Analysis of the replication of HIV-1 forced to use tRNA(Met(i) )supports a link between primer selection, translation and encapsidation

BACKGROUND: Previous studies have suggested that the process of HIV-1 tRNA primer selection and encapsidation of genomic RNA might be coupled with viral translation. In order to further investigate this relationship, proviruses were constructed in which the primer-binding site (PBS) was altered to be complementary to elongator tRNA(Met )(tRNA(Met(e))) (HXB2-Met(e)) or initiator tRNA(Met )(tRNA(Met(i))) (HXB2-Met(i)). These tRNA(Met )not only differ with respect to the 3' terminal 18-nucleotides, but also with respect to interaction with host cell proteins during protein synthesis. RESULTS: Consistent with previous studies, HXB2-Met(e) were infectious and maintained this PBS following short-term in vitro culture in SupT1 cells. In contrast, transfection of HBX2-Met(i) produced reduced amounts of virus (as determined by p24) and did not establish a productive infection in SupT1 cells. The low infectivity of the virus with the PBS complementary to tRNA(Met(i) )was not due to differences in endogenous levels of cellular tRNA(Met(i) )compared to tRNA(Met(e)); tRNA(Met(i) )was also capable of being selected as the primer for reverse transcription as determined by the endogenous reverse transcription reaction. The PBS of HXB2-Met(i) contains an ATG, which could act as an upstream AUG and syphon scanning ribosomes thereby reducing initiation of translation at the authentic AUG of Gag. To investigate this possibility, a provirus with an A to G change was constructed (HXB2-Met(i)AG). Transfection of HXB2-Met(i)AG resulted in increased production of virus, similar to that for the wild type virus. In contrast to HXB2-Met(i), HXB2-Met(i)AG was able to establish a productive infection in SupT1 cells. Analysis of the PBS following replication revealed the virus favored the genome with the repaired PBS (A to G) even though tRNA(Met(i) )was continuously selected as the primer for reverse transcription. CONCLUSION: The results of these studies suggest that HIV-1 has access to both tRNA(Met )for selection as the replication primer and supports a co-ordination between primer selection, translation and encapsidation during virus replication

Management of technology licensing as a foreign market entry mode:the case of leading Italian pharmaceutical and biotech companies

Technology licensing has been recognized for decades as one of the new market entry modes. Companies often issue licenses in foreign countries in order to enter a new market. This paper aims to unearth how companies manage the technology licensing, purposely used by firms in order to enter new markets. Starting from the perspectives given in the Dunning’s eclectic theory on foreign market entry modes, and by adopting the process view perspective from the technology management literature, and also incorporating the Dynamic Capabilities Framework, this paper tries to explain the managerial aspects of technology licensing as the foreign market entry mode. Although technology licensing as a market entry mode has been previously thoroughly explored, limited attention has been given to the possible ways companies approach in managing technology licensing for the new market entry purpose. In the paper authors rely on the multiple case study research approach in order to reveal the relevant managerial aspects implemented by Italian pharmaceutical and biotech companies that exploit technology licensing for the new market entry purpose. The key findings in this paper indicate two points: (i) companies adopt the process view perspective for managing technology licensing as the foreign market entry mode and (ii) throughout the stages of this process firms tend to develop their dynamic capabilities (sensing, seizing and reconfiguring). These research findings contribute to a deeper understanding of technology licensing as a market entry mode in the Innovation and Technology Management literature, but also in the Internationalization literature, by integrating the elements coming from these two research streams. The managerial implications resulting from this paper may be especially useful for the firms operating in the research intensive industries (like chemical, semi-conductor, biotech, etc.), enabling them to recognize the relevant issues in technology licensing process for the market entry purpose.<br

The Drift Chambers Of The Nomad Experiment

We present a detailed description of the drift chambers used as an active target and a tracking device in the NOMAD experiment at CERN. The main characteristics of these chambers are a large area, a self supporting structure made of light composite materials and a low cost. A spatial resolution of 150 microns has been achieved with a single hit efficiency of 97%.Comment: 42 pages, 26 figure

CMBPol Mission Concept Study: Probing Inflation with CMB Polarization

We summarize the utility of precise cosmic microwave background (CMB) polarization measurements as probes of the physics of inflation. We focus on the prospects for using CMB measurements to differentiate various inflationary mechanisms. In particular, a detection of primordial B-mode polarization would demonstrate that inflation occurred at a very high energy scale, and that the inflaton traversed a super-Planckian distance in field space. We explain how such a detection or constraint would illuminate aspects of physics at the Planck scale. Moreover, CMB measurements can constrain the scale-dependence and non-Gaussianity of the primordial fluctuations and limit the possibility of a significant isocurvature contribution. Each such limit provides crucial information on the underlying inflationary dynamics. Finally, we quantify these considerations by presenting forecasts for the sensitivities of a future satellite experiment to the inflationary parameters.Comment: 107 pages, 14 figures, 17 tables; Inflation Working Group contribution to the CMBPol Mission Concept Study; v2: typos fixed and references adde

Computerized cognitive training and brain derived neurotrophic factor during bed rest: Mechanisms to protect individual during acute stress

Acute stress, as bed rest, was shown to increase plasma level of the neurotrophin brain-derived neurotrophic factor (BDNF) in older, but not in young adults. This increase might represent a protective mechanism towards acute insults in aging subjects. Since computerized cognitive training (CCT) is known to protect brain, herein we evaluated the effect of CCT during bed rest on BDNF, muscle mass, neuromuscular function and metabolic parameters. The subjects that underwent CCT did not show an increase of BDNF after bed rest, and showed an anti-insular modification pattern in metabolism. Neuromuscular function parameters, already shown to beneficiate from CCT, negatively correlated with BDNF in research participants undergoing CCT, while positively correlated in the control group. In conclusion, BDNF increase can be interpreted as a standardized protective mechanism taking place whenever an insult occurs; it gives low, but consistent preservation of neuromuscular function. CCT, acting as an external protective mechanism, seems to modify this standardized response, avoiding BDNF increase or possibly modifying its time course. Our results suggest the possibility of differential neuroprotective mechanisms among ill and healthy individuals, and the importance of timing in determining the effects of protective mechanism

Cardiac damage after treatment of childhood cancer: A long-term follow-up

<p>Abstract</p> <p>Background</p> <p>With improved childhood cancer cure rate, long term sequelae are becoming an important factor of quality of life. Signs of cardiovascular disease are frequently found in long term survivors of cancer. Cardiac damage may be related to irradiation and chemotherapy.</p> <p>We have evaluated simultaneous influence of a series of independent variables on the late cardiac damage in childhood cancer survivors in Slovenia and identified groups at the highest risk.</p> <p>Methods</p> <p>211 long-term survivors of different childhood cancers, at least five years after treatment were included in the study. The evaluation included history, physical examination, electrocardiograpy, exercise testing and echocardiograpy. For analysis of risk factors, beside univariate analysis, multivariate classification tree analysis statistical method was used.</p> <p>Results and Conclusion</p> <p>Patients treated latest, from 1989–98 are at highest risk for any injury to the heart (73%). Among those treated earlier are at the highest risk those with Hodgkin's disease treated with irradiation above 30 Gy and those treated for sarcoma. Among specific forms of injury, patients treated with radiation to the heart area are at highest risk of injury to the valves. Patients treated with large doses of anthracyclines or concomitantly with anthracyclines and alkylating agents are at highest risk of systolic function defect and enlarged heart chambers. Those treated with anthracyclines are at highest risk of diastolic function defect. The time period of the patient's treatment is emerged as an important risk factor for injury of the heart.</p

The NOMAD Experiment at the CERN SPS

The NOMAD experiment is a short base-line search for ν&lt;sub&gt;μ&lt;/sub&gt; − ν&lt;sub&gt;τ&lt;/sub&gt; oscillations in the CERN neutrino beam. The ν&lt;sub&gt;τ&lt;/sub&gt;'s are searched for through their charged current interactions followed by the observation of the resulting τ− through its electronic, muonic or hadronic decays. These decays are recognized using kinematical criteria necessitating the use of a light target which enables the reconstruction of individual particles produced in the neutrino interactions. This paper describes the various components of the NOMAD detector: the target and muon drift chambers, the electromagnetic and hadronic calorimeters, the preshower and transition radiation detectors and the veto and trigger scintillation counters. The beam and data acquisition system are also described. The quality of the reconstruction and individual particles is demonstrated through the ability of NOMAD to observe K&lt;sub&gt;s&lt;/sub&gt;&lt;sup&gt;0&lt;/sup&gt;'s, Λ&lt;sup&gt;0&lt;/sup&gt;'s and π&lt;sup&gt;0&lt;/sup&gt;'s. Finally, the observation of τ− through its electronic decay being one of the most promising channels in the search, the identification of electrons in NOMAD is discussed

Astro2020 APC White Paper: The MegaMapper: a z &gt; 2 spectroscopic instrument for the study of Inflation and Dark Energy

MegaMapper is a proposed ground-based experiment to measure Inflation parameters and Dark Energy from galaxy redshifts at