gebhart/patrepeval huggingface dataset:
Contribution of the 8-Methoxy Group to the Activity of Gatifloxacin against Type II Topoisomerases of Streptococcus pneumoniae (2002)

The inhibitory activities (50% inhibitory concentrations [IC(50)s]) of gatifloxacin and other quinolones against both DNA gyrase and topoisomerase IV of the wild-type Streptococcus pneumoniae IID553 were determined. The IC(50)s of 10 compounds ranged from 4.28 to 582 microg/ml against DNA gyrase and from 1.90 to 35.2 microg/ml against topoisomerase IV. The inhibitory activity against DNA gyrase was more varied than that against topoisomerase IV among fluoroquinolones. The IC(50)s for DNA gyrase of the 8-methoxy quinolones gatifloxacin and AM-1147 were approximately seven times lower than those of their 8-H counterparts AM-1121 and ciprofloxacin, whereas the IC(50)s for topoisomerase IV were 1.5 times lower. Moreover, the IC(50) ratios (IC(50) for DNA gyrase/IC(50) for topoisomerase IV) of gatifloxacin, AM-1147, and moxifloxacin, which possess 8-methoxy groups, were almost the same. The 8-methoxy quinolones showed higher antibacterial activity and less mutant selectivity against IID553 than their 8-H counterparts. These results suggest that the 8-methoxy group enhances both target inhibition, especially for DNA gyrase, leading to potent antipneumococcal activity and dual inhibition against both DNA gyrase and topoisomerase IV in the bacterial cell.
A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma (2016)

More than 90% of clear cell renal cell carcinomas (ccRCC) exhibit inactivation of the von Hippel-Lindau (pVHL) tumor suppressor, establishing it as the major underlying cause of this malignancy. pVHL inactivation results in stabilization of the hypoxia-inducible transcription factors, HIF1α and HIF2α, leading to expression of a genetic program essential for the initiation and progression of ccRCC. Herein, we describe the potent, selective, and orally active small-molecule inhibitor PT2385 as a specific antagonist of HIF2α that allosterically blocks its dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. PT2385 inhibited the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts. Treatment of tumor-bearing mice with PT2385 caused dramatic tumor regressions, validating HIF2α as a pivotal oncogenic driver in ccRCC. Notably, unlike other anticancer agents that inhibit VEGF receptor signaling, PT2385 exhibited no adverse effect on cardiovascular performance. Thus, PT2385 represents a novel class of therapeutics for the treatment of RCC with potent preclincal efficacy as well as improved tolerability relative to current agents that target the VEGF pathway. Cancer Res; 76(18); 5491-500. ©2016 AACR.
Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis, characterization, and preliminary release studies of protein drugs (2002)

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.
Carotenoid biosynthesis in microorganisms and plants (1994)

CONTENTS. Carotenogenic in vitro systems – Strategies for the cloning of carotenogenic genes – Enzymology and molecular genetics of the reactions leading to cyclic carotenoids – Synthesis of GGPP – Phytoene synthesis – Desaturation sequence of phytoene to lycopene – Mechanism – Isomerization – Genes and phylogenetic relationship – Enzyme purification – Localization – Regulation of the pathway and modulation of activity – Developmental and physiological regulation – Lycopene cyclization – Formation of xanthophylls derived from cyclic carotenoids – Hydroxy carotenoids – Keto carotenoids – Epoxy carotenoids – Formation of acyclic xanthophylls in Rhodobacter – Conclusion and outlook
Development of drug loaded nanoparticles for tumor targeting. Part 1: synthesis, characterization, and biological evaluation in 2D cell cultures (2013)

Nanoparticles (NPs) are being extensively studied as carriers for drug delivery, but they often have limited penetration inside tumors. We envision that by targeting an endocytic receptor on the cell surface, the uptake of NPs can be significantly enhanced through receptor mediated endocytosis. In addition, if the receptor is recycled to the cell surface, the NP cargo can be transported out of the cells, which is then taken up by neighboring cells thus enhancing solid tumor penetration. To validate our hypothesis, in the first of two articles, we report the synthesis of doxorubicin (DOX)-loaded, hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44, a receptor expressed on the cancer cell surface. HA was conjugated onto amine-functionalized SNPs prepared through an oil-water microemulsion method. The immobilization of the cytotoxic drug DOX was achieved through an acid sensitive hydrazone linkage. The NPs were fully characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements, thermogravimetric analysis (TGA), UV-vis absorbance, and nuclear magnetic resonance (NMR). Initial biological evaluation experiments demonstrated that compared to ligand-free SNPs, the uptake of HA-SNPs by the CD44-expressing SKOV-3 ovarian cancer cells was significantly enhanced when evaluated in the 2D monolayer cell culture. Mechanistic studies suggested that cellular uptake of HA-SNPs was mainly through CD44 mediated endocytosis. HA-SNPs with immobilized DOX were endocytosed efficiently by the SKOV-3 cells as well. The enhanced tumor penetration and drug delivery properties of HA-SNPs will be evaluated in 3D tumor models in the subsequent paper.
Smart mobile SoCs driving the semiconductor industry: Technology trend, challenges and opportunities (2013)

The explosive growth of smart mobile wireless devices in recent years has fundamentally transformed the semiconductor industry. Mobile system-on-chips (SoCs) has become the leading product driver for technology definition and manufacturing for the semiconductor industry. This trend was first observed in 28 nm and will continue for 20 nm, 16/14 nm, and 10 nm adoption and production ramp. Recent mobile SoC performance increase was achieved mainly through silicon technology scaling, and from single to dual- and quad-core. For mobile SoCs to continue offering new and exciting user-experiences, and longer battery life, a holistic approach in orthogonal system scaling to break out of the box of (speed*density/power/cost) constrains is mandated. Examples in the new paradigm of mobile heterogeneous computing are: energy-efficient transistors/memories/interconnects in expanding and boosting existing SoC functionalities (e.g., SiGe/III-V FinFET, GAA-FET, TFET, and RRAM/MRAM etc.), all-inclusive technology/design co-optimization to extract more values from silicon tech, RFFE system integration, and the multi-die integration by system partitioning that allows each component to be optimized and integrated closely together for lower cost and power, higher performance, and reduced form factor. Numerous challenges are ahead yet tremendous opportunities exist for collaborative and multiplicative innovations in the industry to enable the continued growth of mobile SoCs.
Vehicle monitoring and telecommunication systems for enhancement of trucking operations (2003)

The authors review current research dealing with potential applications of advanced vehicle monitoring and control systems. The University effort focuses on trucking operations, satellite telecommunications systems, and man-machine interfaces. The proposed system will provide position determination, two-way data communication and, eventually, voice communication capabilities. In addition to technical areas such as radio reception and protocol modifications, cost savings and other benefits are being studied. In investigating the human interface problem, research seeks to compensate for the possibly marginal communication skills of the driver, as well as the special nature of the satellite communication links.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Nickel Superoxide Dismutase Maquette That Reproduces the Spectroscopic and Functional Properties of the Metalloenzyme (2006)

Described herein is a nickel superoxide dismutase (NiSOD) maquette ([Ni(SOD(M1))]) based on the first 12 residues from the N-terminal sequence of Streptomyces coelicolor NiSOD. The apopeptide (SOD(M1)) was prepared by standard solid-phase Fmoc peptide synthesis. SOD(M1) will readily coordinate Ni(II) in a 1:1 ratio in slightly basic aqueous sodium phosphate buffer (0.1 M; pH = 7.2) forming a lightly colored beige/pink solution. Unlike NiSOD, which is isolated as a 1:1 mixture of oxidized (Ni(III)) and reduced (Ni(II)) forms, [Ni(SOD(M1))] can only be isolated in the Ni(II) oxidation state. The UV/vis, X-ray absorption, and CD spectra of [Ni(II)(SOD(M1))] correspond well with those reported for the reduced form of NiSOD. Despite the fact that [Ni(III)(SOD(M1))] is not isolable, [Ni(SOD(M1))] has an appropriate redox potential to act as an SOD (E(1/2) = 0.70(2) V vs Ag/AgCl) and in fact will catalytically disproportionate >40 000 equiv of KO(2).
SV2, a Brain Synaptic Vesicle Protein Homologous to Bacterial Transporters (1992)

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein specifically localized to secretory vesicles in neurons and endocrine cells. As a first step toward understanding the function of SV2 in neural secretion, a rat brain complementary DNA (cDNA) that encodes SV2 was isolated and characterized. Analyses of this cDNA predict that SV2 contains 12 transmembrane domains. The NH2-terminal half of the protein shows significant amino acid sequence identity to a family of bacterial proteins that transport sugars, citrate, and drugs. Expression of the SV2 cDNA in COS cells yielded a high level of SV2-like immunoreactivity distributed in a reticular and punctate pattern, which suggests localization to intracellular membranes. Its localization to vesicles, predicted membrane topology, and sequence identity to known transporters suggest that SV2 is a synaptic vesicle-specific transporter.
Deep Models Under the GAN: Information Leakage from Collaborative Deep Learning (2017)

Deep Learning has recently become hugely popular in machine learning, providing significant improvements in classification accuracy in the presence of highly-structured and large databases. Researchers have also considered privacy implications of deep learning. Models are typically trained in a centralized manner with all the data being processed by the same training algorithm. If the data is a collection of users' private data, including habits, personal pictures, geographical positions, interests, and more, the centralized server will have access to sensitive information that could potentially be mishandled. To tackle this problem, collaborative deep learning models have recently been proposed where parties locally train their deep learning structures and only share a subset of the parameters in the attempt to keep their respective training sets private. Parameters can also be obfuscated via differential privacy (DP) to make information extraction even more challenging, as proposed by Shokri and Shmatikov at CCS'15. Unfortunately, we show that any privacy-preserving collaborative deep learning is susceptible to a powerful attack that we devise in this paper. In particular, we show that a distributed, federated, or decentralized deep learning approach is fundamentally broken and does not protect the training sets of honest participants. The attack we developed exploits the real-time nature of the learning process that allows the adversary to train a Generative Adversarial Network (GAN) that generates prototypical samples of the targeted training set that was meant to be private (the samples generated by the GAN are intended to come from the same distribution as the training data). Interestingly, we show that record-level DP applied to the shared parameters of the model, as suggested in previous work, is ineffective (i.e., record-level DP is not designed to address our attack).
Spatial frequency antiwindup strategy for cross-directional control problems (2002)

A MIMO antiwindup strategy for cross-directional control of web forming processes is presented. The scheme relies on a basis function expansion of the system interaction matrix which allows one to analyse the problem in terms of the spatial frequency components of the web profile. Antiwindup protection is achieved by prioritising the control directions in which the available control authority is employed. In particular, disturbance compensation is first sought in those spatial frequency components associated with the largest gain, that is, where the required control effort is smaller. Stability of the scheme is analysed for the case in which complete knowledge of the input and output rotation matrices is assumed. Simulation results show that the steady-state performance attained with the proposed strategy is superior to that achieved by traditional MIMO antiwindup schemes and is close to an optimal QP solution to the problem.
Epitaxially grown Si/SiGe interband tunneling diodes with high room-temperature peak-to-valley ratio (2000)

Room-temperature current–voltage characteristics of Si/Si1−xGex/Si p+-i-n+ interband tunneling diodes are presented. Special attention is paid to the peak current density (PCD) and the peak-to-valley current ratio (PVCR) of the devices. A variation of the SiGe layer width between 4 and 2 nm changes the PCD from 0.4 to 12.6 kA/cm2, at the same time conserving a PVCR of more than 4.1. The optimization of the Ge concentration x in the Si1−xGex layer results in a PVCR of 5.1 for x=48%. Tuning the position of the Si0.52Ge0.48 layer within the intrinsic zone culminates in a structure with a PCD of 8 kA/cm2 and improves the PVCR to the value of 5.45.
Substituent effects in the reaction of N-benzoyl-.beta.-arylserinates with thionyl chloride (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituent effects in the reaction of N-benzoyl-.beta.-arylserinates with thionyl chlorideSeemon H. Pines and Matthew A. KozlowskiCite this: J. Org. Chem. 1972, 37, 2, 292–297Publication Date (Print):January 1, 1972Publication History Published online1 May 2002Published inissue 1 January 1972https://pubs.acs.org/doi/10.1021/jo00967a023https://doi.org/10.1021/jo00967a023research-articleACS PublicationsRequest reuse permissionsArticle Views158Altmetric-Citations8LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Species specificity of prorenin binding to the pro renin receptor in vitro (2010)

In this study, binding properties of human prorenin to rat (pro)renin receptor (r(P)RR) and rat prorenin to human (pro)renin receptor (h(P)RR) were elucidated in vitro to investigate species specificity of prorenin bindings to (P)RR. Both (P)RRs were expressed in vitro based on wheat germ lysate and purified using His trap column. The association and dissociation rate constants of human and rat prorenin for the immobilized r(P)RR and h(P)RR were 6.64 x 10(6) and 1.01 x 10(6) M-1.s-1 and, 0.024 and 8.45 x 10(-3) s-1, respectively. Their KD values were 3.7 nM (3-fold higher than that of human prorenin vs h(P)RR (1.2 nM)) and 8.3 nM (1.2-fold lower than that of rat prorenin vs r(P)RR (10.2 nM)), respectively. Additionally, human and rat prorenin bound to the pre-adsorbed rat and human (P)RR, respectively, performed enzymatic activities. Their molecular activities were 4.1h-1 (almost similar (3.8h -1) to human prorenin vs h(P)RR) and 0.98 h-1 (approximately 2-fold lower than rat prorenin vs r(P)RR), respectively. Thus, these results suggest the species specificity for bindings of prorenin to (P)RR, which could be useful in elucidating the biochemical properties of prorenin binding to the receptor.
Additives To Lower and Stabilize the Viscosity of Pyrolysis Oils during Storage (1997)

The initial development of additives to stabilize the viscosity of biocrude during long-term storage has produced dramatic results. The additives investigated were ethyl acetate, methyl isobutyl ketone and methanol, acetone, methanol, acetone and methanol, and ethanol. These additives represent three chemical families, which all demonstrated the ability to drastically reduce the aging rate of biocrude, as defined by the increase in viscosity with time. Accelerated aging tests were run at 90 °C to screen the additives. The additives not only lowered the initial viscosity at 40 °C by half but also reduced the aging rate of a hot gas filtered pyrolysis oil made from hybrid poplar (NREL run 175) by factors of 1−18 compared to the original pure oil. With the best additive, methanol, at a 10 wt % level in the pyrolysis oil, the modified biocrude was still a single-phase liquid and still met the ASTM No. 4 diesel fuel specification for viscosity even after 96 h exposure to 90 °C. Based on the aging rate at 90 °C recently determined for pure biocrude without additives, the pure biocrude tested would have exceeded the allowable ASTM No. 4 viscosity after only 2.6 h. In addition, the unmodified biocrude formed a waxy precipitate that floated on top of the liquid phase after 8 h exposure to 90 °C. Use of methanol with previously aged oils greatly reduces the resultant viscosity, but not quite as effectively as the use of the methanol shortly after the pyrolysis oil is produced. The cost of the additive, e.g., methanol, may be offset by the heating value it adds to the pyrolysis oil, depending on the local cost of each.
A novel amphoteric, pH‐sensitive, biodegradable poly[chitosan‐g‐(L‐lactic‐co‐citric) acid] hydrogel (2003)

Abstract The novel amphoteric, pH‐sensitive, biodegradable poly([chitosan‐ g ‐( L ‐lactic‐ co ‐citric) acid]) hydrogel (CLC) was synthesized through the reaction of chitosan (CS) with poly( L ‐lactic‐ co ‐citric acid) (PLCA). The structure of CLC was characterized by Fourier transform infrared spectroscopy, elemental analysis, and wide‐angle X‐ray diffraction measurement. The degree of substitution of CS amino groups was evaluated from salicylaldehyde analysis. The swelling behavior of CLC film in an aqueous solution with various pHs and the apparent swelling kinetics were studied. The swelling mechanisms of CLC film in acidic and alkaline mediums are discussed. The results showed that CLC hydrogel had a higher degree of swelling in the pH range of 4 &gt; pH &gt; 8 and that the swelling rate order in different buffers was neutral &gt; acidic &gt; basic mediums. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3850–3854, 2003
Effects of neuro-electric therapy (N.E.T.) in drug addiction: interim report. (1977)

The treatment of drug addiction be electro-acupuncture was described by Dr. Wen,1in Hong Kong in 1973, following on a visit to China in 1972 to study the techniques used there. He had started investigating electro-acupuncture in order to use it a sanalgesia in his operations, when some of the patients on whom he was experimenting volunteered the fact that after 40 minutes of electroacupuncture, they lost their desire for heroin. (Hong Kong has a massive drug problem and it is estimated that an average of 15 per cent of the hospital's surgical patients were opiate addicts.)
A Kingdom-Level Phylogeny of Eukaryotes Based on Combined Protein Data (2000)

Current understanding of the higher order systematics of eukaryotes relies largely on analyses of the small ribosomal subunit RNA (SSU rRNA). Independent testing of these results is still limited. We have combined the sequences of four of the most broadly taxonomically sampled proteins available to create a roughly parallel data set to that of SSU rRNA. The resulting phylogenetic tree shows a number of striking differences from SSU rRNA phylogeny, including strong support for most major groups and several major supergroups.