Topological Evolution of Dynamical Networks: Global Criticality from Local Dynamics

We evolve network topology of an asymmetrically connected threshold network by a simple local rewiring rule: quiet nodes grow links, active nodes lose links. This leads to convergence of the average connectivity of the network towards the critical value $K_c =2$ in the limit of large system size $N$. How this principle could generate self-organization in natural complex systems is discussed for two examples: neural networks and regulatory networks in the genome.Comment: 4 pages RevTeX, 4 figures PostScript, revised versio

Few-Body Dynamics Underlying Postcollision Effects in the Ionization of H₂ by 75-KeV Proton Impact

We have measured fully differential cross sections (FDCS) for ionization in 75-keVp+H2 collisions for ejected electron speeds close to the projectile speed. The data were analyzed in dependence on both the electron emission angle and the projectile scattering angle. Pronounced postcollisional effects between the projectile and the ejected electrons were observed. Significant differences between experiment and theory and between two conceptually very similar theoretical models were found. This shows that in the region of electron-projectile velocity-matching the FDCS is very sensitive to the details of the underlying few-body dynamics

Fully Differential Investigation of Two-Center Interference in Dissociative Capture in p + H₂ Collisions

We have measured and calculated fully differential cross sections for vibrational dissociation following capture in 75-keV p + H2 collisions. For a molecular orientation perpendicular to the projectile beam axis and parallel to the transverse momentum transfer we observe a pronounced interference structure. The positions of the interference extrema suggest that the interference term is afflicted with a phase shift which depends on the projectile scattering angle. However, no significant dependence on the kinetic-energy release was observed. Considerable discrepancies between our calculations and experimental data were found

Topographic variability and the influence of soil erosion on the carbon cycle

Soil erosion, particularly that caused by agriculture, is closely linked to the global carbon (C) cycle. There is a wide range of contrasting global estimates of how erosion alters soil-atmosphere C exchange. This can be partly attributed to limited understanding of how geomorphology, topography, and management practices affect erosion and oxidation of soil organic C (SOC). This work presents a physically based approach that stresses the heterogeneity at fine spatial scales of SOC erosion, SOC burial, and associated soil-atmosphere C fluxes. The Holcombe's Branch watershed, part of the Calhoun Critical Zone Observatory in South Carolina, USA, is the case study used. The site has experienced some of the most serious agricultural soil erosion in North America. We use SOC content measurements from contrasting soil profiles and estimates of SOC oxidation rates at multiple soil depths. The methodology was implemented in the tRIBS-ECO (Triangulated Irregular Network-based Real-time Integrated Basin Simulator-Erosion and Carbon Oxidation), a spatially and depth-explicit model of SOC dynamics built within an existing coupled physically based hydro-geomorphic model. According to observations from multiple soil profiles, about 32% of the original SOC content has been eroded in the study area. The results indicate that C erosion and its replacement exhibit significant topographic variation at relatively small scales (tens of meters). The episodic representation of SOC erosion reproduces the history of SOC erosion better than models that use an assumption of constant erosion in space and time. The net atmospheric C exchange at the study site is estimated to range from a maximum source of 14.5 g m−2 yr−1 to a maximum sink of −18.2 g m−2 yr−1. The small-scale complexity of C erosion and burial driven by topography exerts a strong control on the landscape's capacity to serve as a C source or a sink

Specific mutations in the D1–D2 linker region of VCP/p97 enhance ATPase activity and confer resistance to VCP inhibitors

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Valosin-containing protein (VCP), together with several partner proteins, extracts ubiquitinated client proteins from E3 ligase complex and facilitates their degradation through ubiquitin–proteasome system. Therefore, it plays an important role in regulating protein quality control and various cellular pathways. Recent studies also identified VCP as a lineage-specific essential gene in ovarian cancer. An orally bioavailable VCP inhibitor, CB-5083, is currently in Phase I clinical trials because it shows therapeutic effects in multiple tumor xenograft models. However, the mechanism of resistance to CB-5083 is unknown. Here, we characterized molecular mechanism of resistance to CB-5083. Using incremental exposure to CB-5083, we established CB-5083-resistant ovarian cancer cells that showed five- to six-fold resistance in vitro compared with parental cells. Genomic and complementary DNA sequencing of the VCP coding region revealed a pattern of co-selected mutations: (1) missense mutations at codon 470 in one copy resulting in increased ATPase activity and (2) nonsense or frameshift mutations at codon 606 or codon 616 in another copy causing the loss of allele-specific expression. Unbiased molecular docking studies showed codon 470 as a putative binding site for CB-5083. Furthermore, the analysis of somatic mutations in cancer genomes from the Cancer Genome Atlas (TCGA) indicated that codon 616 contains hotspot mutations in VCP. Thus, identification of these mutations associated with in vitro resistance to VCP inhibitors may be useful as potential theranostic markers while screening for patients to enroll in clinical trials. VCP has emerged as a viable therapeutic target for several cancer types, and therefore targeting such hyperactive VCP mutants should aid in improving the therapeutic outcome in cancer patients

Magnetorheological brushes – Scarcely explored class of magnetic material

Magnetic materials such as magnetorheological (MR) fluids, and magnetorheological elastomers exhibit a broad change in their material properties, for example, viscosity and storage modulus in the presence of a magnetic field. Studies related to such MR fluid and elastomer materials are extensively available. The MR brush, meanwhile, is less frequently explored and understood. An MR brush is defined by the brush-like structures formed from chains of magnetic particles embedded within a carrier matrix, typically fluids or elastomers. In this study, we explore magnetorheological fluid (MRF) brush and magnetorheological elastomer (MRE) brush and investigate their magneto-mechanical properties. The investigation measured the stiffness and the MR response, defined as the change in properties in the presence of a magnetic field for MRF and MRE brushes. Further dependence of the magnetic effect on material and preparation parameters, mainly concentration of magnetic particles and curing flux density (for MRE brush) were investigated. The responsiveness of the brushes is compared using the Magnetorheological response index, as a proposed metric in this study. The results indicate that the MRE brush possess a greater absolute stiffness, but a lower MR response than that of the MRF brush. Both MRF and MRE brushes show an increase in the MR response with an increased concentration of magnetic fillers. MRE brush further demonstrate an enhanced MR response, which could be highly comparable to MRF brush coinciding with an increase in the magnetic flux density during the curing process. The fundamental investigation of both solid and fluid MR brushes in this study opens a new avenue in the area of magnetic materials. This new class of magnetically controllable materials could potentially be employed in applications where soft and tuneable bristle-like structures are desired

Projectile Coherence Effects in Simple Atomic Systems

Recent studies of projectile coherence effects in ion-atom collisions are presented. For intermediate-energy proton collisions an extensive literature provides strong support for the importance of such effects. In this regime coherence effects are now used as a tool to study the few-body dynamics very sensitively. In contrast, for high-energy ion impact the literature is much sparser and here an important role of coherence effects cannot be regarded as being established. In this context, a recent claim that in COLTRIMS experiments the coherence properties are determined only by the target beam is rebutted

Target Dependence of Postcollision Interaction Effects on Fully Differential Ionization Cross Sections

We have measured and calculated fully differential cross sections (FDCS) for ionization of helium by 75-keV proton impact. Ejected electrons with a speed close to and above the projectile speed were investigated. This range of kinematics represents a largely unexplored regime. A high sensitivity of the FDCS to the details of the description of the few-body dynamics, reported earlier for ionization of H2, was confirmed. A peak structure was found in an electron angular range between the regions where the so-called binary and recoil peaks are usually observed. The need for nonperturbative calculations using a two-center basis set is demonstrated

The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins.

Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state

MiR-212-3p Functions as a Tumor Suppressor Gene in Group 3 Medulloblastoma via Targeting Nuclear Factor I/B (NFIB)

Haploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors and associated with poor survival. NFIB silencing reduced cancer cell proliferation, migration, and invasion. Concurrently, reduced medullosphere formation and stem cell markers (Nanog, Oct4, Sox2, CD133) were noted. These results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and identify a novel oncogenic target implicated in metastasis and tumor recurrence