gebhart/patrepeval huggingface dataset:
A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore (2009)

As the need for novel antibiotic classes to combat bacterial drug resistance increases, the paucity of leads resulting from target-based antibacterial screening of pharmaceutical compound libraries is of major concern. One explanation for this lack of success is that antibacterial screening efforts have not leveraged the eukaryotic bias resulting from more extensive chemistry efforts targeting eukaryotic gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on antibacterial target space resembling these eukaryotic targets, we used whole-cell screening to identify a series of antibacterial pyridopyrimidines derived from a protein kinase inhibitor pharmacophore. In bacteria, the pyridopyrimidines target the ATP-binding site of biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid biosynthesis. These inhibitors are effective in vitro and in vivo against fastidious gram-negative pathogens including Haemophilus influenzae. Although the BC active site has architectural similarity to those of eukaryotic protein kinases, inhibitor binding to the BC ATP-binding site is distinct from the protein kinase-binding mode, such that the inhibitors are selective for bacterial BC. In summary, we have discovered a promising class of potent antibacterials with a previously undescribed mechanism of action. In consideration of the eukaryotic bias of pharmaceutical libraries, our findings also suggest that pursuit of a novel inhibitor leads for antibacterial targets with active-site structural similarity to known human targets will likely be more fruitful than the traditional focus on unique bacterial target space, particularly when structure-based and computational methodologies are applied to ensure bacterial selectivity.
Recent advances in development of amphotericin B formulations for the treatment of visceral leishmaniasis (2012)

Liposomal AmpB (AmBisome) has become a standard treatment, by intravenous infusion, for visceral leishmaniasis and the basis for new short course treatments. There have been extensive efforts to develop new AmpB formulations on the basis of polymers, lipids or physical aggregates of AmpB to replace the costly lipid-based formulations. However, no nonlipid-based AmpB delivery systems have yet reached the clinic.
Particle morphology, crystal orientation, and electrochemical reactivity of LiFePO4 synthesized by the hydrothermal method at 443 K (2007)

LiFePO4 (space group: Pnma) was synthesized by the hydrothermal method at 443 K. The pH of the precursor solution was systematically changed between 2.5 and 9.5. The particle morphology, crystal orientation, and electrochemical reactivity of the prepared LiFePO4 particles changed depending on the concentration of the Li source and pH of the precursor. The particles obtained from acidic solutions (pH ≈ 3.5) were needle-like particles. On the other hand, plate-like crystals were obtained from weak acidic solutions of 4 < pH < 6.5. At higher pH than 7.2, the particles became randomly shaped. The plate-like crystal had a large facet in the ac-plane, while the needle-like particles had a large facet in the bc-plane. The electrochemical properties of the prepared LiFePO4 were characterized in a mixed solvent of ethylene carbonate and diethyl carbonate with volume ratio of 1 : 1 containing 1.0 mol dm−3 LiClO4 at room temperature. The plate-like crystals exhibited the highest electrochemical reactivity among the prepared samples, and the discharge capacity was 163 mA h g−1 measured at a current density of 17 mA g−1.
Time Domain Modeling of Lasing Dynamics in Hyperbolic Metamaterials (2017)

We use a semi-classical approach to model interaction of light wave with media and phenomenological approach to describe spontaneous emission that feeds the lasing modes to study a hyperbolic metamaterial coated with different gain materials.
The metal gate MOS reliability with improved sputtering process for gate electrode (2003)

The impacts of the N/sub 2/ introduced reactive sputtering deposition of WN/sub x/ or TiN gate electrodes on the gate leakage current and the dielectric reliability of the metal gate MOS capacitors are investigated. The surface nitridation of the gate dielectric during the reactive sputtering deposition dramatically improves the gate dielectric characteristics, being comparable to those of the poly-Si gate. The activation energy of charge-to-breakdown (Q/sub bd/) of the metal gates is identical with that of the poly-Si gate under the gate injection stress. Under the substrate injection stress, however, the activation energy of the metal gates is lower than that of the poly-Si gate due to the enhanced electron trapping of the metal gates.
Array Comparative Genomic Hybridization Identifies Genetic Subgroups in Grade 4 Human Astrocytoma (2005)

Alterations of DNA copy number are believed to be important indicators of tumor progression in human astrocytoma. We used an array of bacterial artificial chromosomes to map relative DNA copy number in 50 primary glioblastoma multiforme tumors at approximately 1.4-Mb resolution. We identified 33 candidate sites for amplification and homozygous deletion in these tumors. We identified three major genetic subgroups within these glioblastoma multiforme tumors: tumors with chromosome 7 gain and chromosome 10 loss, tumors with only chromosome 10 loss in the absence of chromosome 7 gain, and tumors without copy number change in chromosomes 7 or 10. The significance of these genetic groups to therapeutics needs further study.
Atomically precise control of rotational dynamics in charged rare-earth complexes on a metal surface (2022)

Complexes containing rare-earth ions attract great attention for their technological applications ranging from spintronic devices to quantum information science. While charged rare-earth coordination complexes are ubiquitous in solution, they are challenging to form on materials surfaces that would allow investigations for potential solid-state applications. Here we report formation and atomically precise manipulation of rare-earth complexes on a gold surface. Although they are composed of multiple units held together by electrostatic interactions, the entire complex rotates as a single unit when electrical energy is supplied from a scanning tunneling microscope tip. Despite the hexagonal symmetry of the gold surface, a counterion at the side of the complex guides precise three-fold rotations and 100% control of their rotational directions is achieved using a negative electric field from the scanning probe tip. This work demonstrates that counterions can be used to control dynamics of rare-earth complexes on materials surfaces for quantum and nanomechanical applications.
Microprocessor architecture utilizing redundant-binary operation (1999)

In conventional microprocessors, add/subtract instructions require longer execution times than logic/shift operations, caused by carry propagation delay. Therefore, the cycle time is not fully utilized in the execution of such instructions. In this article, an ALU architecture utilizing the redundant binary operations is proposed. Such an architecture admits redundant binary code outputs, and all ALU operations including add/subtract are executed in a short time regardless of the bit width, so that it becomes possible to shorten the stage time of the microprocessor. Further, the specific features of a designed microprocessor using this ALU architecture are investigated. In this microprocessor, fetch and decode instructions and register write-back are carried out as two parallel instructions in two-way superscalars. On the other hand, execution of instructions is carried out one by one in double-clock-speed pipelines. Using this architecture, it becomes possible to execute two simultaneously decoded instructions even if they are dependent on each other. ©1999 Scripta Technica, Syst Comp Jpn, 30(13): 106–115, 1999
Data from Applications of ImmunoPET: Using <sup>124</sup>I-Anti-PSCA A11 Minibody for Imaging Disease Progression and Response to Therapy in Mouse Xenograft Models of Prostate Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to &lt;sup&gt;18&lt;/sup&gt;F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Osteoblastic, PSCA-expressing, LAPC-9 intratibial xenografts were imaged with serial &lt;sup&gt;124&lt;/sup&gt;I-anti-PSCA A11 minibody immunoPET and &lt;sup&gt;18&lt;/sup&gt;F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and posttreatment. &lt;i&gt;Ex vivo&lt;/i&gt; flow cytometry measured the change in PSCA expression in response to androgen deprivation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A11 minibody demonstrated improved sensitivity and specificity over &lt;sup&gt;18&lt;/sup&gt;F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect &lt;i&gt;in vivo&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; A11 minibody immunoPET has the potential to improve the sensitivity and specificity of clinical prostate cancer metastasis detection over bone scans, which are the current clinical standard-of-care. A11 minibody immunoPET additionally has the potential to image the activity of the androgen signaling axis &lt;i&gt;in vivo&lt;/i&gt; which may help evaluate the clinical response to androgen deprivation and the development of castration resistance. &lt;i&gt;Clin Cancer Res; 20(24); 6367–78. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Squeaking Hips (2008)

Walter, William L. MBBS, FRACS, PhD; Waters, Tim S. FRCS(Tr&Orth); Gillies, Mark PhD; Donohoo, Shane BEng; Kurtz, Steven M. PhD; Ranawat, Amar S. MD; Hozack, William J. MD; Tuke, Michael A. HNC, ME Author Information
Supplementary Tables S1-S4 from Autoantibody Landscape in Patients with Advanced Prostate Cancer (2023)

&lt;p&gt;Supplementary Tables S1-S4&lt;/p&gt;
The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes (2019)

In cancer biology, tumor-promoting inflammation and an inflammatory microenvironment play a vital role in disease pathogenesis. In the past decade, aberrant innate immune activation and proinflammatory signaling within the malignant clone and the bone marrow (BM) microenvironment were identified as key pathogenic drivers of myelodysplastic syndromes (MDS). In particular, S100A9-mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation directs an inflammatory, lytic form of cell death termed pyroptosis that underlies many of the hallmark features of the disease. This circuit and accompanying release of other danger-associated molecular patterns expands BM myeloid-derived suppressor cells, creating a feed-forward process propagating inflammasome activation. Furthermore, somatic gene mutations of varied functional classes license the NLRP3 inflammasome to generate a common phenotype with excess reactive oxygen species generation, Wnt/β-catenin-induced proliferation, cation flux-induced cell swelling, and caspase-1 activation. Recent investigations have shown that activation of the NLRP3 inflammasome complex has more broad-reaching importance, particularly as a possible disease-specific biomarker for MDS, and, mechanistically, as a driver of cardiovascular morbidity/mortality in individuals with age-related, clonal hematopoiesis. Recognition of the mechanistic role of aberrant innate immune activation in MDS provides a new perspective for therapeutic development that could usher in a novel class of disease-modifying agents.
Cation dynamics in sodalite, cubic and rhombohedral zeolite A and faujasite: Fourier transform far-infrared probe of densely and dispersely packed cations (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCation dynamics in sodalite, cubic and rhombohedral zeolite A and faujasite: Fourier transform far-infrared probe of densely and dispersely packed cationsJohn Godber and Geoffrey A. OzinCite this: J. Phys. Chem. 1988, 92, 10, 2841–2849Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/j100321a029https://doi.org/10.1021/j100321a029research-articleACS PublicationsRequest reuse permissionsArticle Views206Altmetric-Citations25LEARN 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 Other access options Get e-Alerts
Follow‐up after incomplete hysteroscopic removal of uterine fibroids (2006)

The results indicate that incomplete removal does not always seem to necessitate subsequent surgery. Instead of subsequent surgery immediately post-operatively, a wait and see policy is worth considering after incomplete removal.
Flame retardancy and thermal and mechanical performance of intercalated, layered double hydroxide composites of polyamide 11, aluminum phosphinate, and sulfamic acid (2016)

ABSTRACT Sulfamic acid‐intercalated MgAl‐layered double hydroxide (SA‐LDH) was prepared and added with aluminum phosphinate (AlPi) into polyamide 11 (PA11). The results showed that AlPi/SA‐LDH made a positive contribution to both flame retardancy and thermostability, and the effect was demonstrated with the limiting oxygen index (LOI), vertical burning tests (UL‐94), cone calorimetry (CONE), and thermogravimetric analysis (TGA). The char morphologies were observed by SEM, and its chemical composition was investigated by Fourier transform infrared spectroscopy (FTIR). The decomposition mechanism was examined by TGA‐FTIR. The results showed that the LOI of PA11 was only 23.0 and cannot pass any UL‐94 rating. The addition of 20% AlPi increased the LOI to 31.5 and passed the UL‐94 V‐1 rating, and AlPi/SA‐LDH 15%/5% increased the LOI to 32.4 and also passed the UL‐94 V‐1 rating. The CONE results revealed that 20% of either AlPi or AlPi/SA‐LDH brought about a 30% decrease in the peak heat release rate (pHRR). The contribution of SA‐LDH to flame behavior was especially reflected in the postponement of pHRR. SEM showed that the char morphologies became denser after SA‐LDH incorporation. The improvement in thermal stability of the AlPi/SA‐LDH combination was documented by TGA in both N 2 and air atmospheres. The mechanical performance deterioration caused by AlPi was partly improved by SA‐LDH. The storage modulus ( E′ ) below the T g of AlPi/SA‐LDH 15%/5% was about 300 MPa higher than with 20% AlPi. This was attributed to a compatibility improvement. The interaction forces among PA11, AlPi, and SA‐LDH were probed by X‐ray photoelectron spectrometry. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 43370.
Optimized pulse‐feeding fed‐batch fermentation for enhanced lignin to polyhydroxyalkanoate transformation (2022)

With an anticipated growth of Bio-Circular-Green economy, the amount of lignin generated as by-product from biorefineries is increasing. Hence, lignin valorising strategies become a very interesting option to improve economic viability of the biorefineries. This study revealed the development of bioprocesses for upgrading lignin into bioplastic. Specifically, a novel strain of Pseudomonas fulva has been applied for microbial bioconversion of organosolv lignin to fermentative polyhydroxyalkanoate (PHA) production. Fed-batch fermentation of lignin-to-PHA with pulse-feeding approach was optimized using Design of Experiment. Effects of C:N ratio and feeding profiles on PHA accumulation in P. fulva were investigated to determine optimal operation. Under optimized fed-batch, the PHA concentration of 195.2 ± 6.6 mg/L could be reached and the PHA content was more than 2 folds enhancement compared to batch process. Type of PHA produced was also characterized for chemical composition via GC-MS analysis. The established lignin to PHA conversion could provide platform for developing integrated lignin bioprocessing to promote cost-effective biorefineries.
Transplantation of bone marrow cells from transgenic mice expressing the human MDR1 gene results in long-term protection against the myelosuppressive effect of chemotherapy in mice (1992)

Abstract Many human cancers that are initially responsive to chemotherapy eventually fail to respond to treatment. For some drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow (BM) limit cytotoxic therapy. Approaches to prevent or circumvent BM toxicity are therefore a high priority of research on dose escalation protocols. In this study, we have transplanted BM cells from transgenic mice that constitutively express physiologic amounts of a functional human multidrug resistance (MDR1) cDNA to lethally irradiated C57BL/6 x SJL F1 mice (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and BM specimens as indicated by Southern blot analysis, and expressed MDR1 messenger RNA in BM samples as detected by slot blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal BM were drug sensitive. Finally, the chemoprotection afforded by the MDR1 gene could readily be reversed by adding chemosensitizers such as cyclosporin A and R-verapamil to chemotherapy. Hence, it appears that BM cells expressing the human MDR1 gene maintain this function after transplantation to host animals for a minimum of 10 months, and confer multidrug resistance to these BM recipients. This selective advantage conferred by expression of the MDR1 cDNA suggests a strategy for the use of MDR1 gene therapy in cancer chemotherapy and for the introduction of otherwise nonselectable genes into BM.
Characterization of Cutting-Induced Heat Generation in Ultra-Precision Milling of Aluminium Alloy 6061 (2013)

The technology of ultra-precision machining with single crystal diamond tool produces advanced components with higher dimensional accuracy and better surface quality. The cutting-induced heat results in high temperature and stress at the chip-tool and tool-workpiece interfaces therefore affects the materials and the cutting tool as well as the surface quality. In the ultra-precision machining of al6061, the cutting-induced heat generates precipitates on the machined surface and those precipitates induce imperfections on the machined surface. This paper uses the time-temperature-precipitation characteristics of aluminum alloy 6061 (al6061) to investigate the effect of feed rate on the cutting-induced heat generation in ultra-precision multi-axis milling process. The effect of feed rate and feed direction on the generation of precipitates and surface roughness in ultra-precision raster milling (UPRM) is studied. Experimental results show that heat generation in horizontal cutting is less than that in vertical cutting and a larger feed rate generates more heat on the machined workpiece. A smaller feed rate produces a better surface finish and under a larger feed rate, scratch marks are produced by the generated precipitates and increase surface roughness.
Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells (2002)

Cell-selective intracellular targeting is a key element of more specific and safe enzyme, toxin, and gene therapies. Endothelium poorly internalizes certain candidate carriers for vascular immunotargeting, such as antibodies to platelet endothelial cell adhesion molecule 1 (PECAM-1). Conjugation of poorly internalizable antibodies with streptavidin (SA) facilitates the intracellular uptake. Although both small and large (100-nm versus 1000-nm diameter) anti-PECAM/SA-beta galactosidase (SA-beta-gal) conjugates bound selectively to PECAM-expressing cells, only small conjugates showed intracellular accumulation of active beta-gal. To study whether size of the conjugates controls the uptake, a series of anti-PECAM/SA and anti-PECAM/bead conjugates ranging from 80 nm to 5 microm in diameter were produced. Human umbilical vein endothelial cells and PECAM-transfected mesothelioma cells internalized 80- to 350-nm anti-PECAM conjugates, but not conjugates larger than 500 nm. Further, size controls intracellular targeting of active therapeutic cargoes in vitro and in vivo. Small anti-PECAM/DNA conjugates transfected target cells in culture 5-fold more effectively than their large counterpart (350- versus 4200-nm diameter). To evaluate the practical significance of the size-controlled subcellular addressing, we coupled glucose oxidase (GOX) to anti-PECAM and antithrombomodulin. Both types of conjugates had equally high pulmonary uptake after intravenous injection in mice, yet only small (200- to 250-nm), not large (600- to 700-nm), GOX conjugates caused profound oxidative vascular injury in the lungs, presumably owing to intracellular generation of H(2)O(2). Thus, engineering of affinity carriers of specific size permits intracellular delivery of active cargoes to endothelium in vitro and in vivo, a paradigm useful for the targeting of drugs, genes, and toxins.
Does Prolonged Use of Walkers in Shoulder Arthroplasty Patients Lead to Accelerated Failure Rates? (2019)

Routine use of a walker does not appear to lead to a markedly increased rate of SA failure at mid-term follow-up. Concerning radiographic findings were more common after HA and anatomic TSA than after RSA. Longer follow-up is required to determine the long-term impact of walker use on SA.