Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Defect healing and enhanced nucleation of carbon nanotubes by low-energy ion bombardment

Structural defects inevitably appear during the nucleation event that determines the structure and properties of single-walled carbon nanotubes. By combining ion bombardment experiments with atomistic simulations we reveal that ion bombardment in a suitable energy range allows these defects to be healed resulting in an enhanced nucleation of the carbon nanotube cap. The enhanced growth of the nanotube cap is explained by a nonthermal ion-induced graphene network restructuring mechanism.

Effect of ion current density on the properties of vacuum arc-deposited TiN coatings

The influence of ion current density on the thickness of coatings deposited in a vacuum arc setup has been investigated to optimize the coating porosity. A planar probe was used to measure the ion current density distribution across plasma flux. A current density from 20 to 50 A/m2 was obtained, depending on the probe position relative to the substrate center. TiN coatings were deposited onto the cutting inserts placed at different locations on the substrate, and SEM was used to characterize the surfaces of the coatings. It was found that lowdensity coatings were formed at the decreased ion current density. A quantitative dependence of the coating thickness on the ion current density in the range of 20-50 A/m2 were obtained for the films deposited at substrate bias of 200 V and nitrogen pressure 0.1 Pa, and the coating porosity was calculated. The coated cutting inserts were tested by lathe machining of the martensitic stainless steel AISI 431. The results may be useful for controlling ion flux distribution over large industrial-scale substrates.

Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34

Ubiquitin (Ub)-conjugating enzymes (E2s) and ubiquitin ligases (E3s) catalyze the attachment of Ub to lysine residues in substrates and Ub during monoubiquitination and polyubiquitination. Lysine selection is important for the generation of diverse substrate-Ub structures, which provides versatility to this pathway in the targeting of proteins to different fates. The mechanisms of lysine selection remain poorly understood, with previous studies suggesting that the ubiquitination site(s) is selected by the E2/E3-mediated positioning of a lysine(s) toward the E2/E3 active site. By studying the polyubiquitination of Sic1 by the E2 protein Cdc34 and the RING E3 Skp1/Cul1/F-box (SCF) protein, we now demonstrate that in addition to E2/E3-mediated positioning, proximal amino acids surrounding the lysine residues in Sic1 and Ub are critical for ubiquitination. This mechanism is linked to key residues composing the catalytic core of Cdc34 and independent of SCF. Changes to these core residues altered the lysine preference of Cdc34 and specified whether this enzyme monoubiquitinated or polyubiquitinated Sic1. These new findings indicate that compatibility between amino acids surrounding acceptor lysine residues and key amino acids in the catalytic core of ubiquitin-conjugating enzymes is an important mechanism for lysine selection during ubiquitination.

Air ion concentrations under overhead power lines

Corona discharge is responsible for the flux of small ions from overhead power lines, and is capable of modifying the ambient electrical environment, such as the air ion concentrations at ground level. Once produced, small ions quickly attach to aerosol particles in the air, producing ‘large ions’, approximately 1 nm to 1 µm in diameter. However, very few studies have measured air ion concentrations directly near high voltage transmission lines. The present study involved the simultaneously measurement of small ion concentration and net large ion concentration using air ion counters and an aerosol electrometer at four power line sites. Both positive and negative small ion concentration (<1.6nm), net large ion concentration (2nm-5μm) and particle number concentration (10nm-2μm) were measured using air ion counters and an aerosol electrometer at four power line sites. Measurements at sites 1 and 2 were conducted at both upwind and downwind sides. The results showed that total ion concentrations on the downwind side were 3-5 times higher than on the upwind side, while particle number concentrations did not show a significant difference. This result also shows that a large number of ions were emitted from the power lines at sites 1 and 2. Furthermore, both positive and negative ions were observed at different power line sites. Dominant positive ions were observed at site 1, with a concentration of 4.4 x 103 ions cm-3, which was 10 times higher than on the upwind side. Contrary to site 1, sites 2 to 4 showed negative ion emissions, with concentrations of -1.2 x 103, -460 and -410 ions cm-3, respectively. These values were higher than the background urban negative ion concentration of 400 cm-3. At site 1 and site 2, the net ion concentration and net particle charge concentration on downwind side of the lines showed same polarities. Further investigations were also conducted into the correlation between net ion concentration and net charge particle concentration 20 m downwind of the power lines at site 2. The two parameters showed a correlation coefficient of 0.72, indicating that a substantial number of ions could attach to particles and affect the particle charge status within a short distance from the source.

Prediction of thermal expansion properties of carbon nanotubes using molecular dynamics simulations

The axial coefficients of thermal expansion (CTE) of various carbon nanotubes (CNTs), i.e., single-wall carbon nanotubes (SWCNTs), and some multi-wall carbon nanotubes (MWCNTs), were predicted using molecular dynamics (MDs) simulations. The effects of two parameters, i.e., temperature and the CNT diameter, on CTE were investigated extensively. For all SWCNTs and MWCNTs, the obtained results clearly revealed that within a wide low temperature range, their axial CTEs are negative. As the diameter of CNTs decreases, this temperature range for negative axial CTEs becomes narrow, and positive axial CTEs appear in high temperature range. It was found that the axial CTEs vary nonlinearly with the temperature, however, they decrease linearly as the CNT diameter increases. Moreover, within a wide temperature range, a set of empirical formulations was proposed for evaluating the axial CTEs of armchair and zigzag SWCNTs using the above two parameters. Finally, it was found that the absolute value of the negative axial CTE of any MWCNT is much smaller than those of its constituent SWCNTs, and the average value of the CTEs of its constituent SWCNTs. The present fundamental study is very important for understanding the thermal behaviors of CNTs in such as nanocomposite temperature sensors, or nanoelectronics devices using CNTs.

Field-effect transistors based on self-organized molecular nanostripes

Charge transport properties in organic semiconductors depend strongly on molecular order. Here we demonstrate field-effect transistors where drain current flows through a precisely defined array of nanostripes made of crystalline and highly ordered molecules. The molecular stripes are fabricated across the channel of the transistor by a stamp-assisted deposition of the molecular semiconductors from a solution. As the solvent evaporates, the capillary forces drive the solution to form menisci under the stamp protrusions. The solute precipitates only in the regions where the solution is confined by the menisci once the critical concentration is reached and self-organizes into molecularly ordered stripes 100-200 nm wide and a few monolayers high. The charge mobility measured along the stripes is 2 orders of magnitude larger than the values measured for spin-coated thin films.

High mobility organic thin film transistor and efficient photovoltaic devices using versatile donor-acceptor polymer semiconductor by molecular design

In this work, we report a novel donor-acceptor based solution processable low band gap polymer semiconductor, PDPP-TNT, synthesized via Suzuki coupling using condensed diketopyrrolopyrrole (DPP) as an acceptor moiety with a fused naphthalene donor building block in the polymer backbone. This polymer exhibits p-channel charge transport characteristics when used as the active semiconductor in organic thin-film transistor (OTFT) devices. The hole mobilities of 0.65 cm2 V-1 s-1 and 0.98 cm2 V -1 s-1 are achieved respectively in bottom gate and dual gate OTFT devices with on/off ratios in the range of 105 to 10 7. Additionally, due to its appropriate HOMO (5.29 eV) energy level and optimum optical band gap (1.50 eV), PDPP-TNT is a promising candidate for organic photovoltaic (OPV) applications. When this polymer semiconductor is used as a donor and PC71BM as an acceptor in OPV devices, high power conversion efficiencies (PCE) of 4.7% are obtained. Such high mobility values in OTFTs and high PCE in OPV make PDPP-TNT a very promising polymer semiconductor for a wide range of applications in organic electronics.

Experimental evidence for competitive N–O and O–C bond homolysis in gasphase alkoxyamines

The extensive use of alkoxyamines in controlled radical polymerisation and polymer stabilisation is based on rapid cycling between the alkoxyamine (R1R2NO–R3) and a stable nitroxyl radical (R1R2NO•) via homolysis of the labile O–C bond. Competing homolysis of the alkoxyamine N–O bond has been predicted to occur for some substituents leading to production of aminyl and alkoxyl radicals. This intrinsic competition between the O–C and N–O bond homolysis processes has to this point been difficult to probe experimentally. Herein we examine the effect of local molecular structure on the competition between N–O and O–C bond cleavage in the gas phase by variable energy tandem mass spectrometry in a triple quadrupole mass spectrometer. A suite of cyclic alkoxyamines with remote carboxylic acid moieties (HOOC–R1R2NO–R3) were synthesised and subjected to negative ion electrospray ionisation to yield [M – H]− anions where the charge is remote from the alkoxyamine moiety. Collision-induced dissociation of these anions yield product ions resulting, almost exclusively, from homolysis of O–C and/or N–O bonds. The relative efficacy of N–O and O–C bond homolysis was examined for alkoxyamines incorporating different R3 substituents by varying the potential difference applied to the collision cell, and comparing dissociation thresholds of each product ion channel. For most R3 substituents, product ions from homolysis of the O–C bond are observed and product ions resulting from cleavage of the N–O bond are minor or absent. A limited number of examples were encountered however, where N–O homolysis is a competitive dissociation pathway because the O–C bond is stabilised by adjacent heteroatom(s) (e.g., R3 = CH2F). The dissociation threshold energies were compared for different alkoxyamine substituents (R3) and the relative ordering of these experimentally determined energies is shown to correlate with the bond dissociation free energies, calculated by ab initio methods. Understanding the structure-dependent relationship between these rival processes will assist in the design and selection of alkoxyamine motifs that selectively promote the desirable O–C homolysis pathway.

Molecular phylogeny, biogeography, and habitat preference evolution of marsupials

Marsupials exhibit great diversity in ecology and morphology. However, compared to their sister group, the placental mammals, our understanding of many aspects of marsupial evolution remains limited. We use 101 mitochondrial genomes and data from 26 nuclear loci to reconstruct a dated phylogeny including 97% of extant genera and 58% of modern marsupial species. This tree allows us to analyze the evolution of habitat preference and geographic distributions of marsupial species through time. We found a pattern of mesic-adapted lineages evolving to use more arid and open habitats, which is broadly consistent with regional climate and environmental change. However, contrary to the general trend, several lineages subsequently appear to have reverted from drier to more mesic habitats. Biogeographic reconstructions suggest that current views on the connectivity between Australia and New Guinea/Wallacea during the Miocene and Pliocene need to be revised. The antiquity of several endemic New Guinean clades strongly suggests a substantially older period of connection stretching back to the Middle Miocene, and implies that New Guinea was colonized by multiple clades almost immediately after its principal formation.