gebhart/patrepeval huggingface dataset:
Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C β-Lactamase from Escherichia coli (2020)

Resistance to β-lactam antibacterials, importantly via production of β-lactamases, threatens their widespread use. Bicyclic boronates show promise as clinically useful, dual-action inhibitors of both serine- (SBL) and metallo- (MBL) β-lactamases. In combination with cefepime, the bicyclic boronate taniborbactam is in phase 3 clinical trials for treatment of complicated urinary tract infections. We report kinetic and crystallographic studies on the inhibition of AmpC, the class C β‑lactamase from <i>Escherichia coli</i>, by bicyclic boronates, including taniborbactam, with different C-3 side chains. The combined studies reveal that an acylamino side chain is not essential for potent AmpC inhibition by active site binding bicyclic boronates. The tricyclic form of taniborbactam was observed bound to the surface of crystalline AmpC, but not at the active site, where the bicyclic form was observed. Structural comparisons reveal insights into why active site binding of a tricyclic form has been observed with the NDM-1 MBL, but not with other studied β-lactamases. Together with reported studies on the structural basis of inhibition of class A, B and D β‑lactamases, our data support the proposal that bicyclic boronates are broad-spectrum β‑lactamase inhibitors that work by mimicking a high energy 'tetrahedral' intermediate. These results suggest further SAR guided development could improve the breadth of clinically useful β-lactamase inhibition.
Optimal design of rotor geometry in interior permanent magnet machine (2019)

Interior permanent magnet machine has been widely used in electric vehicles due to its high-power density and good flux weakening performance. This paper firstly introduces the principle of flux-weakening control, which are the foundation to describe the effect of d-axis inductance and q-axis induc tance on the speed range of motor. Secondly, regarding an interior permanent magnet synchronous motor with V -type permanent magnet structure as the research object, an improved rotor structure has been proposed which concludes asymmetric segmentations of permanent magnets and protuberances from centers of every magnetic poles toward airgap. Furthermore, the Taguchi method is utilized to optimize the proposed improved structure. Finally, the optimized rotor structure which meet the requirement of d-axis inductance, q-axis inductance and electromagnetic torque has been obtained. Compared with the initial structure, the optimized rotor structure can increase d-axis inductance effectively, and hence broaden the speed range with constant power operation.
Production and isolation of rabbit anti-idiotypic antibodies directed against the human monocyte receptor for yeast beta -glucans. (1990)

beta-Glucan receptors are present on mammalian phagocytic cells and provide an important physiologic mechanism for opsonin-independent clearance of yeasts and fungi. To prepare an immunologic probe to human monocyte beta-glucan receptors, an approach was taken that focused on the ligand specificity of the receptors as expressed by an anti-Id. The algal beta-glucan laminarin was chemically coupled to protein carriers to prepare an immunogenic beta-glucan. Three mouse IgG2a mAb were raised against laminarin, and one, mAb OEA10, exhibited specificity for the soluble unit ligand yeast heptaglucoside and the ligands present on zymosan and glucan particles that are recognized by monocyte beta-glucan receptors. These findings prompted usage of mAb OEA10 as immunogen for the preparation of an anti-Id. The resulting rabbit antiserum was subjected to sequential immunoaffinity chromatography to purify anti-idiotypic antibodies. The final product contained only IgG by SDS-PAGE and was shown to be specific by its selectively blocking binding of 125I-mAb OEA10 to laminarin. Pretreatment of adherent monocytes with 0.4 micrograms/ml of the anti-Id reduced the numbers of monocytes ingesting zymosan and glucan particles by 64 and 43%, respectively, whereas ingestion of IgG-coated SRBC was unaffected by as much as 16 micrograms/ml of the anti-Id. Incubation of adherent monocytes with increasing amounts of 125I-anti-Id in the absence and presence of 40-fold molar excess unlabeled anti-Id revealed dose-dependent specific binding, which approached plateau levels with 1 microgram/ml of labeled anti-Id. Thus, the anti-Id binds to monocytes and displays functional characteristics of soluble beta-glucan ligands, indicating that some of the anti-idiotypic antibodies recognize epitopes within monocyte beta-glucan receptors.
Aurora kinase-A regulates microtubule organizing center (MTOC) localization, chromosome dynamics, and histone-H3 phosphorylation in mouse oocytes (2010)

Aurora kinases (AURKs) are conserved serine/threonine kinases, crucial in regulating cell cycle events. Mammalian oocytes express all three Aurk isoforms throughout meiosis, with AurkA being the predominant isoform. Inhibition of all AURK isoforms by pharmacological means disrupts oocyte meiosis. Therefore, AurkA short interfering RNA (siRNA) was performed to silence AurkA gene expression in mouse oocytes and to further assess the function of AurkA during meiosis by analyzing subsequent loss-of-function oocyte phenotypes. Results indicated that AurkA siRNA applied in our experiments specifically knocked down both AurkA gene and protein expression without influencing transcript levels of AurkB/AurkC and other endogenous protein expression, such as GAPDH and ERK-2. AURKA was not essential for resumption of meiosis, but it potentiated oocyte meiotic progression. Knockdown of AurkA led to a significant reduction in the number of oocytes proceeding to metaphase II (MII). AurkA siRNA resulted in abnormal spindle assembly, improper localization of microtubule organizing centers (MTOCs) and misalignment of chromosomes in metaphase I (MI) oocytes. Co-immunoprecipitations demonstrated that AURKA was physically associated with phospho-Histone H3 ser10 in meiotic oocytes. AurkA siRNA dramatically reduced Histone H3 ser10 phosphorylation, but not ser28, and resulted in a significant increase of abnormal chromosome segregation in MII oocytes. In conclusion, as a predominant isoform among Aurks in oocytes, AurkA plays critical roles in mouse oocyte meiosis by regulating spindle and chromosome dynamics.
Two N-Linked Glycosylation Sites (Asn18 and Asn106) Are Both Required for Full Enzymatic Activity, Thermal Stability, and Resistance to Proteolysis in Mammalian Deoxyribonuclease I (2008)

Deoxyribonuclease I (DNase I) is known to be a glycoprotein, and two potential N-linked glycosylation sites (N18 and N106) are known for mammalian enzymes. In the present study, N18 and N106 were mutated in order to investigate the biological role of N-linked glycosylation in three mammalian (human, bovine, and equine) DNases I. The enzyme activities of N18Q and N106Q were lower than that of the wild type, and that of the double mutant (N18Q/N106Q) was lower than those of the single mutants, in accord with the sugar moiety contents in the three mammals. In addition, all mutant enzymes were unstable to heat, suggesting that both sites are required for heat stability. Moreover, in human and equine enzymes, the N18Q and N106Q mutant enzymes were less resistant to trypsin, while N18Q/N106Q was the most sensitive to trypsin. As for bovine DNase I, the trypsin resistance of N18Q and N106Q was similar to that of the wild type, but that of N18Q/N106Q decreased in a time-dependent manner. On the other hand, N-linked glycosylation was not related to pH sensitivity. The results of the present study suggest that N18 and N106 are both necessary for (i) full enzymatic activity, (ii) heat-stability, and (iii) trypsin resistance.
Summary Abstract: Thermomechanical properties of glow discharge deposited silicon and silicon oxide films (1988)

First Page
The controversial discussions (2018)

In 1941, the British Psychoanalytic Society entered into what has become known as the Controversial Discussions. The controversial discussions, in many ways, presaged debates that continued over the next several decades. This chapter demonstrates the particular way underlying attitudes about the possibility of objectivity permeated the theoretical discussions of phantasy in the Controversial Discussions. Melanie Klein was not always a controversial figure in British psychoanalysis. While her ideas on child analysis had aroused considerable dissent during her early years in Berlin, they found fertile ground when she arrived in London in 1926; by the end of the 1920s, Klein’s ideas had assumed some prominence in the British Society. These were the foundational ego psychological and Kleinian positions of the 1940s, as viewed in relief through the lens of the Controversial Discussions. After reading the controversial discussions, one can see the overwhelming importance of Freud at this historical juncture.
ChemInform Abstract: Palladium‐Catalyzed Arylation of β‐Methylene C(sp3)—H Bonds at Room Temperature: Desymmetrization of Simple Cycloalkyl Carboxylic Acids. (2016)

Abstract In most cases, the β methylene C—H bonds of cycloalkylcarboxamides of varied ring size are monoarylated giving products with excellent cis‐diastereoselectivity whereby, diarylated products are also observed as by‐products.
Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells (2007)

Aberrant micro RNA (miRNA) expression has been described in human malignancies including B-cell lymphomas. We here report BCR-ABL- and c-MYC-dependent regulation of miRNA expression in chronic myeloid leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific quantitative real-time reverse transcriptase-polymerase chain reaction (miR-qRT-PCR). In 3 bcr-abl-positive cell lines, expression of miRNAs encoded within the polycistronic miR-17-92 cluster is specifically down-regulated (2- to 5-fold) by both imatinib treatment and anti-BCR-ABL RNA interference (RNAi). In addition, anti-c-MYC RNAi reduces miR-17-92 expression in K562 cells in which miRNAs can specifically repress reporter gene expression, as demonstrated by specific miRNA inhibition with antagomirs. Furthermore, lentivirus-mediated overexpression of polycistronic miRNAs in K562 cells confers increased proliferation, partial resistance against anti-c-MYC RNAi, and enhanced sensitivity to imatinib-induced cell death. Finally, we determined miR-17-92 expression in purified normal (n = 4), early chronic-phase (CP) (n = 24), and blast-crisis (BC) (n = 7) CML CD34(+) cells and found up-regulation of polycistronic pri-miRNA transcripts in CML and mature miRNAs in CP but not in BC CML. These data are in accordance with a BCR-ABL-c-MYC-miR-17-92 pathway that mediates enhanced miRNA expression in CP but not BC CML CD34(+) cells. Altered miRNA expression may contribute to the pathophysiology of the disease and may provide potential targets for therapeutic intervention.
Cytotoxicity and Sister Chromatid Exchanges Induced In Vitro by Six Anticancer Drugs Developed in the People's Republic of China<xref ref-type="fn" rid="FN2">2</xref> (1983)

Growth inhibition in the Chinese hamster cell line V79 and in the human lymphoid cell line Raji and induction of sister chromatid exchange(s) (SCE) in V79 cells after treatment with six anticancer drugs [harringtonine (HRT), homoharringtonine (HHRT), camptothecin (CPT), hydroxycamptothecin (HCPT), lycobetaine (LBT), and oxalysine (OXL)] developed in the People's Republic of China were studied. OXL is a new antibiotic; all other drugs are plant extracts. All drugs caused a dose-dependent growth inhibition in both cell types, as evidenced by decreases in plating efficiencies of V79 cells and in viable cell counts of Raji. However, the degree of inhibition differed widely among the drugs. HRT, HHRT, CPT, and HCPT were the most potent growth inhibitors, LBT was next, and OXL was the least effective inhibitor. SCE analyses were made in V79 cells treated with a drug in the presence or absence of the metabolic activation system S9 mixture (S9 mix), except for the HRT assay in which the S9 mix was not used. CPT, HCPT, and LBT induced a dose-dependent increase in SCE frequencies, while HRT, HHRT, and OXL caused no SCE induction at any dose level used. CPT was the most powerful SCE inducer. HCPT induced SCE but at a much reduced rate when compared to that of CPT. LBT was a weak SCE inducer; SCE induction was seen only in cultures treated with 40 micrograms or more LBT/ml. Addition of the S9 mix did not alter SCE frequencies, indicating that the drugs were direct-acting agents. HRT and HHRT were highly toxic, but they induced no increases in SCE frequency, indicating that cytotoxicity of a compound does not necessarily correlate with SCE induction.
Phase Separation in Oxide−Borate Mixed Systems (2002)

Single crystalline GdCa4O(BO3)3 and YCa4O(BO3)3 show one DTA melting peak at = 1490 °C or = 1504 °C, respectively. Only pure GdCa4O(BO3)3 and mixed crystals Gd1-xYxCa4O(BO3)3 with x ≲ 0.46 showed one single peak also during cooling or during subsequent heating runs. The melting points of such intermediate compositions can be described well assuming ideal behavior of the solid as well as of the liquid phase resulting in a conventional quasibinary phase diagram with complete solubility and a narrow two-phase region solid/liquid. Compositions with x ≥ 0.5307 show a miscibility gap in the liquid phase. For solidified pure YCa4O(BO3)3 (x = 1), the content of the crucible was found to consist of the congruently melting compounds Y2Ca3(BO3)4, Ca3(BO3)2, Y2O3 and of the original YCa4O(BO3)3. The first three compounds built up a partial system of the concentration triangle B2O3, CaO, and Y2O3.
Thiosugars. XIII. An Attempt at Thiosugar Synthesis having a Vicinal cis-Dimercapto Group in the Pyranose Ring (1968)

Methyl 2, 3-dideoxy-2, 3-dimercapto-α-D-mannopyranoside, isolated as sirupy tetraacetate (XIII), was synthesized in 13% yield by reduction of methyl 2, 3-dithio-4, 6-O-benzylidene-α-D-mannopyranoside 2, 3-S-carbonate (IX) with sodium in liquid ammonia. The product was also obtainable in the same yield by alkaline treatment of methyl 2, 3-dithio-4, 6-di-O-acetyl-α-D-mannopyranoside 2, 3-S-carbonate (XII). Dithiocarbonate (IX), a key intermediate of the synthesis was obtained by the following route : epoxide opening in methyl 2, 3-anhydro-4, 6-O-benzylidene-α-D-allopyranoside (II) with sodium N, N-dimethyldithiocarbamate (I) to give methyl 2-deoxy-2 (N, N-dimethyl dithiocarbamoyl)-4, 6-O-benzylidene-α-D-altropyranoside (III), sulfonation of III, and successive intramolecular ring formation in the pyranose ring involving trans-diaxial elimination by treatment of the sulfonate (VII or VIII) with potassium acetate.
The usefulness of contrast enhanced magnetic resonance angiography in the early period after renal transplantation (2022)

Jeong Kye Hwang, Hyung-Jin Cho, MI-Hyeong Kim, Tae-Hyun Ban, Jeong-Min Lee, Chang-ho Jeon, Bum-Soon Choi, Mi-Kyung Park, Ji-Hyang Lim. Korean J Transplant 2022;36:310. https://doi.org/10.4285/ATW2022.F-4501
Application of Dependency Structure Matrix to Airspace Sectorization and Improving the Distribution of the Workload Among Controllers (2014)

No AccessRisk and change management in complex systemsJul 2014Application of Dependency Structure Matrix to Airspace Sectorization and Improving the Distribution of the Workload Among ControllersMahsa Farsad, Seyed Mohammad-Bagher MalaekMahsa Farsad, Seyed Mohammad-Bagher MalaekDepartment of Aerospace Engineering, Sharif University of Technology, Tehran, Iranhttps://doi.org/10.3139/9781569904923.015SectionsAboutPDF ToolsAdd to FavoritesDownload CitationTrack CitationsCopy LTI LinkPDF key 'share (en)' returned an object instead of string.FacebookTwitterEmailLinkedIn previous chapternext chapter FiguresReferencesRelatedDetails 2014Pages: 147-156Print ISBN: 978-1-56990-491-6eISBN: 978-1-56990-492-3 Copyright & Permissions© 2014 Carl Hanser Verlag GmbH & Co. KGPDF downloadLoading ...
Surface Induced Alignment Transition in a Nematic Layer with Symmetrical Boundary Conditions (1991)

Abstract The inner surfaces of a cell of conventional type were covered with an SiO, aligning layer evaporated at an angle α = 60° and subsequently treated with lecithin in order to achieve symmetrical boundary conditions. The alignment of a nematic liquid crystal layer with negative dielectric anisotropy (Δε < 0) was found to be homeotropic below a critical temperature Tc, (low temperature range). Above that particular temperature the homeotropic alignment abruptly transforms into a planar one, which remains with increasing temperature up to the clearing point TNI (high temperature range). The alignment transition was found to be reversible, and is attributed to a packing change of the lecithin layer with the temperature. A simple model based on the different temperature dependence of the anchoring strengths W H, (T) and W P, (T), characterizing the homeotropic and planar alignment respectively, is proposed to explain the surface induced alignment transition.
Metallodielectric antenna for spontaneous emission enhancement (2017)

Semiconductors have an intrinsically slow spontaneous emission rate, on the order of 1ns. Consequently, light emitting diodes (LEDs) can be directly modulated at a maximum rate of 250 MHz (in contrast to lasers, which can be directly modulated at a maximum rate of about 50 GHz). The slow spontaneous emission rate can fundamentally be attributed to the mismatch between the wavelength of light emission and a characteristic dipole length, which is approximately given by the lattice period. In other words, bare LEDs serve as poor antennas for their own radiation.
The Rule of Law and the Pattern of Environment Protection (2002)

The views expressed in this Working Paper are those of the author(s) and do not necessarily represent those of the IMF or IMF policy.
Effects of dosage and infusion time on the incorporation of 5‐fluorouracil into DNA and RNA of normal tissues and an adenocarcinoma transplanted to rat liver (1988)

In a model of secondary liver cancer in Wistar rats the incorporation of 5-FUra into the acid soluble fraction, RNA, and DNA of several normal tissues and of an adenocarcinoma of the colon transplanted to the liver was determined; 300, 1,200 or 24,000 nmoles of 5-FUra were infused via the gastroduodenal artery for 0.5, 2, or 24 hr. The rats were killed 1.5, 3, or 24 hr after the beginning of the infusions. In general, higher doses resulted in a higher labelling. However, the ratio of incorporation into tumor RNA compared to normal tissue RNA was higher at the 1,200 than at the 24,000 nmole dosage. There was a decreased RNA/DNA ratio in the tumor at 24 hr after 24,000 nmoles of 5-FUra had been infused over 0.5 or 2 hr, indicating decreased synthesis and/or increased breakdown of RNA.
Influence of <i>in-situ</i> Sb-Doping on Crystalline and Electrical Characteristics of <i>n</i>-type Ge<sub>1-x</sub>Sn<sub>x</sub> Epitaxial Layer (2015)

2015 International Conference on Solid State Devices and Materials,Influence of <i>in-situ</i> Sb-Doping on Crystalline and Electrical Characteristics of <i>n</i>-type Ge<sub>1-x</sub>Sn<sub>x</sub> Epitaxial Layer
Left ventricular apex occluder. Description of a Ventricular Partitioning Device. (2006)

Description Implant device and delivery system. The Ventricular Partitioning Device (VPD) is an intraventricular Implant that is deployed in the Left Ventricle (LV) in patients with regional wall motion abnormalities following myocardial infarction (MI). The implant device is delivered via a guiding catheter and delivery system introduced percutaneously from the femoral artery by the standard techniques for left heart catheterization. The implant device is an ePTFE membrane bonded to an expanded NiTi frame in the configuration of an inverted umbrella. (Figure 1) The stem of the umbrella is positioned in the apex of the
Simultaneous Selection for Yield and Resistance to Brown Stem Rot of Soybean in Hill Plots1 (1983)

The yield of soybean [ Glycine max (L.) Merr.] grown in row plots can be reduced by brown stem rot [caused by Phialophora gregata (Allington and Chamberlain) W. Gams]. Our objective was to evaluate the effectiveness of simultaneous selection among soybean lines for yield and resistance to brown stem rot in hill plots planted on soil infested with the causal organism. Ninety‐six random F 4 ‐derived lines from an intermated population were grown in three replications of single, unbordered hill plots on four fields infested with P. gregata and on four uninfested fields. Selection for yield alone was not effective in identifying lines with a low percentage of stem browning. The correlation between yield and percentage of stem browning (r = −0.19) was not significant. Twenty‐three of the 48 lines with the highest average yield had below‐average resistance to brown stem rot. There was a high correlation for yield of the 96 lines on infested and uninfested soil (r = 0.80, P &lt;0.01). When hill plots are used to determine the yield potential of soybean lines, resistance to brown stem rot should be evaluated independently by growing the lines on infested soil and splitting stems to determine the extent of infection. Evaluation of yield potential in hill plots can be done equally well on infested and uninfested soil.
Long-term bortezomib treatment decreases allergen-specific IgE but fails to amend chronic asthma in mice (2012)

Since allergen-specific immuno-globulin E (IgE) enables mast cells and eosinophils to react on allergen-contact it plays a critical role in the formation of allergic inflammation and has been identified as a target for asthma therapy. By inhibiting the proteasome complex Bortezomib efficiently depletes Ig-secreting plasma cells and, thus, reduces Ig-serum titers. The present study evaluates the therapeutic potential of Bortezomib in a mouse model of chronic experimental asthma. Therefore, BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA-aerosol for twelve weeks. Bortezomib treatment was started after six weeks of challenge, and continued for one week (short-term) or six weeks (long-term), respectively, with a dosage of 0.75 mg/kg body weight with two intra-venous injections weekly. Airway responsiveness to metacholine, lung histology, Ig serum titers, and plasma cell numbers were assessed. In mice with chronic experimental asthma short-term treatment resulted in decreased eosinophil numbers in BAL fluids, while long-term treatment significantly lowered serum titers of anti-OVA IgE. Nevertheless, neither short-term nor long-term treatment significantly diminish ed plasma cell numbers, anti-OVA IgG1 serum titers, allergic airway inflammation or improved lung function. These results demonstrate that Bortezomib has no therapeutic effect on chronic experimental asthma in mice. Therefore, Bortezomib treatment could have only limited value as plasma cell depleting therapy against allergic bronchial asthma.