A gene for FG syndrome maps in the Xq12-q21.31 region

AIMS: An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. METHODS AND RESULTS: We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. CONCLUSIONS: As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

Implementation of a third-generation 1.1-GHz 64-bit microprocessor

This third-generation 1.1-GHz 64-bit UltraSPARC microprocessor provides 1-MB on-chip level-2 cache, 4-Gb/s off chip memory bandwidth, and a new 200 MHz JBus interface that supports one to four processors. The 87.5-million transistor chip is implemented in a seven-layer-metal copper 0.13-/spl mu/m CMOS process and dissipates 53 W at 1.3 V and 1.1 GHz.     

Government spending and credit market: Evidence from Italian (NUTS 3) provinces

This study examines the effects of government spending shocks on the Italian credit market using NUTS 3 data over the sample period 2011–2018. The empirical methodology is based on a local projection IV and the identification of a public spending shock is achieved by constructing a Bartik instrument. The empirical evidence shows a mild positive effect of 1% increase in government spending relative to GDP on the growth of the volume loans relative to GDP. However, the empirical findings show that government spending does not help to ameliorate neither the “size bias,” that is the financial constraints which small firms face relative to larger ones, nor the “home bias” in lending related to the process of bank consolidation in Italy.     

Electrodeposition of nanostructured bioactive hydroxyapatite-heparin composite coatings on titanium for dental implant applications

In this paper we describe the one-pot fabrication of hydroxyapatite (HA)-heparin composites by electrodeposition onto Ti substrates and their characterisation in terms of structure, morphology, heparin content and bioactivity. HA coatings are well known and widely applied osteointegration enhancers, but post-implant healing rate in dental applications is still suboptimal: e.g. coagulation control plays a key role and the incorporation of an anticoagulant is considered a highly desirable option. In this study, we have developed an improved, simple and robust growth procedure for single-phase, pure HA-heparin films of thickness 1/3 μm. HA-heparin, forming nanowires, has the ideal morphology for bone mineralisation. Staining assays revealed homogeneous incorporation of sizable amounts of heparin in the composite films. The bioactivities of the HA and HA-heparin coatings on Ti were compared by HeLa cell proliferation/viability tests and found to be enhanced by the presence of the anticoagulant.     

Synthesis of Diverse Azolo[c]quinazolines by Palladium(II)‐ Catalyzed Aerobic Oxidative Insertion of Isocyanides

We report the palladium(II)‐catalyzed aerobic oxidative coupling of isocyanides with various (2‐aminophenyl)azoles using air as the stoichiometric oxidant. A diverse range of medicinally valuable azolo[c]quinazolines was obtained by this new approach.

     

A Novel Multiscale Methodology for Simulating Tunnel Ventilation Flows During Fires

This paper applies a novel and fast modelling approach to simulate tunnel ventilation flows during fires. The complexity and high cost of full CFD models and the inaccuracies of simplistic zone or analytical models are avoided by efficiently combining mono-dimensional (1D) and CFD (3D) modelling techniques. A simple 1D network approach is used to model tunnel regions where the flow is fully developed (far field), and a detailed CFD representation is used where flow conditions require 3D resolution (near field). This multi-scale method has previously been applied to simulate tunnel ventilation systems including jet fans, vertical shafts and portals (Colella et al., Build Environ 44(12): 2357–2367, 2009) and it is applied here to include the effect of fire. Both direct and indirect coupling strategies are investigated and compared for steady state conditions. The methodology has been applied to a modern tunnel of 7 m diameter and 1.2 km in length. Different fire scenarios ranging from 10 MW to 100 MW are investigated with a variable number of operating jet fans. Comparison of cold flow cases with fire cases provides a quantification of the fire throttling effect, which is seen to be large and to reduce the flow by more than 30% for a 100 MW fire. Emphasis has been given to the discussion of the different coupling procedures and the control of the numerical error. Compared to the full CFD solution, the maximum flow field error can be reduced to less than few percents, but providing a reduction of two orders of magnitude in computational time. The much lower computational cost is of great engineering value, especially for parametric and sensitivity studies required in the design or assessment of ventilation and fire safety systems.     

Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3: role of complex formation and the E3 N-terminal domain

The human double-stranded RNA (dsRNA)-dependent protein kinase PKR inhibits protein synthesis by phosphorylating translation initiation factor 2alpha (eIF2alpha). Vaccinia virus E3L encodes a dsRNA binding protein that inhibits PKR in virus-infected cells, presumably by sequestering dsRNA activators. Expression of PKR in Saccharomyces cerevisiae inhibits protein synthesis by phosphorylation of eIF2alpha, dependent on its two dsRNA binding motifs (DRBMs). We found that expression of E3 in yeast overcomes the lethal effect of PKR in a manner requiring key residues (Lys-167 and Arg-168) needed for dsRNA binding by E3 in vitro. Unexpectedly, the N-terminal half of E3, and residue Trp-66 in particular, also is required for anti-PKR function. Because the E3 N-terminal region does not contribute to dsRNA binding in vitro, it appears that sequestering dsRNA is not the sole function of E3 needed for inhibition of PKR. This conclusion was supported by the fact that E3 activity was antagonized, not augmented, by overexpressing the catalytically defective PKR-K296R protein containing functional DRBMs. Coimmunoprecipitation experiments showed that a majority of PKR in yeast extracts was in a complex with E3, whose formation was completely dependent on the dsRNA binding activity of E3 and enhanced by the N-terminal half of E3. In yeast two-hybrid assays and in vitro protein binding experiments, segments of E3 and PKR containing their respective DRBMs interacted in a manner requiring E3 residues Lys-167 and Arg-168. We also detected interactions between PKR and the N-terminal half of E3 in the yeast two-hybrid and lambda repressor dimerization assays. In the latter case, the N-terminal half of E3 interacted with the kinase domain of PKR, dependent on E3 residue Trp-66. We propose that effective inhibition of PKR in yeast requires formation of an E3-PKR-dsRNA complex, in which the N-terminal half of E3 physically interacts with the protein kinase domain of PKR.     

Stage I seminoma of the testis: long term results and toxicity with adjuvant radiotherapy

AIMS AND BACKGROUND: Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento, METHODS: From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. RESULTS: The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespread metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. CONCLUSIONS: In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.     

Emergence of fluconazole-resistant strains of Blastoschizomyces capitatus causing nosocomial infections in cancer patients

Blastoschizomyces capitatus strains resistant to fluconazole were isolated in three cancer patients. All of the strains had identical genomic DNA restriction profiles. Our findings give evidence for the emergence of fluconazole-resistant B. capitatus and suggest a nosocomial acquisition emanating from a common source within the hospital environment.