gebhart/patrepeval huggingface dataset:
Tailoring Tryptophan Synthase TrpB for Selective Quaternary Carbon Bond Formation (2019)

We previously engineered the tryptophan synthase beta-subunit (TrpB), which catalyzes the condensation reaction between L-serine and indole to form L-tryptophan, to synthesize a range of modified tryptophans from serine and indole derivatives. In this study, we used directed evolution to engineer TrpB to accept 3-substituted oxindoles and form C–C bonds leading to new quaternary stereocenters. At first, the TrpBs that could use 3-substituted oxindoles preferentially formed N–C bonds by attacking the oxindole N1 atom. We found, however, that protecting the nitrogen encouraged evolution towards C-alkylation, which persisted even when this protection was removed. After seven rounds of evolution leading to a 400-fold improvement in activity, variant Pfquat efficiently alkylates 3-substituted oxindoles to selectively form new stereocenters at the γ-position of the amino acid products. The configuration of the new γ-stereocenter of one of the products was determined from the crystal structure obtained by microcrystal electron diffraction (MicroED). Substrates structurally related to 3-methyloxindole such as lactones and ketones can also be used by the enzyme for quaternary carbon bond formation, where the biocatalyst exhibits excellent regioselectivity for the tertiary carbon atom. Highly thermostable and expressed at > 500 mg/L E. coli culture, TrpB Pfquat provides an efficient and environmentally-friendly platform for the preparation of noncanonical amino acids bearing quaternary carbons.
Defucosylated Anti-CCR4 Monoclonal Antibody Exerts Potent ADCC against Primary ATLL Cells Mediated by Autologous Human Immune Cells in NOD/Shi-<i>scid</i>, IL-2Rγnull Mice In Vivo (2009)

There is a lack of suitable small animal models to evaluate human Ab-dependent cellular cytotoxicity (ADCC) in vivo, because of the species incompatibility between humans and animals or due to nonspecific allogeneic immune reactions. To overcome these problems, we established a human tumor-bearing mouse model, using NOD/Shi-scid, IL-2Rgamma(null) (NOG) mice as recipients, in which autologous human immune cells are engrafted and mediate ADCC but in which endogenous murine cells are unable to mediate ADCC. In the present study, we used NOG mice bearing primary adult T cell leukemia/lymphoma (ATLL) cells and a therapeutic chimeric anti-CCR4 mAb, the Fc region of which is defucosylated to enhance ADCC. We report significant antitumor activity in vivo associated with robust ADCC mediated by autologous effector cells from the same patients. The present study is the first to report a mouse model in which a potent antitumor effect of the therapeutic mAb against primary tumor cells is mediated by autologous human immune cells. Human autologous ADCC in mice in vivo was confirmed by the depletion of human immune cells before ATLL PBMC inoculation. In addition, NOG mice bearing primary ATLL cells presented features identical with patients with ATLL. In conclusion, this approach makes it possible to model the human immune system active in Ab-based immunotherapy in vivo, and thus to perform more appropriate preclinical evaluations of novel therapeutic mAb. Furthermore, the potent ADCC mediated by defucosylated anti-CCR4 mAb, observed here in vivo in humanized mice, will be exploited in clinical trials in the near future.
Positive effects of polyethylene glycol conjugation to generation‐4 polyamidoamine dendrimers as macromolecular MR contrast agents (2001)

Macromolecules conjugated with polyethylene glycol (PEG) acquire more hydrophilicity, resulting in a longer half-life in circulation and lower immunogenicity. Two novel conjugates for MRI contrast agents were synthesized from a generation-4 polyamidoamine dendrimer (G4D), 2-(p-isothiocyanatobenzyl)-6methyl-diethylenetriaminepentaacetic acid (1B4M), and one or two PEG molecules with a molecular weight of 20000 Da (PEG 2 -G4D-(1B4M-Gd) 62 (MW: 96 kD), PEG 1 -G4D-(1B4M-Gd) 63 (MW: 77 kD)). Their pharmacokinetics, excretion, and properties as vascular MRI contrast agents were evaluated and compared with those of G4D-(1B4M-Gd) 64 (MW: 57 kD). PEG 2 -G4D-(1B4M-Gd) 62 remained in the blood significantly longer and accumulated significantly less in the liver and kidney than the other two preparations (P < 0.01). Although the blood clearance was slower, PEG 2 -G4D-(1B4M-Gd) 62 was excreted more readily without renal retention than the other two preparations. In conclusion, the positive effects of PEG conjugation on a macromolecular MRI contrast agent were found to be prolonged retention in the circulation, increased excretion, and decreased accumulation in the organs.
Heat‐sealing properties of soy protein isolate/poly(vinyl alcohol) blend films: Effect of the heat‐sealing temperature (2009)

Abstract To promote the heat‐sealing properties of soy protein isolate (SPI) films applied in the packaging field, we mixed a synthetic polymer of poly(vinyl alcohol) (PVA) with SPI to fabricate blend films by a solution‐casting method in this study. To clarify the relationship between the heat‐sealing properties and the heat‐sealing temperature, strength, melting process, crystalline structure, and microstructure, variations of the heat‐sealing parts of the films were evaluated by means of differential scanning calorimetry, tensile testing, scanning electron microscopy, X‐ray diffraction, and Fourier transform infrared spectroscopy, respectively. The test results showed that both the PVA and glycerol contents greatly affected the melting behavior and heat of fusion of the SPI/PVA blends; these blend films had a higher melting temperature than the pure SPI films. The peel strength and tensile strength tests indicated that the long molecular chain of PVA had a main function of enhancing the mechanical properties above the melting temperature. With increasing heat‐sealing temperature, all of the mechanical properties were affected by the microstructure of the interface between the laminated films including the chain entanglement, crystallization, and recrystallization. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Role of the Adiponectin Binding Protein, T-Cadherin (cdh13), in Pulmonary Responses to Subacute Ozone (2013)

Adiponectin, an adipose derived hormone with pleiotropic functions, binds to several proteins, including T-cadherin. We have previously reported that adiponectin deficient (Adipo(-/-)) mice have increased IL-17A-dependent neutrophil accumulation in their lungs after subacute exposure to ozone (0.3 ppm for 72 hrs). The purpose of this study was to determine whether this anti-inflammatory effect of adiponectin required adiponectin binding to T-cadherin. Wildtype, Adipo(-/-) , T-cadherin deficient (T-cad(-/-) ), and bideficient (Adipo(-/-)/T-cad(-/-) ) mice were exposed to subacute ozone or air. Compared to wildtype mice, ozone-induced increases in pulmonary IL-17A mRNA expression were augmented in T-cad(-/-) and Adipo(-/-) mice. Compared to T-cad(-/-) mice, there was no further increase in IL-17A in Adipo(-/-)/T-cad(-/-) mice, indicating that adiponectin binding to T-cadherin is required for suppression of ozone-induced IL-17A expression. Similar results were obtained for pulmonary mRNA expression of saa3, an acute phase protein capable of inducing IL-17A expression. Comparison of lung histological sections across genotypes also indicated that adiponectin attenuation of ozone-induced inflammatory lesions at bronchiolar branch points required T-cadherin. BAL neutrophils and G-CSF were augmented in T-cad(-/-) mice and further augmented in Adipo(-/-)/T-cad(-/-) mice. Taken together with previous observations indicating that augmentation of these moieties in ozone exposed Adipo(-/-) mice is partially IL-17A dependent, the results indicate that effects of T-cadherin deficiency on BAL neutrophils and G-CSF are likely secondary to changes in IL-17A, but that adiponectin also acts via T-cadherin independent pathways. Our results indicate that T-cadherin is required for the ability of adiponectin to suppress some but not all aspects of ozone-induced pulmonary inflammation.
8.5 A sub-1.75W full-duplex 10GBASE-T transceiver in 40nm CMOS (2014)

The IEEE802.3an 10GBASE-T standard describes full-duplex 10Gb/s Ethernet transmission over four pairs of up to 100m UTP cable. For the implementation of high-density 10GBASE-T network switches, highly integrated transceivers are required that have both a small form factor and high power efficiency. This paper describes an analog front-end (AFE) that is used in a quad-port 10GBASE-T transceiver chip. The small form factor of the AFE allows for the use of a 23×23mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> BGA package, enabling implementation of 48-port switches with all transceivers in a single row on the PCB pitch-matched to the RJ45 connector arrays. The design achieves >62dBc transmitter SFDR, >62dBc echo cancellation (EC) SFDR, and >60dBc receiver SFDR up to 400MHz. It occupies an area of 15.1mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> per port in a 40nm CMOS process. At 100m full 10Gb/s traffic, the AFE dissipates less than 1.75W.
Synthesis and Applications of Isocyanate Free Polyurethane Materials (2016)

The manufacture of conventional polyurethanes include the use of isocyanates, which in turn require using toxic and hazardous phosgene. The safety devices are necessary to prepare these monomers. Therefore, the huge investment is inevitable for this process. Also, these monomers cannot be considered as environmentally friendly chemicals. The increasing global awareness for protection of environment from chemical pollutants has created a necessary demand for environmentally benign products. The reaction of cyclic carbonates (polycarbonates) with amines results in formation of hydroxyurethanes that can be taken into account as a unique reaction. This specific reaction has been investigated over last few years. Most chemists have been strongly attracted by this technique that is due to its potential application to prepare the green, non-toxic, non-sensitive towards moisture isocyanate free polyurethanes. This review is focused on the variety of catalysts used to prepare isocyanate free polyurethanes from five membered cyclic polycarbonates. Also, the reaction mechanism and kinetics for their synthesis have been discussed. In this review, the six-membered cyclic carbonates depicted the higher reactivity rather than five-membered cyclic carbonates for production of non-isocyanate polyurethanes. The various functions of isocyanate free polyurethanes in different fields such as coatings, construction and bio-composites have been summarized.
Multilevel finite ground coplanar line transitions for high-density packaging using silicon micromachining (2002)

A 3D photolithographic technique is exploited to produce finite ground coplanar (FGC) transmission lines that transition into and out of silicon micromachined cavities. Each transition was found to introduce an average loss of less than 0.08 dB across the 2-40 GHz range for a cavity depth of 110 /spl mu/m. The demonstration of this technology is a significant step toward fully realizing the circuit packaging capabilities of micromachined silicon and offers the possibility of novel, broadband vertical transitions.
Post‐training excitotoxic lesions of the dorsal hippocampus attenuate forward trace, backward trace, and delay fear conditioning in a temporally specific manner (2002)

The present study sought to determine whether post-training excitotoxic lesions of the dorsal hippocampus would disrupt retention of fear conditioned using a trace procedure. Rats were trained using one of six procedures. Forward trace conditioning consisted of 10 trials in which a 16-s tone conditional stimulus (CS) was followed by a 28-s stimulus-free trace interval and then a mild footshock unconditional stimulus (US). We used two forms of delay conditioning where the tone and footshock co-terminated. Short delay used a 16-s tone and long delay used a 46-s tone. Backward trace conditioning was the same as forward trace, except that the order of the CS and US was reversed. CS-only and US-only were similar to forward trace except that the footshock or tone, respectively, was eliminated. One day later, animals received either an N-methyl-D-aspartate (NMDA)-induced lesion of the dorsal hippocampus or sham surgery. One week later, the rats were tested for freezing to the tone in a novel context. The next day, they were tested for freezing to the original training context. Hippocampal lesioned trace conditioned rats showed significantly less freezing during the tone compared with their sham lesioned controls. The lesion did not affect freezing during the tone in delay conditioning, nor in the other training conditions. During the 1-min period after tone offset, there was a trend in all hippocampal lesioned animals toward a deficit in freezing, compared with their corresponding sham lesioned controls, although only short delay, forward and backward trace groups showed a significant deficit. Hippocampal lesions also attenuated contextual conditioning. Thus, the hippocampus is critical for the consolidation and/or expression of a trace fear conditioned stimulus.
IV.C.3 Low Platinum Loading Catalysts for Fuel Cells (2005)

Approach • Develop low-Pt-loading electrocatalysts by placing a submonolayer-to-monolayer of Pt on nanoparticles of suitable metals or alloys to obtain electrocatalysts with the following characteristics: – Ultimately reduced Pt loading – Enhanced Pt activity – Complete utilization of Pt • Two methods were developed for depositing a Pt monolayer: – Electroless (spontaneous) Pt deposition on Ru – Pt deposition by replacing an underpotential deposition (UPD) metal adlayer
Discovery of Nonpeptidic Small-Molecule AP-1 Inhibitors:  Lead Hopping Based on a Three-Dimensional Pharmacophore Model (2005)

We designed and synthesized small-molecule activator protein-1 (AP-1) inhibitors based on a three-dimensional (3D) pharmacophore model that we had previously derived from a cyclic decapeptide exhibiting AP-1 inhibitory activity. New AP-1 inhibitors with a 1-thia-4-azaspiro[4.5]decane or a benzophenone scaffold, which inhibit the DNA-binding and transactivation activities of AP-1, were discovered using a “lead hopping” procedure. An additional investigation of the benzophenone analogues confirmed the reliability of the pharmacophore model, its utility to discover AP-1 inhibitors, and the potency of the benzophenone derivatives as a lead series.
Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different? (1996)

Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.
Effect of a Selective Thrombin Inhibitor MCI-9038 on Fibrinolysis In Vitro and In Vivo (1986)

The effect of a selective thrombin inhibitor, (2R, 4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]- L-arginyl]-2-piperidinecarboxylic acid (MCI-9038), on the fibrinolysis induced by t-PA and u-PA was studied in vitro and in vivo. MCI-9038 remarkably reduced the lysis time of the plasma clot generated by the addition of calcium chloride to the plasma at the concentration ranging from 0.01 to 0.3 microM. Heparin also reduced the plasma clot lysis time with a lower effect than MCI-9038. The fibrin crosslinkage in the plasma clot was inhibited by MCI-9038 or heparin. MCI-9038 potently inhibited the factor XIIIa generation from factor XIII by thrombin. The effect on the in vivo thrombolysis was studied on the arterial thrombosis generated by the endothelial cell injury of the rabbit carotid artery by acetic acid. t-PA dissolved the thrombi with the infusion at 0.96 mg/kg over 2 h without a significant activation of a systemic fibrinolysis. u-PA dissolved the thrombi with the infusion at 180,000 and 360,000 IU/kg over 2 h. At a dose of 0.48 mg/kg t-PA or 90,000 IU/kg u-PA, the thrombi were not dissolved, but the combined use of MCI-9038 at 1.2 mg/kg over 2 h effectively dissolved the thrombi. Thus, combination of MCI-9038 with plasminogen activators accelerated thrombolysis of an experimental thrombosis in rabbits.
Comparison on inducing methods of large-scale production of triploid Pacific oyster (Crassostrea gigas (Thunberg)) (2000)

Triploid Pacific oyster were induced for large-scale aquaculture by 6-DMAP and cold shock, which indicated that hatchery rate decreased by 6-DMAP treatment which damaged development of embryo to rather extent, but rate of triploid could be stabled at more than percent of 60. It was thought that 6-DMAP can be taken as a rather ideal chemical reagent for large-scale production of triploid pacific oyster.
Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin (1994)

The muscle-specific intermediate filament protein, desmin, is one of the earliest myogenic markers whose functional role during myogenic commitment and differentiation is unknown. Sequence comparison of the presently isolated and fully characterized mouse desmin cDNA clones revealed a single domain of polypeptide similarity between desmin and the basic and helix-loop-helix region of members of the myoD family myogenic regulators. This further substantiated the need to search for the function of desmin. Constructs designed to express anti-sense desmin RNA were used to obtain stably transfected C2C12 myoblast cell lines. Several lines were obtained where expression of the anti-sense desmin RNA inhibited the expression of desmin RNA and protein down to basal levels. As a consequence, the differentiation of these myoblasts was blocked; complete inhibition of myoblast fusion and myotube formation was observed. Rescue of the normal phenotype was achieved either by spontaneous revertants, or by overexpression of the desmin sense RNA in the defective cell lines. In several of the cell lines obtained, inhibition of desmin expression was followed by differential inhibition of the myogenic regulators myoD and/or myogenin, depending on the stage and extent of desmin inhibition in these cells. These data suggested that myogenesis is modulated by at least more than one pathway and desmin, which so far was believed to be merely an architectural protein, seems to play a key role in this process.
Nucleophilic substitution studies on nitroimidazoles, and applications to the synthesis of biologically active compounds (2000)

Abstract The rationalization of the synthesis of substituted analogs of megazol, a biologically active 5‐nitroimidazole at position 4 of the imidazole ring, had led to the study of intermediate steps. The methylation by diazomethane of 2,4‐(5)dihalogeno‐5‐(4)nitroimidazole is regioselective leading to 2,4‐dihalogeno‐1‐methyl‐5‐nitroimidazole 2. On this compound 2 , hard nucleophiles such as cyanide, methoxide or hydride anions react only with the halogen at the 2 position; whereas soft nucleophiles such as amine, thiol or trifluoromethyl anion from an organocopper species react only with the halogen at postion 4 in the intermediate 3b or compound 4b.
TFIIB Recognition Elements Control the TFIIA-NC2 Axis in Transcriptional Regulation (2008)

TFIIB recognizes DNA sequence-specific motifs that can flank the TATA elements of the promoters of protein-encoding genes. The TFIIB recognition elements (BRE(u) and BRE(d)) can have positive or negative effects on transcription in a promoter context-dependent manner. Here we show that the BREs direct the selective recruitment of TFIIA and NC2 to the promoter. We find that TFIIA preferentially associates with BRE-containing promoters while NC2 is recruited to promoters that lack consensus BREs. The functional relevance of the BRE-dependent recruitment of TFIIA and NC2 was determined by small interfering RNA-mediated knockdown of TFIIA and NC2, both of which elicited BRE-dependent effects on transcription. Our results confirm the established functional reciprocity of TFIIA and NC2. However, our findings show that TFIIA assembly at BRE-containing promoters results in reduced transcriptional activity, while NC2 acts as a positive factor at promoters that lack functional BREs. Taken together, our results provide a basis for the selective recruitment of TFIIA and NC2 to the promoter and give new insights into the functional relationship between core promoter elements and general transcription factor activity.
Filum Ependymoma Mimicking Spontaneous Intracranial Hypotension (2005)

A 34-year-old man with a 2-week history of orthostatic headaches and a "dry tap" at lumbar puncture was found to have a lumbar intradural mass on magnetic resonance imaging (MRI) examination. A myxopapillary ependymoma was resected and the patient's headache completely resolved. The combination of spontaneous orthostatic headaches and a "dry tap" at the time of lumbar puncture does not always indicate the presence of a spontaneous cerebrospinal fluid (CSF) leak and intracranial hypotension.
Super-Resolved Fine-Scale Sea Ice Motion Tracking (2017)

Monitoring sea ice activities is particularly critical to safe naval operations in the Arctic Ocean. Accurately tracking sea ice motions is essential to validate or even improve sea ice models for ice hazard forecasts at a fine scale. Fine-scale motions can be tracked from high-resolution radar or optical satellite imagery but with limited coverage. Daily motions over the entire Arctic are retrievable from passive microwave data, but at a much lower spatial resolution. Thus, providing motions at the passive microwave spatial and temporal coverage, but at an enhanced spatial resolution, will be a significant benefit. To break the resolution limitation and to boost tracking accuracy, a sequential super-resolved fine-scale sea ice motion tracking framework is proposed in which a hybrid example-based single image super-resolution algorithm is employed before the tracking procedure. Experiments demonstrate that the proposed framework significantly improves the tracking performance in both accuracy and robustness for a benchmark algorithm and a recently proposed state-of-the-art tracking algorithm.
Prototypes for Use in Broadbanding Reflection Amplifiers (1963)

This paper tabulates, as functions of reflection gain and ripple, the element values of negative-resistance terminated, prototype, low-pass, lumped-element ladder networks of normalized impedance and bandwidth. (the values are calculated using known synthesis methods.) Next, it provides a technique for relating the characteristics of any actual narrow-band, negative-resistance device to the value of the prototype susceptive element adjacent to the negative resistance. When an actual negative-resistance device has been related to a prototype in this manner, the performance of the device with one, two or three additional cascaded resonators can be predicted from given graphs. This allows trade-offs among gain, ripple, and bandwidth, within limits. Finally, the predicted performance can be used with simple formulas and the table of prototype element values to design suitable resonators to broadband the actual amplifier. The tables and techniques of this paper are used successfully to broadband tunnel-diode, maser and parametric-amplifier circuits. This paper allows the practical engineer to estimate the broad-banding potential of any given negative-resistance device and provides him with the proper element values to do so with only a few very simple calculations required.