gebhart/patrepeval huggingface dataset:
An Expedient Approach to Allenes and Polycyclic Structures Using Propargyl Radicals. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Cell-free synthesis of functional antibody fragments to provide a structural basis for antibody–antigen interaction (2018)

Growing numbers of therapeutic antibodies offer excellent treatment strategies for many diseases. Elucidation of the interaction between a potential therapeutic antibody and its target protein by structural analysis reveals the mechanism of action and offers useful information for developing rational antibody designs for improved affinity. Here, we developed a rapid, high-yield cell-free system using dialysis mode to synthesize antibody fragments for the structural analysis of antibody–antigen complexes. Optimal synthesis conditions of fragments (Fv and Fab) of the anti-EGFR antibody 059–152 were rapidly determined in a day by using a 30-μl-scale unit. The concentration of supplemented disulfide isomerase, DsbC, was critical to obtaining soluble antibody fragments. The optimal conditions were directly applicable to a 9-ml-scale reaction, with linear scalable yields of more than 1 mg/ml. Analyses of purified 059-152-Fv and Fab showed that the cell-free synthesized antibody fragments were disulfide-bridged, with antigen binding activity comparable to that of clinical antibodies. Examination of the crystal structure of cell-free synthesized 059-152-Fv in complex with the extracellular domain of human EGFR revealed that the epitope of 059-152-Fv broadly covers the EGF binding surface on domain III, including residues that formed critical hydrogen bonds with EGF (Asp355EGFR, Gln384EGFR, H409EGFR, and Lys465EGFR), so that the antibody inhibited EGFR activation. We further demonstrated the application of the cell-free system to site-specific integration of non-natural amino acids for antibody engineering, which would expand the availability of therapeutic antibodies based on structural information and rational design. This cell-free system could be an ideal antibody-fragment production platform for functional and structural analysis of potential therapeutic antibodies and for engineered antibody development.
Development of an Experimental Rig for Investigation of Higher Order Modes in Ducts (2006)

Continued progress to reduce fan noise emission from high bypass ratio engine ducts in aircraft increasingly relies on accurate description of the sound propagation in the duct. A project has been undertaken at NASA Langley Research Center to investigate the propagation of higher order modes in ducts with flow. This is a two-pronged approach, including development of analytic models (the subject of a separate paper) and installation of a laboratory-quality test rig. The purposes of the rig are to validate the analytical models and to evaluate novel duct acoustic liner concepts, both passive and active. The dimensions of the experimental rig test section scale to between 25% and 50% of the aft bypass ducts of most modern engines. The duct is of rectangular cross section so as to provide flexibility to design and fabricate test duct liner samples. The test section can accommodate flow paths that are straight through or offset from inlet to discharge, the latter design allowing investigation of the effect of curvature on sound propagation and duct liner performance. The maximum air flow rate through the duct is Mach 0.3. Sound in the duct is generated by an array of 16 high-intensity acoustic drivers. The signals to the loudspeaker array are generated by a multi-input/multi-output feedforward control system that has been developed for this project. The sound is sampled by arrays of flush-mounted microphones and a modal decomposition is performed at the frequency of sound generation. The data acquisition system consists of two arrays of flush-mounted microphones, one upstream of the test section and one downstream. The data are used to determine parameters such as the overall insertion loss of the test section treatment as well as the effect of the treatment on a modal basis such as mode scattering. The methodology used for modal decomposition is described, as is a description of the mode generation control system. Data are presented which demonstrate the performance of the controller to generate the desired mode while suppressing all other cut on modes in the duct.
Dose‐finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors (2018)

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m<sup>2</sup> and the global-recommended dose based on a US study of 105 mg/m<sup>2</sup> , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was <33% at the lower dose. Safety measures, pharmacokinetics and antitumor activity were assessed. A total of 12 patients were treated. Two patients, one in each dose group, experienced dose-limiting toxicities of febrile neutropenia, one grade 4 and the other grade 3; both patients recovered and continued the study treatment. The grade 4 treatment-emergent adverse events related to study treatment were neutropenia (6 patients [50.0%]), leukopenia (4 patients [33.3%]), and 1 instance each (8.3%) of anemia, febrile neutropenia and thrombocytopenia. Neutropenia was generally transient and reversible; 11 patients (91.7%) required granulocyte colony-stimulating factor treatment during the study. There were no discontinuations due to adverse events or deaths. The prexasertib pharmacokinetics displayed dose-independent and time-independent behavior across both dose levels, similar to the profile observed in the US-based phase 1 study. Eight patients had a best overall response of stable disease. These data are consistent with the known safety profile for prexasertib and confirm its tolerability in Japanese patients with advanced solid tumors.
Wearable Electronics: A Single Integrated 3D‐Printing Process Customizes Elastic and Sustainable Triboelectric Nanogenerators for Wearable Electronics (Adv. Funct. Mater. 46/2018) (2018)

In article number 1805108, Zhengwei You and co-workers report a simple and versatile 3D-printing strategy to efficiently fabricate a triboelectric nanogenerator (3DP-TENG) with an unique hierarchical porous structure, excellent elasticity, and superior energy output. 3DP-TENGs with diverse 3D shapes are readily tailored to act as wearable energy harvesters and self-powered sensors. The biobased, biodegradable, and biocompatiable matrix makes 3DP-TENGs eco-friendly and sustainable.
Synthèse et études structurales de nouveaux complexes polyhydroxamiques du fer(III) potentiellement utilisables en imagerie par résonance magnétique nucléaire. I: Obtention des ligands (1991)

With a view to preparing stable iron(III) complexes that can be used as contrast agents in magnetic resonance imaging, we have prepared a series of dihydroxamates that are analogs of rhodotorulic acid, a natural siderophore. These new ligands have been synthesized by condensation of 2,6-pyridine dicarboxylic acid chloride with protected N-aminopropyl-N-acetylhydroxylamine. In addition to the ligand derived from 2,6-pyridine dicarboxylic acid, four other ligands have thus been prepared, having substituents O-C 2 H 5 , O-nC 5 H 11 , O-nC 3 H 6 CN, O-nC 4 H 8 NH 2 •HCl. respectively, in the 4 position. Key words: medical imaging, contrast agents, rhodotorulic acid, synthesis of analogs.
ChemInform Abstract: Stabilized Zirconia‐Based NOx Sensor Using ZnFe2O4 Sensing Electrode. (2001)

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.
Elucidating in Vivo Structural Dynamics in Integral Membrane Protein by Hydroxyl Radical Footprinting (2009)

We describe here a novel footprinting technique to probe the in vivo structural dynamics of membrane protein. This method utilized in situ generation of hydroxyl radicals to oxidize and covalently modify biomolecules on living Escherichia coli cell surface. After enriching and purifying the membrane proteome, the modified amino acid residues of the protein were identified with tandem mass spectrometry to map the solvent-accessible surface of the protein that will form the footprint of in vivo structure of the protein. Of about 100 outer membrane proteins identified, we investigated the structure details of a typical beta-barrel structure, the porin OmpF. We found that six modified tryptic peptides of OmpF were reproducibly detected with 19 amino acids modified under the physiological condition. The modified amino acid residues were widely distributed in the external loop area, beta-strands, and periplasmic turning area, and all of them were validated as solvent-accessible according to the crystallography data. We further extended this method to study the dynamics of the voltage gating of OmpF in vivo using mimic changes of physiological circumstance either by pH or by ionic strength. Our data showed the voltage gating of porin OmpF in vivo for the first time and supported the proposed mechanism that the local electrostatic field changes in the eyelet region may alter the porin channels to switch. Thus, this novel method can be a potentially efficient method to study the structural dynamics of the membrane proteins of a living cell.
Three-dimensional passive localization of cavitation activity for quality assessment of clinical high-intensity focused ultrasound devices. (2010)

The widespread adoption of high-intensity focused ultrasound (HIFU) as a modality for non-invasive treatment of malignant tissue will rely heavily on the implementation of robust and reliable quality assessment (QA) procedures. Previous work has demonstrated the viability of using cavitation emissions as a QA tool for rapid mapping of the acoustic fields generated by HIFU transducers. The present work details the design, implementation, and experimental validation of a cylindrical array surrounding the HIFU focus for 3-D passive mapping of cavitating fields produced by clinical HIFU transducers. The configuration of array elements was first optimized for accurate mapping of cavitation activity both on-axis and off-axis by modeling the received signal from a collection of broadband sources. A novel 50-element array was subsequently manufactured from PVDF using a novel printed circuit board technique. Testing of the array has been conducted by mapping the extent and evolution of the cavitation field produced by various HIFU intensities in a tissue-mimicking material, and the results have been compared to the extent of the region over which cavitation would be expected from hydrophone-based characterizations of the HIFU field.
Modeling precision treatment of breast cancer (2013)

These results suggest that matching patients to treatments based on transcriptional subtype will improve response rates, and inclusion of additional features from other profiling data types may provide additional benefit. Further, we suggest a systems biology strategy for guiding clinical trials so that patient cohorts most likely to respond to new therapies may be more efficiently identified.
The Use of Clinically Measurable Cochlear Parameters in Cochlear Implant Surgery as Indicators for Size, Shape, and Orientation of the Scala Tympani (2021)

While there is generally enough space within the ST for CI, strong intracochlear anatomical variations could be observed highlighting the relevance of both soft surgical technique as well as a highly flexible and self-adapting cochlear implant electrode array design. Cochlear dimensions (especially at the round window) could potentially be used to indicate surgically challenging anatomies.
Orbital distortion arising from remote substituents nitration and reduction of spiro(cyclopenta-1,9'-fluorene)-2-ones. (1991)

Nitration of spiro[cyclopenta-1, 9'-fluorene]-2-one with acetyl nitrate predominantly gave the 4-nitro derivative. In the reduction of substituted spiro[cyclopenta-1, 9'-fluorene]-2-ones, the anti-alcohols were favored in all cases. Both anomalous distributions of the products can be interpreted in terms of interactions of the π orbitals of the aromatic and the carbonyl moieties. This example of stereoelectronic effects demonstrates intrinsic reciprocal distortion between sterically unbiased π frameworks of the molecule.
TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2 (2023)

The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.
Source mechanism solutions of low frequency Martian events based on body wave coda from a single seismic station (2020)

&amp;lt;p&amp;gt;On the 26th of November 2018, NASA&amp;amp;#8217;s InSight lander successfully touched down on the Martian ground in Elysium Planitia. The lander transported among other instruments a single three-component broadband seismometer to measure seismic events and subsequently determine the seismic activity level and eventually the internal structure of Mars. In this study we focus on characterizing the source mechanisms of the highest-quality marsquakes detected so far: The events with highest SNR occurred on sols 173 (S0173a, May 23rd 2019) and 235 (S0235b, July 27th 2019) with Mw &amp;gt; 3.5, showing clearly polarized P and S waves. The InSight MarsQuake Service has estimated their distances to be around 27 degrees, nearby the Cerberus Fossae Graben system. Two more events, S0183a and S0325b have less clear body wave phases and locations, but are also interpreted to be related to it.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;We have developed a grid-search based method to fit synthetic waveforms to the observed first arriving P and S wave trains. The four source parameters we invert for in this study are the three unique orientation angles of the source mechanism, strike (&amp;amp;#966;), dip (&amp;amp;#948;) and rake (&amp;amp;#955;), and the depth of the event. Synthetic seismograms are generated by computing Green&amp;amp;#8217;s functions based on the epicentral distance determined by the InSight MarsQuake Service (MQS) and radially symmetric velocity models. These Green&amp;amp;#8217;s function are then convolved with a source time function including an estimated global body wave attenuation to obtain realistic seismograms.&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;The two high-quality event recordings originating from the Cerberus Fossae (CF) fault system were analyzed. Multiple velocity models, frequency bands and window lengths around the arriving phases were used to explore the non-uniqueness in the inverse problem of the inherently ambiguous single-station data. We found that using plausible structural models based on geophysical modeling, the first 10-15 seconds of the waveforms can be fit, constraining the source mechanism and depth, but that the estimation of the uncertainty remains challenging.&amp;lt;/p&amp;gt;
Concordant Memory Design: An Integrated Statistical Design Approach for Multi-Gigabit DRAM (2005)

Concordant memory design incorporates fluctuation in device parameters statistically into signal-to-noise ratio analysis in DRAM. In this design, the effective signal voltage of all cells in a chip is calculated, and the failed bit count of the chip is estimated. The proposed design approach gives us a quantitative evaluation of the memory array and assures 1.4-V array operation of 100-nm-1-Gb DRAM. Calculated dependence of the failed bit count on the array voltage is in close agreement with measured data for the 512-Mb DRAM chip.
A multi-institution phase I trial of ruxolitinib in chronic myelomonocytic leukemia (CMML). (2015)

7021 Background: CMML is a lethal myelodysplastic/myeloproliferative neoplasm (MDS/MPN) characterized by peripheral monocytosis and bone marrow (BM) dysplasia with limited therapeutic options. Preclinical studies have identified the JAK2 inhibitors as therapeutic candidates. We conducted the first phase 1 clinical trial exploring the safety and efficacy of ruxolitinib, an FDA approved JAK1/2 inhibitor, in patients with CMML. Methods: All CMML WHO subtypes were included without regard to previous therapy. Key exclusion criteria included an ANC < 0.25x103 c/dL and a platelet count < 35x103c/dL. The use of GM-CSF analogs was prohibited. Four cohorts were enrolled using a “rolling six” study design, with doses ranging from 5mg BID to 20mg BID in 5mg dose escalations. Descriptive statistics were used to report baseline characteristics and response rates. The study was registered at clinicaltrials.gov NCT01776723 Results: Between March 2013 and January 2015, 19 patients (pts) were enrolled and treated with ruxolitinib. The Median age was 71 years and all pts had CMML-1. MPN-CMML by FAB criteria constituted 67% of pts and 47% had higher-risk disease by the Global MD Anderson Scoring System. Eleven pts (58%) received prior therapy and 8 pts (42%) received a prior hypomethylating agent. No dose limiting toxicities for ruxolitinib were identified. One subject had Grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Of 15 pts evaluable for response, 3 had hematologic improvement and one pt had a partial response per 2006 IWG criteria. Six of 9 pts with splenomegaly had a > 50% reduction in spleen size. Fourteen of 15 pts with reported B-symptoms had clinically meaningful or complete resolution on ruxolitinib. There was no change in allelic burden of somatic mutations in responders; broad spectrum cytokine profiling will be available at the time of presentation. Conclusions: The recommended phase 2 dose of ruxolitinib is 20mg BID. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease related B-symptoms. A phase 2 study is planned to further test the efficacy of ruxolitinib in CMML. Clinical trial information: NCT01776723.
Mussel-Mimetic Protein-Based Adhesive Hydrogel (2014)

Hydrogel systems based on cross-linked polymeric materials which could provide both adhesion and cohesion in wet environment have been considered as a promising formulation of tissue adhesives. Inspired by marine mussel adhesion, many researchers have tried to exploit the 3,4-dihydroxyphenylalanine (DOPA) molecule as a cross-linking mediator of synthetic polymer-based hydrogels which is known to be able to achieve cohesive hardening as well as adhesive bonding with diverse surfaces. Beside DOPA residue, composition of other amino acid residues and structure of mussel adhesive proteins (MAPs) have also been considered important elements for mussel adhesion. Herein, we represent a novel protein-based hydrogel system using DOPA-containing recombinant MAP. Gelation can be achieved using both oxdiation-induced DOPA quinone-mediated covalent and Fe3+-mediated coordinative noncovalent cross-linking. Fe3+-mediated hydrogels show deformable and self-healing viscoelastic behavior in rheological analysis, which is also well-reflected in bulk adhesion strength measurement. Quinone-mediated hydrogel has higher cohesive strength and can provide sufficient gelation time for easier handling. Collectively, our newly developed MAP hydrogel can potentially be used as tissue adhesive and sealant for future applications.
Handbook of People Research: Deriving Value by Asking Questions (2024)

This book is a practical guide to succeeding at People Research in creative, technical and business domains. Presented here is a basic framework for conducting research with people to inform design, in four parts: planning, engagement, analysis and reporting. The content is presented as a handbook that includes worksheets, tools and tips for people who plan to actually conduct People Research. It is a practical, hands-on guide that you will refer to again and again.
Treatment Patterns for Colorectal Cancer Patients at the National Cancer Center Korea in 2003 (2007)

Purpose: In Korea, colorectal cancer (CRC) is one of the most sharply-increasing m alignancies, and the National Colorectal Cancer Screening Program for persons over 50 years of age began in 2004. To determine the effectiveness of the program, comparative data regarding CRCs treated prior to 2004 must be analyzed. The present study assessed CRC status at diagnosis and treatment patterns in 2003. Methods: In 2003, 503 patients were newly diagnosed with CRC and were treated at the Center for Colorectal Cancer, National Cancer Center (NCC). Clinical data were retrospectively review ed. Results: The 503 patients included 256 colon and 247 rectal cancer patients. Of the 256 colon cancer patients, 5 (2.0% ) were diagnosed during screening colonoscopies and were successfully treated using an endoscopic mucosal resection (EM R), and 17 (6.6% ) received only palliative chemotherapy because of distant metastases. Forty patients (15.6% ) were treated with palliative surgery and chemotherapy, and 194 (75.8% ) with curative surgery with or without adjuvant chemotherapy. O f the 247 rectal cancer patients, 9 (3.6% ) were treated with an EMR, 20 (8.1%) with palliative chemotherapy with or without radiotherapy, 19 (7.7% ) with palliative surgery and chemoradiotherapy, and 199 (80.6% ) with curative surgery with or without chem oradiotherapy. Treatm ent with curative intent was possible in 199 of 256 (77.7% ) colon cancer patients and in 208 of 247 (84.2% ) rectal cancer patients. C onclusions: Only 12.1% of colon and 8.5% of rectal cancer patients were diagnosed early and treated without adjuvant therapies at the NCC in Korea in 2003.
ChemInform Abstract: Synthesis of Fused Pyridopyrrolidine Dione Derivatives Using Hetero Diels—Alder Reactions. (2002)

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.
GENETIC INFLUENCES OF BETA ADRENOCEPTOR SINGLE NUCLEOTIDE POLYMORPHISMS ON HYPERTENSIVE COMPLICATIONS (2004)

: Wednesday, June 16, 2004: POSTER SESSIONS: Poster Session 52: Genetics and Molecular Biology