gebhart/patrepeval huggingface dataset:
Synthesis and Structure–Activity Relationship of 3-Hydroxypyridine-2-thione-Based Histone Deacetylase Inhibitors (2013)

We previously identified 3-hydroxypyridine-2-thione (3HPT) as a novel zinc binding group for histone deacetylase (HDAC) inhibition. Early structure-activity relationship (SAR) studies led to various small molecules possessing selective inhibitory activity against HDAC6 or HDAC8 but devoid of HDAC1 inhibition. To delineate further the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi), we have extended the SAR studies to include the linker region and the surface recognition group to optimize the HDAC inhibition. The current efforts resulted in the identification of two lead compounds, 10d and 14e, with potent HDAC6 and HDAC8 activities that are inactive against HDAC1. These new HDACi possess anticancer activities against various cancer cell lines including Jurkat J.γ1 for which SAHA and the previously disclosed 3HPT-derived HDACi were inactive.
Disulfide bond bridged divalent antibody-toxin, (Fab-PE38fl)2, with the toxin PE38 fused to the light chain. (2008)

B3 antibody specifically binds the LewisY-related carbohydrate antigen of many carcinomas, and it is used as a model antibody in this study. In a previous study, the Fab fragment of the antibody was fused to a 38 kDa truncated form of Pseudomonas exotoxin A, PE38, to make Fab- PE38, where PE38 is fused to the Fd fragment of the Fab domain. This parent monomer molecule, Fab-PE38, had no cysteine in the hinge region, and it could not make a disulfide bond to form a disulfide bond bridged homodimer. In this study, we constructed three different kinds of divalent Fab-toxin fusion homodimers where the toxin is fused to the light chain of Fab, (Fab-PE38fl)2. In addition to the PE38 toxin fused to the light chain, these three molecules have different hinge sequences h1, h2, and h3 making Fabh1-, Fabh2-, and Fabh3-PE38fl monomers, respectively. These hinges contain only one cysteine on different positions of the hinge sequence. The disulfide bond between the hinge region of two monomers forms homodimers (Fabh1-PE38fl)2, (Fabh2-PE38fl)2, and (Fabh3- PE38fl)2. The refolding yields of these dimers were 5- 16-fold higher than a previously constructed dimer where the PE38 was fused to the Fd fragment (Fabh1-PE38)2. Our data suggest that the steric repulsion between the two PE38s in (Fabh1-PE38)2 during disulfide bridge formation is relieved by fusing it at the end of the light chain. The best cytotoxicity value of these dimers showed about 2.5-fold higher on an MCF7 cell line than that of the monovalent reference molecule in ng/ml scale, which is 15-fold higher in pM scale.
PET camera qualification criteria for brain amyloid imaging: Gray/white contrast of Hoffman phantom images (2014)

2059 Objectives Although PET imaging of beta-amyloid with 11C-PiB and other tracers may be useful for early and/or differential diagnosis of Alzheimer’s disease, detection of mild gray-matter(GM) uptake is challenging due to physiological uptake by the white-matter(WM). While spatial resolution is important, other factors such as scatter and attenuation may also affect the GM/WM contrast. We have devised criteria of qualifying PET cameras to be used in multicenter studies based on the phantom-measured GM/WM contrast. Methods In the imaging site qualification process of Japanese Alzheimer9s Disease Neuroimaging Initiative (J-ADNI), PET images of Hoffman 3D phantom were acquired with each PET camera in 23 sites having a total of 13 different models, and reconstruction parameters were determined to meet the criteria of 8mm FWHM or better resolution, which was estimated by comparison with the digital Hoffman phantom filtered with various Gaussian. Meanwhile, GM/WM contrast was calculated as contrast recovery using formula, (GM/WM-1)/(4/1-1), on the phantom images of each camera as well as on the digital phantom filtered with various Gaussians using ROIs defined on the digital phantom. We also examined the quality of PiB PET images on all subjects in J-ADNI study reviewed in the blind reading. Results In J-ADNI, 168 PiB PET scans were performed, all with sufficient quality for reading. The digital phantom showed GM/WM contrast of 65 % when filtered with 8mm FWHM Gaussian. The measured GM/WM contrast ranged from 46% to 75% (median= 61%) for the J-ADNI Hoffman phantom data acquired with the 23 PET cameras, of which 10 cameras showed higher than 65% and 19 showed higher than 55%. Conclusions Measurement of GM/WM contrast in addition to spatial resolution in the Hoffman 3D phantom images is necessary for qualification of PET cameras in a multicenter amyloid imaging study. Based on J-ADNI data in 23 sites using 13 camera models, we propose 55% or higher GM/WM contrast as practical qualification criteria, which is met by most of the currently used PET cameras. Research Support J-ADNI research groups.
The Ecstasy and Agony of Assay Interference Compounds (2017)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTThe Ecstasy and Agony of Assay Interference CompoundsCourtney Aldrich, Carolyn Bertozzi, Gunda I. Georg, Laura Kiessling, Craig Lindsley, Dennis Liotta, Kenneth M. Merz, Jr., Alanna Schepartz, and Shaomeng WangView Author Information ACS Infectious Diseases ACS Central Science Journal of Medicinal Chemistry ACS Chemical Biology ACS Chemical Neuroscience ACS Medicinal Chemistry Letters Journal of Chemical Information and Modeling Biochemistry Journal of Medicinal ChemistryCite this: ACS Chem. Neurosci. 2017, 8, 3, 420–423Publication Date (Web):February 28, 2017Publication History Published online28 February 2017Published inissue 15 March 2017https://pubs.acs.org/doi/10.1021/acschemneuro.7b00064https://doi.org/10.1021/acschemneuro.7b00064editorialACS PublicationsCopyright © 2017 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2121Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (376 KB) Get e-AlertscloseSUBJECTS:Assays,Drug discovery,Inhibition,Molecules,Screening assays Get e-Alerts
Biological drivers of clinical phenotype in myelofibrosis (2022)

Myelofibrosis (MF) is a myeloproliferative disorder that exhibits considerable biological and clinical heterogeneity. At the two ends of the disease spectrum are the myelodepletive or cytopenic phenotype and the myeloproliferative phenotype. The cytopenic phenotype has a high prevalence in primary MF (PMF) and is characterized by low blood counts. The myeloproliferative phenotype is typically associated with secondary MF (SMF), mild anemia, minimal need for transfusion support, and normal to mild thrombocytopenia. Differences in somatic driver mutations and allelic burden, as well as the acquisition of non-driver mutations further influences these phenotypic differences, prognosis, and response to therapies such as JAK2 inhibitors. The outcome of patients with the cytopenic phenotype are comparatively worse and frequently pose a challenge to treat given the inherent exacerbation of cytopenias. Recent data indicate that an innate immune deregulated state that hinges on the myddosome-IRAK-NFκB axis favors the cytopenic myelofibrosis phenotype and offers opportunity for novel treatment approaches. We will review the biological and clinical features of the MF disease spectrum and associated treatment considerations.
<title>Digital Holograms: A Guide To Reducing Quantization And Phase Encoding Errors</title> (1983)

The computation of binary Fourier transform holograms can be viewed as three sequential steps: 1) quantization of the object spectrum, 2) sampling of the object spectrum, and 3) binarization of the quantized, sampled spectrum to form the plottable hologram. The errors from each step in the computation are cumulative, and depend on the particular hologram encoding method used, as well as the parameter values associated with the process. A number of different methods for hologram synthesis are compared experimentally in terms of these errors. The results are related to an earlier analysis of images reconstructed from digital holograms. A procedure for optimally quantizing the object spectrum is also described.
Production of tyrosine through phenylalanine hydroxylation bypasses the intrinsic feedback inhibition in Escherichia coli (2015)

Tyrosine is a proteinogenic aromatic amino acid that is often used as a supplement of food and animal feed, as well as a (bio-)synthetic precursor to various pharmaceutically or industrially important molecules. Extensive metabolic engineering efforts have been made towards the efficient and cost-effective microbial production of tyrosine. Conventional strategies usually focus on eliminating intrinsic feedback inhibition and redirecting carbon flux into the shikimate pathway. In this study, we found that continuous conversion of phenylalanine into tyrosine by the action of tetrahydromonapterin (MH4)-utilizing phenylalanine 4-hydroxylase (P4H) can bypass the feedback inhibition in Escherichia coli, leading to tyrosine accumulation in the cultures. First, expression of the P4H from Xanthomonas campestris in combination with an MH4 recycling system in wild-type E. coli allowed the strain to accumulate tyrosine at 262 mg/L. On this basis, enhanced expression of the key enzymes associated with the shikimate pathway and the MH4 biosynthetic pathway resulted in the elevation of tyrosine production up to 401 mg/L in shake flasks. This work demonstrated a novel approach to tyrosine production and verified the possibility to alleviate feedback inhibition by creating a phenylalanine sink.
Metal ion concentrations in retrieved polyethylene total hip inserts and implications for artifactually high readings in tissue (1994)

1350. The PCA* (Howmedica) retrieved insert was not heat pressed but was machined.
Gene Fusion Markup Language: a prototype for exchanging gene fusion data (2012)

The Gene Fusion Markup Language (GFML) presented here could facilitate the development of a standard format for organizing, integrating and representing the significant features of gene fusion data in an inter-operable and query-able fashion that will enable biologically intuitive access to gene fusion findings and expedite functional characterization. A similar model is envisaged for other NGS data analyses.
Safety and efficacy of laparoscopic cholecystectomy using monopolar electrocautery in the porcine model. (1991)

Recent reports suggest that laparoscopic laser cholecystectomy may become the preferred therapy for symptomatic cholelithiasis. To assess the efficacy and safety of this technique, using monopolar electrocautery instead of laser for the gallbladder dissection, laparoscopic cholecystectomy was performed on 11 pigs. Under general anesthesia, a pneumoperitoneum was established, and four sheaths were placed into the abdomen for introduction of instruments. Using video laparoscopic guidance, the cystic duct and artery were isolated, clipped, and divided. Monopolar electrocautery was used to dissect the gallbladder from its fossa. Five animals were sacrificed immediately, without visible evidence of injury to the bile ducts, liver, or intestine. The remaining six pigs were allowed to recover. One animal died 10 days postoperatively due to adhesive small bowel obstruction. The remainder survived in good health until sacrifice at 1 month. Histologic examination of the gallbladder bed and liver revealed no evidence of ongoing local hepatocyte destruction or chronic cholestasis. Cholangiography demonstrated the bile ducts to be intact. Mean (+/- SEM) total serum bilirubin (TB), alkaline phosphatase (AP), and glutamic oxalacetic transaminase (SGOT) at the time of sacrifice were similar to nonoperated swine (n = 10): TB, 0.12 +/- 0.02 versus 0.11 +/- 0.01 mg/dl; AP, 175 +/- 23 versus 162 +/- 10 IU/L; SGOT, 37 +/- 4 versus 55 +/- 7 IU/L, respectively (p > 0.05). We conclude that laparoscopic cholecystectomy can be performed using monopolar electrocautery without significant acute injury to the liver, bile ducts, or surrounding viscera. Furthermore, the porcine model can be utilized by surgeons to attain competence in this technique prior to instituting clinical application in humans.
1 THz-Bandwidth Optical Comb Generation using Mach-Zehnder-Modulator-Based Flat Comb Generator with Optical Feedback Loop (2011)

We demonstrated broadband comb generation using a Mach-Zehnder-modulator-based flat comb generator with an optical feedback loop. A 1 THz-width comb signal was successfully generated by increment of the modulation depth.
A Generalized Modulation Scheme for Soft Switched Dual Active Bridge Converter With Wide Voltage and Power Ranges (2018)

Bidirectional power conversion with wide voltage and power range is important for various applications such as renewable source and energy storage integration, automotive applications etc. Dual active bridge converter is a good candidate for its ease of control and reliability. Modulating the phase shifted PWM for dual active bridge is a very important part of deign and can be used to achieve better performances such as soft switching, control of rms current etc. Out of many proposed modulation scheme, triangular modulation stands out to be highly efficient scheme, however it suffers from low power flow range and limitations on output and input voltage ratio. In this paper, a new modulation scheme is proposed which allows higher power flow range without any limitation on the voltage gain, at the same time retaining majority of loss less switching properties similar to triangular modulation scheme. Thus, improving converter power density significantly. Simulation and experimental results confirms the performance of the modulation scheme.
Distributed feedback EBS in a coaxial cable by means of periodical mechanical section modification (2006)

Microwave filtering is an essential function required for signal generation, detection and processing. Narrowband, high isolation filters are needed for many applications such as antennas and power amplifiers. Since the introduction of electronic band-gap structure (EBS), many applications of EBS have been demonstrated where a spatially periodic perturbation of the waveguide gives rise to a stop-band [1]. In this paper we report the results of the application of fibre Bragg gratings (FBG) theory [2] to coaxial cable distributed feed-back structures. We have created a narrowband transmission filter by inscribing a distributed feedback (DFB) grating in the cable with a pre-specified phase-shift within the structure. We modify the mechanical dimensions of the cross section of the cable and induce a periodic change in the effective propagation index of the mode propagating in the cable.
Stickstoff‐Übertragung von einem Diazoalkan auf ein Metallzentrum (1976)

Die Stickstoff‐Übertragung von einem Diazoalkan auf ein Metallzentrum wurde erstmals beobachtet. Aus (η‐CH 3 C 5 H 4 )Mn(CO) 2 THF erhält man mit F 3 C—CHN 2 den Komplex ( 1 ), dessen Struktur röntgenographisch bewiesen wurde. Thermisch oder katalytisch aus F 3 C—CHN 2 freigesetzter Stickstoff kann für die Reaktion nicht verantwortlich sein. magnified image
Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis (2015)

Mastocytosis (M) is a clonal myeloid-disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a synthetic purine analog cytoreductive treatment, for which efficacy is mostly reported in advanced M. Here we report, with a long-term follow-up period (>10 years) efficacy and safety in 68 adult patients with M (36 [53%] had indolent M and 32 [47%] had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1-9). The overall response rate was 72% (complete remission [R]/major/partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (major/partial R: 56%/36%) and 50% (major/partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10 of 11 mediator release and 6 of 7 mast cell infiltration-related symptoms including urticaria pigmentosa and organomegaly (P < .02). Serum tryptase levels decreased (P = .01). Median durations of response were 3.71 (0.1-8) and 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies.
Thermal design of a disk‐array system (2003)

Abstract A procedure for solving the thermal problems of a fan‐cooled disk‐array system is developed for industrial application. The procedure requires both the measurements of the temperatures of key components at various air flow rates across a single hard‐disk and the computational simulations of isothermal flows for a preliminarily designed mechanical configuration of a system by employing a commercial CFD software package. The flow rate and pressure drop of the air stream across a single‐disk are measured with an AMCA 210 flow bench. The temperatures of the components are detected by the fine‐wire thermocouples. The methodology of the development of the disk array and the like is illustrated by an example. The results show that the single‐disk experiment can provide the designer a quick guide to determine the air flow rate for desired operation temperatures of key components. The calculated flow rate and pressure drop can be used to match selected fans to the system. The prediction correlates well with the experimental values. The calculated flow patterns can be used to improve the preliminary design of the system mechanical configuration.
Microwave Induced Membrane Distillation for Enhanced Ethanol–Water Separation on a Carbon Nanotube Immobilized Membrane (2019)

This article demonstrates the enhanced organic separation via microwave-induced sweep gas membrane distillation from its aqueous mixture. Microwave heated ethanol–water mixtures were separated on polytetrafluoroethylene (PTFE) and carbon nanotube immobilized membranes (CNIM). The membrane performances in terms of ethanol vapor flux and separation factors were evaluated and compared between microwave-induced membrane distillation (MIMD) and MD using conventional heating. The combination of CNIM and microwave heating was most effective where the ethanol flux reached up to 11.3 L/m2 h and separation factor was 13.7, which were 46% and 102% higher than that by conventional MD. The mass transfer coefficient in CNIM-MIMD was also 81% higher than what was achieved by conventional MD. While the plain PTFE membrane was not as effective as CNIM, MIMD on PTFE also showed significant enhancement over conventional MD. Performance improvements in MIMD were due to nonthermal effects such as localized superheating and break down of hydrogen-bonded ethanol–water clusters. Moreover, MIMD required less energy to operate than conventional MD under similar conditions. The lower energy consumption along with higher flux and separation factor in MIMD represents a major advancement in the state of the art in solvent separation by MD.
Reliability Studies and Implementation of Remote Monitoring and Self-Diagnosis on a Smart System for Fast Transients Characterization in Power Networks (2006)

The paper presents the results of a study performed on a measurement system for voltage fast transients detection and characterization in medium voltage power networks. Such a system is thought for working in stand-alone mode for a preset number of months and far away. To this the system reliability study (performed by means of the Markov technique) have been carried out along with the implementation onto the system of a remote-monitoring & self-diagnostic procedures for assuring correct operating conditions by means of both preventive or corrective maintenance of the system. In the present paper the architecture of the self-diagnostic & remote-communication system along with the results of the system reliability study will be presented and discussed
Arsenic trioxide followed by autologous stem cell transplant for patients with relapsed APL. (2011)

6619 Background: Arsenic trioxide (ATO) can induce remission in 80-90% of patients (pts) with relapsed APL. For pts achieving a 2nd remission autologous stem cell transplant (ASCT) improves 5-year disease-free survival (DFS) to 70-80%. However, few series have assessed outcomes after ASCT following ATO reinduction. We performed a retrospective analysis of ATO followed by ASCT for pts with relapsed APL. Methods: Pts who underwent ASCT in 2nd or greater remission were identified at the University of Michigan, Stanford University, Memorial Sloan-Kettering Cancer Center, and Loyola University. Pts who were in remission following an ATO based regimen were selected for study. No pts had ATO as part of initial therapy. Results: 21 pts were identified who had received ASCT from 8/1999-5/2009. Median age at diagnosis was 31 (1-54). 4 pts had WBC > 10x109/L (0.6-129) at diagnosis and 13 had platelet counts < 40 k/mm3. All first line induction regimens contained all-trans retinoic acid. 18 (85%) received maintenance therapy following consolidation in CR1. Median duration of CR1 was 17.6 mos (3.07-108). 2 CNS and 1 skin relapse occurred; other relapses were molecular/ hematologic. Median age at transplant was 33 yrs (2-58). Reinduction regimens included single agent ATO (15 pts), ATO plus intrathecal therapy (2 pts), and ATO plus cytotoxic chemotherapy (4 pts). 20 patients achieved a complete molecular remission following a median of 2 ATO cycles (1-5). Treatment related toxicity of ATO included APL differentiation syndrome (3 pts), prolonged QTc (3 pts), grade (gr) 3 infection (2 pts), and gr 2/3 transaminitis (2 pts). Gr 3 mucositis (4 pts) was the only gr 3/4 toxicity related to ASCT. Median interval between CR2 to ASCT was 90 days (11-299). 1 pt was excluded from DFS analysis due to graft failure followed by allogeneic transplant. 5 pts (25%) relapsed with median time to relapse of 384 days (126-513). The median DFS for the entire cohort was 4 years (0.34-10.8). Conclusions: For pts with relapsed APL, ATO and ASCT are effective therapies for reinduction and consolidation of remission. The combination is well tolerated and produces durable responses. The role of maintenance strategies following ASCT should be explored to further improve outcome.
A Radical Route to α-Substituted Enones (2022)

A versatile strategy for the α-substitution of enones through the formal fusion between enones and unactivated alkenes is described. It relies on the formation and use of α-xanthyl-β-hydroxy ketones, which can be considered as synthetic equivalents of the high energy and difficult to tame alkenyl radicals. The process, which can often be accomplished one-pot, could be extended in one case to an <i>α,β</i>-unsaturated ester.