Virus-host interactions in an ovine model of lung cancer

Ovine pulmonary adenocarcinoma (OPA) is a respiratory disease caused by jaagsiekte sheep retrovirus (JSRV). This virus induces the growth of large lung tumours in affected sheep and is a significant problem for the sheep industry. An interesting feature of OPA is that it occurs only in sheep. Goats may also be infected by JSRV but disease progression is limited to the early stages so that clinical signs do not develop. The ability of a virus to replicate in its host is dependent on a wide range of cellular proteins, including essential, required (‘dependency’) factors, and proteins that act to inhibit replication, referred to as restriction factors. Greater understanding of the roles of dependency and restriction factors can provide insights into pathogenesis and the species-specificity of infection. The aim of this study was to investigate the potential role of previously identified restriction factors on the replication of JSRV, and specifically whether APOBEC3 or TRIM5 proteins are responsible for the specificity of OPA for sheep. To examine this question, ruminant genes for APOBEC3 were cloned and their activity against JSRV was tested using a replication-defective reporter virus that expresses GFP. This system allows the activity of putative restriction factors to be measured quantitatively by flow cytometry. These experiments revealed that ruminant APOBEC3 proteins, including those from sheep, inhibit JSRV infection in vitro. Further analysis of the mechanism of restriction of JSRV by sheep APOBEC3 provided evidence for cytidine deaminase-dependent and independent mechanisms against this virus. In order to extend the studies on the species-specificity of APOBEC, several human and mouse APOBEC proteins were analysed for their activity against JSRV. Murine APOBEC3 and human APOBEC3F were both able to restrict JSRV in vitro, while other human APOBECs tested were not. These results have impact for the development of murine model of OPA and for the development of JSRV as a gene delivery vector. To assess the impact of TRIM5 on JSRV replication, derivatives of the permissive cell line CRFK were created that stably express TRIM5 from a range of ruminant and primate species. Infection studies performed in cell culture indicated that none of the TRIM5 proteins tested restrict JSRV, at least during the early stages of virus infection. Further studies are needed to examine other potential mechanisms of activity of TRIM5 against JSRV. This thesis has revealed new insights into host-pathogen interactions in OPA that may contribute to the development of control strategies against this disease. In addition, these data provide a background for the future development of JSRV as a gene delivery vector

Analysis of Distributed Systems Dynamics with Erlang Performance Lab

Modern, highly concurrent and large-scale systems require new methods for design, testing and monitoring. Their dynamics and scale require real-time tools, providing a holistic view of the whole system and the ability of showing a more detailed view when needed. Such tools can help identifying the causes of unwanted states, which is hardly possible with static analysis or metrics-based approach. In this paper a new tool for analysis of distributed systems in Erlang is presented. It provides real-time monitoring of system dynamics on different levels of abstraction. The tool has been used for analyzing a large-scale urban traffic simulation system running on a cluster of 20 computing nodes

Electrocardiographic algorithms to guide a management strategy of idiopathic outflow tract ventricular arrhythmias

The current guidelines of the European Society of Cardiology outlined electrocardiographic (ECG) differentiation of the site of origin (SoO) in patients with idiopathic ventricular arrhythmias (IVAs). The aim of this study was to compare 3 ECG algorithms for differentiating the SoO and to determine their diagnostic value for the management of outflow tract IVA. We analyzed 202 patients (mean age [SD]: 45 [16.7] years; 133 women [66%]) with IVAs with the inferior axis (130 premature ventricular contractions or ventricular tachycardias from the right ventricular outflow tract [RVOT]; 72, from the left ventricular outflow tract [LVOT]), who underwent successful radiofrequency catheter ablation (RFCA) using the 3‑dimensional electroanatomical system. The ECGs before ablation were analyzed using custom‑developed software. Automated measurements were performed for the 3 algorithms: 1) novel transitional zone (TZ) index, 2) $V_{2}S/V_{3}R$, and 3) $V_{2}$ transition ratio. The results were compared with the SoO of acutely successful RFCA. The $V_{2}S/V_{3}R$ algorithm predicted the left‑sided SoO with a sensitivity and specificity close to 90%. The TZ index showed higher sensitivity (93%) with lower specificity (85%). In the subgroup with the transition zone in lead V3 (n = 44, 15 from the LVOT) the sensitivity and specificity of the V2– transition‑ratio algorithm were 100% and 45%, respectively. The combined TZ index+$V_{2}S/V_{3}R$ algorithm (LVOT was considered only when both algorithms suggested the LVOT SoO) can increase the specificity of the LVOT SoO prediction to 98% with a sensitivity of 88%. The combined TZ‑index and $V_{2}S/V_{3}R$ algorithm allowed an accurate and simple identification of the SoO of IVA. A prospective study is needed to determine the strategy for skipping the RVOT mapping in patients with LVOT arrhythmias indicated by the 2 combined algorithms

Use of luminescent solar concentrators in architectural solutions

Artykuł dotyczy charakterystyki i zastosowania luminescencyjnych koncentratorów słonecznych LSC (ang. Luminescent Solar Concentrator) w rozwiązaniach architektonicznych. Opisano metodę działania koncentratorów luminescencyjnych oraz wskazano kierunki ich zastosowania. Poruszone zostały kwestie wykorzystania luminescencyjnych koncentratorów i związane z tym możliwości rozwoju energii odnawialnej w rozwiązaniach architektonicznych. W oparciu o studium przypadku opisano wybrane projekty rozwiązań architektonicznych z użyciem technologii opartej na luminescencyjnych koncentratorach słonecznych. Efektem artykułu jest zidentyfikowanie obszarów w zakresie wykorzystania luminescencyjnych koncentratorów słonecznych w rozwiązaniach architektonicznych.The article concerns the characteristics and application of Luminescent Solar Concentrators (LSC) in architectural solutions. The method of operation of luminescent concentrators was described and the directions of their application were indicated. The issues of the use of luminescent concentrators and the related opportunities for the development of renewable energy in architectural solutions were discussed. Based on a case study, selected designs of architectural solutions with the use of technology based on luminescent solar concentrators were described. The result of the article is to identify areas in the use of solar luminescent concentrators in architectural solutions

Case reportCongestive heart failure and continuous murmur in patient after lumbar disc surgery – a case report

We present a case of a 61-year-old female who was admitted to the hospital with symptoms of congestive heart failure. Diagnosis of arteriovenous fistula was suggested by the echocardiographic signs of high-output state and a continuous murmur heard especially close to the surgical scar from an intervention on the L4-L5 disc that the patient had undergone eight months before. Aortography confirmed arteriovenous fistula between the right common iliac artery and inferior vena cava. After surgical closure of the fistula, normal cardiac function was restored

Chorzy trudni nietypowiObwodowa postać przewlekłego zakrzepowo-zatorowego nadciśnienia płucnego. Trudności diagnostyczne, nowe możliwości terapeutyczne

We present a case of a 77-year-old female with distal chronic thromboembolic pulmonary hypertension. Diagnostic and therapeutic difficulties are discussed. Clinical and haemodynamic benefits resulting from treprostinil therapy added to continuous anticoagulation are shown