Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

Alignment of the ALICE Inner Tracking System with cosmic-ray tracks

37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe

Clinical monitoring of cardiac output assessed by transoesophageal echocardiography in anaesthetised dogs: a comparison with the thermodilution technique

BACKGROUND: Cardiac output (CO) is an important haemodynamic parameter to monitor in patients during surgery. However, the majority of the techniques for measuring CO have a limited application in veterinary practice due to their invasive approach and associated complexity and risks. Transoesophageal echocardiography (TEE) is a technique used to monitor cardiac function in human patients during surgical procedures and allows CO to be measured non-invasively. This prospective clinical study aimed to compare the transoesophageal echocardiography using a transgastric view of the left ventricular outflow tract (LVOT) and the thermodilution (TD) technique for the assessment of CO during mean arterial pressure of 65-80 mmHg (normotension) and <65 mmHg (hypotension) in dogs undergoing elective surgery. Eight dogs were pre-medicated with acepromazine (0.05 mg/kg, IM), tramadol (4 mg/kg, IM) and atropine (0.03 mg/kg, IM), followed by anaesthetic induction with propofol (3-5 mg/kg IV) and maintenance with isoflurane associated with a continuous infusion rate of fentanyl (bolus of 3 μg/kg followed by 0.3 μg/kg/min). The CO was measured by TEE (COTEE) and TD (COTD) at the end of expiration during normotension and hypotension (induced by isoflurane). RESULTS: There was a strong positive correlation between COTEE and COTD ​​(r = 0.925; P < 0.0001). The bias between COTD and COTEE was 0.14 ± 0.29 L/min (limits of agreement, -0.44 to 0.72 L/min). The percentage error of CO measured by the two methods was 12.32%. In addition, a strong positive correlation was found between COTEE and COTD during normotension (r = 0.995; P < 0.0001) and hypotension (r = 0.78; P = 0.0223). CONCLUSIONS: The results of this study indicated that the transgastric view of the LVOT by TEE was a minimally invasive alternative to clinically monitoring CO in dogs during anaesthesia. However, during hypotension, the CO obtained by TEE was less reliable, although still acceptable