Plasma-enabled growth of single-crystalline SiC/AlSiC Core–Shell nanowires on porous alumina templates

We report the catalyst-free synthesis of the arrays of core–shell, ultrathin, size-uniform SiC/AlSiC nanowires on the top of a periodic anodic aluminum oxide template. The nanowires were grown using an environmentally friendly, silane-free process by exposing the silicon supported porous alumina template to CH4 + H2 plasmas. High-resolution scanning and transmission electron microscopy studies revealed that the nanowires have a single-crystalline core with a diameter of about 10 nm and a thin (1–2 nm) amorphous AlSiC shell. Because of their remarkable length, high aspect ratio, and very high surface area-to-volume ratio, these unique structures are promising for nanoelectronic and nanophotonic applications that require efficient electron emission, light scattering, etc. A mechanism for nanowire growth is proposed based upon the reduction of the alumina template to nanosized metallic aluminum droplets forming between nanopores. The subsequent incorporation of silicon and carbon atoms from the plasma leads to nucleation and growth from the top of the alumina template.

Metachronous carcinomas in colorectum and its clinicopathological significance

PURPOSE The study was designed to examine the significance of colorectal metachronous carcinoma in a large cohort of patients. METHODS Over a mean follow-up period of 10 years, the clinicopathological features, microsatellite instability (MSI) and clinical follow-up of 56 patients with metachronous colorectal carcinoma were analysed. RESULTS The prevalence of metachronous colorectal carcinoma was 2.1 %. The metachronous colorectal carcinomas appeared between 7 and 246 months (mean = 66 months) after surgical resection of the index colorectal carcinomas. Thirty-six per cent (n = 20) of the metachronous carcinoma occurred more than 5 years after the operation of the index carcinoma. Of the 56 patients, 20 % (n = 11) of the metachronous colorectal carcinomas were mucinous adenocarcinoma. Cancers detected in the secondary operations (metachronous colorectal carcinomas), when compared with the primary index cancers, were smaller, showed higher proportions of mucinous adenocarcinoma and more often located in the proximal colon. Patients with metachronous colorectal cancers had higher prevalence of mucinous adenocarcinoma, loss of staining for MSI markers and better survival rates than other patients with colorectal cancers. CONCLUSIONS Patients with metachronous colorectal carcinomas have characteristic features, and attention to these features is important for better management of this group of cancer.

Wet hail and thunderstorm electrification

Hailstones in wet growth are commonly found in thunderclouds. While the ice-ice relative growth rate mechanism is generally accepted as the most likely cause of thunderstorm electrification, it is uncertain if this mechanism will operate under wet growth conditions because ice crystals are more likely to stick to the wet surface of a hailstone rather than bounce off it. Experiments were carried out in the laboratory to investigate if there was any charge separated when vapor-grown ice crystals bounced off a wet hailstone. A cloud of supercooled droplets, with and without ice crystals, was drawn past a simulated hailstone. In the dry growth regime, the hailstone charged strongly positive when droplets and crystals co-existed in the cloud. With only droplets in the cloud, there was no charging in the dry growth regime. However, as the hailstone attained wet growth, positive charging currents of about 0.5 and 3.5 pA were observed at 12 and 20 m s-1, respectively. We hypothesize that this observed charging was due to the evaporation of melt water. This so called Dinger-Gunn Effect is due to the ejection of negatively charged minute droplets produced by air bubbles bursting at the surface of the melt water. However the charge separated in wet growth was an order of magnitude smaller than that in dry growth and, therefore, we conclude that it is unlikely to play an important role in the electrification of thunderstorms.

Altered JS-2 expression in colorectal cancers and its clinical pathological relevance

JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

GAEC1 and colorectal cancer : a study of the relationships between a novel oncogene and clinicopathologic features

GAEC1 is a novel gene located at 7q22.1 that was detected in our previous work in esophageal cancer. The aims of the present study are to identify the copy number of GAEC1 in different colorectal tissues including carcinomas, adenomas, and nonneoplastic tissues and characterize any links to pathologic factors. The copy number of GAEC1 was studied by evaluating the quantitative amplification of GAEC1 DNA in 259 colorectal tissues (144 adenocarcinomas, 31 adenomas, and 84 nonneoplastic tissues) using real-time polymerase chain reaction. Copy number of GAEC1 DNA in colorectal adenocarcinomas was higher in comparison with nonneoplastic colorectum. Seventy-nine percent of the colorectal adenocarcinomas showed amplification and 15% showed deletion of GAEC1 (P < .0001). Of the adenomas, 90% showed deletion of GAEC1, with the remaining 10% showing normal copy number. The differences in GAEC1 copy number between colorectal adenocarcinoma, colorectal adenoma, and nonneoplastic colorectal tissue are significant (P < .0001). GAEC1 copy number was significantly higher in adenocarcinomas located in distal colorectum compared with proximal colon (P = .03). In conclusion, GAEC1 copy number was significantly different between colorectal adenocarcinomas, adenomas, and nonneoplastic colorectal tissues. The copy number was also related to the site of the cancer. These findings along with previous work in esophageal cancer imply that GAEC1 is commonly involved in the pathogenesis of colorectal adenocarcinoma.

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.

Can larger cemented femoral components reduce periprosthetic fractures?

Introduction The risk for late periprosthetic fractures is higher in patients treated for a neck of femur fracture compared to those treated for osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated if a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite sawbone model. Method A biomechanical composite sawbone model was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented stem were implanted by an experienced surgeon, in 7 sawbones each and loaded at 40 deg/s internal rotation until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874). Data are non-parametric and tested with Mann-Whitney U-test. Results The mean torque load to fracture was 154.1 NM (SD 4.4) for the 44-1 stem and 229 NM (SD10.9) for the 44-4 stem (p = 0.01). The mean fracture energy was 9.6 J (SD1.2) for the 44-1 stem and 17.2 J (SD2.0) for the 44-4 stem (p = 0.14). Conclusion the use of a large body polished tapered cemented stem for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.

Fracture load for short versus standard cemented hip stems : an experimental in vitro study

Introduction: In an attempt to reduce stress shielding in the proximal femur multiple new shorter stem design have become available. We investigated the load to fracture of a new polished tapered cemented short stem in comparison to the conventional polished tapered Exeter stem. Method: A total of forty-two stems, twenty-one short stems and twenty-one conventional stems both with three different offsets were cemented in a composite sawbone model and loaded to fracture. Results: study showed that femurs will break at a significantly lower load to failure with a shorter compared to conventional length Exeter stem. Conclusion: This Both standard and short stem design are safe to use as the torque to failure is 7–10 times as much as the torques seen in activities of daily living.

Metal artifacts from titanium and steel screws in CT, 1.5T and 3T MR images of the tibial Pilon: A quantitative assessment in 3D

Radiographs are commonly used to assess articular reduction of the distal tibia (pilon) fractures postoperatively, but may reveal malreductions inaccurately. While Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are potential 3D alternatives they generate metal-related artifacts. This study aims to quantify the artifact size from orthopaedic screws using CT, 1.5T and 3T MRI data. Three screws were inserted into one intact human cadaver ankle specimen proximal to and along the distal articular surface, then CT, 1.5T and 3T MRI scanned. Four types of screws were investigated: titanium alloy (TA), stainless steel (SS) (Ø = 3.5 mm), cannulated TA (CTA) and cannulated SS (CSS)(Ø = 4.0 mm, Ø empty core = 2.6 mm). 3D artifact models were reconstructed using adaptive thresholding. The artifact size was measured by calculating the perpendicular distance from the central screw axis to the boundary of the artifact in four anatomical directions with respect to the distal tibia. The artifact sizes (in the order of TA, SS, CTA and CSS) from CT were 2.0 mm, 2.6 mm, 1.6 mm and 2.0 mm; from 1.5T MRI they were 3.7 mm, 10.9 mm, 2.9 mm, and 9 mm; and 3T MRI they were 4.4 mm, 15.3 mm, 3.8 mm, and 11.6 mm respectively. Therefore, CT can be used as long as the screws are at a safe distance of about 2 mm from the articular surface. MRI can be used if the screws are at least 3 mm away from the articular surface except SS and CSS. Artifacts from steel screws were too large thus obstructed the pilon from being visualised in MRI. Significant differences (P < 0.05) were found in the size of artifacts between all imaging modalities, screw types and material types, except 1.5T versus 3T MRI for the SS screws (P = 0.063). CTA screws near the joint surface can improve postoperative assessment in CT and MRI. MRI presents a favourable non-ionising alternative when using titanium hardware. Since these factors may influence the quality of postoperative assessment, potential improvements in operative techniques should be considered.

Construction of volcanic records from marine sediment cores : a review and case study (Montserrat, West Indies)

Detailed knowledge of the past history of an active volcano is crucial for the prediction of the timing, frequency and style of future eruptions, and for the identification of potentially at-risk areas. Subaerial volcanic stratigraphies are often incomplete, due to a lack of exposure, or burial and erosion from subsequent eruptions. However, many volcanic eruptions produce widely-dispersed explosive products that are frequently deposited as tephra layers in the sea. Cores of marine sediment therefore have the potential to provide more complete volcanic stratigraphies, at least for explosive eruptions. Nevertheless, problems such as bioturbation and dispersal by currents affect the preservation and subsequent detection of marine tephra deposits. Consequently, cryptotephras, in which tephra grains are not sufficiently concentrated to form layers that are visible to the naked eye, may be the only record of many explosive eruptions. Additionally, thin, reworked deposits of volcanic clasts transported by floods and landslides, or during pyroclastic density currents may be incorrectly interpreted as tephra fallout layers, leading to the construction of inaccurate records of volcanism. This work uses samples from the volcanic island of Montserrat as a case study to test different techniques for generating volcanic eruption records from marine sediment cores, with a particular relevance to cores sampled in relatively proximal settings (i.e. tens of kilometres from the volcanic source) where volcaniclastic material may form a pervasive component of the sedimentary sequence. Visible volcaniclastic deposits identified by sedimentological logging were used to test the effectiveness of potential alternative volcaniclastic-deposit detection techniques, including point counting of grain types (component analysis), glass or mineral chemistry, colour spectrophotometry, grain size measurements, XRF core scanning, magnetic susceptibility and X-radiography. This study demonstrates that a set of time-efficient, non-destructive and high-spatial-resolution analyses (e.g. XRF core-scanning and magnetic susceptibility) can be used effectively to detect potential cryptotephra horizons in marine sediment cores. Once these horizons have been sampled, microscope image analysis of volcaniclastic grains can be used successfully to discriminate between tephra fallout deposits and other volcaniclastic deposits, by using specific criteria related to clast morphology and sorting. Standard practice should be employed when analysing marine sediment cores to accurately identify both visible tephra and cryptotephra deposits, and to distinguish fallout deposits from other volcaniclastic deposits.

Estrogen deficiency-associated bone loss in the maxilla: A methodology to quantify the changes in the maxillary intra-radicular alveolar bone in an ovariectomized rat osteoporosis model

The effects of estrogen deficiency on bone characteristics are site-dependent, with the most commonly studied sites being appendicular long bones (proximal femur and tibia) and axial bones (vertebra). The effect on the maxillary and mandibular bones is still inconsistent and requires further investigation. This study was designed to evaluate bone quality in the posterior maxilla of ovariectomized rats in order to validate this site as an appropriate model to study the effect of osteoporotic changes. Methods: Forty-eight 3-month-old female Sprague-Dawley rats were randomly divided into two groups: an ovariectomized group (OVX, n=24) and Sham-operated group (SHAM, n=24). Six rats were randomly sacrificed from both groups at time points 8, 12, 16 and 20 weeks. The samples from tibia and maxilla were collected for Micro CT and histological analysis. For the maxilla, the volume of interest (VOI) area focused on the furcation areas of the first and second molar. Trabecular bone volume fraction (BV/TV, %), trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular separation (Tb.Sp.), and connectivity density (Conn.Dens) were analysed after Micro CT scanning. Results: At 8 weeks the indices BV/TV, Tb.Sp, Tb.N and Conn.Dens showed significant differences (P<0.05) between the OVX and SHAM groups in the tibia. Compared with the tibia, the maxilla developed osteoporosis at a later stage, with significant changes in maxillary bone density only occurring after 12 weeks. Compared with the SHAM group, both the first and second molars of the OVX group showed significantly decreased BV/TV values from 12 weeks, and these changes were sustained through 16 and 20 weeks. For Tb.Sp, there were significant increases in bone values for the OVX group compared with the SHAM group at 12, 16 and 20 weeks. Histological changes were highly consistent with Micro CT results. Conclusion: This study established a method to quantify the changes of intra-radicular alveolar bone in the posterior maxilla in an accepted rat osteoporosis model. The degree of the osteoporotic changes to trabecular bone architecture is site-dependent and at least 3 months are required for the osteoporotic effects to be apparent in the posterior maxilla following rat OVX.

Structure and function of DsbA, a key bacterial oxidative folding catalyst

Since its discovery in 1991, the bacterial periplasmic oxidative folding catalyst DsbA has been the focus of intense research. Early studies addressed why it is so oxidizing and how it is maintained in its less stable oxidized state. The crystal structure of Escherichia coli DsbA (EcDsbA) revealed that the oxidizing periplasmic enzyme is a distant evolutionary cousin of the reducing cytoplasmic enzyme thioredoxin. Recent significant developments have deepened our understanding of DsbA function, mechanism, and interactions: the structure of the partner membrane protein EcDsbB, including its complex with EcDsbA, proved a landmark in the field. Studies of DsbA machineries from bacteria other than E. coli K-12 have highlighted dramatic differences from the model organism, including a striking divergence in redox parameters and surface features. Several DsbA structures have provided the first clues to its interaction with substrates, and finally, evidence for a central role of DsbA in bacterial virulence has been demonstrated in a range of organisms. Here, we review current knowledge on DsbA, a bacterial periplasmic protein that introduces disulfide bonds into diverse substrate proteins and which may one day be the target of a new class of anti-virulence drugs to treat bacterial infection. Antioxid. Redox Signal. 14, 1729–1760.

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Design and experimental testing of air slab caps which convert commercial electron diodes into dual purpose, correction-free diodes for small field dosimetry

Purpose Two diodes which do not require correction factors for small field relative output measurements are designed and validated using experimental methodology. This was achieved by adding an air layer above the active volume of the diode detectors, which canceled out the increase in response of the diodes in small fields relative to standard field sizes. Methods Due to the increased density of silicon and other components within a diode, additional electrons are created. In very small fields, a very small air gap acts as an effective filter of electrons with a high angle of incidence. The aim was to design a diode that balanced these perturbations to give a response similar to a water-only geometry. Three thicknesses of air were placed at the proximal end of a PTW 60017 electron diode (PTWe) using an adjustable “air cap”. A set of output ratios (ORfclin Det ) for square field sizes of side length down to 5 mm was measured using each air thickness and compared to ORfclin Det measured using an IBA stereotactic field diode (SFD). k fclin, f msr Qclin,Qmsr was transferred from the SFD to the PTWe diode and plotted as a function of air gap thickness for each field size. This enabled the optimal air gap thickness to be obtained by observing which thickness of air was required such that k fclin, f msr Qclin,Qmsr was equal to 1.00 at all field sizes. A similar procedure was used to find the optimal air thickness required to make a modified Sun Nuclear EDGE detector (EDGEe) which s “correction-free” in small field relative dosimetry. In addition, the feasibility of experimentally transferring k fclin, f msr Qclin,Qmsr values from the SFD to unknown diodes was tested by comparing the experimentally transferred k fclin, f msr Qclin,Qmsr values for unmodified PTWe and EDGEe diodes to Monte Carlo simulated values. Results 1.0 mm of air was required to make the PTWe diode correction-free. This modified diode (PTWeair) produced output factors equivalent to those in water at all field sizes (5–50 mm). The optimal air thickness required for the EDGEe diode was found to be 0.6 mm. The modified diode (EDGEeair) produced output factors equivalent to those in water, except at field sizes of 8 and 10 mm where it measured approximately 2% greater than the relative dose to water. The experimentally calculated k fclin, f msr Qclin,Qmsr for both the PTWe and the EDGEe diodes (without air) matched Monte Carlo simulated results, thus proving that it is feasible to transfer k fclin, f msr Qclin,Qmsr from one commercially available detector to another using experimental methods and the recommended experimental setup. Conclusions It is possible to create a diode which does not require corrections for small field output factor measurements. This has been performed and verified experimentally. The ability of a detector to be “correction-free” depends strongly on its design and composition. A nonwater-equivalent detector can only be “correction-free” if competing perturbations of the beam cancel out at all field sizes. This should not be confused with true water equivalency of a detector.