gebhart/patrepeval huggingface dataset:
Abstract 850: Mesothelin targeted thorium-227 conjugate (MSLN-TTC): Preclinical evaluation of a new targeted alpha therapeutic in mesothelin-positive cancers (2018)

Abstract Targeted Thorium-227 Conjugates (TTCs) represent a new class of targeted alpha therapy. In this compound family a 3,2-HOPO chelator, which binds thorium-227 with high affinity, is covalently attached to an antibody. This enables the specific delivery of the alpha particle emitter thorium-227 to tumor cells. Thorium-227 has a half-life of 18.7 days and decays via emission of an alpha particle to radium-223 (half-life of 11.4 days), a calcium-mimetic used in the treatment of CRPC [Henriksen et al. J Nucl Med, 2003]. The high linear energy transfer from the alpha-emitter thorium-227 induces clustered DNA double-strand breaks. Its short penetration range of 2-10 cell diameters limits the damage to the normal tissue surrounding the tumor. We present the preclinical evaluation of a mesothelin targeted thorium-227 conjugate (MSLN-TTC), the first TTC that will enter clinical development in MSLN-positive solid tumor indications, based on the fully human anti-MSLN monoclonal antibody anetumab. MSLN is a 40 kDa membrane-anchored glycoprotein with prominent overexpression in mesothelioma, ovarian, pancreatic, lung and breast cancer. In normal tissue, MSLN is confined mainly to the mesothelial cells of pleura, peritoneum and pericardium. In vitro, the mode of action of MSLN-TTC in cellular assays was demonstrated to induce DNA double strand breaks, leading to cell cycle arrest and subsequent reduced cell viability. In vivo, MSLN-TTC demonstrated potent tumor growth inhibition administered as a single-dose in cell- and patient-derived xenograft tumor models. Similar anti-tumor activity to single dose application was observed when the MSLN-TTC was applied at fractionated doses. A trend for dependence of anti-tumor activity on MSLN expression levels in preclinical tumor models was observed. Biodistribution studies evaluated the tumor accumulation of MSLN-TTC in xenograft models. These studies served to develop a mechanistic PK/PD model, which was used to predict the efficacious dose in humans. The initiation of clinical investigation of the MSLN-TTC in mesothelin positive cancers' is planned for 2018. Citation Format: Urs B. Hagemann, Alexander Kristian, Christine Ellingsen, Katrine Wickstroem, Anne Mobergslien, Jenny Karlsson, Roger M. Bjerke, Christoph Schatz, Christoph Kneip, Joachim Schuhmacher, Liv-Ingrid Oedegaardstuen, Hartwig Hennekes, Anna Tafuri, Dominik Mumberg, Hanno Wild, Karl Ziegelbauer, Alan S. Cuthbertson. Mesothelin targeted thorium-227 conjugate (MSLN-TTC): Preclinical evaluation of a new targeted alpha therapeutic in mesothelin-positive cancers [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 850.
Effect of salbutamol on histamine induced bronchoconstriction in healthy infants. (1993)

Salbutamol significantly speeds the reversal of histamine induced bronchoconstriction in infants during the first 12 months of life. This observation provides further evidence to support the presence of functional beta adrenergic receptors in the airways of infants.
Cryo-Imaging of Hydrogels Supermolecular Structure (2016)

Gelatin, derived from collagen, has both the mechanical properties required for tissue growth, as well the functional domains required for cell binding. In its natural state, gelatin derives its properties from a network of structured, intertwined, triple helical chains, which is stabilized by hydrogen bonds at temperatures below 37 °C. The mechanical properties of such a structure can be further controlled by additional enzymatic cross-linking. But, in contrast to simple polymer systems, the response to an imposed deformation is here determined by two competing factors: the establishment of the cross-linked mesh vs. the self-assembly of the fibrils into larger and stronger hierarchical structures. Therefore, properties deduced from the response to measurements such as rheology or swelling, are a combination of these two very different factors, hence a modeling is impossible unless more precise knowledge regarding the internal structure is available. The cryogenic-temperature scanning electron microscopy (cryo-SEM) was adopted to image the fully hydrated gelatin network in which distinct chain folding was observed at low densities, while cross-linked networks were observed at higher densities. Based on these images, a theoretical model which results in good agreement between the mesh sizes of both networks and their mechanical properties was developed.
Comparative proteomics of Staphylococcus aureus and the response to reactive oxygen species (2006)

Staphylococcus aureus is a major cause of post‐operative and hospital acquired infections. Additionally, the frequency of methicillin and vancomycin resistant S. aureus (MRSA/VRSA) is increasing. Since human neutrophils kill bacteria with reactive oxygen species (ROS), the response of S. aureus oxidative stress is of interest. The IC 50 of H 2 O 2 for two strains of S. aureus , RN6390 and UAMS1, was determined to be 0.06 mM H 2 O 2 and 1.0 mM H 2 O 2 respectively, indicating UAMS1 is significantly more resistant to oxidative stress than RN6390. In order to identify proteins involved in the response to H 2 O 2 , the S. aureus proteome was examined. Both RN6390 and UAMS1 were then grown in the absence of H 2 O 2 , and in the presence of 0.02 mM H 2 O 2 and 0.2 mM H 2 O 2 respectively. Cells were harvested during late exponential phase, lysed, and the supernatant electrophoresed. Proteins were analyzed by LC/MS/MS, generating a protein profile of the two strains when placed under oxidative stress. The profile shows 157 unique UAMS1 proteins, of which there are 78 putative and 79 known proteins. There are 131 unique RN6390 proteins, of which there are 17 putative and 114 known proteins. The large IC 50 variance could be related to the virulence of each strain. Understanding the differential protein expression observed during oxidative stress between these S. aureus aureus strains could provide insight into proteins involved in detoxifying ROS and virulence in these clinically important bacteria.
Mechanical Properties of Si 3 N 4 ‐SiC Three‐Layer Composite Materials (1998)

The effects of microstructure and residual stress on the mechanical properties of Si 3 N 4 ‐based three‐layer composite materials were investigated. The microstructure of each layer was controlled by the addition of two differently sized silicon carbides: fine SiC nanoparticles (∼200 nm) or relatively large SiC platelets (∼20 µm). When the SiC nanoparticles were added, the average grain size of Si 3 N 4 was reduced because of the inhibition of grain growth by the particles. On the other hand, when the SiC platelets were added, the microstructure of Si 3 N 4 was not much changed because of the large size of the platelets. Three‐layer composites were fabricated by placing the Si 3 N 4 /SiC‐nanoparticle layers on the surface of the Si 3 N 4 /SiC‐platelet layer. The residual stress was controlled by varying the amount of SiC added. The mechanical properties of three‐layer composites with various combinations of microstructure and residual stress level were investigated.
On Quantifying the Accuracy of Maximum Likelihood Estimation of Participant Reliability in Social Sensing (2011)

This paper presents a condence interval quantication of maximum likelihood estimation of participant reliability in social sensing applications. The work is motivated by the emergence of social sensing as a data collection paradigm, where humans perform the data collection tasks. A key challenge in social sensing applications lies in the uncertain nature of human measurements. Unlike well-calibrated and well-tested infrastructure sensors, humans are less reliable, and the likelihood that participants’ measurements are correct is often unknown a priori. Hence, it is hard to estimate the accuracy of conclusions made based on social sensing data. In previous work, we developed a maximum likelihood estimator of reliability of both participants and facts concluded from the data. This paper presents an analytically-founded bound that quanties the accuracy of such maximum likelihood estimation in social sensing. A condence interval is derived by leveraging the asymptotic normality of maximum likelihood estimation and computing the approximation of Cramer-Rao bound (CRB) for the estimation parameters. The proposed quantication approach is empirically validated and shown to accurately bound the actual estimation error given sucient number of participants under dierent sensing topologies.
Supplementary Figure 2 from Cisplatin Selects for Multidrug-Resistant CD133<sup>+</sup> Cells in Lung Adenocarcinoma by Activating Notch Signaling (2023)

&lt;p&gt;PDF file - 287K, Cisplatin-induced enrichment of CD133+ cells&lt;/p&gt;
An Analysis Of Three-Phase Rectifiers With Constant Voltage Loads (2010)

In this paper, a numerical analysis of three-phase voltage loaded rectifiers is presented. The simulation is performed on the equation system level, for normalized circuit model. Possible combinations of diode states are analyzed, and it is shown that out of 2^6 = 64 combinations only 13 might occur. For all of the combinations, circuit equations and boundary inequalities are derived. The circuit order is shown to be be zero, one, or two, depending on the diode state combination. Number of boundary inequalities to be monitored is shown to vary from three to six, depending on the diode state combination. Phenomenon of instantaneous combination transitions is analyzed. Modes of the circuit operation are defined. Dependence of various circuit parameters on normalized output voltage is presented. Obtained diagrams may serve as a quick reference guide for the rectifier design, and presented analysis may be of interest in education.
Increase in expression of P2X1 receptors in the atria of patients suffering from dilated cardiomyopathy (1999)

P2X1 receptors are ATP-sensitive ligand-gated cation-selective channels abundant in smooth muscle tissues such as bladder and vas deferens. They have also been detected in the central and peripheral nervous system and in heart tissue. We have earlier reported distinct changes in the expression of the PX1 subtype of P2X receptors in hearts of patients suffering from dilated cardiomyopathy (DCM). The study was, however, based on Western blots from only five DCM samples and three control hearts. Moreover, the antibody was directed against a peptide derived from the sequence of rat P2X1. In the present project we have examined larger groups of both DCM and control hearts (n = 14 and 11, respectively). Furthermore, the antibody used in this paper differs significantly from the one used in our previous report. The present antibody was raised against an 18-residue peptide sequence (Lys 68-84 Val) derived from the human P2X1 sequence. Most of the label in the Western blots was concentrated over a triplet of bands migrating with an apparent Mr of about 45,000. Quantitative densitometry indicated that this band was more strongly expressed (by approximately 80%) in DCM hearts compared with the controls.
Correlation method of circuit-performance and technology fluctuations for improved design reliability (2001)

We propose a method of correlating circuit performance with technology fluctuations during the circuit-design phase.The method employs test circuits sensitive for technology fluctuations and a circuit simulation model which enables to interpret the correlation.We validate our proposal with a cascode-current-source test circuit and the driftdiffusion MOSFET model HiSIM.The chosen test circuit allows to separate intra-chip and inter-chip technology fluctuations and to correlate these fluctuations with circuit-performance fluctuations.One important result is that intra-chip fluctuations increase faster than inter-chip fluctuations with decreasing gate length.Quantitative modeling with HiSIM reveals random fluctuation of the effective gate length as the most likely origin for these findings.
Data from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol homeostasis. Importantly, lower CYP27A1 transcript levels were associated with shorter disease-free survival and higher tumor grade. Loss of CYP27A1 in prostate cancer was confirmed at the protein level by immunostaining for CYP27A1 in annotated tissue microarrays. Restoration of CYP27A1 expression in cells where its gene was silenced attenuated their growth &lt;i&gt;in vitro&lt;/i&gt; and in tumor xenografts. Studies performed &lt;i&gt;in vitro&lt;/i&gt; revealed that treatment of prostate cancer cells with 27-hydroxycholesterol (27HC), an enzymatic product of CYP27A1, reduced cellular cholesterol content in prostate cancer cell lines by inhibiting the activation of sterol regulatory-element binding protein 2 and downregulating low-density lipoprotein receptor expression. Our findings suggest that CYP27A1 is a critical cellular cholesterol sensor in prostate cells and that dysregulation of the CYP27A1/27HC axis contributes significantly to prostate cancer pathogenesis. &lt;i&gt;Cancer Res; 77(7); 1662–73. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Identification and Optimization of Anthranilic Sulfonamides as Novel, Selective Cholecystokinin-2 Receptor Antagonists (2006)

A high throughput screening approach to the identification of selective cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4-ylsulfonyl)amino]-5-chlorobenzoyl]-piperidine (1; CCK-2R, pK(I) = 6.4). Preliminary exploration of the structure-activity relationships around the anthranilic ring and the amide and sulfonamide moieties led to a nearly 50-fold improvement of receptor affinity and showed a greater than 1000-fold selectivity over the related cholecystokinin-1 receptor. Pharmacokinetic evaluation led to the identification of 4-[4-iodo-2-[(5-quinoxalinylsulfonyl)amino]benzoyl]-morpholine, 26d, a compound that demonstrates promising pharmacokinetic properties in the rat and dog with respect to plasma clearance and oral bioavailability and is a potent inhibitor in vivo of pentagastrin-stimulated acid secretion in the rat when dosed orally.
Seismic Facies Interpretation in a Turbiditic Environment from Pre-Stack Data – A Case Study (2004)

D004 SEISMIC FACIES INTERPRETATION IN A TURBIDITIC ENVIRONMENT FROM PRE-STACK DATA: A CASE STUDY Summary 1 Seismic facies analysis aims at interpreting a set of features measured locally in reservoirs in terms of qualitative properties. This paper presents a real-case study from a deep-offshore field located in Brazil. The aim of this work is to interpret pre-stack inversion results (P and S-Impedance cubes) obtained by joint pre-stack stratigraphic inversion in terms of seismic facies. This study tackles some issues such as well-to-seismic data integration upscaling of lithofacies and facies definition and identification in a real world. Introduction In the recent
Tailored Photonic Crystals for Advanced Semiconductor Lasers (2020)

Broad-area manipulations of photons based on tailored photonic crystals including double-lattice structures are discussed. Revolutions in semiconductor lasers may occur, which will contribute for the forthcoming Society 5.0.
Non-Isocyanate Polyurethane Soft Nanoparticles Obtained by Surfactant-Assisted Interfacial Polymerization (2017)

Polyurethanes (PUs) are considered ideal candidates for drug delivery applications due to their easy synthesis, excellent mechanical properties, and biodegradability. Unfortunately, methods for preparing well-defined PU nanoparticles required miniemulsion polymerization techniques with a nontrivial control of the polymerization conditions due to the inherent incompatibility of isocyanate-containing monomers and water. In this work, we report the preparation of soft PU nanoparticles in a one-pot process using interfacial polymerization that employs a non-isocyanate polymerization route that minimizes side reactions with water. Activated pentafluorophenyl dicarbonates were polymerized with diamines and/or triamines by interfacial polymerization in the presence of an anionic emulsifier, which afforded non-isocyanate polyurethane (NIPU) nanoparticles with sizes in the range of 200-300 nm. Notably, 5 wt % of emulsifier was required in combination with a trifunctional amine to achieve stable PU dispersions and avoid particle aggregation. The versatility of this polymerization process allows for incorporation of functional groups into the PU nanoparticles, such as carboxylic acids, which can encapsulate the chemotherapeutic doxorubicin through ionic interactions. Altogether, this waterborne synthetic method for functionalized NIPU soft nanoparticles holds great promise for the preparation of drug delivery nanocarriers.
Keeping Secrets on Low-Cost Chips (2013)

In the mass markets in which chips are integrated into everyday objects, the cost pressures are great, but so is the need for security. To help resolve the conflict between cost and security, a new strategy embeds cryptographic algorithms into a cryptographic protocol such that they only need to be protected against single-execution side-channel attacks. To do this, the strategy introduces a key derivation function that's particularly easy to implement and protect.
Population pharmacokinetics of low dose suramin as a chemosensitizer in pet dogs with naturally occurring tumors (2004)

2003 Suramin is an inhibitor of multiple growth factors including fibroblast growth factors. Our preclinical in vitro and in vivo studies showed that suramin reversed FGF-induced chemoresistance in a narrow therapeutic range from ∼ 10-50 μM, with antagonism at higher concentrations. Suramin is currently under investigation in a Phase II trial as a chemosensitizer in human non-small cell lung cancer patients treated with standard chemotherapy (paclitaxel plus carboplatin). A separate phase I/II trial evaluates the effectiveness of low dose suramin in pet dogs with naturally occurring tumors. The present study was to determine the pharmacokinetics of suramin in dogs, in order to identify the target suramin dose, in combination with chemotherapy. Eighteen dogs with late stage carcinoma, hemangiopericytoma, hemangiosarcoma or lymphoma were treated with suramin in combination with doxorubicin, receiving a total of 53 courses. Suramin was given at a fixed dose of 6.75 mg/kg as a 20-min infusion, and doxorubicin was given 3 hr later as 20-30 min infusion at a dose of 30 mg/m2 (or 1 mg/kg for body weight below 15 kg). The suramin pharmacokinetic data were analyzed using a nonlinear mixed-effect model (NONMEM) with a one-compartment model. The physiological parameters evaluated were age, body weight, body surface area (BSA), and gender. PBPK analysis of data obtained from 13 patients who received more than one treatment showed significant correlations between suramin clearance (CL) and BSA, CL and body weight, and volume of distribution (V) and BSA. Incorporation of the remaining covariates into the model did not significantly improve the model performance. These results led to a BSA-based suramin dose calculation method for individual patients, thereby eliminating the need of real-time pharmacokinetic monitoring for the use of low dose suramin as a chemosensitizer. Supported by R01CA 91457 and R01CA78577, NCI, NIH.
Triple echo steady‐state (TESS) relaxometry (2013)

TESS offers rapid T1 and T2 quantification within one single scan, and in particular B1 -insensitive T2 estimation. As a result, the new proposed method is of high interest for fast and reliable high-resolution T2 mapping, especially of the musculoskeletal system at high to ultra-high fields.
Rapidly Growing Vaginal Leiomyoma: Case Report (2003)

A rare case of rapidly growing vaginal leiomyoma initially mimicked a prolapsed uterus. After careful examination, we confirmed the diagnosis and removed the leiomyoma via simple excision. The clinical presentation, ultrasound findings, cystoscopic, and surgical findings are presented. The characteristics, differential diagnosis, association with pregnancy, presurgical evaluations, including sonography, intravenous pyelography and magnetic resonance imaging of vaginal leiomyoma, are discussed.
Global distributed file append using log-structured file system (2023)

Techniques are provided for globally appending data from a group of distributed processes to a shared file using a log-structured file system. Data generated by a plurality of processes in a parallel computing system are appended to a shared file by storing the data to the shared file using a log-structured file system (such as a Parallel Log-Structured File System (PLFS)); and generating an index entry for the data, the index entry comprising a logical offset entry and a timestamp entry indicating a time of the storage, wherein the logical offset entry is resolved at read time. The logical offset entry can be populated with an append placeholder that is resolved when the shared file is read. At read time, a plurality of the index entries associated with the shared file can be sorted using the timestamp entry to deliver the requested shared file to a requesting application.
Figure S3 from Tumor-Specific Inhibition of <i>In Situ</i> Vaccination by Distant Untreated Tumor Sites (2023)

&lt;p&gt;The presence of an untreated secondary tumor influences the effect of RT on the ratio of tumor infiltrating CD8+:FoxP3+ cells at a radiated tumor site.&lt;/p&gt;
Cover Picture: Eur. J. Immunol. 9/09 (2009)

Abstract This cover is specifically designed to celebrate the 2nd European Congress of Immunology ( www.eci‐berlin2009.com ), to be held September 13–16, 2009 in Berlin. The cover consists of a collage of images from Iwanami et al. (pp 2606–2616) with Berlin's historic Bradenburg Gate, Brandenburger Tor, in the forefront (image of the Brandenburg Gate r ImageState'. Iwanami et al.'s elegant study shows that, in addition, to defective thymus development, teleosts with mutations in KIAA1440, TRRAP, and SKIV2L2 also exhibit defective development of multiple organs, thus identifying previously unknown roles of these genes in organ development.