype favoring production of circulating tumor cells and metastasis to bone.
WHO Trial Registration Data Set (TRDS) Extension for Traditional Chinese Medicine 2020: Recommendations, Explanation, and Elaboration (2020)

Abstract Background: Although the WHO Trial Registration Data Set (TRDS) has been published for many years, the quality of clinical trial registrations with traditional Chinese medicine (TCM) is still not satisfactory, especially about the inadequate reporting on TCM interventions. The development of the WHO TRDS for TCM Extension 2020 (WHO TRDS-TCM 2020) aims to address this inadequacy. Methods: A group of clinical experts, methodologists, epidemiologists, and editors has developed this WHO TRDS-TCM 2020 through a comprehensive process, including publication of the literature review, consensus collection of the initial items, three-round of Delphi survey, solicitation of comments, revision, and finalization. Results: The WHO TRDS-TCM 2020 statement extends the latest version (V.1.3.1) of TRDS published in November 2017. The checklist includes 11 extended items (including subitems), namely Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (Item B1). For Item 13 (Interventions), three common TCM interventions--i.e., Chinese herbal medicine formulas, acupuncture and moxibustion—are elaborated. Conclusions: The group hopes that the WHO TRDS-TCM 2020 can improve the reporting quality and transparency of TCM trial registrations, assist registries in assessing the registration quality of TCM trials, and help readers understand TCM trial design.
Interferon alpha response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus (1998)

International audience
Preservation of spinach by isochoric (constant volume) freezing (2019)

Summary Efforts are currently directed towards improving the quality of vegetables after freezing and thawing. One of the methods under investigation is isochoric freezing. In this study, we evaluated isochoric freezing for preserving the quality of baby‐leaf spinach. We compared the properties of thawed spinach frozen to −4°C in an isochoric system with those of fresh spinach, thawed spinach frozen to −4°C in an isobaric system and thawed spinach that were commercially frozen. Spinach leaves frozen under isobaric conditions lost mass and thickness, making them softer and translucent. They also lost much of their nutrient content. In comparison, isochoric freezing maintained cell integrity and turgidity. Thawed leaves remained crunchy with characteristics similar to fresh leaves. Isochoric freezing also preserved nutritional content better than isobaric freezing, although significant nutrient losses still occurred.
A broadband optical switch based on adiabatic couplers (2016)

We designed and fabricated a broadband thermo-optic Mach-Zehnder Interferometer switch using two 3-dB adiabatic couplers on the 500 nm Silicon-On-Insulator platform. The fabricated switch has shown 120 nm optical bandwidth with more than 15 dB extinction ratios.
Inside Cover: “Illusionary” Polymerase Activity Triggered by Metal Ions: Use for Molecular Logic‐Gate Operations (Angew. Chem. Int. Ed. 50/2010) (2010)

“Illusionary” polymerase activity was proved to be intentionally triggered by Hg2+ and Ag+ ions through their interaction with the mismatched base pairs T–T and C–C to result in a nonnatural amplification reaction. In their Communication on page 9757 ff., H. G. Park and co-workers describe how rational design of the primers and selection of the type of DNA polymerase was used to construct molecular-scale logic gates.
A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (2023)

No RECIST responses were observed after combination therapy in this trial. Although we could not detect the anticipated tumor-intrinsic effects of guadecitabine, the addition of hypomethylating agent to ICI therapy induced immune activation in a few patients, which associated with longer patient survival.
Transceiver Optimization for Block-Based Multiple Access Through ISI Channels (2004)

In this paper, we describe a formulation of the minimum mean square error (MMSE) joint transmitter-receiver design problem for block-based multiple access communication over intersymbol interference (ISI) channels. Since the direct formulation of this problem turns out to be nonconvex, we develop various alternative convex formulations using techniques of linear matrix inequalities (LMIs) and second-order cone programming (SOCP). In particular, we show that the optimal MMSE transceiver design problem can be reformulated as a semidefinite program (SDP), which can be solved using highly efficient interior point methods. When the channel matrices are diagonal (as in cyclic prefixed multicarrier systems), we show that the optimal MMSE transceivers can be obtained by subcarrier allocation and optimal power loading to each subcarrier for all the users. Moreover, the optimal subcarrier allocation and power-loading can be computed fairly simply (in polynomial time) by the relative ratios of the magnitudes of the subchannel gains corresponding to all subcarriers. We also prove that any two users can share no more than one subcarrier in the optimal MMSE transceivers. By exploiting this property, we design an efficient strongly polynomial time algorithm for the determination of optimal powerloading and subcarrier allocation in the two-user case.
Current understanding of fungal microflora in inflammatory bowel disease pathogenesis (2008)

Inflammatory bowel diseases are a current and growing public health problem, with a prevalence that appears to be increasing in most countries and cultures. While most research into the triggering phenomenon has focused on the interaction between commensal bacteria and inflammatory bowel disease, enteric fungi may also be important in determining disease susceptibility. Herein we review what is known about enteric fungi and the mechanisms by which they and their dysregulation might be involved in triggering inflammatory diseases of the bowel.
Single cell nanoparticle tracking to model cell cycle dynamics and compartmental inheritance (2010)

Single cell encoding with quantum dots as live cell optical tracers for deriving proliferation parameters has been developed using modelling to investigate cell cycle and proliferative outputs of human osteosarcoma cells undergoing mitotic bypass and endocycle routing. A computer-based simulation of the evolving cell population provides information on the dilution and segregation of nanoparticle dose cell by cell division and allows quantitative assessment of patterns of division, at both single cell and including whole population level cell cycle routing, with no a-priori knowledge of the population proliferation potential. The output therefore provides a unique mitotic distribution function that represents a convolution of cell cycle kinetics (cell division) and the partitioning coefficient for the labelled cell compartment (daughter-daughter inheritance or lineage asymmetry). The current study has shown that the cellular quantum dot fluorescence reduced over time as the particles were diluted by the process of cell division and had the properties of a non-random highly asymmetric event. Asymmetric nanoparticle segregation in the endosomal compartment has major implications on cell-fate determining signaling pathways and could lead to an understanding of the origins of unique proliferation and drug-resistance characteristics within a tumour cell lineage.
HERV-K(HML-2) rec and np9 transcripts not restricted to disease but present in many normal human tissues (2015)

HERV-K(HML-2) rec and np9 transcripts from different HERV-K(HML-2) loci appear to be present in various normal human tissues. It is conceivable that Rec and Np9 proteins and variants of those proteins are part of the proteome of normal human tissues and thus various cell types. Transcription of HERV-K(HML-2) may thus also have functional relevance in normal human cell physiology.