gebhart/patrepeval huggingface dataset:
Abstract 1975: Discovery of a potent and selective Jak2 inhibitor that suppresses GM-CSF-induced STAT5 phosphorylation and Erythropoietin-induced reticulocytosis in vivo (2011)

Abstract Essential thrombocythemia (ET), polythemia vera (PV) and myelofibrosis (MF) are myeloproliferative disorders (MPDs) characterized by a chronic excessive production of cells from one or more myeloid lineages and/or bone marrow fibrosis, and have the potential to progress to AML. Recently, gain-of-function mutations in intracellular tyrosine kinase Janus kinase 2 (Jak2) were identified to be associated with MPDs. Jak2 is a member of the Jak family of kinases including Jak1, Jak3, and Tyk2 and is the most proximal signaling component for a number of cytokine receptors. The most common Jak2 mutation identified in MPDs is a substitution of valine to phenylalanine at codon 617 (V617F) located in the pseudokinase domain, which results in the loss of its repressive function, and subsequently leads to the constitutive activation of Jak2 and downstream signaling pathways (STAT, MAP kinase, and PI3 kinase) which affect the survival, differentiation and proliferation of hematopoietic progenitors. Highly selective Jak2 inhibitors may provide a better therapeutic window in chronic dosing settings (ET and PV patients) than non-selective Jak inhibitors. Here we report the discovery of a potent and highly selective Jak2 inhibitor, AMG-Jak2-01. In enzyme assays, AMG-Jak2-01 was potent (3 nM) and selective over other Jak family kinases (&amp;gt; 2000-fold over Jak1, 10-fold over Jak3 and &amp;gt; 400-fold over Tyk2). In isogenic BaF3 cell lines expressing constitutively active Jak kinases (Tel-Jak fusion), AMG-Jak2-01 showed over 40-fold Jak2 selectivity against Jak1 or Tyk2 and 10-fold selectivity against Jak3 based on the inhibition of STAT5 phosphorylation (pSTAT5 – detected with AlphaScreen®). In cytokine-stimulated primary PBMC or whole blood assays, AMG-Jak2-01 demonstrated more than 25-fold Jak2 selectivity over Jak1and Jak3 based on inhibition of pSTAT5 (detected by flow cytometry). In vivo, oral administration of AMG-Jak2-01 at 100 mg/kg for 1 hr inhibited GM-CSF-induced pSTAT5 by approximately 70% (p&amp;lt;0.01) in a mouse peripheral blood pharmacodynamic assay. Finally, two doses of AMG-Jak2-01(100 mg/kg) given 4 hrs apart were able to suppress Epo-induced reticulocytosis in the mouse by 70% (p&amp;lt;0.02). In summary, we have discovered a potent Jak2 inhibitor, AMG-Jak2-01, which is selective over other Jak family members in both enzyme and cell-based assays and demonstrates inhibitory activity in GM-CSF-induced STAT5 phosphorylation and erythropoietin-induced reticulocytosis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1975. doi:10.1158/1538-7445.AM2011-1975
Performance evaluation of multiversion with the Oracle synchronization (1986)

In this paper we present a new analytical model for performance measurements of timestamp driven databases. The model is based on two-dimensional Poisson processes where one coordinate represents the real arrival time and the other the timestamp of an arriving messages. The notion of preemption is defined which serves as a model for synchronization. Preemption naturally implies such performance measures as response time and amount of abortion in the system. The concept of oracle is introduced which allows evaluation of a lower bound on the synchronization cost. Preemption and the oracle are then used to evaluate performance of the Multiversion synchronization. We present the distribution and the expectation of the synchronization cost. The analysis is then applied to a database with exponential communication delays (a) and the intensity of transaction l. It is shown that for Multiversion, this cost depends linearly on l/a and logarithmically on l.
High‐efficient characterization of complex protein drugs by imaged capillary isoelectric focusing with high‐resolution ampholytes (2022)

Abstract A carrier ampholyte is a molecule containing both acid and base functionality that is critical for imaged capillary isoelectric focusing. The quality of an imaged capillary isoelectric focusing separation for protein charge variants’ characterization is highly dependent on attributes of the carrier ampholytes used including baseline signal, linearity of the pH gradient, pI discrimination, and consistency between manufactured lots. AESlytes are a high‐resolution carrier ampholyte series that have been developed for the high‐resolution and selective characterization of diverse and complex protein drugs including diverse fusion proteins, antibody‐drug‐conjugate, bi‐specific antibodies, and viral proteins. While routine commercial ampholytes usually cannot solve such challenges, AESlytes demonstrate a reduction in baseline noise and distinguishably increased consistency between lots as compared to other commercial ampholytes. Here we apply AESlytes for the imaged capillary isoelectric focusing separation of several commercial fusion proteins and biosimilars with excellent repeatability. In addition, AESlytes with narrow‐range pH were employed directly coupled to a mass spectrometer for optimizing the separation resolutions allowing more reliable and accurate protein charge variant identification. Our study demonstrates that innovative high‐resolution carrier ampholytes as critical reagents play an essential role in high‐performance imaged capillary isoelectric focussing and tandem mass spectrometry analysis the routinely commercial ampholytes cannot achieve, especially for extremely complex protein drugs.
17O NMR spectroscopy: Proton–oxygen coupling in simple alcohols at natural abundance (1992)

Abstract 17 O NMR data are reported for 3‐pentanol ( 1 ), cyclopentanol ( 2 ), cyclohexanol ( 3 ), and cycloheptanol ( 4 ). The 17 O NMR signals for 1–4 appeared as doublets, shown to arise from proton–oxygen coupling ( 1 J OH = 76 ± 3 Hz) by proton decoupling experiments. The effect of concentration, temperature, and solvent was examined in detail for 2 . Proton—oxygen coupling was observed at low concentrations, decreased at lower temperatures, and was sensitive to solvent.
Comparison of texture evolution in Ag and Ag(Al) alloy thin films on amorphous SiO2 (2004)

The thermal stability of Ag metallization on SiO2 was improved by using Ag(Al) alloy films instead of pure Ag thin films which agglomerate at high temperature. X-ray diffraction techniques were used to study the texture evolution of Ag and Ag(Al) films. Different behaviors were observed in texture evolution of Ag and Ag(Al) films. Detailed information about the texture of Ag and Ag(Al) films was obtained by performing pole-figure analysis. Two different changes in texture are explained using a grain-growth mechanism and an agglomeration phenomenon, both of which work to reduce the total free energy of the system at high temperature. Based on the data obtained in this study, the texture evolution of Ag film, induced by agglomeration, and Ag(Al) film is discussed.
Ambient noise correlation-based imaging with moving sensors (2017)

Waves can be used to probe and image an unknown medium. Passive imaging uses ambient noise sources to illuminate the medium. This paper considers passive imaging with moving sensors. The motivation is to generate large synthetic apertures, which should result in enhanced resolution. However Doppler effects and lack of reciprocity significantly affect the imaging process. This paper discusses the consequences in terms of resolution and it shows how to design appropriate imaging functions depending on the sensor trajectory and velocity.
Effects of leminoprazole, omeprazole and sucralfate on indomethacininduced delayed healing of kissing gastric ulcers in rats (1996)

We have examined whether or not repeated treatment with indomethacin delays the healing of kissing gastric ulcers induced in rats. The effects of leminoprazole, omeprazole and sucralfate on any delay in ulcer healing caused by indomethacin were also determined in relation to myeloperoxidase activity. Kissing gastric ulcers were induced by luminal application of an acetic acid solution. Indomethacin significantly delayed ulcer healing in a dose-dependent manner. Leminoprazole and omeprazole decreased the size and depth of ulcers, the healing of which was delayed by indomethacin, while sucralfate only decreased the ulcer depth. Histological studies showed that indomethacin inhibited tissue contraction and regeneration of the ulcerated mucosa. Leminoprazole and omeprazole prevented the inhibition of these parameters. The myeloperoxidase (MPO) activity of the ulcer portion in animals treated with indomethacin was markedly higher than in the control group. Both leminoprazole and omeprazole, but not sucralfate, significantly reduced MPO activity in contrast to the control value (in the presence of indomethacin). There was a significant relationship between the ulcerated area and myeloperoxidase activity. These results suggested that: (i) leminoprazole and omeprazole prevent the indomethacin-induced delay in ulcer healing by promoting tissue contraction and regeneration of the ulcerated mucosa; (ii) sucralfate prevents the indomethacin-induced delay in ulcer healing via the promotion of the formation of granulation tissue; and (iii) MPO activity will be useful to biochemically ensure the healing state of ulcers.
The electronic document display: A 6.3‐million‐pixel AMLCD (1996)

Abstract— This paper describes 6.3‐million‐pixel active‐matrix displays in monochrome and color (1.6 million color groups) with a diagonal dimension of 33 cm (13 in.), first discussed by Martin et al. in 1993. These displays have the largest number of pixels of any AMLCDs thus far reported. The monochrome display is intended for office‐automation applications where there is a requirement for electronically controlled image reproduction with characteristics similar to those of a conventional laser print. This display achieves the resolution, luminance, and viewing angle required for these applications through a binary driving scheme.
Accommodating Thickness in Origami-Based Deployable Arrays (2013)

The purpose of this work is to create deployment systems with a large ratio of stowed-to-deployed diameter. Deployment from a compact form to a final flat state can be achieved through origami-inspired folding of panels. There are many models capable of this motion when folded in a material with negligible thickness; however, when the application requires the folding of thick, rigid panels, attention must be paid to the effect of material thickness not only on the final folded state, but also during the folding motion (i.e., the panels must not be required to flex to attain the final folded form). The objective is to develop new methods for deployment from a compact folded form to a large circular array (or other final form). This paper describes a mathematical model for modifying the pattern to accommodate material thickness in the context of the design, modeling, and testing of a deployable system inspired by an origami six-sided flasher model. The model is demonstrated in hardware as a 1/20th scale prototype of a deployable solar array for space applications. The resulting prototype has a ratio of stowed-to-deployed diameter of 9.2 (or 1.25 m deployed outer diameter to 0.136 m stowed outer diameter).
Model-Based Vehicle Pose Estimation and Tracking in Videos Using Random Forests (2013)

This paper presents a computational effective framework for tracking and pose estimation of vehicles in videos reaching comparable performance to state-of-the-art methods. We cast the problem of vehicle tracking as ranking possible poses for each frame and connecting subsequent poses by exploiting a feasible motion model over time. As a novelty, we use random forests trained on a set of existing 3D models for estimating the pose. We discretize the viewpoint space for training, where a synthetic camera is orbiting around the models. To compare projections of 3D models to real world 2D input frames, we introduce simple but discriminative principle gradient features to describe both images. A Markov Random Field ensures to pick the perfect pose over time and the vehicle to follow a feasible motion. As can be seen from our experiments performed on a variety of videos with vast variation of vehicle types, the proposed framework achieves similar results in less computational time compared to state-of-the-art methods.
Creation of Aggregation‐Defective α‐Synuclein Variants by Engineering the Sequence Connecting β‐Strand‐Forming Domains (2011)

The aggregation of α-synuclein (αS), which is implicated in the pathology of Parkinson's disease, produces fibrils in which layers of parallel, in-register β-sheet-loop-β-sheets are formed. The effects of sequence variation in the loop-forming region (referred to as the linker region) on αS aggregation have yet to be systematically studied. In the study described here, we created and characterized αS variants containing mutations in the linker regions. Our results indicate that although the physicochemical properties of the linker region, evaluated based on an intrinsic property of a single amino acid, still play a significant role in aggregation, additional factors can also determine aggregation of αS linker mutants. Our analyses suggest that these factors include a pairwise potential for parallel in-register β-sheet formation. A linker variant displaying significantly reduced self-aggregation interfered with αS aggregation by inhibiting the conversion of αS soluble species to αS insoluble fibrils. We anticipate that linker mutations could serve as a novel method of creating αS variants that are aggregation-defective and/or inhibit αS aggregation.
Genomic integration of the full‐length dystrophin coding sequence in Duchenne muscular dystrophy induced pluripotent stem cells (2017)

The plasmid vectors that express the full-length human dystrophin coding sequence in human cells was developed. Dystrophin, the protein mutated in Duchenne muscular dystrophy, is extraordinarily large, providing challenges for cloning and plasmid production in Escherichia coli. The authors expressed dystrophin from the strong, widely expressed CAG promoter, along with co-transcribed luciferase and mCherry marker genes useful for tracking plasmid expression. Introns were added at the 3' and 5' ends of the dystrophin sequence to prevent translation in E. coli, resulting in improved plasmid yield. Stability and yield were further improved by employing a lower-copy number plasmid origin of replication. The dystrophin plasmids also carried an attB site recognized by phage phiC31 integrase, enabling the plasmids to be integrated into the human genome at preferred locations by phiC31 integrase. The authors demonstrated single-copy integration of plasmid DNA into the genome and production of human dystrophin in the human 293 cell line, as well as in induced pluripotent stem cells derived from a patient with Duchenne muscular dystrophy. Plasmid-mediated dystrophin expression was also demonstrated in mouse muscle. The dystrophin expression plasmids described here will be useful in cell and gene therapy studies aimed at ameliorating Duchenne muscular dystrophy.
Abstract 5606: Detection of circulating tumor DNA in early and late stage human malignancies (2014)

Abstract The development of minimally-invasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital PCR-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We initially use targeted, exomic, or whole genome sequencing to identify sequence or structural alterations in tumor tissues of 410 patients using targeted, exomic, or whole genome sequencing. We found that at least one tumor-specific mutant molecule could be identified in &amp;lt;5 mL of plasma in &amp;gt;75% of patients with advanced ovarian, colorectal, bladder, gastroesophoageal, pancreatic, breast, melanoma, hepatocellular and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73%, 57%, 48% and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. Circulating tumor DNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% while and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor (EGFR) blockade in 24 patients who objectively responded to therapy but who subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase (MAPK) pathway. Remarkably, nearly half (45%) of the observed mutations observed were in codon 61 of either the KRAS or NRAS gene. Taken together, these data suggest that ctDNA is a broadly applicable, sensitive, specific and robust biomarker that can be used for a variety of clinical and research purposes in patients with several multiple different types of cancer. Note: This abstract was not presented at the meeting. Citation Format: Chetan Bettegowda, Mark Sausen, Rebecca Leary, Isaac Kinde, Nishant Agrawal, Bjarne Bartlett, Hao Wang, Brandon Luber, Kenneth Kinzler, Bert Vogelstein, Nickolas Papadopoulos, Luis Diaz. Detection of circulating tumor DNA in early and late stage human malignancies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5606. doi:10.1158/1538-7445.AM2014-5606
Perioperative Plasma Volume Expansion Reduces the Incidence of Gut Mucosal Hypoperfusion During Cardiac Surgery (1995)

Perioperative plasma volume expansion with colloid during cardiac surgery, guided by esophageal Doppler measurement of cardiac stroke volume, reduced the incidence of gut mucosal hypoperfusion. This group of patients also had an improved outcome when compared with controls.
Komplikationen nach sanierenden Mittelohroperationen: Ist eine prä- oder perioperative Risikostratifizierung möglich? (2019)

Während in allgemeinchirurgischen Fächern bisher zahlreiche Risikofaktoren für das Auftreten von Komplikationen bekannt sind, ist eine vergleichbare Datenlage in der Ohrchirurgie nicht verfügbar. Um bereits eine prä- bzw. perioperative Riskostratifizierung zu ermöglichen, erfolgt erstmalig eine detaillierte Analyse der Komplikationshäufigkeit sowie im klinischen Alltag diskutierter möglicher Einflussfaktoren.
Optimization of an Antibody Light Chain Framework Enhances Expression, Biophysical Properties and Pharmacokinetics (2019)

Efficacy, safety, and manufacturability of therapeutic antibodies are influenced by their biopharmaceutical and biophysical properties. These properties can be optimized by library approaches or rationale protein design. Here, we employed a protein engineering approach to modify the variable domain of the light chain (VL) framework of an oxidized macrophage migration inhibitory factor (oxMIF)-specific antibody. The amendment of the antibody sequence was based on homology to human germline VL genes. Three regions or positions were identified in the VL domain-L1-4, L66, L79-and mutated independently or in combination to match the closest germline V gene. None of the mutations altered oxMIF specificity or affinity, but some variants improved thermal stability, aggregation propensity, and resulted in up to five-fold higher expression. Importantly, the improved biopharmaceutical properties translated into a superior pharmacokinetic profile of the antibody. Thus, optimization of the V domain framework can ameliorate the biophysical qualities of a therapeutic antibody candidate, and as result its manufacturability, and also has the potential to improve pharmacokinetics.
Asymmetric Pictet-Spengler Reactions: Synthesis of 1,2,3,4-Tetrahydroisoquinoline Carboxylic Acid (Tic) Chimeras (2002)

A preparatively simple diastereoselective synthesis of the amino acid chimera (1S,3S)-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid from hexafluoroacetone-protected phenylalanine and glyoxylic acid hydrate via Pictet-Spengler reaction is described. The potential of the reaction of hexafluoroacetone-protected phenylalanine with other aldehydes was scrutinized.
Simulation of Temperature Field Induced by 8-Element Phased Array HIFU Transducer with Concave Spherical Surface (2011)

Multi‐element High Intensity Focused Ultrasound (HIFU) transducers can change their focal lengths and form multi‐foci. In this paper the Westervelt formula and Pennes bio‐heat transfer equation have been used along, with the Finite Difference Time Domain (FDTD) method, to study the temperature distribution induced by an 8‐element phased array HIFU transducer inside the human body. We evaluated the effects of the gap in the arc between two rings, the frequency of excitation function and pre‐focal length on the temperature field. For HIFU therapy, skin burns were caused by high frequency, small pre‐focal length, or a big gap between two rings. The focal region may be no longer an ellipsoid due to high frequency. In addition, the actual focal length is slightly different from the pre‐focal length.
A new regulator linking quorum sensing and iron uptake in Pseudomonas aeruginosa (2004)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.