gebhart/patrepeval huggingface dataset:
Field inversion gel electrophoresis applied to the rapid, multi-enzyme restriction mapping of phage lambda clones (1990)

Journal Article Field inversion gel electrophoresis applied to the rapid, multi-enzyme restriction mapping of phage lambda clones Get access Donna L. Daniels, Donna L. Daniels University of Wisconsin, Laboratory of GeneticsMadison, Wl 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol H. Olson, Carol H. Olson University of Wisconsin, Laboratory of GeneticsMadison, Wl 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Brumley, Robert Brumley University of Wisconsin, Laboratory of GeneticsMadison, Wl 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick R. Blattner Frederick R. Blattner University of Wisconsin, Laboratory of GeneticsMadison, Wl 53706, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 5, 11 March 1990, Page 1312, https://doi.org/10.1093/nar/18.5.1312 Published: 11 March 1990 Article history Received: 24 August 1989 Published: 11 March 1990
Original Paper : Microneedle-Mediated Transdermal Delivery of Chondroitin Sulfate (2009)

Microneedle-mediated transdermal drug delivery is a non-invasive delivery method for drugs through the various layers of the skin to reach systemic circulation. Microneedles are large enough to permeate through skin and form microconduits that allow drugs to penetrate into skin, but small enough to avoid causing pain. In this study, we prepared a microneedle dermaroller composed of 3600 microneedles with 230 ?m in length and examined the effects of microneedle pretreatment on the skin permeation of chondroitin sulfate. t was confirmed that microneedles created microconduits that allow chondroitin sulfate to permeate into skin. The more microneedle treatment created more microconduits, leading to the more permeation of CS-FITC into skin. Microneedle treatment in mutual cross direction is more effective in CS-FITC-permeation than in parallel direction. After microneedle pretreatment, CSFITC exhibited a more permeationinto skin in the formulation of hydrogel than in solution. This work demonstrates the feasibilityof microneedle-mediated transdermal delivery of chondroitin sulfate.
Highly Efficient Interfaces in Nanocomposites Based on Polyethylene and ZnO Nano/Hierarchical Particles: A Novel Approach toward Ultralow Electrical Conductivity Insulations (2016)

Polyethylene nanocomposites based on functionalized ZnO nano/hierarchical particles with highly effective interfacial surface area are presented, for the next generation of ultralow transmission-loss high-voltage DC insulating materials.
NetAdaptV2: Efficient Neural Architecture Search with Fast Super-Network Training and Architecture Optimization (2021)

Neural architecture search (NAS) typically consists of three main steps: training a super-network, training and evaluating sampled deep neural networks (DNNs), and training the discovered DNN. Most of the existing efforts speed up some steps at the cost of a significant slowdown of other steps or sacrificing the support of non-differentiable search metrics. The unbalanced reduction in the time spent per step limits the total search time reduction, and the inability to support non-differentiable search metrics limits the performance of discovered DNNs. In this paper, we present NetAdaptV2 with three innovations to better balance the time spent for each step while supporting non-differentiable search metrics. First, we propose channel-level bypass connections that merge network depth and layer width into a single search dimension to reduce the time for training and evaluating sampled DNNs. Second, ordered dropout is proposed to train multiple DNNs in a single forward-backward pass to decrease the time for training a super-network. Third, we propose the multi-layer coordinate descent optimizer that considers the interplay of multiple layers in each iteration of optimization to improve the performance of discovered DNNs while supporting non-differentiable search metrics. With these innovations, NetAdaptV2 reduces the total search time by up to $5.8\times$ on ImageNet and $2.4\times$ on NYU Depth V2, respectively, and discovers DNNs with better accuracy-latency/accuracy-MAC trade-offs than state-of-the-art NAS works. Moreover, the discovered DNN outperforms NAS-discovered MobileNetV3 by 1.8% higher top-1 accuracy with the same latency. The project website is http://netadapt.mit.edu.
Interpretation of Activation Volumes for Water Exchange Reactions Revisited:  Ab Initio Calculations for Al3+, Ga3+, and In3+, and New Experimental Data (1998)

The water exchange mechanisms on the hexaaqua ions of Al3+, Ga3+, and In3+ in aqueous solution have been modeled by using ab initio calculations at the Hartree−Fock level. As an approximation aqua clusters in vacuo involving seven water molecules were considered. For species with five, six, or seven water molecules in the first coordination shell of the cation, stable intermediates and transition states have been optimized and characterized from vibrational analyses. Water exchange reaction pathways could then be proposed via interconnected intermediates and transition states. The calculations provide theoretical evidence for a break in kinetic behavior between Al3+ and Ga3+ on one side and In3+ on the other. Hexaaqua complexes of Al3+ and Ga3+ show no tendency to increase their coordination number over six and, despite the high positive charge on the central ion, water exchange proceeds via a D mechanism involving a pentacoordinated intermediate [M(OH2)5·(OH2)]3+. This is in agreement with experimental volumes of activation ΔV⧧ that are the highest measured up to date for trivalent metal cations. For [In(OH2)6]3+ a dissociative exchange reaction is in principle feasible, but an associative A mechanism via a 7-fold coordinated reactive intermediate [In(OH2)7]3+ is energetically much more favorable. Theoretical arguments and indirect experimental evidence in favor of an A and against an Ia mechanism are discussed. The experimentally still lacking activation volume ΔV⧧ for water exchange on [In(OH2)6]3+ has been predicted to be −5 ± 1 cm3mol-1. The computed activation energies ΔE⧧ for Al3+ and Ga3+ are in remarkable quantitative agreement with the experimental values for ΔH⧧. This lends support to the applied theoretical model and suggests that for this class of aqua ions, with a spherical and strongly bound first hydration shell, cluster calculations in vacuo are a viable approach to reproduce the structural changes and the activation parameters for water exchange reactions in aqueous solution. Attempts have been made to determine the water exchange rate at In3+(aq), Lu3+(aq), and Zn2+(aq) by using Tb3+(aq) as a shift reagent. While none of these attempts proved successful, new lower limits for water exchange on these three ions can be given as 1 × 107 (In3+), 1 × 107 (Lu3+), and 5 × 107 s-1 (Zn2+).
Production of biologically active forms of recombinant hepcidin, the iron‐regulatory hormone (2008)

Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor, prohepcidin, which is processed to produce the biologically active mature 25 amino acid peptide. This peptide is secreted and acts by controlling the concentration of the membrane iron exporter ferroportin on intestinal enterocytes and macrophages. Hepcidin binds to ferroportin, inducing its internalization and degradation, thus regulating the export of iron from cells to plasma. The aim of the present study was to develop a novel method to produce human and mouse recombinant hepcidins, and to compare their biological activity towards their natural receptor ferroportin. Hepcidins were expressed in Escherichia coli as thioredoxin fusion proteins. The corresponding peptides, purified after cleavage from thioredoxin, were properly folded and contained the expected four-disulfide bridges without the need of any renaturation or oxidation steps. Human and mouse hepcidins were found to be biologically active, promoting ferroportin degradation in macrophages. Importantly, biologically inactive aggregated forms of hepcidin were observed depending on purification and storage conditions, but such forms were unrelated to disulfide bridge formation.
Cladding-pumped erbium-doped multicore fiber amplifier (2012)

A cladding pumped multicore erbium-doped fiber amplifier for simultaneous amplification of 6 channels is demonstrated. Peak gain over 32 dB has been obtained at a wavelength of 1560 nm and the bandwidth measured at 20-dB gain was about 35 nm. Numerical modeling of cladding pumped multicore erbium-doped amplifier was also performed to study the properties of the amplifier. The results of experiment and simulation are found to be in good agreement.
Mid-infrared (MIR) Mach-Zehnder Silicon Modulator at 2µm Wavelength based on Interleaved PN Junction (2018)

In this paper, a MIR silicon modulator operating at 2 µm wavelength is experimentally demonstrated. The modulator shows 9.7 GHz 3-dB electro-optic bandwidth at Vbias= −3V. We also present optical modulation at 12.5 Gb/s.
Identification of a Cell of Origin for Human Prostate Cancer (2010)

Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.
In Vitro Reconstitution and Analysis of the Chain Initiating Enzymes of the R1128 Polyketide Synthase (2001)

Biosynthesis of the carbon chain backbone of the R1128 substances is believed to involve the activity of a ketosynthase/chain length factor (ZhuB/ZhuA), an additional ketosynthase (ZhuH), an acyl transferase (ZhuC), and two acyl carrier proteins (ACPs; ZhuG and ZhuN). A subset of these proteins initiate chain synthesis via decarboxylative condensation between an acetyl-, propionyl-, isobutyryl-, or butyryl-CoA derived primer unit and a malonyl-CoA derived extender unit to yield an acetoacetyl-, beta-ketopentanoyl-, 3-oxo-4-methylpentanoyl-, or beta-ketohexanoyl-ACP product, respectively. To investigate the precise roles of ZhuH, ZhuC, ZhuG, and ZhuN, each protein was expressed in Escherichia coli and purified to homogeneity. Although earlier reports had proposed that ZhuC and its homologues played a role in primer unit selection, direct in vitro analysis of ZhuC showed that it was in fact a malonyl-CoA:ACP malonyltransferase (MAT). The enzyme could catalyze malonyl transfer but not acetyl- or propionyl-transfer onto R1128 ACPs or onto ACPs from other biosynthetic pathways, suggesting that ZhuC has broad substrate specificity with respect to the holo-ACP substrate but is specific for malonyl-CoA. Thus, ZhuC supplies extender units to both the initiating and elongating ketosynthases from this pathway. To interrogate the primer unit specificity of ZhuH, the kinetics of beta-ketoacyl-ACP formation in the presence of various acyl-CoAs and malonyl-ZhuG were measured. Propionyl-CoA and isobutyryl-CoA were the two most preferred substrates of ZhuH, although acetyl-CoA and butyryl-CoA could also be accepted and elongated. This specificity is not only consistent with earlier reports demonstrating that R1128B and R1128C are the major products of the R1128 pathway in vivo, but is also in good agreement with the properties of the ZhuH substrate binding pocket, as deduced from a recently solved crystal structure of the enzyme. Finally, to investigate the molecular logic for the occurrence of not one but two ACP genes within the R1128 gene cluster, the inhibition of ZhuH-catalyzed formation of beta-ketopentanoyl-ACP was quantified in the presence of apo-ZhuG or apo-ZhuN. Both apo-proteins were comparable inhibitors of the ZhuH catalyzed reaction, suggesting that the corresponding apo-proteins can be used interchangeably during chain initiation. Together, these results provide direct biochemical insights into the mechanism of chain initiation of an unusual bacterial aromatic PKS.
Abstract LB-21: Emergence of castration resistant prostate cancer class defined by recurrent ERG fusion (2010)

Abstract The role of recurrent ETS gene fusions in castration resistant prostate cancer (CRPC) is poorly understood. We characterized the transcriptome of CRPC by interrogating a cohort of 54 men with locally advanced or metastatic CRPC using a gene expression profiling method recently established for formalin-fixed paraffin-embedded tissue. We found increased expression of multiple genes in ERG rearranged tumors which suggests a selective growth advantage under oxygen poor conditions. We discovered that trefoil factor 3 (TFF3) is the top differentially regulated gene by both ERG rearrangement and resistance to therapy. Conventional chromatin immunoprecipitation (ChIP)-PCR and ChIP-seq data revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG rearranged prostate cancer cell lines, which was confirmed in ERG rearranged hormone naïve prostate cancer (HNPC) and CRPC tissue samples. In vitro data suggested that ERG has an inhibitory effect on TFF3 expression in hormone naïve cancer, which was relieved in CRPC depending on the level of AR expression. These findings reveal an interplay between ERG rearrangement and AR signaling in CRPC, and provide perspective towards novel therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-21.
Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide‐induced inflammatory cystitis (2010)

This is the first report of immunosuppression in bladder by intravesical delivery of tacrolimus using liposomes. LFK significantly inhibited CYP induced inflammatory cystitis through the modulation of IL2, PGE2, and EP4 function. These findings support investigation of local tacrolimus in cases of inflammatory cystitis refractory to conventional therapy.
P1‐121: Pharmacokinetics and pharmacodynamics following γ‐secretase modulator and inhibitor treatment of Cynomolgus monkeys (Macaca fascicularis) (2011)

The γ-secretase enzyme complex is responsible for the release of the C-terminus of amyloid ß (Aß) from amyloid precursor protein (APP), leading to the formation of Aß species of different length. Aß ending at amino acid 42 (Aß42) is particularly neurotoxic and it is the first and predominant Aß species deposited in brains of Alzheimer's disease (AD) patients. Numerous studies support that accumulation of Aß42 in brain is central to AD pathogenesis and consequently, reduction of Aß42 levels in brain represents a valid therapeutic disease-modifying approach for AD. While γ-secretase inhibitors (GSI) show side effects due to concomitant inhibition of Notch processing, γ-secretase modulators (GSM) have the potential to specifically decrease Aß42 production without affecting Notch processing. We investigated the pharmacokinetic and pharmacodynamic profile of GSI LY-450139 and GSM E-2012 in cerebrospinal fluid (CSF) of young cynomolgus monkeys (Macaca fascicularis) following oral administration. Seven animals with surgically implanted cisterna magna catheters received treatment using a staggered study design of four treatment arms each in phase 1 (vehicle, 1.25, 2.5 and 7.5 mg/kg LY-450139) and phase 2 (vehicle, 20, 40 and 80 mg/kg E-2012), respectively. There was a seven-day interval between treatment arms and between study phases. Blood and CSF samples for pharmacokinetic and pharmacodynamic analyses were collected at various time points. Oral treatment of cynomolgus monkeys with E-2012 resulted in an increased Aß38/Aß42 ratio in CSF. Interestingly, analysis of the PK/PD relationship utilizing a linear mixed regression analysis revealed a differential effect of LY-450139 treatment on Aß38, Aß40 and Aß42 levels in monkey CSF. LY-450139 treatment did not result in a significant Aß rebound effect in monkey CSF. Our data confirm the feasibility of Aß reduction through modulation or inhibition of γ-secretase in a preclinical, non-human primate model. Moreover, we show a differential effect of GSI treatment on distinct Aß species, an observation that might have significant implications for the potential of this approach for the treatment of AD.
Self-consistent evolution of plasma discharge and electromagnetic fields in a microwave pulse compressor (2015)

Nanosecond-scale evolution of plasma and RF electromagnetic fields during the release of energy from a microwave pulse compressor with a plasma interference switch was investigated numerically using the code MAGIC. The plasma was simulated in the scope of the gas conductivity model in MAGIC. The compressor embodied an S-band cavity and H-plane waveguide tee with a shorted side arm filled with pressurized gas. In a simplified approach, the gas discharge was initiated by setting an external ionization rate in a layer crossing the side arm waveguide in the location of the electric field antinode. It was found that with increasing ionization rate, the microwave energy absorbed by the plasma in the first few nanoseconds increases, but the absorption for the whole duration of energy release, on the contrary, decreases. In a hybrid approach modeling laser ignition of the discharge, seed electrons were set around the electric field antinode. In this case, the plasma extends along the field forming a filament and the plasma density increases up to the level at which the electric field within the plasma decreases due to the skin effect. Then, the avalanche rate decreases but the density still rises until the microwave energy release begins and the electric field becomes insufficient to support the avalanche process. The extraction of the microwave pulse limits its own power by terminating the rise of the plasma density and filament length. For efficient extraction, a sufficiently long filament of dense plasma must have sufficient time to be formed.
XL-Xantphos: Design and Synthesis of a Mechanistic Probe of Xantphos O-Coordination in Catalytic Reactions (2019)

The synthesis and characterization of an analog of the Xantphos ligand that is geometrically incapable of coordination of the xanthene bridging oxygen atom is reported. This new ligand, XL-Xantphos, ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(4,1-phenylene))bis(diphenylphosphane), was studied in homogeneous, catalytic reactions for comparison with Xantphos. The XL-Xantphos ligand performed essentially identically to Xantphos in Rh-catalyzed hydroformylation of 1-octene, which suggests that the high regioselectivity for linear aldehyde is due to the large bite angle of these ligands and is not influenced by oxygen coordination to the metal. The Pd-catalyzed amidocarbonylation of 4-bromoanisole with dimethylhydroxylamine hydrochloride similarly showed no difference between Xantphos and XL-Xantphos. Computations on Pd(II) phosphine complexes at the DLPNO–CCSD(T) level of theory indicated that these ligands have different preferences for cis and trans coordination modes. The XL-Xantphos ligand has a thermodynamic preference for trans-chelated structures, whereas the cis-[(Xantphos)PdCl2] isomer was calculated to be thermodynamically more stable than its trans isomer. Given the key role of d8 square planar Pd intermediates in many catalytic cycles, the greater preference of Xantphos to form cis chelates may indeed be a factor which has made this ligand particularly effective.
Brucella β 1,2 Cyclic Glucan Is an Activator of Human and Mouse Dendritic Cells (2012)

Bacterial cyclic glucans are glucose polymers that concentrate within the periplasm of alpha-proteobacteria. These molecules are necessary to maintain the homeostasis of the cell envelope by contributing to the osmolarity of Gram negative bacteria. Here, we demonstrate that Brucella β 1,2 cyclic glucans are potent activators of human and mouse dendritic cells. Dendritic cells activation by Brucella β 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14. The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared to LPS and triggered antigen-specific CD8(+) T cell responses in vivo. These cyclic glucans also enhanced antigen-specific CD4(+) and CD8(+) T cell responses including cross-presentation by different human DC subsets. Brucella β 1,2 cyclic glucans increased the memory CD4(+) T cell responses of blood mononuclear cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic glucans represent a new class of adjuvants, which might contribute to the development of effective antimicrobial therapies.
The Origin of Stereoselectivity in Primary Amino Acid Catalyzed Intermolecular Aldol Reactions (2005)

Combined forces: Theory and experiment are used together to determine the mechanism of primary amino acid catalyzed intermolecular aldol reactions. A six-membered chairlike structure is determined to be the transition state for the reaction between benzaldehyde and cyclohexanone catalyzed by (S)-alanine (see scheme), and a carboxylic acid catalyzed enamine mechanism is shown to be the most favorable reaction pathway. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z502388_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A comparison of electric and magnetic compound action signals as quantitative assays of peripheralo nerve regeneration (1993)

The evaluation of peripheral nerve regeneration is of great interest in clinical as well as in experimental situations. However, there are few techniques that give early and quantitative information on the status of the regeneration process. If quantitative assays would be available, different surgical techniques and medications could be evaluated more accurately in relation to axonal ingrowth and functional recovery. The purpose of this study was to investigate the merits of nerve compound action signals (NCASs) recorded electrically and signals recorded with a novel magnetic recording technique. We compared the two techniques in the rabbit peroneal nerve, 2, 4, 6, and 8 weeks after a nerve reconstruction. Our conclusions are that the signals recorded with the magnetic sensor are far more reproducible and less prone to stimulus artifact than the electrically recorded signals. Furthermore, the magnetic recording shows that the number of axons that have regenerated increases with time. Previously, this could only be determined with histological studies. Other ingrowth parameters that can be quantified are the average ingrowth distance, and the variation between axons in ingrowth velocity.
Regional citrate-calcium anticoagulation during polymyxin-B hemoperfusion: A case series (2018)

To our knowledge, this is the second published report on the use of citrate anticoagulation during polymyxin-B hemoperfusion. Our case series continued to show that regional citrate anticoagulation regimen is feasible and safe during polymyxin-B hemoperfusion treatment in postsurgical septic patients.