gebhart/patrepeval huggingface dataset:
Confirmation test for nonlinear excitation control system using state-space linearization (2003)

Conventional power system stabilizers (PSSs) for generators are designed by linearization under one operating point. So they might not always work effectively after a large power system change due to disturbances. We have been developing nonlinear control systems which can operate effectively under various kinds of system conditions. We designed a nonlinear optimal excitation control (NOEC) system using an exact linearization approach for a one machine-infinite bus model. Confirmation tests of the prototype controller were carried out using a real time digital simulator (RTDS) to evaluate dynamic performance of the developed control system, and effectiveness of the controller was confirmed.
Trade-offs in the realization of electrically pumped vertical external cavity surface emitting lasers (2010)

External cavity surface emitting lasers are becoming widespread due to the possibility of power scaling and high beam qualities. However, optical pumping currently limits application to high price systems. We report on the design and realisation of electrically pumped devices to reduce cost and complexity.
Electronically Tunable Chiral Ligands for Rhodium-CatalyzedConjugate Addition (2010)

The scaleable chemoenzymatic synthesis provides a practical synthetic route to chiral diene ligands. The flexibility of the synthesis allows for electronic tuning of the ligands, which show improved activity and enantioselectivity in conjugate additions.
The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer (2021)

Despite the availability of multiple human epidermal growth factor receptor 2-targeted (HER2-targeted) treatments, therapeutic resistance in HER2+ breast cancer remains a clinical challenge. Intratumor heterogeneity for HER2 and resistance-conferring mutations in the PIK3CA gene (encoding PI3K catalytic subunit α) have been investigated in response and resistance to HER2-targeting agents, while the role of divergent cellular phenotypes and tumor epithelial-stromal cell interactions is less well understood. Here, we assessed the effect of intratumor cellular genetic heterogeneity for ERBB2 (encoding HER2) copy number and PIK3CA mutation on different types of neoadjuvant HER2-targeting therapies and clinical outcome in HER2+ breast cancer. We found that the frequency of cells lacking HER2 was a better predictor of response to HER2-targeted treatment than intratumor heterogeneity. We also compared the efficacy of different therapies in the same tumor using patient-derived xenograft models of heterogeneous HER2+ breast cancer and single-cell approaches. Stromal determinants were better predictors of response than tumor epithelial cells, and we identified alveolar epithelial and fibroblastic reticular cells as well as lymphatic vessel endothelial hyaluronan receptor 1-positive (Lyve1+) macrophages as putative drivers of therapeutic resistance. Our results demonstrate that both preexisting and acquired resistance to HER2-targeting agents involve multiple mechanisms including the tumor microenvironment. Furthermore, our data suggest that intratumor heterogeneity for HER2 should be incorporated into treatment design.
Identification of ciliary neurotrophic factor receptor α as a mediator of neurotoxicity induced by α‐synuclein (2010)

Accumulating evidence suggests that extracellular alpha-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques - stable isotope labeling of amino acid in cell cultures (SILAC), biotin labeling of plasma membrane proteins followed by affinity purification, and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor, which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.
Study of the Relationship between the Acuracy in Co2 Laser Cutting and the Assist Gas. (1993)

Some investigations were carried out to elucidate the effect of oxygen gas purity on the cutting speed using a Co2 laser. However, it is still difficult to estimate the cutting quality when the purity of cutting oxygen varies. In this report, the edge quality of thick plate cutting and the allowance of the condition parameters are studied. In order to define the influence of the purity of cutting oxygen on the cutting quality in laser beam cutting, an experiment on thick plate cutting using a side gas nozzle was conducted. Furthermore, the applicability of a dual nozzle to thick plate cutting is confirmed. Consequently, the edge quality was improved and the allowance of the condition parameters at the focal point was magnified.
Supplementary Figure 1 A-C from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer (2023)

Supplementary Figure 1 A-C from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer
ChemInform Abstract: Synthesis of 3,5‐O‐Benzylidene‐2‐deoxy‐L‐riboaldose from 5,5‐Dihydroxy‐2‐phenyl‐1,3‐dioxane. (2000)

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.
Improved liquid-chromatographic determination of mexiletine, an antiarrhythmic drug, in plasma. (1984)

In this improved reversed-phase liquid-chromatographic procedure for determination of mexiletine in plasma, mexiletine and an internal standard, chlorodisopyramide, are extracted with methylene chloride from 0.5 mL of serum or plasma; the extract is then concentrated and injected onto a C18 chromatographic column. Mexiletine in the column effluent is detected by monitoring absorbance at 210 nm. It is quantified by use of mexiletine-internal standard peak-height ratios. The relation between this ratio and mexiletine concentration is linear from 0.1 to 5.0 mg/L. The lower limit of detection is about 50 micrograms/L. At a mexiletine concentration of 2.0 mg/L in serum, intrarun precision (CV) is 2.9% and inter-run precision is 5.9%; at 0.5 mg/L, these CVs are 5.7% and 9.6%, respectively. Analytical recovery of added mexiletine in serum is 68-88%. Therapeutic concentrations of some commonly administered drugs in patients' specimens did not interfere. In serum from 38 patients receiving mexiletine for cardiac arrhythmia, concentrations measured by this method correlated with therapeutic efficacy.
Abstract 2415: Evaluation of a DNA vaccine and adjuvant construct for producing anti tumor immunity targeting IGFBP2 (2010)

Abstract DNA based vaccines offer the advantage of stability, low cost, and longer duration of antigen exposure than protein based vaccines. We sought to evaluate strategies to augment the anti tumor potency. Using three immunogenic peptides from the ovarian cancer antigen, human insulin-like growth factor binding protein-2 (IGFBP2) we created a DNA epitope construct that encodes these three peptides in sequence and vaccinated mice with the epitope vaccine or an admixture of the peptides or plasmids expressing either the full length human or mouse genes. Mice received three vaccinations separated by two weeks followed fourteen days later by a lethal injection of syngeneic MMC tumor cells known to express IGFBP2. The DNA epitope vaccine produced a greater level of protection than any of the other constructs proving it to be the best formulation for inducing protective anti tumor responses. Full length human and mouse IGFBP2 DNA constructs induced a similar level of protection as the peptide based vaccine. This IGFBP2 epitope DNA vaccine was then tested in conjunction with plasmids encoding murine GM-CSF and IL-12 either alone or in combination in an identical vaccination strategy. Each genetic adjuvant either alone or in combination improved the level of protection induced by the IGFBP2 DNA epitope vaccine though no difference in tumor protection was seen between adjuvants used either alone or together. Evaluation of the inoculation site revealed a persistence of CD11c+ dendritic cells and CD3+ T cells fourteen days after final vaccination predominantly in mice who received plasmids containing the cytokines versus those who received soluble protein. These data support the use of epitope based DNA vaccines in conjunction with genetic adjuvants for the production of anti tumor efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2415.
Reidentification of Ebola Virus E718 and ME as Ebola Virus/H.sapiens-tc/COD/1976/Yambuku-Ecran (2014)

Ebola virus (EBOV) was discovered in 1976 around Yambuku, Zaire. A lack of nomenclature standards resulted in a variety of designations for each isolate, leading to confusion in the literature and databases. We sequenced the genome of isolate E718/ME/Ecran and unified the various designations under Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Ecran.
ChemInform Abstract: Synthesis and Dopaminergic Activity of trans‐6‐Methyl‐7a,8,9,10,11,11a‐hexahydro‐ 7H‐pyrrolo[3,2,1‐gh]‐4,7‐phenanthroline and trans‐1,2,3,4,4a,5,6,10b‐Octahydro‐ 4,7‐phenanthroline Derivatives. (1986)

Abstract Reaktion der trans‐Octahydrophenanthroline (I) mit Bromaceton (II) und nachfolgende basenkatalysierte Cyclisierung der Bromide (III) liefern die Pyrrolophenanthroline (IV), die zu den N‐Alkyl‐Derivaten (V) reduziert werden.
Structural features of mTORC2 that control substrate-specific activities (2022)

Abstract mTORC2 is a multi-subunit kinase complex that is central to multiple essential signaling pathways. Two core subunits, Rictor and mSin1 distinguish it from its relative, mTORC1 and support context-dependent phosphorylation of its substrates. mTORC2 structures have been determined previously, however, important questions remain, particularly regarding structural determinants of substrate specificity and context dependent activities. We used cryo-EM to obtain high resolution structures of the human mTORC2 apo-complex, as well as structures in the presence of substrates, Akt and SGK1. Specific predictions suggested by substrate-induced structural changes were tested in functional assays. First, side chain interactions between Rictor and mTOR that prevent recruitment of mTORC1 substrates and confer resistance to the mTORC1 inhibitor rapamycin were visualized for the first time in the apo-state, demonstrating the steric occlusion that prevents mTORC2 interaction with mTORC1 substrates and rapamycin. Also in the apo-state, mSin1 was seen to form extensive contacts with Rictor, including a pair of short α-helices nestled between two Rictor helical repeat clusters, followed by an extended strand, which makes multiple weak contacts with Rictor helical cluster 1. In co-complex structures, SGK1, but not Akt, markedly altered the conformation of the mSin1 N-terminal extended strand, disrupting multiple weak interactions while inducing a large rotation of mSin1/Arg-83, which comes to interact with a negative patch within Rictor. Mutation of Arg-83 to Ala selectively disrupted mTORC2 dependent phosphorylation of SGK1 but not of Akt, supporting context-dependent substrate selection. These findings provide new structural and functional insights into mTORC2 specificity and context-dependent activities.
OPLS potential functions for nucleotide bases. Relative association constants of hydrogen-bonded base pairs in chloroform (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOPLS potential functions for nucleotide bases. Relative association constants of hydrogen-bonded base pairs in chloroformJulianto Pranata, Scott G. Wierschke, and William L. JorgensenCite this: J. Am. Chem. Soc. 1991, 113, 8, 2810–2819Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://pubs.acs.org/doi/10.1021/ja00008a002https://doi.org/10.1021/ja00008a002research-articleACS PublicationsRequest reuse permissionsArticle Views2521Altmetric-Citations493LEARN 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
Correlation of gene expression signatures and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab (MK-3475). (2015)

3026 Background: Pembrolizumab, an anti–PD-1 monoclonal antibody, has shown antitumor activity in advanced gastric cancers. Hypothesis testing of 4 prespecified multigene immune expression signatures enriched for T-cell mediated interferon signaling and antigen presentation genes was used to evaluate associations with clinical outcomes in patients with gastric cancer enrolled in KEYNOTE-012, a multicohort, phase 1 study of pembrolizumab in patients with PD-L1+tumors. Methods: 33 of 39 pembrolizumab-treated advanced gastric cancer patients had RNA expression profiling data of sufficient quality. RNA was extracted from formalin-fixed, paraffin-embedded samples and analyzed using the NanoStringnCounter system. Hypothesis testing was conducted on 4 prespecified signatures (“Interferon-gamma,” “TCR-signaling,” “Expanded-immune,” and “Denovo”) that were constructed based on analyses in patients with melanoma and prior to linking any NanoString data to clinical outcome data. Results: In the patients with NanoString data, ORR was 30%. For ORR, all 4 signatures showed a P value <0.10 (Table). For PFS, all signatures achieved P< 0.05. All signatures showed a general pattern such that pts with very low signature scores did not respond. ROC analyses suggest that cutoffs with high sensitivity and a resultant high negative predictive value (NPV) can readily be achieved. The cutoff associated with the Youden Index of the ROC curve for the Interferon-gamma signature yielded a positive predictive value (PPV) of 45% with a NPV at 92%. Conclusions: Immune response signatures were associated with clinical benefit from anti–PD-1 therapy with pembrolizumab in patients with advanced gastric cancer enrolled in KEYNOTE-012. Clinical trial information: NCT01848834. Signature Nominal One-Sided Pa ORR N = 33 PFS N = 33 IFNγ (6 gene) 0.077 0.032 TCR Signaling (13 gene) 0.034 0.024 Expanded Immune (18 gene) 0.062 0.049 Denovo (33 gene) 0.068 0.037 aFrom logistic or Cox regression for ORR and PFS, respectively.
Concurrent Serotyping and Genotyping of Pneumococci by Use of PCR and Electrospray Ionization Mass Spectrometry (2012)

ABSTRACT A pneumococcal serotyping/genotyping system (PSGS) was developed based upon targeted PCR, followed by electrospray ionization mass spectrometry and amplicon base composition analysis. Eight multiplex PCRs, 32 targeting serotype-determining capsular biosynthetic loci, and 8 targeting multilocus sequence typing (MLST) loci were employed for each of 229 highly diverse Streptococcus pneumoniae isolates. The most powerful aspect of the PSGS system was the identification of capsular serotypes accounting for the majority of invasive and carried pneumococcal strains. Altogether, 45 different serotypes or serogroups were correctly predicted among the 196 resolvable isolates, with only 2 unexpected negative results. All 33 isolates that represented 23 serotypes not included in the PSGS yielded negative serotyping results. A genotyping database was constructed using the base compositions of 65- to 100-bp sections of MLST alleles compiled within http://www.mlst.net . From this database, one or more MLST sequence types (STs) that comprised a PSGS genotype were identified. The end result of more PSGS genotypes (163) than conventional STs actually tested (155) was primarily due to amplification failures of 1 to 3 targets. In many instances, the PSGS genotype could provide resolution of single- and double-locus variants. This molecular serotyping/genotyping scheme is well suited to rapid characterization of large sets of pneumococcal isolates.
SNUPI (2010)

A persistent concern of wireless sensors is the power consumption required for communication, which presents a significant adoption hurdle for practical ubiquitous computing applications. This work explores the use of the home powerline as a large distributed antenna capable of receiving signals from ultra-low-power wireless sensor nodes and thus allowing nodes to be detected at ranges that are otherwise impractical with traditional over-the-air reception. We present the design and implementation of small ultra-low-power 27 MHz sensor nodes that transmit their data by coupling over the powerline to a single receiver attached to the powerline in the home. We demonstrate the ability of our general purpose wireless sensor nodes to provide whole-home coverage while consuming less than 1 mW of power when transmitting (65 ¼W consumed in our custom CMOS transmitter). This is the lowest power transmitter to date compared to those found in traditional whole-home wireless systems.
Binding energy and specificity in the catalytic mechanism of yeast aldose reductases (1999)

Derivatives of d-xylose and d-glucose, in which the hydroxy groups at C-5, and C-5 and C-6 were replaced by fluorine, hydrogen and azide, were synthesized and used as substrates of the NAD(P)H-dependent aldehyde reduction catalysed by aldose reductases isolated from the yeasts Candida tenuis, C. intermedia and Cryptococcus flavus. Steady-state kinetic analysis showed that, in comparison with the parent aldoses, the derivatives were reduced with up to 3000-fold increased catalytic efficiencies (k(cat)/K(m)), reflecting apparent substrate binding constants (K(m)) decreased to as little as 1/250 and, for d-glucose derivatives, up to 5.5-fold increased maximum initial rates (k(cat)). The effects on K(m) mirror the relative proportion of free aldehyde that is available in aqueous solution for binding to the binary complex enzyme-NAD(P)H. The effects on k(cat) reflect non-productive binding of the pyranose ring of sugars; this occurs preferentially with the NADPH-dependent enzymes. No transition-state stabilization energy seems to be derived from hydrogen-bonding interactions between enzyme-NAD(P)H and positions C-5 and C-6 of the aldose. In contrast, unfavourable interactions with the C-6 group are used together with non-productive binding to bring about specificity (6-10 kJ/mol) in a series of d-aldoses and to prevent the reaction with poor substrates such as d-glucose. Azide introduced at C-5 or C-6 destabilizes the transition state of reduction of the corresponding hydrogen-substituted aldoses by approx. 4-9 kJ/mol. The total transition state stabilization energy derived from hydrogen bonds between hydroxy groups of the substrate and enzyme-NAD(P)H is similar for all yeast aldose reductases (yALRs), at approx. 12-17 kJ/mol. Three out of four yALRs manage on only hydrophobic enzyme-substrate interactions to achieve optimal k(cat), whereas the NAD(P)H-dependent enzyme from C. intermedia requires additional, probably hydrogen-bonding, interactions with the substrate for efficient turnover.
Abstract 5654: Affinity tuned Xmab®2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells (2020)

Abstract Mesothelin (MSLN) is a tumor-associated antigen highly expressed in ovarian tumors. Current treatment options for ovarian cancer have only modest efficacy and there remains a large unmet need for new targeted therapies. We generated targeted T cell engager bispecific antibodies that bind MSLN on tumor cells and CD3 on T cells. The humanized and affinity-optimized MSLN x CD3 bispecific antibodies are in an XmAb® 2+1 Fab2-scFv-Fc format that bind bivalently to MSLN and monovalently to CD3. The affinity of the MSLN-targeting arms was reduced to promote avid binding to MSLN expressing cancer cell lines and to minimize reactivity on normal surrogate cell lines. We correlated the expression of MSLN on cancer cell lines to 191 biopsy cores of serous and mucinous ovarian cancer tissues by IHC to identify surrogate cell lines to test for T cell-dependent cellular cytotoxicity (TDCC) activity. MSLN-transfected A549 cells were found to stain as intensely as ovarian cancer tumors expressing high amounts of MSLN. OVCAR-8 cancer cells were found to correlate with a medium MSLN level density on ovarian cancer tumors while ASPC-1 cells represented low MSLN-expressing tumors. Finally, we correlated expression of MSLN to non-cancer adjacent tissues and identified SKOV3, HT29, MCF7, and A549 (parental) cancer cells as appropriate surrogates of normal tissues. Reduction of MSLN affinity of MSLN x CD3 XmAb® 2+1 bispecific antibodies led to preferential killing of MSLN-high target cells, with up to 45-fold more potent TDCC activity on OVCAR8 and ASPC-1 cancer cells compared to the selected normal surrogate cell lines. Engineering of selective MSLN x CD3 bispecific antibodies allows for preferential killing of cancer cells, potentially minimizing on-target/off-tumor effects that may contribute to dose-limiting toxicities. Citation Format: Veronica G. Zeng, Matthew S. Faber, Matthew J. Bernett, Kendra N. Avery, John L. Zeytounian, Rumana Rashid, Umesh S. Muchhal, Gregory L. Moore, John R. Desjarlais, Michael Hedvat. Affinity tuned Xmab®2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5654.
Supplementary Methods, Figure Legend, Table 1 from Low Levels of Circulating Estrogen Sensitize PTEN-Null Endometrial Tumors to PARP Inhibition <i>In Vivo</i> (2023)

&lt;p&gt;PDF file - 84K, Supplementary Table S1. Antibodies used for immunostaining.&lt;/p&gt;