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P-loop NTPases comprise one of the major superfamilies of nucleotide binding proteins, which mediate a variety of cellular processes, such as mRNA translation, signal transduction, cell motility, and growth regulation. In this review, we discuss the structure and function of two members of the ancient Obg-related family of P-loop GTPases: human Obg-like ATPase 1 (hOLA1), and its bacterial/plant homolog, YchF. After a brief discussion of nucleotide binding proteins in general and the classification of the Obg-related family in particular, we discuss the sequence and structural features of YchF and hOLA1. We then explore the various functional roles of hOLA1 in mammalian cells during stress response and cancer progression, and of YchF in bacterial cells. Finally, we directly compare and contrast the structure and function of hOLA1 with YchF before summarizing the future perspectives of hOLA1 research. This review is timely, given the variety of recent studies aimed at understanding the roles of hOLA1 and YchF in such critical processes as cellular-stress response, oncogenesis, and protein synthesis.

AN 8-WEEK INSTITUTE WAS HELD TO PREPARE SELECTED HIGH SCHOOL TEACHERS TO INITIATE AND DEVELOP VOCATIONAL PROGRAMS. THE PROJECT INCLUDED FOLLOWUP ACTIVITY FOR 1 YEAR TO IDENTIFY THE APPLICATION OF LEARNINGS ACQUIRED IN THE SUMMER INSTITUTE. THE INSTITUTE PROGRAM WAS WELL RECEIVED, AND ITS GENERAL EVALUATION WAS HIGHLY FAVORABLE. IT WAS RECOMMENDED, HOWEVER, THAT SUCH FUTURE TRAINING INSTITUTES BE NO LESS THAN 9 WEEKS IN LENGTH AND INCLUDE AT LEAST 3 WEEKS FOR FIELD STUDY. (GD)

Developed out of a concern for the role postsecondary education should play in middle management development, this report presents an exploratory study of those factors influencing the nature and characteristics of middle management in the retail department store. The research involved personal interviews with retail department store executives and middle managers in the East North Central Region of the United States and sought answers to questions such as "What kind of education?" and "What is the appropriate source of education?" The findings of this research provide new insights and important clues concerning the characteristics, educational needs, duties, and projected needs for retail middle managers. The six chapters of this report include information on (1) the dynamics of retailing, (2) the functions performed by retail firms, (3) the functions of middle management, (4) the description of middle managers, (5) ideal source of training, and (6) middle management needs. The report includes 67 tables and a comprehensive appendix of supporting data. (Author/JS)

Two regional workshops were held to expedite development and improvement in the scope and quality of project training in distributive education. The activities center around the development of instructional projects for high school level distributive education students. Each workshop consisted of about 42 hours of formal instruction, 30 hours of preparation and reporting, plus pre- and post workshop organizing of project materials. A total of 52 experienced distributive education coordinators participated in developing 22 group projects and 52 individual projects which can be found in "Workshop Report: Distributive Education Project Development Workshop at Rutgers" (VT 007 375) and "Workshop Report: Distributive Education Project Development Workshop at the University of Wisconsin" (VT 007 377). This report contains a summary of the development and conduct of the project development workshops and the evaluation of each workshop and subsequent dissemination success. A total of 19 recommendations are made by the project review committee relative to project development workshops. (MM)

Biomolecular interactions facilitate the biochemical processes that sustain life. Proteins, RNAs, and ribonucleoprotein complexes perform cellular functions that range from catalyzing the formation or cleavage of bonds to being structural building blocks, both of which are only possible through the interaction with their respective biomolecular partner(s). Having access to the parameters that describe these interactions is important for our understanding of the principles that underlie enzymatic and nonenzymatic processes. Here we describe two fluorescence-based approaches to determine two key parameters, the affinity and the rate of association/dissociation of a protein and a ligand. Considerations are provided to expand the described approach to other experimental systems.

Biomolecular interactions facilitate the biochemical processes that sustain life. Proteins, RNAs, and ribonucleoprotein complexes perform cellular functions that range from catalyzing the formation or cleavage of bonds to being structural building blocks, both of which are only possible through the interaction with their respective biomolecular partner(s). Having access to the parameters that describe these interactions is important for our understanding of the principles that underlie enzymatic and nonenzymatic processes. Here we describe two fluorescence-based approaches to determine two key parameters, the affinity and the rate of association/dissociation of a protein and a ligand. Considerations are provided to expand the described approach to other experimental systems.

Objective: International differences in colorectal cancer (CRC) survival and stage at diagnosis have been reported previously. They may be linked to differences in time intervals and routes to diagnosis. The International Cancer Benchmarking Partnership Module 4 (ICBP M4) reports the first international comparison of routes to diagnosis for patients with CRC and the time intervals from symptom onset until the start of treatment. Data came from patients in 10 jurisdictions across six countries (Canada, the UK, Norway, Sweden, Denmark and Australia). Design: Patients with CRC were identified via cancer registries. Data on symptomatic and screened patients were collected; questionnaire data from patients’ primary care physicians and specialists, as well as information from treatment records or databases, supplemented patient data from the questionnaires. Routes to diagnosis and the key time intervals were described, as were between-jurisdiction differences in time intervals, using quantile regression. Participants: A total of 14 664 eligible patients with CRC diagnosed between 2013 and 2015 were identified, of which 2866 were included in the analyses. Primary and secondary outcome measures: Interval lengths in days (primary), reported patient symptoms (secondary). Results: The main route to diagnosis for patients was symptomatic presentation and the most commonly reported symptom was ‘bleeding/blood in stool’. The median intervals between jurisdictions ranged from: 21 to 49 days (patient); 0 to 12 days (primary care); 27 to 76 days (diagnostic); and 77 to 168 days (total, from first symptom to treatment start). Including screen-detected cases did not significantly alter the overall results. Conclusion: ICBP M4 demonstrates important differences in time intervals between 10 jurisdictions internationally. The differences may justify efforts to reduce intervals in some jurisdictions.

Letter to James Goldie from E. Harland, dated April 21, 1908. The letter invites James Goldie to visit and stay for dinner.

The universally conserved GTPase HflX is a putative translation factor whose GTPase activity is stimulated by the 70S ribosome as well as the 50S but not the 30S ribosomal subunit. However, the details and mechanisms governing this interaction are only poorly understood. In an effort to further elucidate the functional mechanism of HflX, we examined its interaction with the 70S ribosome, the two ribosomal subunits (50S and 30S), as well as its ability to interact with guanine nucleotides in the respective ribosomal complexes using a highly purified in vitro system. Binding studies reported here demonstrate that HflX not only interacts with 50S and 70S particles, but also with the 30S subunit, independent of the nucleotide-bound state. A detailed pre-steady-state kinetic analysis of HflX interacting with a non-hydrolyzable analog of mant-GTP, coupled with an enzymatic probing assay utilizing limited trypsinolysis, reveal that HflX·GTP exists in a structurally distinct 50S- and 70S-bound form that stabilizes GTP binding up to 70 000-fold and that may represent the “GTPase-activated” state. This activation is likely required for efficient GTP-hydrolysis, and may be similar to that observed in elongation factor G. Results reported here address the surprising low affinity of free HflX for GTP and suggest that cellular HflX will mainly exist in the HflX·GTP·ribosome-bound form. A minimal model for the functional cycle of HflX is proposed.

Using a combination of biochemical, structural probing and rapid kinetics techniques we reveal for the first time that the universally conserved translational GTPase (trGTPase) HflX binds to the E-site of the 70S ribosome and that its GTPase activity is modulated by peptidyl transferase centre (PTC) and peptide exit tunnel (PET) binding antibiotics, suggesting a previously undescribed mode of action for these antibiotics. Our rapid kinetics studies reveal that HflX functions as a ribosome splitting factor that disassembles the 70S ribosomes into its subunits in a nucleotide dependent manner. Furthermore, our probing and hydrolysis studies show that the ribosome is able to activate trGTPases bound to its E-site. This is, to our knowledge, the first case in which the hydrolytic activity of a translational GTPase is not activated by the GTPase activating centre (GAC) in the ribosomal A-site. Furthermore, we provide evidence that the bound state of the PTC is able to regulate the GTPase activity of E-site bound HflX.

As U.S. families continue to allocate more of their food dollar to the foodservice industry, it becomes increasingly important to explore market segmentation strategies. Family life cycle (FLC) mod...

Synthetic biology and the rational design of biological devices depend on the availability of standardized and interchangeable biological parts with diverse range of functions. Reliable access to different reading frames during translation has largely been overlooked as functionality for bioengineering applications. Here we report the construction and initial characterization of the first member of such a class of biological parts that conforms to the BioBrick Standard (RFC25), allowing its interchangeable use in biological devices. Using our standardized frameshifting signal consisting of a UUUAAAG slippery sequence, a 6 nt spacer and an engineered pseudoknot based on the infectious bronchitis virus pseudoknot PK401 embedded in a dual reporter construct, we confirm that the frameshifting activity is comparable to the previously published frequency despite the introduced sequence changes. The frameshifting activity is demonstrated using SDS-PAGE and fluorescence spectroscopy. Standardized programmable ribosomal frameshift parts with specific frameshifting frequencies will be of utility for applications such as double coding DNA sequences by expanding the codable space into the -1 frame. Programmed shifting into the -1 frame to bypass a stop codon allows labeling of a protein pool with a fixed stoichiometry of fusion protein, as well as the construction of multi-enzyme expression constructs with specific expression ratios. A detailed understanding of the structural basis of programmed frameshifting will provide the opportunities to rationally design frameshifting elements with a wide range of applications in synthetic biology, including signals that are regulated by small ligands.

ABSTRACT The discovery of major natural gas reserves underlying State and federal waters in and near Mobile Bay, Alabama, beginning in 1979, led to a number of business and technical challenges that were addressed quite differently by industry operators. This paper describes one operator's overall approach to the preparation and execution of an economic development plan for the production of deep, hot, sour, high pressure gas in a shallow water, environment tally sensitive area. Extensive reservoir modeling, based on limited geophysical, geological, and well test data combined with technical evaluation of a number of development alternatives, led to an eleven well, three field development spread over 61,000 acres, with offshore production collected and dehydrated at three offshore platforms and pipelined to a 300 MCFD onshore treating facility. Production began in late 1993. Unique design and construction features are summarized, and serve as an introduction to a series of papers that cover selected features in more detail. Location of Leases-Figure 1(Available in full paper) INTRODUCTION On October 20, 1993, production began from the first of three offshore sour gas fields comprising Exxon's Mobile Bay Project, culminating a twelve-Year exploration and development effort. Within a few weeks, as the other fields and the onshore treating facility were brought on line, the overall production rate surpassed the nominal 300 MCFD design basis, making it the world's largest offshore sour gas development. The $1 billion, grassroots project will develop over one trillion cubic feet of Norphlet gas reserves off the coast of Alabama. LOCATION AND LEASEHOLDINGS The offshore portion of the Mobile Bay Project is located in State of Alabama and adjacent Federal offshore waters, about 30 miles south of the city of Mobile, Alabama, Figure 1. Most of the twelve State and five federal leases, covering 61,000 acres, were acquired in State and federal sales in 1981-84, for lease bonuses totaling $400 million. Except for the State Tract 114 Unit, in which Hunt has a 25% interest, all of the leases are 100% Exxon. Royalties vary from 1/6 on OCS leases to 28% on some State leases. State severance taxes vary from six to eight per cent, and Baldwin County also currently levies an additional one per cent.Discovered in 1983, the unitized Bon Secour Bay (BSB) Field (State Tracts 62, 63, 64, 78 and part of 77), lies inside Mobile Bay, about three to five miles north of the mouth of the Bay.The North Central Gulf (NCG) Field, discovered in 1984, is located on State and federal leases two to six miles south of Fort Morgan peninsula, It is made up of three units: the Block 827 unit (OCS Blocks 827 and 828), the Tract 116 Unit (State Tracts 115 and 11 6), and the Tract 114 Unit (State Tract 114 and part of 113).The Northwest Gulf (NWG) area is three to eight miles south of Dauphin Island. It includes the unitized NWG Field (State Tracts 111, 112, and 131), and the OCS Block 867 Unit (OCS Block 867 and part of 91 1).

Dear Sir, The authors read with interest Abdelmageid’s case report (2005) and appreciate the diverse and often ingenious way women of different cultures use everyday objects to reduce prolapse. The first author (PC) once worked as a Medical Officer in Sabah, a state in East Malaysia, where part of his remit was to run a Women’s Health Clinic. In one of these sessions, he was asked by a middle-aged Chinese woman for a routine gynaecological examnination. While on the couch, she deftly removed from her vagina a jade bangle that she had routinely used to reduce her uterovaginal prolapse. Speculum examination revealed no vaginal mucosal ulceration and the bangle was reinserted expertly by the patient herself. Among the Chinese, jade (yu) is believed to be imbued with vitalyang energy and thus slow down the ageing process (Nott 1966). Jade is also thought to assist women during childbirth and ‘‘render help to those suffering from abdominal ailments’’ (Wallis Budge 1930). It is therefore not surprising that a jade ring pessary, with properties that may induce good health, would be used for the purpose of reducing prolapse. However, despite its alleged beneficial properties, the authors feel that its’ cost (excess of £200 vs £20 for a Portex ring pessary), rigidness and lack of randomised control trials would make it difficult to recommend that jade bangles replace the usual polypropylene ring pessaries in the conservative management of uterovaginal prolapse in the United Kingdom.

Implications of Bureau of Labor Statistics projections for education in business and marketing. (SB)