gebhart/patrepeval huggingface dataset:
DNA interstrand cross-linking, DNA sequence specificity, and induced conformational changes produced by a dimeric analog of (+)-CC-1065. (1991)

U-77779 is a symmetrical dimer of the spirocyclopropyl alkylating subunit of (+)-CC-1065 in which the linker consists of two indole subunits separated by a ureido group. This compound was synthesized by scientists of the Upjohn Company and was found to be more active in both anti-tumor efficacy and cytotoxicity than its mono-alkylating analogs. Using three different 21-base pair DNA duplexes containing U-77779 reactive sequences, we have shown that U-77779 produces a stable interstrand cross-linked species that loses its internal self complementarity. A comparison of U-77779 with the mono-alkylating analogs of (+)-CC-1065 shows that it appears to have an increased sequence selectivity such that, while mono-alkylating compounds like (+)-CC-1065 react at more than one site, U-77779 reacts only at sites where there are two suitably positioned alkylation sites. Chemical footprinting with 1,10-phenanthroline-copper complex revealed a six base pair cross-linked region between the two covalently modified adenines with modulated cleavage outside this region. In the case of hydroxyl radical footprinting, considerable variability of the extent of cleavage within the cross-linked sequence was found. These results are discussed in terms of likely induced conformational changes in DNA. In contrast to (+)-CC-1065, non-denaturing gel electrophoresis did not reveal any net bending of DNA due to U-77779, which we believe is due to the 180 degrees out-of-phase bending produced on opposite strands of DNA by the cross-linker.
Membrane-bound D-gluconate dehydrogenase of Serratia marcescens: Purification and properties. (1978)

Membrane-bound D-gluconate dehydrogenase, which catalyzes oxidation of D-gluconate to 2-keto-n-gluconate in the presence of an electron transport system, was purified to homo-geneous state from Serratia marcescens IFO 3054. Purification was achieved at about 450-fold with an overall yield of 18% from the particulate fraction by solubilization with Triton X-100, subsequent fractionations on DEAE-cellulose and DEAE-Sephadex column chromato-graphies, and precipitation with polyethylene glycol 6000. The purified enzyme preparation was found to be an enzyme-cytochrome complex and the dehydrogenase protein tightly bound cytochrome c1 component which had the absorption maxima at 418, 523 and 554nm. The substrate specificity of the enzyme seemed to be restricted to only D-gluconate and the apparent Km value of the purified enzyme for D-gluconate was 0.8×10-3M. Enzyme activity was inhibited by pyruvate competitively and by oxamate noncompetitively.
Tumor margin assessment of surgical tissue specimen of cancer patients using label-free hyperspectral imaging (2017)

We are developing label-free hyperspectral imaging (HSI) for tumor margin assessment. HSI data, hypercube (x,y,λ), consists of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on the HSI image has an optical spectrum. We developed preprocessing and classification methods for HSI data. We used spectral features from HSI data for the classification of cancer and benign tissue. We collected surgical tissue specimens from 16 human patients who underwent head and neck (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and fluorescence images with 2-NBDG and proflavine from the specimens. Digitized histologic slides were examined by an H&N pathologist. The hyperspectral imaging and classification method was able to distinguish between cancer and normal tissue from oral cavity with an average accuracy of 90±8%, sensitivity of 89±9%, and specificity of 91±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94±6%, sensitivity of 94±6%, and specificity of 95±6%. Hyperspectral imaging outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study suggests that label-free hyperspectral imaging has great potential for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the hyperspectral imaging technology is warranted for its application in image-guided surgery.
Cellular immunolocalization of gastric and pancreatic lipase in various tissues obtained from dogs (2002)

We concluded that cGL and cPL are exclusively expressed in gastric glands and pancreatic acinar cells, respectively. Also, evidence for cross-immunoreactivity with other lipases or related proteins expressed by other tissues was not found for either protein. Analysis of these data suggests that gastric lipase is a specific marker for gastric glands and that pancreatic lipase is a specific marker for pancreatic acinar cells. These markers may have clinical use in the diagnosis of gastric and exocrine pancreatic disorders, respectively.
The Murine Version of BAN2401 (mAb158) Selectively Reduces Amyloid-β Protofibrils in Brain and Cerebrospinal Fluid of tg-ArcSwe Mice (2014)

Amyloid-β (Aβ) immunotherapy for Alzheimer's disease (AD) has good preclinical support from transgenic mouse models and clinical data suggesting that a long-term treatment effect is possible. Soluble Aβ protofibrils have been shown to exhibit neurotoxicity in vitro and in vivo, and constitute an attractive target for immunotherapy. Here, we demonstrate that the humanized antibody BAN2401 and its murine version mAb158 exhibit a strong binding preference for Aβ protofibrils over Aβ monomers. Further, we confirm the presence of the target by showing that both antibodies efficiently immunoprecipitate soluble Aβ aggregates in human AD brain extracts. mAb158 reached the brain and reduced the brain protofibril levels by 42% in an exposure-dependent manner both after long-term and short-term treatment in tg-ArcSwe mice. Notably, a 53% reduction of protofibrils/oligomers in cerebrospinal fluid (CSF) that correlated with reduced brain protofibril levels was observed after long-term treatment, suggesting that CSF protofibrils/oligomers could be used as a potential biomarker. No change in native monomeric Aβ42 could be observed in brain TBS extracts after mAb158-treatment in tg-ArcSwe mice. By confirming the specific ability of mAb158 to selectively bind and reduce soluble Aβ protofibrils, with minimal binding to Aβ monomers, we provide further support in favor of its position as an attractive new candidate for AD immunotherapy. BAN2401 has undergone full phase 1 development, and available data indicate a favorable safety profile in AD patients.
Learning Montezuma's Revenge from a Single Demonstration (2018)

We propose a new method for learning from a single demonstration to solve hard exploration tasks like the Atari game Montezuma's Revenge. Instead of imitating human demonstrations, as proposed in other recent works, our approach is to maximize rewards directly. Our agent is trained using off-the-shelf reinforcement learning, but starts every episode by resetting to a state from a demonstration. By starting from such demonstration states, the agent requires much less exploration to learn a game compared to when it starts from the beginning of the game at every episode. We analyze reinforcement learning for tasks with sparse rewards in a simple toy environment, where we show that the run-time of standard RL methods scales exponentially in the number of states between rewards. Our method reduces this to quadratic scaling, opening up many tasks that were previously infeasible. We then apply our method to Montezuma's Revenge, for which we present a trained agent achieving a high-score of 74,500, better than any previously published result.
Integrated Hybrid Silicon Transmitters (2011)

We review recent progress made on the hybrid silicon platform towards realizing an integrated WDM transmitter on silicon. Using ion implantation enhanced quantum well intermixing, four band gaps are integrated on a single chip and used to demonstrate a DFB laser-EAM array. The latest results on design changes to improve Mach-Zender and EA modulator performance are also described and the prospects for fabricating an integrated terabit per second transmitter on silicon are presented.
Absolute configuration of atrovenetin and related compounds (1971)

Chemical correlation of a degradation product of isoherqueinone with S-(–)-ethyl lactate has established that herqueinone and isoherqueinone have the R- and S-configuration respectively at the asymmetric centre in the side-chain; it follows that atrovenetin possesses the R-configuration.
Rigid Dipeptide Mimetics:  Efficient Synthesis of Enantiopure Indolizidinone Amino Acids (1996)

An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from l- and d-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of β-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric α,ω-bis[N-(PhF)amino]azelate δ-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl 2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric α,ω-bis[N-(PhF)amino]azelate δ-alcohol 7a, which upon mesylation and intramolecular SN2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]indolizidinone methyl ester 12 with NaN(SiMe3)2 and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation−activity relationships of various biologically active peptides.
Cutting Edge: TGF-β-Induced Expression of Foxp3 in T cells Is Mediated through Inactivation of ERK (2008)

The peripheral induction of T regulatory cells can be accomplished by TGF-beta through an epigenetic regulation leading to the expression of Foxp3. However, the exact mechanism of such a TGF-beta-mediated action remains unclear. In the current study, we found that TGF-beta treatment of CD4+CD25- T cells during T cell activation led to a transient inhibition of the phosphorylation of ERK followed by the induction of Foxp3 expression in these cells. Direct treatment with a specific ERK inhibitor, UO126, during CD4+CD25- T cell activation also induced Foxp3 expression and conferred a suppressive function to the induced Foxp3+ T cells. Furthermore, treatment of T cells with either TGF-beta or UO126 significantly down-regulated the expression of DNMTs, a reaction normally elicited by demethylation agents, such as 5-Aza-2'-deoxycytidine. These results indicate that the epigenetic regulation of TGF-beta-induced expression of Foxp3 may be mediated through the inactivation of ERK.
Applicable Protocol for Updating Firmware of Automotive HVAC Electronic Control Units (ECUs) Over the Air (2018)

Electronic control units (ECUs) are proliferating in modern intelligent vehicles these days. These ECUs maintain diverse functions in the vehicle with the aid of firmware. Automotive manufacturers usually develop firmware updates to fix the bugs or upgrade the functionality of the vehicle. Software update procedure is critical and time consuming in the automotive domain. However, telecommunications industry takes advantage of innovative mobile software management technology to remotely update the system called firmware-over-the-air (FOTA). FOTA enables device manufacturers and mobile operators to provide efficient and timely software updates for their products. Proposing FOTA technology in the automotive industry reduces costs and promotes customer satisfaction by avoiding yearly vehicle recalls. This paper is proposing and testing an ECU firmware update process for commercial vehicles based on FOTA technology. Through this article, the Mobile Climate Control Group (MCC)-FOTA protocol for the vehicles in the controller area network (CAN) bus network is analyzed and evaluated. The advantages and challenges of using the MCC-FOTA protocol to update embedded ECUs of commercial vehicles is confirmed, performing on-field testing.
Synthesis of Bottlebrush Polystyrenes with Uniform, Alternating, and Gradient Distributions of Brushes Via Living Anionic Polymerization and Hydrosilylation (2015)

By combining living anionic polymerization and hydrosilylation, densely grafted bottlebrush polymers with controlled spacing of branch points are prepared. Dimethyl(4-vinylphenyl)silane and dimethyl(4-(1-phenylvinyl)phenyl)silane are anionically (co)polymerized to synthesize uniform, alternating, and gradient in-chain silyl-hydride (Si-H) functionalized backbones. The spacing of branch points is controlled effectively by regulating the distribution of Si-H groups along the backbones. Three backbones with a similar number of Si-H groups but variable distributions are used to synthesize corresponding bottlebrush polymers via hydrosilylation between the backbones and chain-end vinyl functionalized polystyrene. The uniformly grafted bottlebrush exhibits the highest hydrodynamic radius (Rh ) of 5.6 nm and the lowest Tg of 79 °C which may be attributed to its compact grafted structure. This methodology exhibits high efficiency and convenience for the construction of bottlebrushes with controlled distribution of brushes.
Efficient coverage analysis metric for HDL design validation (2001)

Simulation is still the primary approach for the functional verification of register-transfer level circuit descriptions written in hardware description language (HDL). The major problem of the simulation approach is to choose a good metric to gauge the quality of the test patterns. The finite state machine (FSM) coverage test can find most of the design errors in a FSM. However, it is impractical for large designs because of the state explosion problem. In the paper, a higher-level FSM model is proposed to replace the conventional FSM model in the coverage test. The state transition graph can be significantly reduced in the model so that the complexity of the test sets becomes acceptable, even for large designs. This higher-level FSM model, called the semantic finite state machine (SFSM) model, can be easily extracted from the original HDL code automatically with little computation overhead. The advantages of using this model instead of the conventional FSM model in HDL design validation are thoroughly discussed. The implementation results show that it is indeed a promising functional coverage metric.
Modifications in the phase transition properties of predeposited VO2 films (1984)

Thin films of the phase transition material vanadium dioxide (VO2) were deposited by thermal oxidation of e-beam evaporated vanadium on a variety of bulk materials. Substrate effects on transition temperature are confirmed as being due to a mismatch between film and substrate thermal expansion coefficients. Decreasing tensile stress results in a lowering of VO2 transition temperature. Effects of low-energy Ar+ bombardment on the electrical and optical properties of these predeposited VO2 films were investigated. Bombardment energies in the range 138–500 eV at 1.0–1.3 mA/cm2 for 120–180 s were provided by a Commonwealth Millatron. The higher Ar+ energies resulted in collapse of the VO2 optical transmittance hysteresis loop, while low-energy Ar+ ions caused both a downward shift in the transition temperature and a decrease in hysteresis loop width, suggesting a dependence of these quantities on intrinsic stress. In addition, large decreases in cold-state resistivity are reported and attributed to a reduction of the surface oxide by the low energy argon beam.
Use of antennas as sensors to discover signals to form mobile broadband networks (2009)

Antennas are not generally thought of as a sensor in a classic sense. An antenna used in combination with a radio form a technology capable of being classified as a sensor; specifically, when the system is used in the process of discovery or other similar systems in an uncertain task environment. In this research, antennas are used with radios and other mechanical devices and software to create nodes which can autonomously form mobile broadband networks. Each node of the network must sense and discover other nodes via a process of search, identification and connection. As each of the nodes connects to others, the end result will be a broadband network of potentially many nodes covering a great physical distance. This self-configuring network can be used in defense, homeland security, emergency response, agriculture and many other specific areas where communication is of paramount importance.
Use of a cholesterol-rich bovine lipoprotein to enhance cholesterol concentrations in the preparation of serum control materials. (1976)

We describe a process for preparing a cholesterol-rich lipoprotein extract from bovine serum. The material is used to enhance cholestrol concentration up to 3.5 g/liter in a clear control material from human serum. The optical clarity of the enriched serum is only slightly affected by lyophilization and reconstitution. The lipoprotein additive neither produces any evidnet interference in the measurement of the commonly analyzed consitutents nor affects the stability of components after lyophilization and reconstitution.
Current Status of Antioxidant Therapy for Alzheimer's Disease (1998)

Accumulating evidence from preclinical and clinical studies supports the hypothesis that oxidative stress may be associated with the onset and progression of Alzheimer's Disease (AD). Antioxidant therapies are being promoted in the lay press to enhance mental functions and delay cognitive losses with aging. An increasing number of physicians are also recommending antioxidant therapies, such as high dose vitamin E, for subjects with AD and other neurodegenerative disorders. High dose vitamin E, ginkgo biloba, and selegiline are three putative antioxidants that have been tested in randomized multicenter trial conditions in the US. This paper summarizes the oxidative stress hypothesis of AD and reviews the strengths and limitations of published antioxidant studies in AD in relation to the role of such therapies in practice.
Increased Sedoheptulose-1,7-Bisphosphatase Activity in Transgenic Tobacco Plants Stimulates Photosynthesis and Growth from an Early Stage in Development (2005)

Activity of the Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase (SBPase) was increased by overexpression of an Arabidopsis (Arabidopsis thaliana) cDNA in tobacco (Nicotiana tabacum) plants. In plants with increased SBPase activity, photosynthetic rates were increased, higher levels of Suc and starch accumulated during the photoperiod, and an increase in leaf area and biomass of up to 30% was also evident. Light saturated photosynthesis increased with increasing SBPase activity and analysis of CO2 response curves revealed that this increase in photosynthesis could be attributed to an increase in ribulose 1,5-bisphosphate regenerative capacity. Seedlings with increased SBPase activity had an increased leaf area at the 4 to 5 leaf stage when compared to wild-type plants, and chlorophyll fluorescence imaging of these young plants revealed a higher photosynthetic capacity at the whole plant level. Measurements of photosynthesis, made under growth conditions integrated over the day, showed that mature plants with increased SBPase activity fixed 6% to 12% more carbon than equivalent wild-type leaves, with the young leaves having the highest rates. In this paper, we have shown that photosynthetic capacity per unit area and plant yield can be increased by overexpressing a single native plant enzyme, SBPase, and that this gives an advantage to the growth of these plants from an early phase of vegetative growth. This work has also shown that it is not necessary to bypass the normal regulatory control of SBPase, exerted by conditions in the stroma, to achieve improvements in carbon fixation.
Evidence for altered regulation of I kappa B α degradation in human colonic epithelial cells (1997)

The nuclear factor kappaB (NF-kappaB) regulates the transcription of genes bearing the kappaB consensus motif. Transmigration of NF-kappaB from the cytoplasm to the nucleus is regulated by the IkappaB family of inhibitory NF-kappaB-binding proteins. Dissociation of the NF-kappaB-IkappaB complex requires both phosphorylation and degradation of IkappaBs. We demonstrate that IL-1beta induces complete IkappaB alpha degradation in Caco-2 cell lines but not in HT-29, T84, SW-480 transformed cell lines, or native colonic epithelial cells. A similar lack of IkappaB alpha degradation in HT-29 cells followed TNF-alpha and bacterial polymer stimulation. IL-1beta stimulated NF-kappaB nuclear translocation and NF-kappaB-dependent IL-1beta and IL-8 expression in both Caco-2 and HT-29 cells as assayed by electrophoretic mobility shift assay, immunofluorescence, kappaB-luciferase transfection, reverse transcriptase-PCR analysis and ELISA. In HT-29 cells stimulated with IL-1beta, IkappaB alpha was phosphorylated and when cycloheximide blocked new protein synthesis, IkappaB alpha was partially degraded. NF-kappaB cytoplasmic to nuclear transmigration was incomplete and preceded IkappaB alpha degradation in 9T-29 cells, in contrast to complete coordinated NF-kappaB nuclear translocation and IkappaB alpha degradation in Caco-2 cells. Greater sensitivity of HT-29 cells to a calpain inhibitor, as measured by IL-8 secretion, suggested enhanced resistance to IkappaB alpha proteolysis. These data show that IL-1beta induces NF-kappaB activity and expression of NF-kappaB-dependent genes in colonic epithelial cells and suggest altered regulation of IkappaB alpha degradation compared with other cell lineages, which may result in their increased responsiveness to therapeutic blockade.
Cloning and expression of a cDNA for the rat <i>k</i>‐opioid receptor (1993)

We cloned a cDNA for the rat kappa-opioid receptor from a rat thalamus cDNA library. The deduced amino acid sequence consists of 380 residues with features shared by members of the G protein-coupled receptor family. The specific binding of [3H]bremazocine to the membrane of COS-7 cells transfected with the cDNA was displaced by kappa-specific opioid ligands, but not by mu- and delta-specific ligands. Xenopus oocytes injected with the in vitro transcribed mRNA responded to opioid ligands with the same subtype specificity. Northern blot analysis demonstrated that kappa-opioid receptor mRNA is expressed in a regionally specific manner in rat brain.