GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Chemically induced residual stresses in dental composites

In several European countries, dental composites are replacing mercury-containing amalgams as the most common restorative materials. One problem with dental composites is residual stresses which may lead to poor performance of the restoration. In the present study, a combined modeling and materials characterization approach is presented and predictions compare well with experimental data on residual stresses. The model takes stress relaxation into account through the complete relaxation time spectrum of the resin. The approach allows for detailed parametric studies where resin and composite composition as well as cure conditions may be tailored with respect to residual stress generation.     

Fast Parallel Reordering and Isomorphism Testing of k -Trees

In this paper two problems on the class of k -trees, a subclass of the class of chordal graphs, are considered: the fast reordering problem and the isomorphism problem. An O(log ² n) time parallel algorithm for the fast reordering problem is described that uses O(nk(n-k)/\kern -1ptlog n) processors on a CRCW PRAM proving membership in the class NC for fixed k . An O(nk(k+1)!) time sequential algorithm for the isomorphism problem is obtained representing an improvement over the O(n ² k(k+1)!) algorithm of Sekharan (the second author) [10]. A parallel version of this sequential algorithm is presented that runs in O(log ² n) time using O((nk((k+1)!+n-k))/log n) processors improving on a parallel algorithm of Sekharan for the isomorphism problem [10]. Both the sequential and parallel algorithms use a concept introduced in this paper called the kernel of a k -tree.     

GQR-based models for directional wireless channels

In this paper novel reduced complexity statistical models for the representation of directional wireless channels affected by Rayleigh fading are developed. Their derivation is based on the evaluation of Fourier integrals by means of Gaussian quadrature rules (GQRs). The proposed models represent a communication channel as a tapped-angle and -delay line with non uniform spacing between successive taps. The application of the GQR approach to three different scenarios is also illustrated. Numerical results evidence that these models can provide a simple and accurate stochastic representation of directional fading channels.     

Surgical treatment of atherosclerotic lesions of subclavian artery: carotid-subclavian bypass versus subclavian-carotid transposition

BACKGROUND: The aim of this retrospective study is to analyze the short and long term results of two different surgical treatments in patients with subclavian lesions: common carotid-subclavian artery bypass (CSB) versus transposition of subclavian artery on the common carotid artery (SCT). METHODS: From 1981 until 1995, 40 non randomized patients with symptomatic subclavian steal underwent 20 CSBs and 20 SCTs. Risk factor rates were equally balanced in the two groups. Surgery was carried out routinely under general anesthesia, with electroencephalic continuous monitoring. Patency of revascularization was assessed by physical examination, brachial blood pressure determinations, ultrasound sonography and angiography whenever recurrence of symptoms developed or when the function of repair was in doubt. Patients were examined every year. In Spring 1996 (range 9-189 mos, average 7 years) a general clinical-instrumental follow-up was performed. RESULTS: In the short term (<30 days) mortality was 5%: one death (5%) for pulmonary embolism in a patient with CSB and one for myocardial infarction in a patient with SCT. The early thrombosis rate was 5% (1 CSB and 1 common carotid artery distal to a patent SCT). During follow-up 10 patients (25%) died and 6 were lost. The six-year actuarial patency rate was 100% for SCT and 66% for CSB. Moreover there were 3 thromboses of the vertebral artery homolateral to patent CSBs. CONCLUSIONS: In conclusions SCT should be considered the surgical technical choice for the treatment of proximal subclavian artery lesions.     

Adaptive Radar Detection of Distributed Targets in Homogeneous and Partially Homogeneous Noise Plus Subspace Interference

This paper addresses adaptive radar detection of distributed targets in noise plus interference assumed to belong to a known or unknown subspace of the observables. At the design stage we resort to either the GLRT or the so-called two-step GLRT-based design procedure and assume that a set of noise-only data is available (the so-called secondary data). Detection algorithms have been derived modeling noise vectors, corresponding to different range cells, as independent, zero-mean, complex normal ones, sharing either the same covariance matrix (homogeneous environment) or the same covariance matrix up to possibly different (mean) power levels between primary data, i.e., range cells under test, and secondary ones (partially homogeneous environment). The performance assessment has been conducted by Monte Carlo simulation, also in comparison to previously proposed detection algorithms, and confirms the effectiveness of the newly proposed ones     

Autosensitized Photooxidation of the Rose Hip (Wild Rose) Oil - Mechanism and Quantum Yield for Singlet Molecular Oxygen O2 (1 Δg) Generation

The autosensitized photooxidation of the fatty acid components of rose hip (Wild Rose) oil was studied. Two important facts arise from the present investigation: a) Fatty acids of rose hip oil decompose upon visible light irradiation in the absence of external sensitizers by a mechanism that involves O₂(¹Δ_g). The pigments present in rose hip oil themselves efficiently sensitize the generation of O₂(¹Δ_g) with a quantum yield of 0.038 (upper limit). b) Visible irradiation also produces the degradation of the anthocyanines, native pigments which could behave as O₂(¹Δ_g) sensitizers in the oil. In this case a mechanism involving the production of superoxide ions by the pigment and further attack of the radicals on the phenol groups of the anthocyanine could account for the observed experimental evidences. These results should be carefully considered in a practical sense when rose hip oil is stored or employed under daylight conditions. Exposure to visible radiation may cause irreversible transformations in rose hip oil.     

Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor: an analysis of 497 patients

BACKGROUND: There is great interpatient variability in the number of peripheral blood stem cells collected, as measured by CD34+ cell content, after the administration of chemotherapy and a growth factor. The ability to predict patients who fail to yield adequate quantities of CD34+ cells would be of value. However, very few reports include large numbers of patients treated in an identical fashion. STUDY DESIGN AND METHODS: Between 1991 and 1995, 497 consecutive patients with a variety of malignant diseases received cyclophosphamide (4 g/m2), etoposide (600 mg/m2), and granulocyte-colony-stimulating factor (6 micrograms/kg/day) for mobilization and collection of a target dose > or = 2.5 x 10(8) CD34+ cells per kg. Multivariate analyses were performed to determine the factors associated with failure to achieve this target harvest. RESULTS: A median of 14.71 x 10(6) CD34+ cells per kg (range, 0.08-137.55) was harvested with a median of 2 (range, 1-11) apheresis procedures. Ninety-one percent of patients yielded > or = 2.5 x 10(5) CD34+ cells per kg. Patients with Stage II-III breast cancer, who had pretreatment platelet counts > or = 150 x 10(9) per L and patients who underwent < or = 1 prior chemotherapy regimen had improved CD34+ cell yields. However, most patients with adverse risk factors yielded > or = 2.5 x 10(6) CD34+ cells per kg. CONCLUSION: A regimen of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor led to the successful collection of adequate numbers of CD34+ cells in most patients without excessive toxicity. These observations confirm previous reports that intense prior therapy adversely affects the quantity of CD34+ cells harvested. Pretreatment and posttreatment variables did not predict with any certainty the small fraction of patients who fail to yield > or = 2.5 x 10(6) CD34+ cells per kg via multiple apheresis procedures.     

Growth dynamics in cystic fibrosis

The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71-82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity.