Successful and Safe Long-Term Standard Antiviral Therapy in a Patient with “Explosive” Immune Response in Course of HCV-Related Liver Cirrhosis

Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin’s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen.     

Lactobacillus plantarum 29 Inhibits Penicillium spp. Involved in the Spoilage of Black Truffles (Tuber aestivum)

The effect of an antifungal culture of Lactobacillus plantarum to be used in the storage at refrigeration temperature of fresh black truffles was examined. The strain was selected among 29 lactobacilli isolated from foods and evaluated for their viability and acidification activity at 4 °C, as well as for their inhibitory activity against 11 Penicillium strains isolated from truffles stored at refrigeration temperature. Lb. plantarum 29 showed the ability to hold not only the growth of Penicillium isolated from truffles, but also that of P. digitatum DSM 2750, a green mold involved in the spoilage of truffles. The antifungal activity was observed in vitro and in situ, and the sensory characteristics of truffles were preserved during the cold storage.     

Big science or bricolage: an alternative model for research in technical communication

Two research traditions inform contemporary technical communication research. With its physical science orientation and organizational capaciousness, the tradition of Big Science originated in the laboratory of Ernest O. Lawrence. With its humanistic orientation and individualistic singularity, the tradition of bricolage was identified in the fieldwork of Claude Le/spl acute/vi-Strauss. The current celebration of the former in technical communication research serves to reify a power-driven impulse for utility. The two cultures that result from such an impulse-the organizational professional and the academic researcher-have little common ground for research. To interrupt such harmful dynamics, an orientation to research is offered that celebrates successful past work in technological innovation, information design, the communication process, and the ways those processes emerge in specific contexts. To foster the continuation of such research, a community-based model is offered that draws its strength from the tradition of the bricoleur.     

Differential Effects of Furin Deficiency on Insulin Receptor Processing and Glucose Control in Liver and Pancreatic β Cells of Mice

The insulin receptor (IR) is critically involved in maintaining glucose homeostasis. It undergoes proteolytic cleavage by proprotein convertases, which is an essential step for its activation. The importance of the insulin receptor in liver is well established, but its role in pancreatic β cells is still controversial. In this study, we investigated the cleavage of the IR by the proprotein convertase FURIN in β cells and hepatocytes, and the contribution of the IR in pancreatic β cells and liver to glucose homeostasis. β-cell-specific Furin knockout (βFurKO) mice were glucose intolerant, but liver-specific Furin knockout (LFurKO) mice were normoglycemic. Processing of the IR was blocked in βFurKO cells, but unaffected in LFurKO mice. Most strikingly, glucose homeostasis in β-cell-specific IR knockout (βIRKO) mice was normal in younger mice (up to 20 weeks), and only mildly affected in older mice (24 weeks). In conclusion, FURIN cleaves the IR non-redundantly in β cells, but redundantly in liver. Furthermore, we demonstrated that the IR in β cells plays a limited role in glucose homeostasis.     

An adaptive freeway traffic state estimator

Real-data testing results of a real-time nonlinear freeway traffic state estimator are presented with a particular focus on its adaptive features. The pursued general approach to the real-time adaptive estimation of complete traffic state in freeway stretches or networks is based on stochastic nonlinear macroscopic traffic flow modeling and extended Kalman filtering. One major innovative aspect of the estimator is the real-time joint estimation of traffic flow variables (flows, mean speeds, and densities) and some important model parameters (free speed, critical density, and capacity), which leads to four significant features of the traffic state estimator: (i) avoidance of prior model calibration; (ii) automatic adaptation to changing external conditions (e.g. weather and lighting conditions, traffic composition, control measures); (iii) enabling of incident alarms; (iv) enabling of detector fault alarms. The purpose of the reported real-data testing is, first, to demonstrate feature (i) by investigating some basic properties of the estimator and, second, to explore some adaptive capabilities of the estimator that enable features (ii)-(iv). The achieved testing results are quite satisfactory and promising for further work and field applications.     

The design and performance of the ZEUS global tracking trigger

The Global Tracking Trigger (GTT) of the ZEUS experiment is described. The GTT is data driven at the ZEUS first level trigger rate of and performs event-based track finding on data from the experiment's Central Tracking Detector (CTD), silicon Micro Vertex Detector (MVD) and Straw Tube Tracker (STT) forward detectors. The resulting track-based trigger quantities calculated (track multiplicity, vertices, vector meson masses, background event probabilities, etc.) are available within and are used in the experiment's second level trigger to improve the selection of physics events. Detector information is pushed to the PC farm of the GTT using PowerPC VME board computers which are either embedded within the detector's frontend readout system (MVD) or are parasitically attached to them via multiple serial transputer links (CTD and STT). Data flow and control is performed via point-to-point Fast and Giga ethernet switched network connections using the TCP protocol. The principal design challenges were: integrating new and interfacing to existing frontend systems, providing a useful trigger result, satisfying the rate and latency requirements and not interfering with ongoing data taking during commissioning. These aims have been achieved. The GTT has been actively used in the ZEUS trigger since 2004 when an initial CTD-only algorithm was used; in 2005 this was upgraded to use MVD information which significantly improves track and primary vertex resolutions. Commissioning problems delayed the STT implementation and its use in the GTT has only been tested.     

DECT-based return channel for 42 GHz broadband wireless systems

A modern approach for the implementation of the return channel of broadband wireless systems based on DECT-like layers is described. The physical and MAC features are illustrated and the system performance is evaluated by computer simulations. Numerical results show that the proposed approach yields a high throughput and minimum message delay     

Preparation and properties of multifilament niobium carbonitride superconductor

The preparation and characterization of a multifilament niobium carbonitride yarn is reported here for the first time. The fine diameter multifilament yarn was prepared by chemical conversion of a precursor carbon yarn. The fibers are generally composed of both NbC and NbCN phases and exhibit a Tcof 16-17.5°K and an Hc2of 110- 120kG. Icvalues at zero field of up to 130 amperes have been measured corresponding to a Jcof 10⁶A/cm². Icis proportional to the amount of superconductor phase present as judged by weight gain data. At low conversion levels an anomaly has been detected in critical current behavior of the fibers suggesting a non-continuous superconducting path. Electrical contact to the fibers by copper coating is discussed showing the importance of obtaining a low resistance contact. Jcwas measured as a function of magnetic field for both the pure material and samples doped with silicon using SiCl4. The silicon dopant was found to be effective in reducing the field dependence of the critical current.     

Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.