gebhart/patrepeval huggingface dataset:
Akt–RSK–S6 Kinase Signaling Networks Activated by Oncogenic Receptor Tyrosine Kinases (2010)

Receptor tyrosine kinases (RTKs) activate pathways mediated by serine-threonine kinases, such as the PI3K (phosphatidylinositol 3-kinase)-Akt pathway, the Ras-MAPK (mitogen-activated protein kinase)-RSK (ribosomal S6 kinase) pathway, and the mTOR (mammalian target of rapamycin)-p70 S6 pathway, that control important aspects of cell growth, proliferation, and survival. The Akt, RSK, and p70 S6 family of protein kinases transmits signals by phosphorylating substrates on an RxRxxS/T motif (R, arginine; S, serine; T, threonine; and x, any amino acid). We developed a large-scale proteomic approach to identify more than 300 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor alpha (PDGFRalpha) RTKs. We identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTK inhibitors (RTKIs), as well as by inhibitors of the PI3K, mTOR, and MAPK pathways, and we determined the effects of small interfering RNA directed against these substrates on cell viability. Phosphorylation of the protein chaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) at serine-305 was essential for PDGFRalpha stabilization and cell survival in PDGFRalpha-dependent cancer cells. Our approach provides a new view of RTK and Akt-RSK-S6 kinase signaling, revealing previously unidentified Akt-RSK-S6 kinase substrates that merit further consideration as targets for combination therapy with RTKIs.
Highly Specific Peptide-Mediated Cuvette-Form Localized Surface Plasmon Resonance (LSPR)-Based Fipronil Detection in Egg (2022)

Herein, we have developed peptide-coated gold nanoparticles (AuNPs) based on localized surface plasmon resonance (LSPR) sensor chips that can detect fipronil with high sensitivity and selectivity. The phage display technique has been exploited for the screening of highly specific fipronil-binding peptides for the selective detection of the molecule. LSPR sensor chips are fabricated initially by attaching uniformly synthesized AuNPs on the glass substrate, followed by the addition of screened peptides. The parameters, such as the peptide concentration of 20 µg mL<sup>-1</sup> and the reaction time of 30 min, are further optimized to maximize the efficacy of the fabricated LSPR sensor chips. The sensing analysis is performed systematically under standard fipronil solutions and spike samples from eggs. The developed sensor has shown excellent sensitivity towards both standard solutions and spike samples with limit of detection (LOD) values of 0.01 ppb, respectively. Significantly, the developed LSPR sensor chips offer distinct features, such as a facile fabrication approach, on-site sensing, rapid analysis, cost-effectiveness, and the possibility of mass production, in which the chips can be effectively used as a promising and potential on-site detection tool for the estimation of fipronil.
An Atomic Model for Neutral and Singly Ionized Uranium (1979)

A model for the atomic levels above ground state in neutral, U0, and singly ionized, U+, uranium is described based on identified atomic transitions. We found 168 states in U0 and 95 in U+. A total of 1581 atomic transitions are used to complete this process. Also discussed are the atomic inverse lifetimes and line widths for the radiative transitions as well as the electron collisional cross sections.
Identification of 2-[4-[(4-Methoxyphenyl)methoxy]-phenyl]acetonitrile and Derivatives as Potent Oct3/4 Inducers (2015)

Reprogramming somatic cells into induced-pluripotent cells (iPSCs) provides new access to all somatic cell types for clinical application without any ethical controversy arising from the use of embryonic stem cells (ESCs). Established protocols for iPSCs generation based on viral transduction with defined factors are limited by low efficiency and the risk of genetic abnormality. Several small molecules have been reported as replacements for defined transcriptional factors, but a chemical able to replace Oct3/4 allowing the generation of human iPSCs is still unavailable. Using a cell-based High Throughput Screening (HTS) campaign, we identified that 2-[4-[(4-methoxyphenyl)methoxy]phenyl]acetonitrile (1), termed O4I1, enhanced Oct3/4 expression. Structural verification and modification by chemical synthesis showed that O4I1 and its derivatives not only promoted expression and stabilization of Oct3/4 but also enhanced its transcriptional activity in diverse human somatic cells, implying the possible benefit from using this class of compounds in regenerative medicine.
Failure to Accurately Disclose Conflicts of Interest in Articles Published in JAMA Oncology (2018)

Roberto Salgado, MD, PhD; Carsten Denkert, MD, PhD; Christine Campbell, MSc; Peter Savas, MD; Paolo Nuciforo, MD; Claudia Aura, MD; Evandro de Azambuja, MD, PhD; Holger Eidtmann, MD; Catherine E. Ellis, PhD; José Baselga, MD; Martine J. Piccart-Gebhart, MD, PhD; Stefan Michiels, PhD; Ian Bradbury, PhD; Christos Sotiriou, MD, PhD; Sherene Loi, MD, PhD
Ultrastructural immunocytochemical localization of myosin in cultured fibroblastic cells. (1981)

Nonmuscle myosin in the cytoplasm of cultured fibroblastic cells has been localized using light and electron microscopic immunocytochemistry. Antibodies to purified fibroblast myosin were produced in goat and rabbit and purified by affinity chromatography. Light microscopic immunofluorescence localization showed patterns similar to those previously published. Electron microscopic localization using the ethyldimethyl aminopropyl carbodiimide-glutaraldehyde-saponin (EGS) fixation-permeabilization procedure and the ferritin bridge localization method produced quantifiable localization in intracellular sites with well-preserved ultrastructural morphology. Myosin was found to be a major component of the cytosol. It was distributed diffusely with no preferential localization on membranous organelles. Myosin was found to be slightly concentrated on the surface of microfilament-containing structures, including the subplasmalemmal microfilament mat and stress fibers, occasionally with an interrupted periodicity. However, no myosin was found in surface ruffles or microvilli. Morphometric quantitation showed that the majority of the cell's myosin was in the cytosol. This location is compatible with myosin being a component of the microtrabecular lattice of the cytoplasmic ground substance. The concentration of myosin in association with microfilaments was only twice that of the cytosol. This interpretation must be somewhat tempered by the possibility that some myosin bound to tightly packed actin may be inaccessible. The significance of this distribution of myosin in cell function is discussed.
Laser trimming of the operating wavelength of silicon nitride racetrack resonators (2020)

We demonstrate the possibility of post-fabrication trimming of the response of nitrogen-rich silicon nitride racetrack resonators by using an ultraviolet laser. The results revealed the possibility to efficiently tune the operating wavelength of fabricated racetrack resonators to any point within the full free spectral range. This process is much faster than similar, previously presented methods (in the order of seconds, compared to hours). This technique can also be applied to accurately trim the optical performance of any other silicon photonic device based on nitrogen-rich silicon nitride.
Horton tables: fast hash tables for in-memory data-intensive computing (2016)

Hash tables are important data structures that lie at the heart of important applications such as key-value stores and relational databases. Typically bucketized cuckoo hash tables (BCHTs) are used because they provide high-throughput lookups and load factors that exceed 95%. Unfortunately, this performance comes at the cost of reduced memory access efficiency. Positive lookups (key is in the table) and negative lookups (where it is not) on average access 1.5 and 2.0 buckets, respectively, which results in 50 to 100% more table-containing cache lines to be accessed than should be minimally necessary.

To reduce these surplus accesses, this paper presents the Horton table, a revamped BCHT that reduces the expected cost of positive and negative lookups to fewer than 1.18 and 1.06 buckets, respectively, while still achieving load factors of 95%. The key innovation is remap entries, small in-bucket records that allow (1) more elements to be hashed using a single, primary hash function, (2) items that overflow buckets to be tracked and rehashed with one of many alternate functions while maintaining a worst-case lookup cost of 2 buckets, and (3) shortening the vast majority of negative searches to 1 bucket access. With these advancements, Horton tables outperform BCHTs by 17% to 89%.
Preparation and Reactivity Study of a Versatile Trifluoromethylthiolating Agent: S‐Trifluoromethyl Trifluoromethanesulfonothioate (TTST) (2023)

Abstract A novel, air and thermally stable, yet highly reactive trifluoromethylthiolating reagent, CF 3 SO 2 SCF 3 ( 1 ), was prepared easily in one step from commercially inexpensive CF 3 SO 2 Na and Tf 2 O. 1 is a highly versatile and atom‐efficient reagent that can generate one equivalent of CF 3 S + , two equivalents of CF 3 S − , or a combination of CF 3 S⋅/CF 3 ⋅ species. Many high‐yielding CF 3 S reactions of C , O , S , and N ‐nucleophiles were achieved, including the simple‐step preparations of many reported CF 3 S reagents. 1 delivered a hitherto hard‐to‐synthesize ArOSCF 3 that was followed by a novel CF 3 S II ‐rearrangement. Through Cu or TDAE/Ph 3 P combinations, 1 generated two equivalents of CF 3 S anion species, and the photo‐catalyzed reactions of alkenes with 1 provided CF 3 /CF 3 S‐containing products in high atom‐efficiency.
An initial investigation of open PET geometries (2007)

A long patient port of PET scanner tends to put stress on patients, especially patients with claustrophobia. It also prevents doctors and technicians from taking care of patients during scanning. In this paper, we propose an “open PET” geometry, which consists of two axially separated detector rings. Long and continuous field-of-view (FOV) including 360-degree opened gap space between two detector-rings can be visualized by 3D image reconstruction from all the possible lines-ofresponse (LORs). Based on the redundant characteristics of 3D PET, oblique LORs between two separated detector-rings compensate the missing LORs in the gap. In order to evaluate imaging performance of the open PET geometries, we simulated dual HR+ scanner (ring diameter=827mm, axial length=153mm x 2) separated by a variable gap. 3D OS-EM with geometrical system modeling was applied. The gap of 153mm was the maximum limit for the simulated scanner to have axially continuous FOV of 459mm though the maximum diameter of FOV at the central slice was limited to 414mm. The results show that high resolution images can be obtained with the gap up to 153mm, though missing LORs increase a little but almost invisible artifacts. We also tested open PET geometries using experimental data obtained by the jPET-D4, a prototype brain scanner. The jPET-D4 has 5 rings of 24 detector blocks. Therefore we simulated open PET data with a gap of 65mm by eliminating 1 block-ring from experimental FDG-PET data. Although some artifacts were seen at both ends of the gap, very similar images were obtained with and without the gap. The open PET geometry is expected to enable in-beam PET, which is a method for an in situ monitoring of charged particle therapy, by letting beams though the gap. The open PET geometry also enables a simultaneous PET/CT scanner to measure the same PET FOV as the CT FOV at the same time, in contrast to conventional PET/CT scanners where each FOVs are separated by several tens centimeters.
Death-associated protein kinase promoter hypermethylation in normal human lymphocytes. (2003)

A high frequency of death-associated protein kinase (DAPK) promoter hypermethylation has been noted in B-cell malignancies, head and neck cancers, and other solid tumors, and it has been used as a tumor marker in molecular detection strategies. Low levels of DAPK promoter hypermethylation, ranging from 0.003 to 1.181%, were detected in peripheral blood cells from 75 of 143 (52%) normal subjects by quantitative methylation-specific PCR (Q-MSP). In 10 of 10 selected patients, MSP amplification of a portion of the DAPK promoter followed by PCR product sequencing confirmed dense hypermethylation of the CpG island in their peripheral blood cells. Q-MSP analysis of fluorescence-activated cell-sorted peripheral blood cells from three of these patients demonstrated that a significantly greater proportion of B cells (1.074-6.026%) were DAPK hypermethylated than were T cells, monocytes, or neutrophils, which were <0.06% hypermethylated. Further analysis after sorting of one subject's B cells into IgM+, IgM-, IgG+, and IgG- subpopulations demonstrated that DAPK hypermethylation was predominantly present in the IgM- compared with IgM+ B cells (3.338% versus 0.436%). DAPK promoter hypermethylation was found in IgM- B cells in normal individuals. The same hypermethylation identified in B-cell malignancies may reflect a clonal outgrowth of B cells arising from this compartment and may indicate a susceptibility to neoplastic transformation in a subset of B cells. Normal circulating lymphocytes with DAPK promoter hypermethylation may act as confounding factors in tumor detection based on DAPK hypermethylation.
Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia (2014)

Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph+ chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. Highly enriched CD34+/CD38- ALL stem cells also expressed Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and growth arrest in the BCR/ABL1+ cell lines, in Ph- lymphoblastic cell lines and in primary Ph+ and Ph- ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of leukemic cells were dose-dependent. In Ph+ ALL, major growth-inhibitory effects of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib-resistant cells. Hsp32-targeting drugs were found to synergize with imatinib, nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph+ ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL cells and to synergize with imatinib in suppressing the growth of ALL cells. In conclusion, Hsp32 is an essential survival factor and potential new target in ALL.
Cathelicidins and functional analogues as antisepsis molecules (2007)

The emergence of antibiotic-resistant bacteria together with the limited success of sepsis therapeutics has lead to an urgent need for the development of alternative strategies for the treatment of systemic inflammatory response syndrome and related disorders. Immunomodulatory compounds that do not target the pathogen directly (therefore limiting the development of pathogen resistance), and target multiple inflammatory mediators, are attractive candidates as novel therapeutics. Cationic host defence peptides such as cathelicidins have been demonstrated to be selectively immunomodulatory in that they can confer anti-infective immunity and modulate the inflammatory cascade through multiple points of intervention. The human cathelicidin LL-37, for example, has modest direct antimicrobial activity under physiological conditions, but has been demonstrated to have potent antiendotoxin activity in animal models, as well as the ability to resolve certain bacterial infections. A novel synthetic immunomodulatory peptide, IDR-1, built on this same theme has no direct antimicrobial activity, but is effective in restricting many types of infection, while limiting pro-inflammatory responses. The ability of these peptides to selectively suppress harmful pro-inflammatory responses, while maintaining beneficial infection-fighting components of host innate defences makes them a good model for antisepsis therapies that merit further investigation.
High mobility SiMOSFETs fabricated in a full 300 mm CMOS process (2021)

Abstract The quality of the semiconductor–barrier interface plays a pivotal role in the demonstration of high quality reproducible quantum dots for quantum information processing. In this work, we have measured SiMOSFET Hall bars on undoped Si substrates in order to investigate the device quality. For devices fabricated in a full complementary metal oxide semiconductor (CMOS) process and of very thin oxide below a thickness of 10 nm, we report a record mobility of 17.5 × 10 3 cm 2 V −1 s −1 indicating a high quality interface, suitable for future qubit applications. We also study the influence of gate materials on the mobilities and discuss the underlying mechanisms, giving insight into further material optimization for large scale quantum processors.
Prediction of Successful Memory Encoding Based on Lateral Temporal Cortical Gamma Power (2021)

Prediction of successful memory encoding is important for learning. High-frequency activity (HFA), such as gamma frequency activity (30-150 Hz) of cortical oscillations, is induced during memory tasks and is thought to reflect underlying neuronal processes. Previous studies have demonstrated that medio-temporal electrophysiological characteristics are related to memory formation, but the effects of neocortical neural activity remain underexplored. The main aim of the present study was to evaluate the ability of gamma activity in human electrocorticography (ECoG) signals to differentiate memory processes into remembered and forgotten memories. A support vector machine (SVM) was employed, and ECoG recordings were collected from six subjects during verbal memory recognition task performance. Two-class classification using an SVM was performed to predict subsequently remembered vs. forgotten trials based on individually selected frequencies (low gamma, 30-60 Hz; high gamma, 60-150 Hz) at time points during pre- and during stimulus intervals. The SVM classifier distinguished memory performance between remembered and forgotten trials with a mean maximum accuracy of 87.5% using temporal cortical gamma activity during the 0- to 1-s interval. Our results support the functional relevance of ECoG for memory formation and suggest that lateral temporal cortical HFA may be utilized for memory prediction.
Synthesis and Reactivity of Heterocyclic a-Diazo Carbonyl Compounds (1978)

Synthesis of rr-diazo substituted 3-carboxylic e s t e r s of isoxazolone and pyrazolone (3 -a, b) by diazo group t r a n s f e r succeeds only with the use of the azidinium salt 2. -The thermodynamically quite stable diazo compounds 3 a, h a r e very resistant to mineral acids but can be readily coupled to form azo derivatives with compounds containing an active C-H bond.Hydrolysis of their labile phosphazines 6 a, and b readily gives the hydrazones 7 5 .b .-.. . --We have made an attempt to transfer the results which we found e a r l i e r on Q-diazo-y-butyrolactone to include the heterocyclic five-membered ring sy-2 s t e m s such a s pyrazole and isoxazole.The two e s t e r s 1 a and b. whose aposition ought already to be activated in such a way a s to allow the diazo 3 group to be introduced directly with diazo group transfer agents , were s elected a s model substances.The diazo transfer was tested f o r with tosyl azide and the azidinium salt 2 3' 4, but only the l a t t e r compound is suitable f o r the synthesis.While 2 reacts to the desired diazo compounds 3 a, and h -. . in good yield a t room temperature even under quite mild conditionsin 1N + Dedicated t o P r o f e s s o r D r .Adolf Butenandt on the occasion of his seventyfifth birthday.sulfuric acidno reaction to 3 a and b was achieved with tosyl azide under . .t h e s e conditions.Diazo t r a n s f e r with t h i s reagent t a k e s place only i n alkaline medium.but simultaneous coupling of the diazo compound f o r m e d with the s t a r t i n g product ensues.70 13 IR ( c H c ~~; c m -l ) C -N M R ( C D C ~ ;pprn) X yield m p C = O 4-C 5 -6 -N2 3 s . .
Loss characteristics of coplanar waveguide transmission lines fabricated with copper nanoparticles (2010)

Abstract This article investigates the high frequency characteristics of coplanar waveguide (CPW) lines fabricated with inkjet‐printing technology on BT substrates. The optimal metallic thickness of a printed CPW line is approximately estimated to be 3 μm. When printed lines with higher electrical conductivity are realized through additional surface preparation steps, the findings of this study suggest that the RF performance level of these printed lines will be comparable to that of the copper clad laminate lines in the microwave frequency region. Finally, aspects of such improvements as well as applications of these types of printed lines are discussed. © 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52: 780–782, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24987
Abstract 727: A novel rMVA combination immunotherapy triggers potent innate and adaptive immune responses against established tumors (2018)

Abstract Virus-based vaccines and appropriate costimulation enhance potent antigen-specific T cell immunity against cancer. However, the tumor microenvironment exerts intrinsic and extrinsic mechanisms to evade tumor destruction. In the present study we exploit both innate and adaptive immune responses triggered by a novel recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors in combination regimes to overcome tumor-induced resistance to immunotherapy. Therapeutic treatment with rMVA-CD40L resulted in strong antitumor effects in unrelated established tumor models. Tumor infiltration was composed of non-exhausted, antigen-specific CD8+ T cells with proliferative capacity after rMVA-CD40L immunization. Strikingly, this antitumor effect was not entirely dependent on cross-presenting CD8α+ DC -induced CD8+ T cell expansion, as experiments with MVA encoding for T. gondii profilin (TLR11 ligand) and using Batf3-/- tumor bearers depicted. Indeed, rMVA-CD40L-induced tumor control did not depend on cytosolic DNA sensor STING. Interestingly, rMVA-CD40L induced strong NK cell activation and thereby potent Antibody Dependent Cell Cytotoxicity (ADCC) against Tumor-Associated Antigen (TAA) targeting antibodies. Hence, the combination of TAA targeting antibodies and rMVA-CD40L resulted in increased therapeutic antitumor efficacy. We describe a novel and translationally relevant therapeutic synergy between viral vaccination and CD40L costimulation. We connect CD40 ligation to cross-presenting CD8α+ DC -mediated expansion of non-exhausted CD8+ T cells in the tumor microenvironment. Taking advantage from intrinsic MVA-induced NK cell activation and further improved NK cell function by CD40 ligation, we show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combining immunotherapeutic regimes. This finding has a direct potential impact in clinical trials where TAA targeting antibodies are currently under evaluation. Citation Format: Jose Medina-Echeverz, Maria Hinterberger, Marco Testori, Marlene Geiger, Raphael Giessel, Paul Chaplin, Hubertus Hochrein, Henning Lauterbach. A novel rMVA combination immunotherapy triggers potent innate and adaptive immune responses against established tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 727.