Configuration of the catalytic GIY-YIG domain of intron endonuclease I-TevI: coincidence of computational and molecular findings.

I-TevI is a member of the GIY-YIG family of homing endonucleases. It is folded into two structural and functional domains, an N-terminal catalytic domain and a C-terminal DNA-binding domain, separated by a flexible linker. In this study we have used genetic analyses, computational sequence analysis andNMR spectroscopy to define the configuration of theN-terminal domain and its relationship to the flexible linker. The catalytic domain is an alpha/beta structure contained within the first 92 amino acids of the 245-amino acid protein followed by an unstructured linker. Remarkably, this structured domain corresponds precisely to the GIY-YIG module defined by sequence comparisons of 57 proteins including more than 30 newly reported members of the family. Although much of the unstructured linker is not essential for activity, residues 93-116 are required, raising the possibility that this region may adopt an alternate conformation upon DNA binding. Two invariant residues of the GIY-YIG module, Arg27 and Glu75, located in alpha-helices, have properties of catalytic residues. Furthermore, the GIY-YIG sequence elements for which the module is named form part of a three-stranded antiparallel beta-sheet that is important for I-TevI structure and function.

CEOs and CFOs express concern about materials management.

In a recent survey, CEOs and CFOs expressed concern regarding the effectiveness of their materials management departments. Both groups of executives would like to see more improvement in their materials managers' supply expense reduction efforts and leadership skills. More than a third of CFOs are even considering outsourcing the materials management function. Both CEOs and CFOs did admit, however, they needed to learn more about materials management, and both groups of executives could lend their authority to materials management programs to ensure their success. CEOs and CFOs need to reach consensus regard materials management priorities, performance levels, and professional characteristics and desired skills. They also should hold materials managers accountable for operations they can and should be managing by using performance-based compensation.

Controlling supply expenses through capitated supply contracting.

Some providers dealing with the financial challenges of managed care are attempting to control supply expenses through capitated supply contracting and similar risk/reward sharing arrangements. Under such arrangements, a supplier sells products and services to a provider for a fixed, prospective price in exchange for the provider's exclusive business. If expenses exceed the prospectively established amount, the supplier and provider share the loss. Conversely, if expenses are less than the fixed amount, they share the savings. For a capitated supply arrangement to be successful, providers must be able to identify and track supply expense drivers, such as clinical pathways, technology utilization, and product selection and utilization. Sophisticated information systems are needed to capture data, such as total and per-transaction product usage/volume; unit price per item; average and cost per item; average and total cost per transaction; and total cost per outcome. Providers also will need to establish mutually cooperative relationships with the suppliers with whom they contract.

Two-domain structure of the td intron-encoded endonuclease I-TevI correlates with the two-domain configuration of the homing site.

I-TevI, the T4 td intron-encoded endonuclease, catalyzes the first step in intron homing by making a double-strand break in the intronless allele within a sequence designated the homing site. The 28 kDa enzyme, which interacts with the homing site over a span of 37 bp, binds as a monomer, contacting two domains of the substrate. In this study, limited proteolysis experiments indicate that I-TevI consists of two domains that behave as discrete physical entities as judged by a number of functional and structural criteria. Overexpression clones for each domain were constructed and the proteins were purified. The carboxy-terminal domain has DNA-binding activity coincident with the primary binding region of the homing site and binds with the same affinity as the full-length enzyme. The isolated amino-terminal domain, contains the conserved GIY-YIG motif, consistent with its being the catalytic domain. Furthermore, site-directed mutagenesis of a conserved arginine residue within the extended motif rendered the full-length protein catalytically inactive, although DNA-binding was maintained. This is the first evidence that the GIY-YIG motif is important for catalytic activity. An enzyme with an N-terminal catalytic domain and a C-terminal DNA-binding domain connected by a flexible linker is in accord with the bipartite structure of the homing site.

CEO/CFO responses to materials management survey.

A national survey of chief executive officers (CEOs) and chief financial officers (CFOs) reveals that while CEOs and CFOs are satisfied overall with materials management at their hospitals, a number of individual facets of materials management need improvement. The survey also shows that reducing supply expenses and better managing operating room (OR) inventories are two of the best ways that materials managers can help reduce hospitals' total annual operating expenses.

Materials management--a department of one.

This article is the result of long and serious thought about the future direction of healthcare and, more specifically, of materials management. As a number of trends emerge, particularly those that already exist in other industries, potential applications of these trends may also apply to materials management. While not all of these concepts and ideas are currently in practice in healthcare settings, the purpose of this article is to initiate thought, conversation, and evaluation of these models and applications.

Inventory to go: can stockless deliver efficiency?

Influenced by the Japanese management concept of "just-in-time," healthcare organizations are looking to their departmental inventories for possible cost reductions. Some organizations have developed a materials management technique known as stockless inventory, in which much of the management of an organization's supplies is switched to an outside vendor. By eliminating its storeroom and many of the staffing needs that go along with it, a hospital with a stockless inventory program can realize significant cost savings. Whether these savings offset potentially large service fees is a question each hospital must decide on its own.

Materials management crucial to overall efficiency.

Because supplies are important to many departments, improved materials management may be an integral part of a hospital's productivity assessment. A successful program should encompass technical as well as managerial aspects of materials management. While looking at national performance statistics may provide a basis, each hospital should set its own standards in line with its strategic plan.

Just-in-time for hospitals--so what's new?

In response to increasing competition, many hospital administrators and managers are giving a close look and, in many cases, a quick trial to management methods, techniques, and concepts used by other industries. One of those concepts is Just-in-Time (JIT) production and inventory management. JIT may not be applicable to the unique characteristics of the hospital/health industry; however, upon closer inspection, it will become evident to the reader that JIT has been used to some extent and in various applications, for many years. It has just not been called such.