Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.

The observed in vitro and in vivo benefit of combination treatment with anti-human immunodeficiency virus (HIV) agents prompted us to examine the potential of resistance development when two protease inhibitors are used concurrently. Recombinant HIV-1 (NL4-3) proteases containing combined resistance mutations associated with BMS-186318 and A-77003 (or saquinavir) were either inactive or had impaired enzyme activity. Subsequent construction of HIV-1 (NL4-3) proviral clones containing the same mutations yielded viruses that were severely impaired in growth or nonviable, confirming that combination therapy may be advantageous. However, passage of BMS-186318-resistant HIV-1 (RF) in the presence of either saquinavir or SC52151, which represented sequential drug treatment, produced viable viruses resistant to both BMS-186318 and the second compound. The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations. The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors. Chimeric virus and in vitro mutagenesis studies indicated that the RF-specific protease sequence, specifically the Ile at residue 10, enabled the NL4-3 strain with the triple mutant to grow. Our results clearly indicate that viral genetic background will play a key role in determining whether cross-resistance variants will arise.

Early termination of R&D projects

Early project termination is one of the most difficult decisions to be made by Research and Development managers. While there is the risk of terminating good projects, there is also the opposite risk of not terminating bad projects and overspend resources in unproductive research. Criteria used for identifying these projects are common subject of research in Business Administration. In addition, companies might take important lessons from its interrupted projects that could improve their overall portfolio technical and commercial success. Finally, the set and weight of criteria, as well as the procedures companies use for achieve learning from cancelled projects may vary depending on the project type. This research intends to contribute to the understanding of policies applied to projects that were once considered attractive, but by some reason is not appreciated anymore. The research addressed the question: How companies deal with projects that become unattractive? More specifically, this research tried to answer the following questions: (1) Are projects killed or (otherwise) they die naturally by lack of resources? (2) What criteria are used to terminate projects during development? (3) How companies learn from the terminated projects to improve the overall portfolio performance? (4) Are the criteria and learning procedures different for different types of projects? In order to answer these questions, we performed a multiple case study with four companies that are reference in business administration and innovation: (1) Oxiteno, considered the base case, (2) Natura, the literal replication, (3) Mahle and (4) AES, the theoretical replications. The case studies were performed using a semi-structured protocol for interviews, which were recorded and analyzed for comparison. We found that the criteria companies use for selecting projects for termination are very similar to those anticipated by the literature, except for a criteria related to compliance. We have evidences to confirm that the set of criteria is not altered when dealing with different project types, however the weight they are applied indeed varies. We also found that learning with cancelled projects is yet very incipient, with very few structured formal procedures being described for capturing learning with early-terminated projects. However, we could observe that these procedures are more common when dealing with projects labeled as innovative, risky, big and costly, while those smaller and cheaper derivative projects aren\'t subject of a complete investigation on the learning they brought to the company. For these, the most common learning route is the informal, where the project team learns and passes the knowledge though interpersonal information exchange. We explain that as a matter of cost versus benefit of spending time to deeply investigate projects with little potential to bring new knowledge to the project team and the organization

A statement of the monies which have been paid, & of the debts which are still due to Thomas Adams formerly College Butler. 15 April 1794

Statement with list of creditors paid with cash from the student accounts.

A statement of the bills due to Thomas Adams, late Butler of Harvard College and the amount of their appropriations to discharge his debts, 1794

Statement with list of creditors owed funds. Verso is dated 1797, and includes list of cash paid out to creditors.

Investigation of Performance Enhancements for a Liquid-Desiccant Solar Air-Conditioner

Thermally driven liquid-desiccant air-conditioners (LDAC) are a proven but still developing technology. LDACs can use a solar thermal system to reduce the operational cost and environmental impact of the system by reducing the amount of fuel (e.g. natural gas, propane, etc.) used to drive the system. LDACs also have a key benefit of being able to store energy in the form of concentrated desiccant storage. TRNSYS simulations were used to evaluate several different methods of improving the thermal and electrical coefficients of performance (COPt and COPe) and the solar fraction (SF) of a LDAC. The study analyzed a typical June to August cooling season in Toronto, Ontario. Utilizing properly sized, high-efficiency pumps increased the COPe to 3.67, an improvement of 55%. A new design, featuring a heat recovery ventilator on the scavenging-airstream and an energy recovery ventilator on the process-airstream, increased the COPt to 0.58, an improvement of 32%. This also improved the SF slightly to 54%, an increase of 8%. A new TRNSYS TYPE was created to model a stratified desiccant storage tank. Different volumes of desiccant were tested with a range of solar array system sizes. The largest storage tank coupled with the largest solar thermal array showed improvements of 64% in SF, increasing the value to 82%. The COPe was also improved by 17% and the COPt by 9%. When combining the heat recovery systems and the desiccant storage systems, the simulation results showed a 78% increase in COPe and 30% increase in COPt. A 77% improvement in SF and a 17% increase in total cooling rate were also predicted by the simulation. The total thermal energy consumed was 10% lower and the electrical consumption was 34% lower. The amount of non-renewable energy needed from the natural gas boiler was 77% lower. Comparisons were also made between LDACs and vapour-compression (VC) systems. Dependent on set-up, LDACs provided higher latent cooling rates and reduced electrical power consumption. Negatively, a thermal input was required for the LDAC systems but not for the VC systems.

Record of undergraduates’ activities in virtual learning environments

Virtual learning environments (VLEs) have witnessed a high evolution, namely regarding their potentialities, the tools and the activities they provide. VLEs enable us to access large quantities of data resulting from both students and teachers’ activities developed in those environments. Monitoring undergraduates’ activities in VLEs is important as it allows us to showcase, in a structured way, a number of indicators which may be taken into account to understand the learning process more deeply and to propose improvements in the teaching and learning strategies as well as in the institution’s virtual environment. Although VLEs provide several data sectorial statistics, they do not provide knowledge regarding the institution’s evolution. Therefore, we consider the analysis of the activity logs in VLEs over a period of five years to be paramount. This paper focuses on the analysis of the activities developed by students in a virtual learning environment, from a sample of undergraduate students, approximately 7000 per year, over a period of five academic years, namely from 2009/2010 to 2013/2014. The main aims of this research work are to assess the evolution of activity logs in the virtual learning environment of a Portuguese public higher education institution, in order to fill possible gaps and to hold out the prospect of new forms of use of the environment. The results obtained from the data analysis show that overall, the number of accesses to the virtual learning environment increased over the five years under study. The most used tools were Resources, Messages and Assignments. The most frequent activities developed with these tools were respectively consulting information, sending messages and submitting assignments. The frequency of accesses to the virtual learning environment was characterized according to the number of accesses in the activity log. The data distribution was divided into five frequency categories named very low, low, moderate, high and very high, determined by the percentiles 20, 40, 60, 80 and 100, respectively. The study of activity logs of virtual learning environments is important not only because they provide real knowledge of the use that undergraduates make of these environments, but also because of the possibilities they create regarding the identification of a need for new pedagogical approaches or a reinforcement of previously consolidated approaches.

Why the Open Method of Coordination (OMC) is bad for you: a letter to the EU. Research Papers in Law, 5/2006

From the Introduction. The aim of the present “letter” is to provoke, rather than to prove. It is intended to further stimulate the – already well engaged – scientific dialogue on the open method of coordination (OMC).1 This explains why some of the arguments put forward are not entirely new, while others are overstretched. This contribution, belated as it is entering into the debate, has the benefit of some hindsight. This hindsight is based on three factors (in chronological order): a) the fact that the author has participated himself as a member of a national delegation in one of the OMC-induced benchmarking exercises (only to see the final evaluation report getting lost in the Labyrinth of the national bureaucracy, despite the fact that it contained an overall favorable assessment), as well as in a OECD led exercise of coordination, concerning regulatory reform; b) the extremely rich and knowledgeable academic input, offering a very promising theoretical background for the OMC; and c) some recent empirical research as to the efficiency of the OMC, the accounts of which are, to say the least, ambiguous. This recent empirical research grounds the basic assumption of the present paper: that the OMC has only restricted, if not negligible, direct effects in the short term, while it may have some indirect effects in the medium-long term (2). On the basis of this assumption a series of arguments against the current “spread” of the OMC will be put forward (3). Some proposals on how to neutralize some of the shortfalls of the OMC will follow (4).

The financial stability risks of ultra-loose monetary policy. Bruegel Policy Contribution Issue 2015/03

Ultra-loose monetary policies, such as very low or even negative interest rates, large-scale asset purchases, long-maturity lending to banks and forward guidance in central bank communication, aim to increase inflation and output, to the benefit of financial stability. But at the same time, these measures pose various risks and might create challenges for financial institutions. • By assessing the theoretical literature and developments in the United States, United Kingdom and Japan, where very expansionary monetary policies were adopted during the past six years, and by examining the euro-area situation, we conclude that the risks to financial stability of ultra-loose monetary policy in the euro area could be low. However, vigilance is needed. • While monetary policy should focus on its primary mandate of area-wide price stability, other policies should be deployed whenever the financial cycle deviates from the economic cycle or when heterogeneous financial developments in the euro area require financial tightening in some but not all countries. These policies include micro-prudential supervision, macro-prudential oversight, fiscal policy and regulation of sectors that pose risks to financial stability, such as construction.

Addressing the immediate needs of the Greek banks. CEPS Commentary, 31 July 2015

Based on a detailed calculation of the recapitalisation requirements of the Greek banks, we find that the sector needs an infusion of capital, but that the level largely depends on the stringency of the capital requirements applied. An expedient quick fix to comply with the minimum capital requirements could be achieved by a bail-in of existing creditors under the EU Bank Recovery and Resolution Directive of around €5 billion, leaving only €6 billion needed for re-capitalisation. If the ‘Cypriot’ standard is applied, however, the required re-capitalisation would be €15 billion. A ‘generous’ approach, which takes into account the phasing in of the new more-stringent capital requirements until 2018, would imply a re-capitalisation of €29 billion (or more bailing-in of creditors). The re-capitalisation should be undertaken preferably by the EIB, the EBRD or the new Greek investment fund, rather than via loans from the ESM to the Greek government.

Addressing climate change under preferential trade agreements: Towards alignment of carbon standards under the Transatlantic Trade and Investment Partnership

With its wide coverage of economic spheres and the variety of trade and investment measures currently under negotiation, the Transatlantic Trade and Investment Partnership opens windows of opportunity for advancing action on climate change. We examine possible avenues and international trade law implications for an alignment of carbon-related standards between the EU and the US. We compare EU and US carbon emissions standards for cars and argue that negotiators should strive for a mutual recognition of their equivalence for a transitional period, while pursuing the goal of full harmonization at the level of the highest standards of two parties at some date in the future. This could be a way to balance between economic and environmental interests and harness economic incentives for the benefit of climate.

The role of the G20 in WTO governance

Report by Professor Sungjoon Cho, Associate Professor of Law, Chicago-Kent College of Law (Chair), and Charlotte Sieber-Gasser, Doctoral Research Fellow, World Trade Institute, University of Bern, Session 27, WTO Public Forum 2010: The Forces Shapping World Trade, pp.29-33. In the course of the financial crisis, the global geography of power has shifted from G8 to G20. The latter, although representing roughly two thirds of global trade, consists of relatively a small number of global players and is consequently excluding many others from decision-making at the international stage. Nevertheless, the G20 has been successful in its reaction to the financial crisis and became therewith an important new player within the international community. When highlighting how the G20 might interfere with the WTO, the panel voiced concerns over the political legitimacy of the G20, given the limited number of members and the global impact of its decisions. It agreed on the impression that although the G20 intends to extend its debates from the financial sector to world economy in general, it has so far little achieved in this direction, particularly when it comes to moving the Doha agenda forward. It remains, thus, open how the G20 will evolve in the coming few years, and what mandates it will shed or adopt. So far, the G20 has complemented the WTO and international financial institutions in handling the financial crisis. Yet, even if there is little evidence pointing towards a less cooperative role in the future, the desirability of a G20 commitment in WTO trade negotiations has yet to be debated. The panel concluded by providing ideas on how the potential of the G20 might be used to serve global interests even better in the future. In their concluding remarks, the panellists agreed that it remains to be seen whether or not the G20 will further broaden its agenda. Given the ebbing away of the financial crisis there is even the question whether the G20 will remain an important international forum for financial collaboration, or whether it has already served its cause and will eventually disappear from the international stage. The Chair concluded the well attended and lively panel with voicing the hope that the two international bodies – the G20 and the WTO – will work in a positive way together in the future and face the challenges and opportunities in their collaboration to the benefit of everyone.

The old South cook book : the best recipes of the best cooks in Montgomery.

Includes English and Italian recipes; some recipes include wine or liquor as an ingredient. Sample recipes: Stuffed oysters, Almond drop cakes, Ravioli.

Letters addressed to the Right Hon. Lord Alvanley, on his pamphlet entitled The state of Ireland considered, and measures proposed for restoring tranquillity to that country /

Includes bibliographical references.

Queen Alexandra Sanatorium, Davos : souvenir & programme of matinee /

Souvenir programme of a variety performance given Tuesday May 11th, 1909 in the Theatre Royal, Drury Lane and directed by Arthur Collins and Cyril Maude for the benefit of the Queen Alexandra Sanatorium. The volume consists of stories, poems, dramatic sketches, caricatures and cartoons, contributed for the occasion.

A catalogue of an exhibition of angling book plates : forming the collection of Daniel B. Fearing, Newport, R.I.

Cover title: A catalogue of angling book plates forming the collection of Daniel B. Fearing, Newport, R.I.