Coefficient of tangential restitution for the linear dashpot model

The linear dashpot model for the inelastic normal force between colliding spheres leads to a constant coefficient of normal restitution, $\epsilon_n=$const., which makes this model very popular for the investigation of dilute and moderately dense granular systems. For two frequently used models for the tangential interaction force we determine the coefficient of tangential restitution $\epsilon_t$, both analytically and by numerical integration of Newton's equation. Although $\epsilon_n=$const. for the linear-dashpot model, we obtain pronounced and characteristic dependencies of the tangential coefficient on the impact velocity $\epsilon_t=\epsilon_t(\vec{g})$. The results may be used for event-driven simulations of granular systems of frictional particles.Comment: 12 pages, 12 figure

Failure to thrive - An overlooked manifestation of KMT2B-related dystonia: A case presentation

Background: KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel KMT2B mutation with several members with failure to thrive to highlight this non-neurologic, but consequential impact of mutation in this gene. Case presentation: We present a case of a 15-year old female who was admitted and evaluated for failure to thrive. On exam, she had severe speech dysfluency, limited ability to protrude the tongue, and generalized dystonia involving the oromandibular region, right upper and left lower extremity with left foot inversion contracture. The proband and her parents underwent whole genome sequencing. A previously undescribed variant, c.4960 T > C (p.Cys1654Arg), was identified in the KMT2B gene in the proband and mother, and this variant was subsequently confirmed in two maternal cousins, one with failure to thrive. Literature review identified frequent reports of prominent bulbar involvement but failure to thrive is rarely mentioned. Conclusion: Failure to thrive is a common pediatric clinical condition that has consequences for growth and development. In the presence of an abnormal neurologic exam, a search for a specific underlying genetic etiology should be pursued. With this case series, we highlight an unusual potentially treatable cause of failure to thrive, reinforce the importance of precise molecular diagnosis for patients with failure to thrive and an abnormal neurologic exam, and underscore the importance of cascade screening of family members

Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis

Centrosomes act as sites of microtubule growth, but little is known about how the number and stability of microtubules emanating from a centrosome are controlled during the cell cycle. We studied the role of the TACC3–XMAP215 complex in this process by using purified proteins and Xenopus laevis egg extracts. We show that TACC3 forms a one-to-one complex with and enhances the microtubule-stabilizing activity of XMAP215 in vitro. TACC3 enhances the number of microtubules emanating from mitotic centrosomes, and its targeting to centrosomes is regulated by Aurora A–dependent phosphorylation. We propose that Aurora A regulation of TACC3 activity defines a centrosome-specific mechanism for regulation of microtubule polymerization in mitosis

Simulation for the oblique impact of a lattice system

The oblique collision between an elastic disk and an elastic wall is numerically studied. We investigate the dependency of the tangential coefficient of restitution on the incident angle of impact. From the results of simulation, our model reproduces experimental results and can be explained by a phenomenological theory of the oblique impact.Comment: 30 pages, 9 figures, submitted to J. Phys. Soc. Japa

Coefficient of normal restitution of viscous particles and cooling rate of granular gases

We investigate the cooling rate of a gas of inelastically interacting particles. When we assume velocity dependent coefficients of restitution the material cools down slower than with constant restitution. This behavior might have large influence to clustering and structure formation processes.Comment: 3 figures, Phys. Rev. E (in press

Dynamic masses for the close PG1159 binary SDSSJ212531.92-010745.9

SDSSJ212531.92-010745.9 is the first known PG1159 star in a close binary with a late main sequence companion allowing a dynamical mass determination. The system shows flux variations with a peak-to-peak amplitude of about 0.7 mag and a period of about 6.96h. In August 2007, 13 spectra of SDSSJ212531.92-010745.9 covering the full orbital phase range were taken at the TWIN 3.5m telescope at the Calar Alto Observatory (Alm\'{e}ria, Spain). These confirm the typical PG1159 features seen in the SDSS discovery spectrum, together with the Balmer series of hydrogen in emission (plus other emission lines), interpreted as signature of the companion's irradiated side. A radial velocity curve was obtained for both components. Using co-added radial-velocity-corrected spectra, the spectral analysis of the PG1159 star is being refined. The system's lightcurve, obtained during three seasons of photometry with the G\"ottingen 50cm and T\"ubingen 80cm telescopes, was fitted with both the NIGHTFALL and PHOEBE binary simulation programs. An accurate mass determination of the PG1159 component from the radial velocity measurements requires to first derive the inclination, which requires light curve modelling and yields further constraints on radii, effective temperature and separation of the system's components. From the analysis of all data available so far, we present the possible mass range for the PG1159 component of SDSSJ212531.92-010745.9.Comment: 8 pages, in "White dwarfs", proceedings of the 16th European White Dwarf Workshop, eds. E. Garcia-Berro, M. Hernanz, J. Isern, S. Torres, to be published in J. Phys.: Conf. Se

The Treatment-Naive Microbiome in New-Onset Crohn\u27s Disease

Inflammatory bowel diseases (IBDs), including Crohn\u27s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD

NirA Is an Alternative Nitrite Reductase from Pseudomonas aeruginosa with Potential as an Antivirulence Target.

The opportunistic pathogen Pseudomonas aeruginosa produces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, antivirulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treat P. aeruginosa infections. To identify P. aeruginosa genes required for virulence in multiple hosts, a random library of Tn5 mutants in strain PAO1-L was previously screened in vitro for those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we identified a Tn5 mutant with an insertion in PA4130 showing reduced levels of a number of virulence traits in vitro Construction of an isogenic mutant in this gene presented results similar to those for the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models of Drosophila melanogaster and Caenorhabditis elegans as well as reduced toxicity in human cell lines. Mice infected with this mutant demonstrated an 80% increased survival rate in acute and agar bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulfite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this enzyme is a nitrite reductase operating in a ferredoxin-dependent manner. The preference for nitrite and production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named NirA.IMPORTANCE The emergence of widespread antimicrobial resistance has led to the need for development of novel therapeutic interventions. Antivirulence strategies are an attractive alternative to classic antimicrobial therapy; however, they require identification of new specific targets which can be exploited in drug discovery programs. The host-specific nature of P. aeruginosa virulence adds complexity to the discovery of these types of targets. Using a sequence of in vitro assays and phylogenetically diverse in vivo disease models, we have identified a PA4130 mutant with reduced production in a number of virulence traits and severe attenuation across all infection models tested. Characterization of PA4130 revealed that it is a ferredoxin-nitrite reductase and hence was named NirA. These results, together with attenuation of nirA mutants in different clinical isolates, high level conservation of its gene product in P. aeruginosa genomes, and the lack of orthologues in human genomes, make NirA an attractive antivirulence target

A novel angiotensin I-converting enzyme mutation (S333W) impairs N-domain enzymatic cleavage of the anti-fibrotic peptide, AcSDKP

BACKGROUND: Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. RESULTS: We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S 1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. Conclusions and Significance A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis