Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Picornavirus 3A Proteins on Protein Transport and GBF1-Dependent COP-I Recruitment

ABSTRACT The 3A protein of the coxsackievirus B3 (CVB3), an enterovirus that belongs to the family of the picornaviruses, inhibits endoplasmic reticulum-to-Golgi transport. Recently, we elucidated the underlying mechanism by showing that CVB3 3A interferes with ADP-ribosylation factor 1 (Arf1)-dependent COP-I recruitment to membranes by binding and inhibiting the function of GBF1, a guanine nucleotide exchange factor that is required for the activation of Arf1 (E. Wessels et al., Dev. Cell 11:191-201, 2006). Here, we show that the 3A protein of poliovirus, another enterovirus, is also able to interfere with COP-I recruitment through the same mechanism. No interference with protein transport or COP-I recruitment was observed for the 3A proteins of any of the other picornaviruses tested here (human rhinovirus [HRV], encephalomyocarditis virus, foot-and-mouth disease virus, and hepatitis A virus). We show that the 3A proteins of HRV, which are the most closely related to the enteroviruses, are unable to inhibit COP-I recruitment, due to a reduced ability to bind GBF1. When the N-terminal residues of the HRV 3A proteins are replaced by those of CVB3 3A, chimeric proteins are produced that have gained the ability to bind GBF1 and, by consequence, to inhibit protein transport. These results show that the N terminus of the CVB3 3A protein is important for binding of GBF1 and its transport-inhibiting function. Taken together, our data demonstrate that the activity of the enterovirus 3A protein to inhibit GBF1-dependent COP-I recruitment is unique among the picornaviruses.
22 kV, 1 cm2, 4H-SiC n-IGBTs with improved conductivity modulation

In this paper, we report our recently developed large area 4H-SiC n-IGBTs that have a chip size of 1 cm2 and an active conducting area of 0.37 cm2. A blocking voltage of 22.6 kV has been demonstrated with a leakage current of 9 μA at a gate bias of 0 V at room-temperature. This is the highest breakdown voltage of a single MOS-controlled semiconductor switch reported to date. To improve the conductivity modulation and lower the conduction losses during the on-state, a thermal oxidation process was applied to enhance the carrier lifetime prior to the device fabrication. Compared to the devices that did not receive this lifetime enhancement process, the lifetime enhanced devices displayed nearly 1 V lower forward voltage drop with little increase in switching energy and no degradation of static blocking characteristics. A specific differential on-resistance of 55 mΩ-cm2 at 20 A and 125 °C was achieved, suggesting that bipolar power devices with thick drift regions can benefit from further enhancement of the ambipolar carrier lifetime.
A polarization independent negative-refractive-index metamaterial for incident plane waves

In this paper a new left-handed artificial dielectric is proposed. Using resonating broadside coupled patches to generate a negative permeability and thin strips to generate negative permittivity, a negative index of refraction that is matched to free space can be designed. This structure is fabricated from a single dielectric sheet printed on both sides by metal patterns that couple to externally incident plane waves of any polarization
A prospective open-label single-arm phase II study of chimeric monoclonal antibody cG250 in advanced renal cell carcinoma patients.

cG250 is an IgG1 kappa light-chain chimeric monoclonal antibody that binds to a cell surface antigen found on 95% of clear-cell renal cancer. A multicentre phase II study was performed to evaluate the safety and efficacy of repeated doses of cG250. Thirty-six patients with metastatic RCC were included. All patients were nephrectomized for the primary tumour. Twenty-one patients were pretreated (e.g. with IL-2, IFN-alpha). A weekly dose of 50 mg cG250 was given by i.v. infusion for 12 weeks. Patients with SD or tumour response (PR, CR) after 12 weeks of treatment could receive additional treatment for 8 more weeks. None of the 36 enrolled patients had any cG250 grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. ELISA testing gave no evidence for relevant amounts of HACA. Eleven patients presented with SD and ten were eligible for extension treatment. After the end of the study in the follow-up period, one patient demonstrated a CR in week 38 and another patient with SD showed a significant reduction of the overall tumour load in week 44. Six additional patients with progressive disease at study entry were stable for more than six months after the treatment start. The weekly schedule of i.v. cG250 in patients with metastatic RCC was safe, very well tolerated and non-immunogenic in a 12-week treatment regimen. cG250 showed anti-tumour activity.
Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor

Cyclin B1 is translocated to the nucleus from the cytoplasm, and plays an essential role in cell proliferation through promotion of mitosis. Although overexpression of cyclin B1 was previously reported in breast carcinomas, the biological significance of the intracellular localization of cyclin B1 remains unclear. Therefore, in this study, we examined cyclin B1 immunoreactivity in 109 breast carcinomas, according to the intracellular localization, that is, nucleus, cytoplasm or total (nucleus or cytoplasm). Total cyclin B1 was detected in carcinoma cells in 42% of breast carcinomas examined, whereas nuclear and cytoplasmic cyclin B1 were positive in 17 and 35% of the cases, respectively. Total or cytoplasmic cyclin B1 were positively associated with histological grade, mitosis, Ki‐67, p53, c‐myc or 14‐3‐3σ, and inversely correlated with estrogen or progesterone receptor. Nuclear cyclin B1 was significantly associated with tumor size, lymph node metastasis, histological grade, mitosis, Ki‐67 or polo‐like kinase 1. Only nuclear cyclin B1 was significantly associated with adverse clinical outcome of the patients, and multivariate analyses of disease‐free and overall survival demonstrated nuclear cyclin B1 as the independent marker. A similar tendency was detected in the patients receiving adjuvant therapy after surgery. These results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo‐like kinase 1 and 14‐3‐3σ. Nuclear cyclin B1‐positive breast carcinoma is resistant to adjuvant therapy, and nuclear cyclin B1 immunoreactivity is a potent prognostic factor in breast carcinoma patients. (Cancer Sci 2007; 98: 644–651)
Digital Identification of Fast Scintillators in Phoswich APD-Based Detectors

Significant progress has been made in the last 15 years to improve the spatial resolution of small animal PET scanners, mainly by reducing the size of detector pixels. Spatial resolution can be further improved by using phoswich scintillator assemblies, either to increase pixellization or to measure the depth-of-interaction. A number of high-density, fast and high light output Ce-activated Lu-based scintillating materials with a range of decay times are now available, which has widened the list of potential candidates for applications in medical imaging. Most of them have suitable emission wavelength (above 400 nm) for readout with APDs, but their decay times are often too similar for accurate identification in phoswich detectors using standard analog pulse shape discrimination techniques. This study investigates the spectroscopic characteristics of these fast Lu-based scintillators and their diverse combinations into phoswich assemblies for high resolution PET detectors. Crystal identification was assessed using advanced numerical methods derived from signal recognition theory to fit a mathematical model to the digitized APD output signals and then to discriminate the crystal of interaction based on model parameters. Identification errors were evaluated as the overlapping peak area in the model parameter spectra. Identification is virtually error-free for decay time differences (Δτ) larger than 20 ns, while the measured error is generally less than 5% for Δτ > 10 ns. Whereas the Δτ between crystals is the major factor influencing identification performance, others factors such as the initial photon emission rate and the decay time also affect the identification accuracy. The phoswich pair consisting of LSO:Ce, Ca (τ = 32 ns) and LGSO (10%Gd-0.75%Ce) (τ = 45 ns) achieves the best overall performance for the PET application.
A PLCδ1‐binding protein, p122/RhoGAP, is localized in caveolin‐enriched membrane domains and regulates caveolin internalization

A GTPase activating protein (GAP), p122, has previously been cloned as a phospholipase C (PLC)δ1‐interacting protein. p122 shows a specific GAP activity for Rho and enhances the enzyme activity of PLCδ1. In this study, we examined the localization and functions of p122/RhoGAP, using enhanced green fluorescent protein (EGFP)‐tagged proteins. EGFP‐p122 was observed as punctate structures at the plasma membrane of BHK (fibroblastic) cells and MDCK (epithelial) cells. This patchy distribution depended on membrane cholesterol levels and the C‐terminal region of p122 containing the GAP domain was responsible for it. Sucrose density gradient centrifugation and immunostaining of caveolin‐1 revealed that p122 was localized in caveolin‐enriched membrane domains mainly via its GAP domain. We demonstrated that transient expression of EGFP‐p122 caused internalization of caveolin‐1. Moreover, when the EGFP‐tagged GAP domain was introduced in another fibroblastic cell line, NRK cells, punctate fluorescent structures were co‐localized with caveolin‐1. In this case, caveolin‐1‐positive structures were found in patches of F‐actin, unlike those of untransfected cells that formed linear arrays along with actin stress fibres. These results suggest that p122 is localized in caveolae and plays an important role in caveolin distribution through reorganization of the actin cytoskeleton.
HCV/ HIV co‐infection: time to re‐evaluate the role of HIV in the liver?

Summary. Because of major advances in the treatment of HIV/AIDS, HIV‐positive persons now live longer, healthier lives; however, hepatitis C virus (HCV) is increasingly recognized as a major cause of morbidity and mortality in this population. Among HCV‐infected persons, HIV co‐infection is associated with increased HCV RNA levels, increased hepatic inflammation and fibrosis, and more rapid progression to cirrhosis and end‐stage liver disease. Compounding this problem are reduced HCV treatment response rates among HCV/HIV co‐infected persons. Moreover, antiretroviral therapy used to suppress HIV replication is often associated with a paradoxical increase in HCV RNA levels, as well as hepatotoxicity. Despite the adverse clinical consequences of HCV/HIV co‐infection, the mechanisms by which these two viruses interact at the cellular level remain largely unexplored. This review focuses on the evidence demonstrating direct infection of hepatocytes by HIV, as well as the indirect mechanisms by which HIV may regulate HCV replication at the cellular level. A comprehensive understanding of virus–virus and virus–cell interactions is critical to the development of novel treatment strategies to combat HCV/HIV co‐infection.
HAT cofactor TRRAP mediates β-Catenin ubiquitination on the chromatin and the regulation of the canonical Wnt pathway

The Wnt pathway is a key regulator of embryonic development and stem cell self-renewal, and hyperactivation of the Wnt signalling is associated with many human cancers. The central player in the Wnt pathway is β-Catenin, a cytoplasmic protein whose function is under tight control by ubiquitination and degradation, however the precise regulation of β-Catenin stability/degradation remains elusive. Here, we report a new mechanism of β-Catenin ubiquitination acting in the context of chromatin. This mechanism is mediated by the histone acetyltransferase (HAT) complex component TRRAP and Skp1, an invariable component of the Skp-Cullin-F-box (SCF) ubiquitin ligase complex. TRRAP interacts with Skp1/SCF and mediates its recruitment to β-Catenin target promoter in chromatin. TRRAP deletion leads to a reduced level of β-Catenin ubiquitination, lower degradation rate and accumulation of β-Catenin protein. Furthermore, recruitment of Skp1 to chromatin and ubiquitination of chromatin-bound β-Catenin is abolished upon TRRAP knock-down, leading to an abnormal retention of β-Catenin at chromatin and concomitant hyperactivation of the canonical Wnt pathway. These results demonstrate that there is a distinct regulatory mechanism for β-Catenin ubiquitination/destruction acting in the nucleus which functionally complements cytoplasmic destruction of β-Catenin and prevents oncogenic stabilization of β-Catenin and chronic activation of the canonical Wnt pathway.
Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation.

AIMS Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction. METHODS AND RESULTS Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation. CONCLUSION Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.
L'intégration économique en Afrique: un Processus en cours / Economic Integration in Africa: an Ongoing Process

Partout dans le monde, l'integration economique regionale permet d'accelerer la croissance et le developpement en apportant une panoplie d'avantages lies a une meilleure cooperation politique, a un commerce intra-regional accru et a la creation d'emplois. Les regions qui sont plus integrees se sont revelees capables de connaitre une croissance plus rapide et ont fait preuve d'une plus grande capacite d'adaptation en periode de ralentissement de l'economie mondiale. Alors que l'economie mondiale lutte pour retrouver ses niveaux de croissance eleves d'il y a dix ans, la stimulation de la croissance interne et regionale est devenue la principale solution strategique pour de nombreux pays et regions. La Chine tisse davantage de liens avec ses voisins, l'Inde fait pareil, et meme dans l'Union Europeenne le commerce intra-regional est en passe de retrouver ses niveaux qui existaient avant la crise financiere. En Afrique, le Maroc et l'Afrique du Sud adoptent aussi des strategies commerciales regionales de maniere vigoureuse, alors que l'Europe reste le principal marche d'exportation de l'Afrique. Le commerce de l'Afrique avec les nations atlantiques de l'Europe se retrecit a un moment ou l'Afrique envisage d'intensifier ses relations commerciales avec elle-meme. Toutefois, a mesure que l'Afrique s'integre dans les chaines de valeur mondiales, on devrait s'attendre a ce que le commerce avec l'Europe continue d'augmenter, sachant que la concurrence avec les autres voisins atlantiques de l'Afrique au sud des Etats-Unis s'accentuera probablement.
Vessel extraction in retinal images using automatic thresholding and Gabor Wavelet

Retinal image analysis has been widely used for early detection and diagnosis of multiple systemic diseases. Accurate vessel extraction in retinal image is a crucial step towards a fully automated diagnosis system. This work affords an efficient unsupervised method for extracting blood vessels from retinal images by combining existing Gabor Wavelet (GW) method with automatic thresholding. Green channel image is extracted from color retinal image and used to produce Gabor feature image using GW. Both green channel image and Gabor feature image undergo vessel-enhancement step in order to highlight blood vessels. Next, the two vessel-enhanced images are transformed to binary images using automatic thresholding before combined to produce the final vessel output. Combining the images results in significant improvement of blood vessel extraction performance compared to using individual image. Effectiveness of the proposed method was proven via comparative analysis with existing methods validated using publicly available database, DRIVE.
Ureteroscopy in the Diagnosis of Upper Tract Transitional Cell Cancer: A 10-Year Experience Providing Outcome Data for Informed Consent

Purpose The aim of the study was to assess the effectiveness of ureteroscopy and biopsy in the diagnosis and management of upper tract urothelial carcinoma. Methods We retrospectively collated data from pathology, radiology and operating theatre data sets from two large UK hospitals. During the 10-year period examined, 160 patients underwent ureteroscopy prior to nephro-ureterectomy (NU)/distal ureterectomy (DU). Results Of the 160 patients identified, 140 were ureteroscopically evaluated and biopsied, 104 (74.3%) had positive biopsies, 5 (3.6%) had negative biopsies and 31 (22.1%) had nondiagnostic biopsies. One hundred and forty patients of 160 (88.8%) resulted in positive findings as a result of their ureteroscopy [positive biopsy/positive operative cytology/visible upper tract urothelial carcinoma (UTUC) at ureteroscopy)]. A total of 108 patients had cytological samples sent for histological analysis where grade was able to be assessed at DU/NU. Of these samples, 35 had positive cytology, 58 had an abnormal result that was not diagnostic and 15 had negative cytology. Patients with positive biopsies had upstaging (58.4%) and/or upgrading (30.5%) of their initial ureteroscopic histology at NU/DU. The overall success rate of ureteroscopy for cancer diagnosis was 88.8%. Conclusions Upper tract endoscopy and biopsy yielded positive biopsy results in 74.3% of cases and confirmed a cancer diagnosis in 88.8%. Five patients had negative histology at biopsy, all of whom eventually underwent a NU/DU confirming cancer.
Magnetic induction tomography: experimental realization

Magnetic induction tomography (MIT) is a new non-contacting technique for visualization of the electrical impedance distribution inside inhomogeneous media. A measuring system for MIT has been developed. An oscillating magnetic field is applied in the system as a sounding agent. The system is designed mainly for biomedical applications. Experiments demonstrate that with proper selection of measurement conditions it is possible to use the phase shifts between inductor and detector signals for image reconstruction by filtered backprojection along magnetic lines. Measurements with saline filled phantoms having various spatial distributions of conductivity were carried out and images were reconstructed. The experiments have demonstrated the applicability of MIT for medical imaging and diagnostics.
Lipoprotein lipase and metabolic activities in incubated bovine adipose tissue explants: effects of insulin, dexamethasone, and fetal bovine serum.

An in vitro system was used to study the regulation of lipoprotein lipase (LPL) activity in bovine adipose tissue. The utilization of two energetic and lipogenic substrates, acetate and glucose, and the activity of glucose-6-phosphate dehydrogenase (G6PDH), an enzyme involved in de novo lipogenesis, were also studied. Nine nonlactating, nonpregnant Holstein cows were given limited amounts of feed for 10 d, then they were overfed for 3 to 5 wk. Samples of perirenal adipose tissue were incubated for 24 or 48 h. Insulin (2 mU/mL) increased (P < .001) daily glucose and acetate utilization and attenuated (P < .001) the loss of G6PDH activity detected after 1 or 2 d of incubation. Dexamethasone (DEX, 10 nM) added to the insulin-supplemented medium decreased (P < .02) glucose utilization, but it did not change acetate utilization or G6PDH activity. A higher concentration of DEX (100 nM) potentiated (P < .004) the ability of insulin to attenuate the decrease in G6PDH activity without changing substrate utilization. Under basal conditions, LPL activity was decreased by approximately 66% after 2 d of incubation. The decline in LPL activity was attenuated by insulin addition (P < .02) and was further attenuated (P < .004) by 100 nM of DEX. The addition of 10% fetal bovine serum alone to the medium had no effect on LPL activity, and fetal bovine serum decreased this activity when it was added to the insulin-supplemented medium.
Conformational analysis of endothelin‐1: Effects of solvation free energy

In order to investigate conformational preferences of the 21‐residue peptide hormone endothelin‐1 (ET‐1), an extensive conformational search was carried out in vacuo using a combination of high temperature molecular dynamics / annealing and a Monte Carlo / minimization search in torsion angle space. Fully minimized conformations from the search were grouped into families using a clustering technique based on rms fitting over the Cartesian coordinates of the atoms of the peptide backbone of the ring region. A wide range of local energy minima were identified even though two disulfide bridges (Cys1‐Cys15 and Cys3‐Cys11) constrain the structure of the peptide. Low energy conformers of ET‐1 as a nonionized species in vacuo arestabilized by intramolecular interaction of the ring region (residues 1‐15) with the tail (residues 16–21). Strained conformations for individual residues are observed. Conformational similarity to protein loops is established by matching to protein crystal structures