Designing Active Site-Directed Covalent Probes for Tyrosine Phosphatases

Tyrosine phosphorylation is an important post-translational modification in cells that modulates key cellular pathways. Tyrosine phosphatases are the class of enzymes that remove this modification from proteins, yet we know relatively little about how they are regulated in various signaling contexts. Activity-based probes that successfully target active sites of tyrosine phosphatases and report on their activities can fill in this gap. We show the assessment of various thiol-reactive groups for their ability to target catalytic cysteine residues with specificity. Then we construct and screen a library of fragment-like compounds for their on-target and off-target reactivities. We also discuss theoretical considerations for screening covalent inhibitors for their kinetic parameters and show this using our experimental data. Lastly, we augment compounds selected from the library to enable click chemistry for reporter group attachment for use on the whole proteome, ultimately through mass spectrometry-based proteomics methods. We show enrichment of target proteins. These target-centric design efforts will yield new insights into the general development processes of activity-based probes or inhibitors

Modeling of Fuel Vapor Jet Eruption Induced by Local Droplet Heating

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140419/1/6.2014-1017.pd

Formation of Warped Disks by Galactic Fly-by Encounters. I. Stellar Disks

Warped disks are almost ubiquitous among spiral galaxies. Here we revisit and test the `fly-by scenario' of warp formation, in which impulsive encounters between galaxies are responsible for warped disks. Based on N-body simulations, we investigate the morphological and kinematical evolution of the stellar component of disks when galaxies undergo fly-by interactions with adjacent dark matter halos. We find that the so-called `S'-shaped warps can be excited by fly-bys and sustained for even up to a few billion years, and that this scenario provides a cohesive explanation for several key observations. We show that disk warp properties are governed primarily by the following three parameters; (1) the impact parameter, i.e., the minimum distance between two halos, (2) the mass ratio between two halos, and (3) the incident angle of the fly-by perturber. The warp angle is tied up with all three parameters, yet the warp lifetime is particularly sensitive to the incident angle of the perturber. Interestingly, the modeled S-shaped warps are often non-symmetric depending on the incident angle. We speculate that the puzzling U- and L-shaped warps are geometrically superimposed S-types produced by successive fly-bys with different incident angles, including multiple interactions with a satellite on a highly elongated orbit.Comment: 16 pages, 13 figures, 3 tables. Accepted for publication in Ap

The Heterogeneity of Reading-Related Difficulties in Chinese

The present chapter reviews cognitive-linguistic skills which are associated with various reading-related difficulties in Chinese. Research findings have showed that rapid naming and orthographic deficits are the unique marker deficits of Chinese developmental dyslexia. However, studies have indicated overlapping and dissociative deficits in dyslexia and spelling difficulties. Findings on dissociation between word reading and spelling difficulties suggest that weaknesses in orthographic processing may specifically cause difficulties in Chinese word spelling. Deficits in rapid naming are more associated with word reading fluency than reading accuracy. Beyond word level processing, there are children who encounter difficulties in reading comprehension even with adequate decoding skills. This group of specific poor comprehenders was found to be weak in some discourse-level skills, like comprehension monitoring and inferencing. Knowledge of these findings will inform us about effective identification of and intervention for children with difficulties in one or a combination of several reading-related difficulties in Chinese

Light scattering by elongated clusters of a-C:H nanoparticles

Abstract We present here the light scattering by elongated clusters consisting of linear chains of spherical a-C:H nanoparticles. The results are compared with light scattering by spherical nanoparticles. This simple experiment, performed by utilizing plasma-grown elongated nanoparticles, demonstrates a possibility and an opportunity to examine the validity of the Davis and Greenstein mechanism: Interstellar polarization might be due to aligned, elongated nanoparticles

Local Hall effect in hybrid ferromagnetic/semiconductor devices

We have investigated the magnetoresistance of ferromagnet-semiconductor devices in an InAs two-dimensional electron gas system in which the magnetic field has a sinusoidal profile. The magnetoresistance of our device is large. The longitudinal resistance has an additional contribution which is odd in applied magnetic field. It becomes even negative at low temperature where the transport is ballistic. Based on the numerical analysis, we confirmed that our data can be explained in terms of the local Hall effect due to the profile of negative and positive field regions. This device may be useful for future spintronic applications.Comment: 4 pages with 4 fugures. Accepted for publication in Applied Physics Letter

Catalytic Performance for Hydrocarbon Production from Syngas on the Promoted Co-Based Hybrid Catalysts; Influence of Pt Contents

Fischer-Tropsch synthesis (FTS) reaction from syngas was investigated on the Pt-promoted cobalt-based hybrid catalysts prepared by co-precipitation method in a slurry of ZSM-5 (Si/Al=25). The hybrid catalysts were compared with each other for the different content of Pt as a promoter and are characterized using BET, XRD, H2-TPR and NH3-TPD. Their physicochemical properties were correlated with the activity and selectivity of the catalysts. As results, all hybrid catalysts show the C5-C9 yield (%) higher than that of Co-Al2O3/ZSM-5 catalyst. The Pt-promoted hybrid catalysts were found to be more promising towards production of the hydrocarbons of gasoline range and over C10.

Influencing Factors for Cure of Clonorchiasis by Praziquantel Therapy: Infection Burden and CYP3A5 Gene Polymorphism

Chemotherapy of clonorchiasis with praziquantel (PZQ) is effective but about 15% of treated cases have been reported uncured. The present study investigated correlation of single nucleotide polymorphisms (SNPs) of the cytochrome P450 gene, CYP3A5 and cure of clonorchiasis. A total of 346 egg passing residents were subjected and treated by 3 doses of 25 mg/kg PZQ. Reexamination recognized 33 (9.5%) uncured and 313 cured. Numbers of eggs per gram of feces (EPGs) before treatment were significantly lower in the cured group than in the uncured group (2,011.2±3,600.0 vs 4,998.5±7,012.0, P<0.001). DNAs of the subjects were screened for SNPs at 7 locations of CYP3A5 using PCR. In the uncured group, the SNP frequencies at g.-20555G>A and g.27526C>T of CYP3A5 were 15.2% and 9.1% while those were 3.8% and 1.0%, respectively, in the cured group. The cure rate was significantly lower in the cases with SNP at g.27526C>T and EPGs≥1,000. In conclusion, EPGs and SNPs of CYP3A5 are factors which influence cure of clonorchiasis by PZQ therapy. It is strongly suggested to recommend 2-day medication for individuals with high EPGs≥1,000