gebhart/patrepeval huggingface dataset:
Synthesis and structure-activity relationships of targeted protein degraders for the understudied kinase NEK9 (2021)

Nek9 is a member of the understudied Nek family of dark kinases. Aberrant activation of Nek9 kinase signaling has been linked to poor keratinocyte differentiation phenotypes, and is a key driver of nevus comedonicus, a rare, localized form of acne. Nek9 also has essential scaffolding roles; during mitosis the non-catalytic C-terminal domain of Nek9 binds to Nek6 and Nek7, releasing them from an auto-inhibitory conformation, and enabling proper mitotic progression. Finally, Nek9 expression has been linked to cancer proliferation. SiRNA mediated Nek9 knock-down in a panel of cancer cell lines induces G1 cell cycle arrest and inhibits proliferation when p53 is also inactivated; cell lines with functional p53 are unaffected. Presently, no selective small molecule Nek9 chemical probes are available, though a subset of promiscuous kinase inhibitors have Nek9 activity. Recently described targeted protein degradation approaches have shown that degrader molecules based on multi-targeted kinase inhibitors may effect selective kinase degradation, despite binding to many targets. In this study we report the identification and SAR of potent degraders of the NEK9 kinase that represent attractive leads for further development. Future work is needed to optimize the selectivity of the compounds.
New Deep-Blue-Emitting Ce-Doped A4–mBnC19+2mX29+m (A = Sr, La; B = Li; C = Si, Al; X = O, N; 0 ≤ m ≤ 1; 0 ≤ n ≤ 1) Phosphors for High-Color-Rendering Warm White Light-Emitting Diodes (2019)

A new sialon Eu<sub>3.60</sub>LiSi<sub>13.78</sub>Al<sub>6.03</sub>O<sub>6.82</sub>N<sub>22.59</sub> has been discovered via the single-particle diagnosis approach. Its crystal structure (space group <i>P</i>3<i>m</i>1) was solved and refined from single-crystal X-ray diffraction data. It has the interesting feature of two types of disorder at the Eu2 site: positional disorder (Eu2a/Eu2b) and substitutional disorder with (Si/Al)<sub>2</sub>(O/N). The structure is generalized to the formula A<sub>4-<i>m</i></sub>B<sub><i>n</i></sub>C<sub>19+2<i>m</i></sub>X<sub>29+<i>m</i></sub> (A = Sr, La, Eu, Ce; B = Li; C = Si, Al; X = O, N; 0 ≤ <i>m</i> ≤ 1; 0 ≤ <i>n</i> ≤ 1), of which Sr<sub>3.61</sub>LiSi<sub>14.27</sub>Al<sub>5.61</sub>O<sub>6.19</sub>N<sub>23.25</sub> (Sr-sialon, <i>m</i> = 0.41, <i>n</i> = 1) and La<sub>2.85</sub>Sr<sub>0.76</sub>LiSi<sub>14.86</sub>Al<sub>4.93</sub>O<sub>2.89</sub>N<sub>26.51</sub> (LaSr-sialon, <i>m</i> = 0.40, <i>n</i> = 1) are two examples that have been obtained as a single-phase powder. Sr-sialon:Eu and LaSr-sialon:Eu both show blue to yellow emission, depending on the Eu concentration, whereas Sr-sialon:1% Ce shows a deep-blue emission band centered at 422 nm with a full width at half-maximum of 80 nm and an internal quantum efficiency of 80% (λ<sub>ex</sub> = 355 nm). The latter phosphor has very good thermal stability of both emission intensity and color. A white light-emitting diode (LED) containing the newly discovered Sr-sialon:5% Ce as the blue phosphor component shows excellent color-rendering indices (<i>R</i><sub><i>a</i></sub> = 96 and <i>R</i><sub>12</sub> = 97) with a correlated color temperature of 4255 K. This indicates that Sr-sialon:Ce is a highly promising deep-blue phosphor for illumination grade white LEDs.
An inhibitory postsynaptic potential in spinal nociceptive neurones is mediated by adenosine through activation of ATP‐sensitive K+ channels (1993)

Abstract Inhibitory processes within the dorsal horn participate in regulating the transmission of nociceptive information. Spinal nociceptive neurones are inhibited by cutaneously applied vibration and we have characterized this inhibition physiologically and pharmacologically [Salter et al., 1993]. This inhibition is evoked by activation of Pacinian corpuscle afferents and is mediated in the spinal cord by adenosine acting through P 1 ‐purinergic receptors. The adenosine‐mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP) produced by activating a K + conductance. Adenosine is known to activate K + currents in a number of different types of cell [Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987; Gerber et al. 1989] and it has been reported that in cardiac muscle cells the + channels [Kirsch et al., 1990]. Therefore, we investigated the possibility that these channels might mediate the IPSP we have observed in nociceptive dorsal horn neurones upon vibratory stimulation applied to the skin. We found that the inhibition of nociceptive neurones by this stimulation is abolished by glibenclamide, a blocker of ATP‐sensitive K + Channels [Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b]. In addition, the IPSP evoked by vibratory stimulation was blocked by direct intracellular injection of AYP. These results suggest that the adenosine‐mediated IPSP in nociceptive spinal neurones results from activating ATP‐sensitive K + channels in these neurones. As this inhibition of nociceptive dorsal horn neurones may be the physiological basis for the analgesia produced by vibratory stimulation in humans [Bini et al., 1984; Lundeberg, 1984; Lundeberg et al., 1984; Ottoson et al., 1981], We suggest that activation of ATP‐sensitive K + channels ion nociceptive neurones may mediate this analgesia. A diversity of drugs exists which act on ATP‐sensitive K + channels and we further suggest that such drugs might be therapeutically useful in enhancing the analgesia produced by vibration or in producing analgesia on their own. © 1993 Wiley‐Liss, Inc.
The bone–metal interface of defect and press‐fit ingrowth of microwave plasma‐chemical vapor deposition implants in the rabbit model (2004)

The evaluation of the curved side of the implant probe showed no great variation of bone-implant contact within the described observation times. This model simulates the usual implant insertion situation. The diamond-coated material becomes osseointegrated at a later time point. The bone-implant contact was only statistically relevant in one group in comparison to uncoated material.
Identification of ubiquinone-50 as the major methylated nonpolar lipid in human monocytes. Regulation of its biosynthesis via methionine-dependent pathways and relationship to superoxide production. (1983)

Human blood monocytes incorporated the methyl group from methionine into their neutral lipids. The major methylated product was identified as ubiquinone-50 in monocytes, lymphocytes, and a variety of human tumor cell lines by several analytical procedures including TLC or high performance liquid chromatography and as ubiquinone-45 in a mouse tumor cell line. Up to three methyl groups were shown to be derived from methionine by mass spectrometry. The rate of synthesis of ubiquinone-50 by monocytes as assessed by measuring labeled methyl group incorporation was shown to be linear over a 3-h period. Degradation of ubiquinone proceeded slowly; 80% of the labeled compound persisted after 18 h. The dependence of ubiquinone-50 synthesis upon methionine concentration was established in monocytes, with an estimated apparent Km for methionine of about 20 microM. The tumor promoter, tetradecanoate phorbol acetate, a potent stimulator of superoxide anion (O2-) production in phagocytic cells, inhibited ubiquinone-50 synthesis at nanomolar concentrations in monocytes, but not in lymphocytes, under conditions where oxidation of methionine takes place. Degradation of the labeled ubiquinone was unaffected. Formylmethionylleucyl-phenylalanine, a chemoattractant peptide which stimulates O2- production in phagocytic cells, also inhibited ubiquinone-50 synthesis. The degree of inhibition by either stimulus was increased when the methionine concentration in the medium was low. These findings demonstrate that in human monocytes ubiquinone-50 biosynthesis is regulable and that methionine concentration modulates both its rate of synthesis and the inhibitory effects of two stimuli of O2- production.
Formation of Branched Ruthenium Nanoparticles for Improved Electrocatalysis of Oxygen Evolution Reaction (2019)

Branched nanoparticles are one of the most promising nanoparticle catalysts as their branch sizes and surfaces can be tuned to enable both high activity and stability. Understanding how the crystallinity and surface facets of branched nanoparticles affect their catalytic performance is vital for further catalyst development. In this work, a synthesis is developed to form highly branched ruthenium (Ru) nanoparticles with control of crystallinity. It is shown that faceted Ru branched nanoparticles have improved stability and activity in the oxygen evolution reaction (OER) compared with polycrystalline Ru nanoparticles. This work achieves a low 180 mV overpotential at 10 mA cm<sup>-2</sup> for hours, demonstrating that record-high stability for Ru nanocrystals can be achieved while retaining high activity for OER. The superior electrocatalytic performance of faceted Ru branched nanoparticles is ascribed to the lower Ru dissolution rate under OER conditions due to low-index facets on the branch surfaces.
A spectroscopic and neutron diffraction investigation of structure, bonding, and molecular dynamics in bis(methylcyclopentadienyl)hafnium bis(tetrahydroborate), (.eta.5-CH3C5H4)2Hf(BH4)2 (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA spectroscopic and neutron diffraction investigation of structure, bonding, and molecular dynamics in bis(methylcyclopentadienyl)hafnium bis(tetrahydroborate), (.eta.5-CH3C5H4)2Hf(BH4)2Paul L. Johnson, Steven A. Cohen, Tobin J. Marks, and Jack M. WilliamsCite this: J. Am. Chem. Soc. 1978, 100, 9, 2709–2716Publication Date (Print):April 1, 1978Publication History Published online1 May 2002Published inissue 1 April 1978https://pubs.acs.org/doi/10.1021/ja00477a024https://doi.org/10.1021/ja00477a024research-articleACS PublicationsRequest reuse permissionsArticle Views95Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The RNA Polymerase II C-terminal Domain-interacting Domain of Yeast Nrd1 Contributes to the Choice of Termination Pathway and Couples to RNA Processing by the Nuclear Exosome (2013)

The RNA polymerase II (RNApII) C-terminal domain (CTD)-interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CID(Rtt103))) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist. Therefore, CTD-CID interactions target specific termination complexes to help choose an RNApII termination pathway. Interactions of Nrd1 with both CTD and nascent transcripts contribute to efficient termination by the Nrd1 complex. Surprisingly, replacing the Nrd1 CID with that from Rtt103 reduces binding to Rrp6/Trf4, and RNA transcripts terminated by Nrd1(CID(Rtt103)) are predominantly processed by core exosome. Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome.
Immunohistochemical study of the distribution of sodium‐dependent vitamin C transporters in adult rat brain (2006)

Sodium-dependent vitamin C transporters (SVCTs) is known to transport the reduced form of ascorbic acid into the cell, whereas the oxidized form of vitamin C (VC) is moved through a facilitative sugar transporter, such as glucose transporter (GLUT). With regard to the distribution of SVCT1 and -2 within the various organs, they were reported to be expressed in different types of cells. Especially in the central nervous system, only SVCT2 mRNA was expressed mainly in neurons and some types of neuroglial cells. However, data on the expression of SVCT proteins in the brain are scant. Therefore, we tried to develop comprehensive data on the distribution of SVCT proteins in adult rat brain by using immunohistochemical techniques for the first time. In our study, SVCT2 immunoreactivities (IRs) were intensely localized in the neurons of cerebral cortex, hippocampus, and Purkinje cells of cerebellum, and much weaker SVCT2 IRs were found in the other brain regions. Judging from double-immunohistochemical data, most of the cells expressing SVCT2 IRs were likely to be neurons or microglia, even though the cells in choroids plexus or ependymal cells around the ventricles also exhibited SVCT2 IRs. Complete mapping of the distribution of SVCT2 IRs was available by using a semiquantitative method. The subcellular localization of SVCT proteins is necessary for understanding the exact role of the protein, so the current overall mapping of SVCT IRs in the rat brain could be the basis for further studies on related subjects.
TCR repertoire analysis from peripheral blood for prognostic assessment of patients during treatment. (2019)

e14040 Background: Immune checkpoint inhibitors offer substantial clinical advantage to a subset of patients but predictive/novel prognostic indicators are still scarce. T cell receptors (TCRs) play a crucial role in adaptive immunity and anti-tumor immune responses. Net diversity of TCR repertoires are altered in patients receiving immune checkpoint inhibitors. To study the prognostic significance of T cell repertoires as a biomarker of immune responses in cancer patients, we characterized TCR repertoires from peripheral blood using high throughput sequencing. Methods: Total RNA from peripheral blood mononuclear cells (PBMCs) was extracted and used to generate sequencing libraries from five pancreatic cancer patients, four triple negative breast cancer (TNBC) patients and two squamous cell carcinoma (SCC+) patients. Blood draws were collected pre- and post-treatment and target lesion analysis was performed using immune-related response criteria (irRC) and Recist1.1. TCR alpha and beta CDR3s were clonotyped for each sample, and profiles of clonotype proportions were tracked through time/serial biopsies. Additionally the Shannon-Wiener diversity metric was calculated for each time point. Results: Patient samples showing consistent positive responses as measured by irRC and Recist1.1 showed TCR clones persisting throughout all time points. A TNBC super responder showed dramatic increases in mean Shannon-Wiener index from 74 prior treatment to 1177 at first biopsy post treatment (34% decrease by irRC and 26% by Recist1.1 analysis) and achieved an index as high as 3516 in a subsequent biopsy (83% and 64% decrease by irRC and Recist 1.1 respectively). Patients that showed poor response by irRC and Recist1.1 showed TCR clones that were in constant flux. Loss of clonality and/or decrease in absolute numbers was observed in previous and later time points. Conclusions: Patients that show positive response had TCR clones that were stable, which may indicate an existing immune related response towards their tumor. Therapy would allow these existing T-cells to overcome blockade by tumor cells. Patients showing poor response show a TCR repertoire that is constantly changing potentially indicating that the tumor cells are not eliciting a strong T cell specific response. Further functional studies of T cell populations would expand our understanding of T cell based immune therapies.
Ultrasound-heated photoacoustic flowmetry (2013)

We report the development of photoacoustic flowmetry assisted by high-intensity focused ultrasound (HIFU). This novel method employs HIFU to generate a heating impulse in the flow medium, followed by photoacoustic monitoring of the thermal decay process. Photoacoustic flowmetry in a continuous medium remains a challenge in the optical diffusive regime. Here, both the HIFU heating and photoacoustic detection can focus at depths beyond the optical diffusion limit (~1 mm in soft tissue). This method can be applied to a continuous medium, i.e., a medium without discrete scatterers or absorbers resolvable by photoacoustic imaging. Flow speeds up to 41 mm·s-1 have been experimentally measured in a blood phantom covered by 1.5-mm-thick tissue.
RF Ion Gun Injector in Support of Fusion Ship II Research and Development (2004)

Ion injection into the Inertial Electrostatic Confinement (IEC) fusion power plant used in the design of the high performance Fusion Ship II (Burton et al., 2003) is a key technological issue for development of this concept. This paper discusses the design and initial experiments with a radiofrequency (RF) ion gun designed for this purpose. The RF Gun design described here was found to have some important advantages over other ion gun designs: simple construction, a higher extraction efficiency; 10 ((mA/cm2)/W), a lower divergence; 10.8 ± 0.36 mrad, and a very intensive ion flux; 6 × 1018 ions/(cm2.sec) measured at 0.27 Pa.
Weder Ostalgie noch Dämonisierung. Vor Ort Ost/Stadt Land Ost – ein fotokünstlerisches Werk als Quelle für den Wandel in der ehemaligen DDR (2004)

Seit einiger Zeit kursiert das Schlagwort „Ostalgie“. Fernsehshows mit ehemaligen Medaillengewinnern, halb vergessenen Prominenten und ergrauten Medienstars boomen. Thema: die DDR im wehmütigen Rückblick. Man gewinnt den Eindruck, dass sich der Deutsche-Ost seine Vergangenheit angesichts der unsicheren Gegenwart gern verklären lässt. Motto: So schlimm war es ja nicht. Der Deutsche-West steht etwas hilflos vor diesem Kessel Buntem, von dem er kaum etwas gesehen oder miterlebt hat.
Performance of the ATLAS Level-1 topological trigger in Run 2 (2021)

Abstract: During LHC Run 2 (2015–2018) the ATLAS Level-1 topological trigger allowed efficient data-taking by the ATLAS experiment at luminosities up to 2.1×1034 cm-2s-1, which exceeds the design value by a factor of two. The system was installed in 2016 and operated in 2017 and 2018. It uses Field Programmable Gate Array processors to select interesting events by placing kinematic and angular requirements on electromagnetic clusters, jets, τ-leptons, muons and the missing transverse energy. It allowed to significantly improve the background event rejection and signal event acceptance, in particular for Higgs and B-physics processes.
Distributed development considered harmful (2013)

We offer a case study illustrating three rules for reporting research to industrial practitioners. Firstly, report “relevant” results; e.g. this paper explores the effects of distributed development on software products. Second: “recheck” old results if new results call them into question. Many papers say distributed development can be harmful to software quality. Previous work by Bird et al. allayed that concern but a recent paper by Posnett et al. suggests that the Bird result was biased by the kinds of files it explored. Hence, this paper rechecks that result and finds significant differences in Microsoft products (Office 2010) between software built by distributed or collocated teams. At first glance, this recheck calls into question the widespread practice of distributed development. Our third rule is to “reflect” on results to avoid confusing practitioners with an arcane mathematical analysis. For example, on reflection, we found that the effect size of the differences seen in the collocated and distributed software was so small that it need not concern industrial practitioners. Our conclusion is that at least for Microsoft products, distributed development is not considered harmful.
ATP citrate lyase is an essential player of the metabolic rewiring induced by PTEN loss during T-ALL development (2023)

Summary Alterations inactivating the tumor suppressor gene PTEN drive the development of solid and hematological cancers, such as T-cell acute lymphoblastic leukemia (T-ALL), whereby PTEN loss defines poor-prognosis patients. We investigated the metabolic rewiring induced by PTEN loss in T-ALL, aiming at identifying novel metabolic vulnerabilities. We showed that the enzyme ATP citrate lyase (ACLY) is strictly required for the transformation of thymic immature progenitors and for the growth of human T-ALL, which remain dependent on ACLY activity even upon transformation. Whereas PTEN mutant mice all died within 17 weeks, the concomitant ACLY deletion prevented disease initiation in 70% of the animals, where it prevented the apoptosis of pre-malignant DP thymocytes by up-regulating BCL-2. Transcriptomic and metabolic analysis of primary T-ALL cells next translated our findings to the human pathology, showing that PTEN-altered T-ALL cells selectively activate ACLY and are specifically sensitive to its genetic targeting. ACLY activation thus represents a metabolic vulnerability with therapeutic potential for high-risk T-ALL patients.
Experiencias en el uso de los modelos numéricos de agua subterránea (2020)

Ponencia presentada en el Seminario Internacional de Modelamiento Hidrologico para la Gestion de Recursos Hidricos, realizado en Lima, el 17 de septiembre de 2020. Los sistemas dinamicos complejos con numerosas variables de influencia diferentes requieren modelos correspondientes que permitan calcular o estimar las relaciones del sistema complejo. Sin embargo, esto generalmente solo es posible con modelos matematicos o numericos como los utilizados en las simulaciones de aguas subterraneas. Simplificados en tales modelos, los procesos, por ejemplo, el flujo de aguas subterraneas, se calculan en una zona determinada, teniendo en cuenta las condiciones limite (entradas por los bordes, retiradas de agua subterraneas, etc.).
ChemInform Abstract: A Simple and Highly Diastereoselective One‐Pot Synthesis of 1,3‐ Diamines. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.