gebhart/patrepeval huggingface dataset:
Abstract PS11-09: Impact of UGT1A1 status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer (2021)

Abstract Background: Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in many epithelial tumors, including triple-negative breast cancer (TNBC). Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, via a unique hydrolyzable linker that allows SN-38 release intracellularly and in the tumor microenvironment (bystander effect). SG received accelerated approval in April 2020 for the treatment of patients with metastatic TNBC (mTNBC) who received at least 2 prior therapies for metastatic disease. The most common adverse events (AEs) observed with SG are neutropenia and gastrointestinal toxicity, also seen with irinotecan. To provide further information on SG, additional safety analyses from ASCENT, a randomized, phase 3 confirmatory study of SG versus standard-of-care chemotherapy in patients with mTNBC, will be reported. Methods: In the global, multicenter, open-label, phase 3 ASCENT study (NCT02574455), 529 patients with mTNBC refractory to or relapsing after at least 2 prior chemotherapies were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8 every 21 days) or single-agent treatment of physician’s choice (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival measured by central independent review per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, overall survival, and safety. An exploratory analysis of incidence of grade 3-5 AEs by UGT1A1 genotype was also performed. Post-hoc analysis of the time to onset and duration of key AEs will be performed, and descriptive analyses on alopecia, nausea and vomiting will also be provided. Results: Exploratory safety analyses by UGT1A1 allele status will be shown as well as time to onset and duration of neutropenia and diarrhea. Further descriptive analyses on alopecia, nausea, and vomiting will be provided along with AE management strategies. Conclusions: These analyses will provide further insights into the safety profile of SG and appropriate AE management strategies for patients with previously treated mTNBC to allow optimal therapeutic exposure. Citation Format: Hope S. Rugo, Sara M. Tolaney, Delphine Loirat, Kevin Punie, Aditya Bardia, Sara A. Hurvitz, Joyce O'Shaughnessy, Javier Cortés, Véronique Diéras, Lisa Carey, Luca Gianni, Martine J. Piccart, Sibylle Loibl, David M. Goldenberg, Quan Hong, Martin Olivo, Loretta M. Itri, Kevin Kalinsky. Impact of UGT1A1 status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-09.
Supplementary Figure S6 from Small Molecule–Mediated Activation of RAS Elicits Biphasic Modulation of Phospho-ERK Levels that Are Regulated through Negative Feedback on SOS1 (2023)

&lt;p&gt;SPRY2 is not phosphorylated on tyrosine residues in response to 1 treatment in cells co-expressing V5-SPRY2 and HA-SOS1 S1178A. 293 cells were transiently transfected with both V5-SPRY2 and HA-SOS1 S1178A and treated with 25 μM 1 over a timecourse of up to 90 minutes. Where indicated, cells were treated with FBS (20% v/v) for 15 minutes. Two biological repeats of this experiment were independently conducted.&lt;/p&gt;
Influenza Virus Subunit Vaccines: Immunogenicity and Lack of Toxicity for Rabbits of Ether- and Detergent-Disrupted Virus (1966)

Summary Three strains of influenza virus (SW, BEL, AS) were disrupted with ether or with sodium deoxycholate and inoculated into rabbits. The intact viruses were pyrogenic; the disrupted preparations were not. The disrupted viruses were immunogenic for rabbits. The ether-treated vaccines induced antihemagglutinin levels that were equal to those induced by the intact viruses. large doses of sodium deoxycholate-treated vaccines induced levels of anti-hemagglutinin comparable to those induced by the intact viruses but at low dosage the deoxycholate-treated material was less immunogenic. Sera prepared against disrupted virus did not differ significantly in avidity and neutralizing potency from sera prepared against intact virus. The antibodies induced in rabbits by the disrupted vaccines showed the same cross-reactions as those induced by the intact viruses. Vaccines produced by treatment with sodium dodecylsulfate were also nonpyrogenic, but induced lower anti-hemagglutinin titers in rabbits than sodium deoxycholate-disrupted viruses.
RNA-Seq analysis of Phanerochaete sordida YK-624 degrades neonicotinoid pesticide acetamiprid (2022)

Acetamiprid (ACE) belongs to the group of neonicotinoid pesticides, which have become the most widely utilised pesticides around the world in the last two decades. The ability of <i>Phanerochaete sordida</i> YK-624 to degrade ACE under ligninolytic conditions has been demonstrated; however, the functional genes involved in ACE degradation have not been fully elucidated. In the present study, the differentially expressed genes of <i>P. sordida</i> YK-624 under ACE-degrading conditions and in the absence of ACE were elucidated by RNA sequencing (RNA-Seq). Based on the gene ontology enrichment results, the cell wall and cell membrane were significantly affected under ACE-degrading conditions. This result suggested that intracellular degradation of ACE might be mediated by this fungus. In addition, genes in metabolic pathways were the most enriched upregulated differentially expressed genes according to the KEGG pathway analysis. Eleven differentially expressed genes characterised as cytochrome P450s were upregulated, and these genes were determined to be particularly important for ACE degradation by <i>P. sordida</i> YK-624 under ligninolytic conditions.
A Discriminative Approach for Wavelet Denoising (2008)

This paper suggests a discriminative approach for wavelet denoising where a set of mapping functions (MFs) are applied to the transform coefficients in an attempt to produce a noise free image. As opposed to the descriptive approaches, modeling image or noise priors is not required here and the MFs are learned directly from an ensemble of example images using least-squares fitting. The suggested scheme generates a novel set of MFs that are essentially different from the traditional soft/hard thresholding in the over-complete case. These MFs are demonstrated to obtain comparable performance to the state-of-the-art denoising approaches. Additionally, this framework enables a seamless customization of the shrinkage operation to a new set of restoration problems that were not addressed previously with shrinkage techniques, such as deblurring, JPEG artifact removal, and various types of additive noise that are not necessarily Gaussian white noise.
White-box testing of big data analytics with complex user-defined functions (2019)

Data-intensive scalable computing (DISC) systems such as Google's MapReduce, Apache Hadoop, and Apache Spark are being leveraged to process massive quantities of data in the cloud. Modern DISC applications pose new challenges in exhaustive, automatic testing because they consist of dataflow operators, and complex user-defined functions (UDF) are prevalent unlike SQL queries. We design a new white-box testing approach, called BigTest to reason about the internal semantics of UDFs in tandem with the equivalence classes created by each dataflow and relational operator.
Synthesis of P-enantiomeric deoxyadenosine cyclic 3, 5-phosphorothioates (1978)

Treatment of diastereoisomeric mixture of deoxyadenosine-3′- (o-chlorophenyl)-phosphoroanilidates (4) with potassium t-butoxide gave deoxyadenosine cyclic 3′,5′-phosphoroanilidates (5) which were further separated by preparative TLC into P-enantiomeric species. Their stereospecific conversion by means of NaH/CS2 produced deoxyadenosine cyclic 3′, 5′-phosphorothioates (1). On the basis of 31P NMR chemical shift data of 5 and known stereochemistry of conversion 5→1 the absolute configuration at P atom in diastereoisomeric pairs of 5 and 1 was assigned.
ChemInform Abstract: Transition Metal‐Catalyzed [5 + 2] Cycloadditions with Substituted Cyclopropanes: First Studies of Regio‐ and Stereoselectivity (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.
Wavelength-selective integrated optical MEMS filter in InP (2005)

This paper presents a low-power, electrostatically-actuated integrated optical filter on an InP MEMS platform. The micromachined filter achieves a resonant wavelength shift of 12nm (1513-1525nm) at a low operating voltage (7V). The filter consists of a half-wavelength long resonant cavity bound by two highly reflective distributed Bragg reflector (DBR) mirrors fabricated by lithography and dry-etching. The filter is integrated monolithically with a doubly-clamped suspended-beam capacitive microactuator and optical waveguides. This paper discusses the fabrication as well as experimental results, showing good agreement between the measured and simulated performance of the filter. The novelty of the device lies in its in-plane MEMS actuation scheme enabling easy integration with other waveguide-based planar integrated optical active and passive components on an InP optoelectronic chip.
Space-Terrestrial Cooperation Over Spatially Correlated Channels Relying on Imperfect Channel Estimates: Uplink Performance Analysis and Optimization (2022)

A whole suite of innovative technologies and architectures have emerged in response to the rapid growth of wireless traffic. This paper studies an integrated network design that boosts system capacity through cooperation between wireless access points (APs) and a satellite for enhancing the network's spectral efficiency. We first mathematically derive an achievable throughput expression for the uplink (UL) data transmission over spatially correlated Rician channels. Our generic achievable throughput expression is applicable for arbitrary received signal detection techniques under realistic imperfect channel estimates. A closed-form expression is then obtained for the ergodic UL data throughput when maximum ratio combining is utilized for detecting the desired signals. As for our resource allocation contributions, we formulate the max-min fairness and total transmit power optimization problems relying on the channel statistics for performing power allocation. The solution of each optimization problem is derived in form of a low-complexity iterative design, in which each data power variable is updated relying on a closed-form expression. Our integrated hybrid network concept allows users to be served that may not otherwise be accommodated due to the excessive data demands. The algorithms proposed to allow us to address the congestion issues appearing when at least one user is served at a rate below the target. The mathematical analysis is also illustrated with the aid of our numerical results that show the added benefits of considering the space links in terms of improving the ergodic data throughput. Furthermore, the proposed algorithms smoothly circumvent any potential congestion, especially in face of high rate requirements and weak channel conditions.
Comparative study of tan-tin and tin gate stacks for thermally stable pfets (2006)

Thermally stable TiN and TaN-TiN laminate metal gates for PFETs are demonstrated using a conventional CMOS process flow with SiON gate dielectric. TaN-TiN laminate gates show enhanced drives (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</sub> ), higher transconductance (G <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</sub> ), higher mobility (mu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">EFF </sub> , and reduced off current (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> ) characteristics compared to TiN gates. The optimum thickness of TaN in the laminate stack is discussed. The as-deposited work function of the TaN-TiN laminate gate stack and TiN was found to be ~ 5.0eV
Determining Diabetes Prevalence: a Rational Basis for the Use of Fasting Plasma Glucose Concentrations? (1990)

The World Health Organization and the National Diabetes Data Group each recommend a diagnostic cut-off point for diabetes of 7.8 mmol l-1 for fasting plasma glucose concentrations as part of the diagnostic criteria for epidemiological studies. However, this cut-off has been shown to be insensitive compared with a screening test based on 2-h plasma glucose levels. In thirteen Pacific populations, from four ethnic groups (Asian Indian, Melanesian, Micronesian, and Polynesian), we have examined whether a different cut-off point for fasting plasma glucose would be more accurate for obtaining an estimate of the prevalence of diabetes when compared with 2-h levels. A fasting plasma glucose diagnostic cut-off of 7.0 mmol l-1 gave an estimate of prevalence not significantly different from that based on the 2-h plasma glucose in 12 of the 13 populations (mean difference 0.27, range -1.51 to +2.44,%). On the other hand, when a cut-off of 7.8 mmol l-1 for fasting plasma glucose was used, the resulting prevalence over-estimated the 2-h glucose prevalence in all populations (mean difference 1.91, range 0.14-5.80,%). Thus for Pacific populations, a fasting plasma glucose cut-off of 7.0 mmol l-1 provides estimates of prevalence that are equivalent to those based on 2-h plasma glucose levels. In epidemiological studies designed to estimate diabetes prevalence, we recommend use of a fasting plasma glucose cut-off of 7.0 mmol l-1 in preference to a detection level of 7.8 mmol l-1, if glucose loading is not possible.(ABSTRACT TRUNCATED AT 250 WORDS)
The V2 receptor antagonist tolvaptan raises cytosolic calcium and preventsAQP2 trafficking and function: anin vitroandin vivoassessment (2017)

Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney. In MDCK, tolvaptan prevented dDAVP-induced increase in ser256-AQP2 and osmotic water permeability. A similar effect on ser256-AQP2 was found in V1aR -/- mice, thus confirming the V2R selectively. Of note, calcium calibration in MDCK showed that tolvaptan per se caused calcium mobilization from the endoplasmic reticulum resulting in a significant increase in basal intracellular calcium. This effect was only observed in cells expressing the V2R, indicating that it requires the tolvaptan-V2R interaction. Consistent with this finding, tolvaptan partially reduced the increase in ser256-AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium-inhibitable AC type VI. Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance.
Influence of Glutathione and its Derivatives on Fibrin Polymerization (2008)

A complex relationship exists between reduced, oxidized, and nitrosated glutathione (GSH, GSSG, and GSNO, respectively). Although previous studies have demonstrated S-nitrosoglutathione (GSNO) has potent antiplatelet efficacy, little work has examined the role of GSNO and related species on subsequent aspects of coagulation (e.g., fibrin polymerization). Herein, the effects of GSH, GSSG, and GSNO on the entire process of fibrin polymerization are described. Relative to normal fibrinogen, the addition of GSH, GSSG, or GSNO leads to prolonged lag times, slower rates of protofibril lateral aggregation and the formation of clots with lower final turbidities. Dose-dependent studies indicate the influence of GSH on fibrin formation is a function of both GSH and fibrinogen concentration. Studies with Aalpha251 recombinant fibrinogen (lacking alphaC regions) showed GSH had no influence on its polymerization, suggesting the glutathione species interact within the alphaC region of fibrinogen.
Optimization of collagen type I-hyaluronan hybrid bioink for 3D bioprinted liver microenvironments (2018)

Current 3D printing of tissue is restricted by the use of biomaterials that do not recapitulate the native properties of the extracellular matrix (ECM). These restrictions have thus far prevented optimization of composition and structure of the in vivo tissue microenvironment. The artificial nature of currently used biomaterials affects cellular phenotype and function of the bioprinted tissues, and results in inaccurate modeling of disease and drug metabolism significantly. Collagen type I is the major structural component in the ECM, and is widely used as a 3D hydrogel, but is less applicable for 3D bioprinting due to low viscosity and slow polymerization. We have hypothesized that a combination of hyaluronic acid with collagen I yields a bioink with the properties required for extrusion bioprinting, while supporting native cell-matrix interactions and preservation of the native microenvironment properties. To test this hypothesis, we tested the viscoelastic properties of three bioink formulations -2:1, 3:1, and 4:1 collagen type I to hyaluronic acid, and examined cellular behavior in order to determine an optimal formulation that allows for bioprinting while supporting biological activity. We then employed this formulation to bioprint 3D liver tissue constructs containing primary human hepatocytes and liver stellate cells and tested the effects of acetaminophen, a common liver toxicant. Our results have shown that the combination of methacrylated collagen type I and thiolated hyaluronic acid yield a simple, printable bioink that allows for modulation that was directly related to stromal cell elongation. Further, the bioink adequately allowed for implementation as a support hydrogel for hepatocytes which were able to remain viable over two weeks and responded to drug treatment appropriately.
The learning curve associated with the implantation of the Nanostim leadless pacemaker (2018)

Learning curves exist for Nanostim LP implantation. Procedure efficiency improved with increased operator experience, according to a decrease in the incidence of SADE, procedure duration, and repositioning attempts.
IDENTIFICATION OF GROUP-II GLYCININ GENES IN SOYBEAN AND THE MOLECULAR CHARACTERIZATION OF A GROUP-II GLYCININ NULL ALLELE (DNA, SOUTHERNS, MUTATIONS, CLONES) (1986)

Two cDNA clones that encode the group-II glycinin subunits, A(,5)A(,4)B(,3) and A(,3)B(,4), were isolated from a cDNA library constructed from polyA('+) RNA of mid-maturation stage soybean (Glycine max L., Merr) embryos. These group-II clones hybridize weakly to group-I clones at low stringency, but fail to hybridize to them at moderate or high stringency. The cDNA clones were used as probes in Southern hybridizations to leaf DNA. This showed that the genes encoding A(,5)A(,4)B(,3) (Gy(,4)) and A(,3)B(,4) (Gy(,5)) were contained on 13 kb and 9 kb EcoRI fragments, respectively. Genomic reconstruction analysis suggested there was one copy of the group-II genes per haploid genome. A genomic clone containing the complete Gy(,4) gene was isolated from a genomic library of soybean leaf DNA (cultivar 'Dare'). RNA protection experiments and DNA sequence analysis revealed that this group-II gene had the same basic intron/exon structure as the group-I genes. Northern hybridizations showed that the sizes of the different glycinin mRNAs were correlated with the sizes of the subunits they encoded. RNA for both groups of glycinin subunits were shown to appear at the same developmental stages of embryogenesis. To identify the genetic lesion responsible for the absence of the A(,5)A(,4)B(,3) subunit in the cultivar 'Raiden', a genomic library was constructed from Raiden leaf DNA and used to isolate Gy(,4). The complete sequence of this gene was determined and compared to the complete sequence of the same gene from a normal cultivar. Only three nucleotide differences were observed. While two of the differences would be expected to have no effect on the expression of the Raiden gene, one caused the elimination of the normal translation start codon. Northern hybridizations indicated that Raiden Gy(,4) RNA was either absent or present in very low amounts in polyA('+) RNA isolated from polysomes. RNA dot blot hybridizations, nuclear run-off transcription experiments and S1 nuclease protection experiments showed that Gy(,4) RNA was present in Raiden embryos. This indicated that the Gy(,4) gene in Raiden is transcribed but the Gy(,4) RNA is not translated into glycinin protein.
Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer (2020)

Although hematopoietic prostaglandin D synthase (H-PGDS) is an attractive target for treatment of a variety of diseases, including allergic diseases and Duchenne muscular dystrophy, no H-PGDS inhibitors have yet been approved for treatment of these diseases. Therefore, the development of novel agents having other mode of actions to modulate the activity of H-PGDS is required. In this study, a chimeric small molecule that degrades H-PGDS via the ubiquitin-proteasome system, PROTAC(H-PGDS)-1, was developed. PROTAC(H-PGDS)-1 is composed of two ligands, TFC-007 (that binds to H-PGDS) and pomalidomide (that binds to cereblon). PROTAC(H-PGDS)-1 showed potent activity in the degradation of H-PGDS protein via the ubiquitin-proteasome system and in the suppression of prostaglandin D2 (PGD2) production. Notably, PROTAC(H-PGDS)-1 was slightly more effective in the suppression of PGD2 production than the known inhibitor, TFC-007. Thus, the H-PGDS degrader—PROTAC(H-PGDS)-1—is expected to be useful in biological research and clinical therapies.