gebhart/patrepeval huggingface dataset:
A nuclear protein in <i>Schizosaccharomyces pombe</i> with homology to the human tumour suppressor Fhit has decapping activity (2002)

A number of eukaryotic proteins are already known to orchestrate key steps of mRNA metabolism and translation via interactions with the 5' m7GpppN cap. We have characterized a new type of histidine triad (HIT) motif protein (Nhm1) that co-purifies with the cap-binding complex eIF4F of Schizosaccharomyces pombe. Nhm1 is an RNA-binding protein that binds to m7GTP-Sepharose, albeit with lower specificity and affinity for methylated GTP than is typical for the cap-binding protein known as eukaryotic initiation factor 4E. Sequence searches have revealed that proteins with strong sequence similarity over all regions of the new protein exist in a wide range of eukaryotes, yet none has been characterized up to now. However, other proteins that share specific motifs with Nhm1 include the human Fhit tumour suppressor protein and the diadenosine 5', 5"'-P1, P4-tetraphosphate asymmetrical hydrolase of S. pombe. Our experimental work also reveals that Nhm1 inhibits translation in a cell-free extract prepared from S. pombe, and that it is therefore a putative translational modulator. On the other hand, purified Nhm1 manifests mRNA decapping activity, yet is physically distinct from the Saccharomyces cerevisiae decapping enzyme Dcp1. Moreover, fluorescence and immunofluorescence microscopy show that Nhm1 is predominantly, although not exclusively, nuclear. We conclude that Nhm1 has evolved as a special branch of the HIT motif superfamily that has the potential to influence both the metabolism and the translation of mRNA, and that its presence in S. pombe suggests the utilization of a novel decapping pathway.
Tubulin-based antimitotic mechanism of E7974, a novel analogue of the marine sponge natural product hemiasterlin (2009)

E7974 is a synthetic analogue of the marine sponge natural product hemiasterlin. Here, we show that E7974, such as parental hemiasterlin, acts via a tubulin-based antimitotic mechanism. E7974 inhibits polymerization of purified tubulin in vitro with IC(50) values similar to those of vinblastine. In cultured human cancer cells, E7974 induces G(2)-M arrest and marked disruption of mitotic spindle formation characteristic of tubulin-targeted anticancer drugs. Extensive hypodiploid cell populations are seen in E7974-treated cells, indicating initiation of apoptosis after prolonged G(2)-M blockage. Consistent with this observation, E7974 induces caspase-3 activation and poly ADP ribose polymerase cleavage, typical biochemical markers of apoptosis. Only a short cellular exposure to E7974 is sufficient to induce maximum mitotic arrest, suggesting that E7974's antitumor effects in vivo may persist even after blood levels of the drug decrease after drug administration. Interactions of E7974 with purified tubulin were investigated using two synthetic tritiated photoaffinity analogues incorporating a benzophenone photoaffinity moiety at two different positions of the E7974 scaffold. Both analogues preferentially photolabeled alpha-tubulin, although minor binding to beta-tubulin was also detected. E7974 thus seems to share a unique, predominantly alpha-tubulin-targeted mechanism with other hemiasterlin-based compounds, suggesting that, unlike many tubulin-targeted natural products and related drugs, the hemiasterlins evolved to mainly target alpha-tubulin, not beta-tubulin subunits.
AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules (2015)

mTOR is an atypical serine threonine kinase involved in regulating major cellular functions, such as nutrients sensing, growth, and proliferation. mTOR is part of the multiprotein complexes mTORC1 and mTORC2, which have been shown to play critical yet functionally distinct roles in the regulation of cellular processes. Current clinical mTOR inhibitors only inhibit the mTORC1 complex and are derivatives of the macrolide rapamycin (rapalogs). Encouraging effects have been observed with rapalogs in estrogen receptor-positive (ER(+)) breast cancer patients in combination with endocrine therapy, such as aromatase inhibitors. AZD2014 is a small-molecule ATP competitive inhibitor of mTOR that inhibits both mTORC1 and mTORC2 complexes and has a greater inhibitory function against mTORC1 than the clinically approved rapalogs. Here, we demonstrate that AZD2014 has broad antiproliferative effects across multiple cell lines, including ER(+) breast models with acquired resistance to hormonal therapy and cell lines with acquired resistance to rapalogs. In vivo, AZD2014 induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of AZD2014 is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. In combination with fulvestrant, AZD2014 induces tumor regressions when dosed continuously or using intermittent dosing schedules. The ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials.
Iterative Decoding : A Unifying Factor Graph Approach (2007)

International audience
Efficacy and safety of early aspirin withdrawal and continuation of ticagrelor monotherapy post PCI for STEMI. A post hoc analysis of the randomized global leaders trial (2021)

Abstract Background Clinical presentation with STEMI is considered as a highly prothrombotic condition often associated with recurrent ischemic events. The role of aspirin as part of antiplatelet regimens in STEMI patients needs to be clarified especially in the context of new potent P2Y12 inhibitors Aim To assess the benefit and risk of 23-month ticagrelor monotherapy after one month of DAPT against the conventional 12-month DAPT with aspirin and ticagrelor followed by aspirin monotherapy among STEMI patients in the GLOBAL LEADERS trial. Methods We did a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial (2092 patients). We compared the experimental ticagrelor monotherapy group (1062 patients) with the standard 12-month DAPT group (1030 patients) in rates of GLOBAL LEADERS predefined primary (composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction (MI) and secondary end points (BARC 3 or 5 bleeding). NACE (Net Adverse Clinical Events) and POCE (Patient- Oriented Composite End points). We also compared GLOBAL LEADERS predefined end points in STEMI, UA, NSTEMI and CCS in both treatment arms. Results At two years, there were no significant differences in rates of GLOBAL LEADERS primary end points in patients who had or did not have STEMI. BARC bleeding in either treatment group didn't vary significantly among STEMI, NSTEMI and UA. Nevertheless, the experimental strategy had led to significant increase in BARC bleeding in CCS compared with STEMI at 1 and 2 years. There were similar rates of NACE and POCE in both the experimental and reference treatment groups at 1 and 2 years post PCI. Conclusions and relevance The incidence of GLOBAL LEADRER defined end points has not been impacted by STEMI presentation. Our findings suggest that an earlier cessation of DAPT at 1 month post primary PCI, with continuation of a potent P2Y12 antagonist monotherapy, could be safe and avoids additional bleeding risk in the STEMI setting. Given the post-hoc nature of the analysis, our findings should not necessitate changes in recommendations for practice by professional associations and regulatory agencies. However, all reported findings should rather be considered only as hypothesis-generating and need be replicated in dedicated large-scale randomized trials to further assess the role of Aspirin free antithrombotic strategies post PCI in STEMI. Funding Acknowledgement Type of funding sources: None.
The<i>FGF14<sup>F145S</sup></i>Mutation Disrupts the Interaction of FGF14 with Voltage-Gated Na<sup>+</sup>Channels and Impairs Neuronal Excitability (2007)

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.
Large scale circuit partitioning with loose/stable net removal and signal flow based clustering (1997)

In this paper, we present an efficient Iterative Improvement based Partitioning (IIP) algorithm called LSR/MFFS, that combines signal flow based Maximum Fanout Free Subgraph (MFFS) clustering algorithm with Loose and Stable net Removal (LSR) partitioning algorithm. The MFFS algorithm generalizes existing MFFC decomposition method from combinational circuits to general sequential circuits in order to handle cycles naturally. We also study the properties of the nets that straddle the cutline carefully, and introduce the concepts of the loose and stable nets as well as effective ways to remove them out of the cutset. The LSR/MFFS algorithm first applies LSR algorithm to clustered netlist generated by MFFS algorithm for global-level cutsize optimization and then declusters netlist for further cutsize refinement. As a result, the LSR/MFFS algorithm has achieved the best cutsize result among all the bipartitioning algorithms published in the literatures with very promising runtime performance. In particular, it outperforms the recent state-of-the-art IIP algorithms LA3-CDIP, CLIP-PROP/sub f/, Strawman, hMetis-FM, and MLc by 17.4%, 12.1%, 5.9%, 3.1%, and 1.9%, respectively. It also outperforms the state-of-the-art non-IIP algorithms Paraboli, FEB, and PANZA by 32.0%, 21.4%, and 1.4%, respectively.
A Cholecystokinin B Receptor-Specific Aptamer Does Not Activate Receptor Signaling (2016)

Targeted nanoparticles which deliver effective doses of chemotherapeutic drugs directly to pancreatic tumors could improve treatment efficacy without the toxicities associated with systemic drug administration. One protein on tumor cells that can be targeted by nanoparticles is a G-protein coupled cell surface receptor, the cholecystokinin B receptor (CCKBR). Previously, we had shown that attaching the CCKBR ligand gastrin to the surface of nanoparticles can enhance their up-take by tumors. The drawback of using gastrin is that it can also activate the receptor, causing tumor cell growth. This study shows that a DNA aptamer that binds to the CCKBR and enhances nanoparticle up-take by tumors does not activate this receptor.\nPANC-1 cells, a cultured human pancreatic cancer cell line, were treated for 24 h with CCKBR aptamer 1153. Cell lysates were run on Bis-Tris gels, transferred to membranes, blocked in 5% BSA and incubated overnight with primary antibodies, including antibodies directly against phosphorylated-Akt (Ser473), total Akt, and beta-actin, a protein loading control. Although the CCKBR aptamer 1153 is internalized by pancreatic cancer cells in a receptor-mediated fashion, it does not stimulate cell proliferation. Because of this, we anticipate that it will not activate CCKBR signaling. If aptamer 1153 does not activate downstream receptor signaling, our future work will test whether the aptamer could be used to specifically direct drug-containing nanoparticles to tumors, making chemotherapy treatments for pancreatic cancer patients more effective with fewer off-target effects and toxicity.
Reversing the Thermodynamics of Galvanic Replacement Reactions by Decreasing the Size of Gold Nanoparticles (2020)

Here, we describe the surprising reactivity between surface-attached (a) 0.9, 1.6, and 4.1 nm diameter weakly stabilized Au nanoparticles (NPs) and aqueous 1.0 × 10<sup>-4</sup> M Ag<sup>+</sup> solution, and (b) 1.6 and 4.1 nm diameter weakly stabilized Au NPs and aqueous 1.0 × 10<sup>-5</sup> M PtCl<sub>4</sub><sup>2-</sup>, which are considered to be antigalvanic replacement (AGR) reactions because they are not thermodynamically favorable for bulk-sized Au under these conditions. Anodic Stripping Voltammetry (ASV) and Scanning Transmission Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (STEM-EDS) mapping provide quantitation of the extent of Ag and Pt replacement as a function of Au NP diameter. The extent of the reaction increases as the Au NP size decreases. The percentage of Ag in the AuAg alloy following AGR based on ASV is 17.8 ± 0.6% for 4.1 nm diameter Au NPs, 87.2 ± 2.9% for 1.6 nm Au NPs, and an unprecedented full 100% Ag for 0.9 nm diameter Au NPs. STEM-EDS mapping shows very close agreement with the ASV-determined compositions. In the case of PtCl<sub>4</sub><sup>2-</sup>, STEM-EDS mapping shows AuPt alloy NPs with 3.9 ± 1.3% and 41.1 ± 8.7% Pt following replacement with 4.1 and 1.6 nm diameter Au NPs, respectively, consistent with qualitative changes to the ASV. The size-dependent AGR correlates well with the negative shift in the standard potential (E<sup>0</sup>) for Au oxidation with decreasing NP size.
Scalable parallel solution coupling for multiphysics reactor simulation (2009)

Reactor simulation depends on the coupled solution of various physics types, including neutronics, thermal/hydraulics, and structural mechanics. This paper describes the formulation and implementation of a parallel solution coupling capability being developed for reactor simulation. The coupling process consists of mesh and coupler initialization, point location, field interpolation, and field normalization. We report here our test of this capability on an example problem, namely, a reflector assembly from an advanced burner test reactor. Performance of this coupler in parallel is reasonable for the chosen problem size and range of processor counts. The runtime is dominated by startup costs, which amortize over the entire coupled simulation. Future efforts will include adding more sophisticated interpolation and normalization methods, to accommodate different numerical solvers used in various physics modules and to obtain better conservation properties for certain field types.
Four New Trimeric Stilbene Glucosides fromWelwitschia mirabilis (2005)

Four new trimeric stilbene glucosides, mirabilosides C-F (1-4) were isolated from MeOH extract of stem and root of Welwitschia mirabilis (Welwitschiaceae) along with three known stilbenoids, resveratrol (5), gnemonoside B (6), and gnetin G (7). The structures of these compounds were elucidated by spectroscopic methods.
Scanning Tunneling Microscopy Study of an Altered Fe&lt;sub&gt;3&lt;/sub&gt;O&lt;sub&gt;4&lt;/sub&gt;(001) Thin Films Surface by Hydrogen Adsorption (2014)

We report on changes of surface structures induced by hydrogen adsorption on a Jahn-Teller distorted magnetite (Fe3O4)(001) surface and priorities of hydrogen-adsorbed sites by means of in-situ scanning tunneling microscopy. The experiments have revealed that surface Fe cations relax toward the bulk-terminated positions by OH species formed between adsorbed-hydrogen and surface ON anion (The labeled “N”in ON denotes that the O-O distance in the surface is compressed compared with bulk). Moreover, two types of surface ON sites were found to be almost equivalent for hydrogen adsorption. [DOI: 10.1380/ejssnt.2014.26]
Discrete white matter hyperintensity (WMH) growth quantification is superior to measurements of total longitudinal WMH volume change: implications for clinical trials in VCID (2022)

Abstract Background Small vessel ischemic disease (SVID) is a major risk factor for late‐life cognitive impairment and dementia (VCID). White matter hyperintensities (WMH) are a SVID biomarker that can be detected on MRI FLAIR imaging. Prior studies show dynamic change in WMH volumes that increase and decrease within subjects over time. We reported a method to quantify discrete WMH volume growth and regression in individuals over one‐year with instrumental validation performed within the MarkVCID consortium. The present study provides preliminary evidence for the clinical relevance of this methodology. Method 3D MRI T1‐weighted and FLAIR images at baseline and 12‐month follow‐up visits for sixty‐one participants (mean age 74 ± 5.9 years, 31 women) were analyzed. The Stroop test was administered using the CANS‐MCI computerized battery. WMH growth and regression were quantified for all participants. A linear regression model was used to assess the association of dynamic WMH changes with Stroop performance. Result WMH growth, but not regression or total WMH volume changes was associated with Stroop performance at the 12‐months (β = ‐0.24, P = 0.02) after controlling for sex, and age (graph). Conclusion These data show that WMH growth, but not regression or total WMH volume change, was associated with a decline in performance on the Stroop test over12‐months. These findings highlight the importance of studying dynamic, within subject, WMH growth and regression rather than solely focusing on longitudinal change in total WMH volume measurements. Measurement of WMH growth may help reduce sample sizes, facilitate clinical trial conduct, and optimize the potential to identify interventions intended to mitigate SVID contributions to VCID.
Effect of RF Signals on TVS Diode Trigger Voltage for ESD Protection (2020)

Discrete transient voltage suppressor devices are used in addition to the on-chip ESD protection to protect the ICs from ESD damage. In applications involving snapback TVS devices, the trigger voltage is selected to be higher than the desired signals on the net. The presence of RF on the net affects the TVS behavior, even if the RF levels are less than the snapback trigger voltage. Known effects are RF intermodulation and harmonic generation, which diminish SNR. This work describes the other effect on the TVS diodes - the observed reduction of the snapback trigger voltage, monotonically dependent on the amplitude of the RF signal. This translates into snapback triggering at lower stress levels than specified in the datasheet or expected by the design engineer. TLP testing was performed using a 100 ns pulse with RF signals from 100 MHz to 2 GHz present at the diode terminals. The results show that the higher frequencies have a weaker impact on the reduction of the snapback trigger voltage. At lower frequencies such as 100 MHz, the overlap of the first few ns of the TLP pulse, the peak voltage, and the phase of the RF signal impact the amount of reduction in the trigger voltage. It is also observed that certain TVS diodes recover from snapback even when the RF amplitude is higher than the holding voltage of the diode.
Set-based State Estimation with Probabilistic Consistency Guarantee under Epistemic Uncertainty (2021)

Consistent state estimation is challenging, especially under the epistemic uncertainties arising from learned (nonlinear) dynamic and observation models. In this work, we propose a set-based estimation algorithm, named Gaussian Process-Zonotopic Kalman Filter (GP-ZKF), that produces zonotopic state estimates while respecting both the epistemic uncertainties in the learned models and aleatoric uncertainties. Our method guarantees probabilistic consistency, in the sense that the true states are bounded by sets (zonotopes) across all time steps, with high probability. We formally relate GP-ZKF with the corresponding stochastic approach, GP-EKF, in the case of learned (nonlinear) models. In particular, when linearization errors and aleatoric uncertainties are omitted and epistemic uncertainties are simplified, GP-ZKF reduces to GP-EKF. We empirically demonstrate our method's efficacy in both a simulated pendulum domain and a real-world robot-assisted dressing domain, where GP-ZKF produced more consistent and less conservative set-based estimates than all baseline stochastic methods.
Impact of buried capping layer on TDDB physics of advanced interconnects (2005)

In Cu/SiOC interconnects, the incorporation of a thin (100/spl Aring/) buried capping layer (BCL) extends the lifetime beyond 10 years when extrapolated to the operating conditions of 105/spl deg/C and 0.5 MV/cm. A thicker (800/spl Aring/) BCL, however, initiates Ta barrier rupture due to thermomechanical stress and degrades lifetime performance. For the first time, three distinctively different failure mechanisms of structures with and without BCL are identified: Cu drift into the bulk SiOC; along the capping layer/SiOC interface; and through the ruptured Ta barrier into the BCL. We demonstrate that BCL engineering is a realizable and potentially promising technique to improve the electrical reliability of advanced interconnects.
Defect Engineering for High Performance and Extremely Reliable a‐IGZO Thin‐Film Transistor in QD‐OLED (2022)

Abstract An amorphous indium‐gallium‐zinc‐oxide (a‐IGZO) thin‐film transistor (TFT), which exhibits the best electrical stability (PBTS ≤ 0.009 V), is implemented to create quantum‐dot organic light‐emitting diode product. Electrical stability has been explained through various mechanisms involving defects related to oxygen and hydrogen. The defects of a‐IGZO are identified and the parameters of the deposition process are utilized to obtain V o + and V Zn − values of 1.7 × 10 17 and 2.4 × 10 18 spins cm −3 , respectively, which are quantified using electron spin resonance for the first time. The defects of the gate insulator (GI) in the upper and lower parts of the a‐IGZO TFT and the oxygen and hydrogen inflow/diffusion generated during the process are also controlled. From well‐controlled a‐IGZO and GI, the defect density at the top‐channel interface and near‐interface of the a‐IGZO TFT is reduced by 85% and 70%, respectively. The defects in the bottom‐channel are also reduced by 83% and 75% for the interface and near‐interface, respectively. Electrical stability is secured by controlling V o + and V Zn − and reducing sub‐gap trap density among interface defects that are not directly observed until now. In this paper, it is reported that the best a‐IGZO TFT performance is achieved through defect engineering.