Structures of FOX-4 cephamycinase in complex with transition-state analog inhibitors

Boronic acid transition-state analog inhibitors (BATSIs) are partners with β-lactam antibiotics for the treatment of complex bacterial infections. Herein, microbiological, biochemical, and structural findings on four BATSIs with the FOX-4 cephamycinase, a class C β-lactamase that rapidly hydrolyzes cefoxitin, are revealed. FOX-4 is an extended-spectrum class C cephalosporinase that demonstrates conformational flexibility when complexed with certain ligands. Like other β-lactamases of this class, studies on FOX-4 reveal important insights into structure–activity relationships. We show that SM23, a BATSI, shows both remarkable flexibility and affinity, binding similarly to other β-lactamases, yet retaining an IC50 value < 0.1 μM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes

Digital Preservation and Copyright: An International Study

The aim of the International Study on the Impact of Copyright Law on Digital Preservation was to review current copyright and related laws and their impact on digital preservation, as well as to make recommendations to help libraries, archives and other preservation institutions sustain digital works. Study partners are based in Australia, the Netherlands, the United Kingdom and the United States. The study found that, in many cases, digital works are not being preserved in a systematic way. This is partly because digital preservation entails more difficult copyright issues than preservation of non-digital material. All the surveyed countries have some form of exception for preservation activities. However, there is inconsistency in the details between the countries’ laws and uncertainty in how they apply in the digital environment. None of the countries surveyed have a uniform national system yet for collecting digital materials. Technological protection measures and licensing arrangements may, in some cases, present significant practical barriers to preservation. Current approaches to address these barriers are ad hoc and include requesting permissions from individual rights holders and some use of model licence terms that permit preservation. Moreover, as yet, there are no effective solutions to the general issue of orphan works. Recommendations of the study include suggestions for drafting national policies and adapting laws to allow digital preservation to be undertaken as necessary, in accordance with international best practice standards, and for promoting national systems for the collection of digital materials by relevant state and national collecting institutions

Digital humanities, digital methods, digital history, and digital outputs: history writing and the digital revolution

While the term ‘digital humanities’ appears inclusive its exact meaning remains unclear and its early association with studies in English Literature means the term has already been partially superceded by ‘digital methods’. However that re-naming is problematic as it emphasises the research tools used while the field itself is adjusting to include new methods, new topics, and new types of production, not just new ways of working with existing materials. Historians have long been alert to new tools as they become available to researchers. However, even as historians have revelled in the increased access to primary sources provided by digitisation, and have analysed the opportunities that access offers, they have been aware of the unevenness of the digitisation process and the gaps it both creates and disguises. Issues of copyright and the ethics of creating public access to private lives have also caused historians concern. More recently discussion about the evaluation of digital scholarship has begun. Often purely digital outputs are not formally recognised by their authors’ institutions, despite having a significant online presence and contributing to scholarship. In parallel with being concerned about fairly assessing the work of peers, historians have also begun to consider how to teach (and assess) the digital skills now expected of history graduates

Bulletin

https://openspace.dmacc.edu/bulletin/1104/thumbnail.jp

Building Preservation Partnerships: The Library of Congress National Digital Information Infrastructure and Preservation Program

Congress authorized the Library of Congress to undertake the National Digital Information Infrastructure and Preservation Program (NDIIPP) to prevent the loss of our digital heritage. This work, as with all digital preservation activities, is challenging because of technical issues and also because traditionally there have been few effective collaborative mechanisms to leverage resources and expertise. NDIIPP aims to address both issues while also ensuring the preservation of at-risk digital content. Concrete steps have been taken recently with the establishment of eight partnership consortia, each of which has committed to working with the other and the Library on collaborative digital preservation initiatives. The eight consortia represent the formal launch of an NDIIPP national network of preservation partners. Currently, NDIIPP is exploring how best to involve states and territories in the network. (from the article)published or submitted for publicatio

NDIIPP Partner Perspectives on Economic Sustainability

This article presents results from the National Digital Information Infrastructure and Preservation Program (NDIIPP) Digital Preservation Sustainability Working Group survey, conducted in 2007. The Library of Congress initiated the working group to gather information about significant issues relating to the economic sustainability of activities that support digital stewardship. The group decided the most useful method to collect information was through a series of structured telephone interviews involving several open-ended questions. Eleven NDIIPP partners were invited to participate. Interviews gathered qualitative information about a variety of economic sustainability issues, including developing business cases, implementing business models, measuring costs, and developing a stable economic basis for digital preservation programs. Survey results revealed a mix of consensus and division on various issues and shed interesting light upon the sustainability of preservation programs generally. The article provides an overview of the survey and its methodology, categorizes the responses, and draws some high-level conclusions. While the survey results should be viewed within the context of NDIIPP, they may be useful for archives, libraries, and other preservation institutions as they consider economic sustainability issues.published or submitted for publicatio

Efficient Execution of Compressed Programs

Code compression is the technique of using data compression to reduce the program memory size for memory-limited, embedded computers. For system-on-a-chip designs, this reduces the system die area which lowers die cost. After compilation, the binary (native code) program is compressed and stored in the embedded system. At run-time, the compressed program is incrementally decompressed and executed. While compressed programs have better code density, their performance is typically lower because additional effort is required to decompress the instruction stream. This dissertation presents methods to improve the performance of compressed programs. Decompression overhead can be minimized by using special-purpose hardware. This dissertation analyzes IBM's CodePack decompression algorithm and proposes optimizations for it. The optimized decompressor can often execute compressed programs faster than the original native program. The performance benefit of using fewer memory transactions to fetch compressed instructions surpasses the small decompression overhead. Therefore, code compression improves performance as well as code density. The decompression hardware can be largely replaced with software. The benefits of software decompression are greater design flexibility, reduced hardware complexity, reduced die area, and reduced cost. However, software decompression is much slower than hardware decompression. On a 5-stage pipelined embedded processor with a 4KB instruction cache, CodePack programs execute 1.3 to 27.0 times slower than native programs and reduce program memory die area (instruction cache and main memory) by 26% to 41%. This dissertation proposes instruction set support to enable efficient software-managed decompression. In addition, it explores two software optimizations, hybrid programs and memoization, to improve the execution time of compressed programs by reducing the compression. Hybrid programs contain both native and compressed code to reduce the number of times the decompressor is invoked. Memoization is a dynamic optimization that caches recent decompression results to also avoid invoking the decompressor. Optimized compressed programs that reduce die area 10% to 33% execute only 1.00 to 1.22 times slower than native code. In addition, loop-oriented (multimedia) programs are nearly as fast as native code.Ph.D.Applied SciencesComputer scienceElectrical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132615/2/9977198.pd