Detecting single quantum dot motion with nanometer resolution for applications in cell biology

Quantum dots (QDs), semiconductor particles of nanometer dimension, have emerged as excellent fluorescent analogs in tracer experiments with single molecule sensitivity for bioassays. Cell imaging greatly benefits from the remarkable optical and physical properties of these inorganic nanocrystals: QDs are much brighter and exhibit a higher resistance to photobleaching than traditional fluorophores, and their narrow emission spectrum and flexible surface chemistry make them particularly suitable for multiplex imaging. Here, we have demonstrated the achievement of a nanometer spatial resolution on the position of a single QD in a simple optomechanical instrument using a high-sensitivity low-noise detector, an intensified CCD camera. Furthermore, nanometer variations in the amplitude of a QD's sinusoidal oscillations could be quantitatively distinguished after fast Fourier transform (FFT) based data processing. As confirmed by experiments where QDs were attached to the surface of bovine aortic endothelial cells, this method can be exploited in biology to assess molecular and subcellular contributions to responses such as motility, intracellular trafficking, and mechanotransduction, with high resolution and minimal disturbance to cells     

Activation of the sodium/hydrogen exchanger via the fibronectin-integrin pathway results in hematopoietic stimulation

A comparison of two assessment methods, consensus among experts and research synthesis of the scientific literature, was performed using a surgical procedure, carotid endarterectomy (CE), as an example. These two methods have been widely advocated as being scientifically valid. While the comparison revealed a number of areas of general agreement, important differences between the two methods emerged. For example, 30-day mortality for asymptomatic patients was considered an effective outcome (ranked first) by the synthesis, but only "equivocal" (ranked third) of six major indicators reported by the consensus method. The synthesis results are also consistent with other literature reviews as well as with recent large-scale randomized trial results. A number of factors that could account for differences between the two methods were examined. Overall, use of consensus panels may be appropriate early in the development of an intervention where the evidence is sparse, while quantitative research synthesis is preferable when a number of high-quality studies have been performed.     

Molecular Biology to Radiation Oncology: A Model for Translational Research? Opportunities in basic and translational research. From a workshop sponsored by the National Cancer Institute, Radiation Research Program, January 26-28, 1997, Bethesda, Maryland

Many exciting discoveries are being made that are providing new insights into how molecules, cells and tissues respond to ionizing radiation. There remains a need, however, to translate these findings into more effective treatments for cancer patients, including those treated with radiation therapy. This complex task will require the collaboration of scientists studying molecular, cellular and tissue responses, and those performing clinical trials of emerging therapies. The Radiation Research Program of the National Cancer Institute sponsored a workshop entitled "Molecular Biology to Radiation Oncology: A Model for Translational Research?" to bring together basic scientists and clinicians to exchange ideas and fundamental concepts and to identify opportunities for future research and collaboration. Four broad topics were addressed: signal transduction and apoptosis, the cell cycle, repair of radiation damage, and the microenvironment. The development, selection and use of appropriate experimental models is crucial to finding and developing new therapies, and opportunities exist in this area as well. This paper and the accompanying paper by Coleman and Harris that provides the viewpoint of radiation oncologists (Radiat. Res. 150, 134-147, 1998) summarize the background concepts and opportunities for translational research identified by the workshop participants.     

A charge-coupled-device camera image analysis system for quantifying DNA distributions in agarose gels after pulsed-field gel electrophoresis

In recent reports of the so-called "floral variant" of follicular lymphoma, an unusual variant of follicular lymphoma mimicking progressive transformation of germinal centers, questions have been raised regarding whether this process represents a malignant lymphoma. We studied 19 examples of the floral variant of follicular lymphoma and report our light microscopic, immunohistochemical, and molecular diagnostic findings. Morphologic changes consisted of effacement of normal lymph node architecture by follicles composed of atypical lymphocytes. The follicles were surrounded by prominent mantle zones that invaginated irregularly into the follicle centers, often imparting a "floral" appearance. Sufficient material was available for immunophenotypic or genotypic studies in 15 biopsies. Twelve of 15 cases studied by immunohistochemistry demonstrated phenotypes supporting a diagnosis of lymphoma. Five demonstrated light-chain restriction; one was an immunoglobulin-negative B-cell neoplasm; and six, in which only formalin-fixed, paraffin-embedded tissue was available, demonstrated overexpression of the bcl-2 protein. Southern blot analysis revealed evidence of clonal immunoglobulin heavy-chain gene rearrangement in all five cases tested. Overall, 12 of the 15 biopsies studied with these techniques showed immunologic or genotypic support for malignant lymphoma. The results of this study demonstrate that the floral variant of follicular lymphoma does indeed represent a malignant lymphoma.     

The Pavement Enterprise at Michigan Technological University

A project-based student Enterprise program was established at Michigan Technological University as part of an effort, funded by the National Science Foundation, related to reform of engineering education. The Enterprise program represents a separate degree track available in all departments of the College of Engineering. The Pavement Design, Construction, and Materials (Pavement) Enterprise was established in the Department of Civil and Environmental Engineering in conjunction with the Thompson Scholars program. The Thompson Scholars program is an asphalt-paving-industry-supported scholarship program. The Pavement Enterprise is composed of a team of students that work in a businesslike setting on projects related to the asphalt paving industry. In addition to their project activities, students are required to participate in paid summer internships in associated industries and organizations. An Advisory Board composed of industry and government leaders meets three times a year to provide advice, guidance, and feedback to the students and associated faculty. The team project activities of the Pavement Enterprise prepares graduates for careers in the pavement engineering field with knowledge and skills well beyond their peers in the traditional civil engineering curriculum. These team projects incorporate “active learning” techniques into the program. The performance of the Pavement Enterprise is demonstrated using student attrition as well as a peer review. Lessons learned in the operation of the program are presented for those institutions considering a similar program.     

Transistor-Level Tools for High-End Processor Custom Circuit Design at IBM

IBM's high-performance microprocessor designs leverage internally developed electronic design automation tools to create high-frequency, power efficient, and robust microprocessors. This paper describes some of the tools employed in the custom circuit design methodology in IBM. The tools described include a transistor-level block-based static timer, a static noise analysis methodology, and a transistor width tuner that optimizes performance and area. We also describe the application of electrical rule checking used to enforce consistent design practices. Finally, we discuss a macro extraction tool that determines parasitic resistance and capacitance of interconnect from a layout     

Effects of extensive crossfostering on performance of pigs on a farm

OBJECTIVE: To compare mortality and growth rates of pigs subjected to continuous or limited crossfostering. DESIGN: Prospective study. ANIMALS: 80 liters containing 879 pigs. PROCEDURE: In half of the litters, crossfostering was limited to the first 2 days of life. In the other litters, pigs were crossfostered throughout the lactation period to maintain uniform body weights within litters. RESULTS: Restricting crossfostering to the first 2 days of life resulted in a 20% increase in body weight at weaning, compared with crossfostering throughout the nursing period. Mortality rates did not differ between the limited and continuous crossfostering groups. CLINICAL IMPLICATIONS: The emphasis placed on reducing variation of body weights within litters is unwarranted and veterinarians should advise limiting crossfostering to the first 2 days of life. Excessive crossfostering late in the nursing period may be identified by low within-litter SD of mean body weight.     

Facilities for Fundamental Neutron Physics Research at the NIST Cold Neutron Research Facility

The features of two fundamental neutron physics research stations at the NIST cold neutron research facility are described in some detail. A list of proposed initial experimental programs for these two stations is also given.     

Do experienced diagnosticians agree about the diagnosis of dementia from survey data? The effects of informants' reports and interviewers' vignettes

Dementia in community settings is often diagnosed by computerized algorithms. This study examines the extent to which independent diagnosticians agreed among themselves in diagnosing dementia, severity and type when presented with data obtained during a population-based incidence study of cognitive decline and dementia. Secondly, it examines how judgements, based initially on respondents' self-reports and cognitive performance, were affected first by informants' reports and then by short case-vignettes written by trained lay interviewers. Thirdly, it compares diagnosticians' diagnosis of dementia with the algorithmic diagnosis (AGECAT). The items presented were selected from two screening interviews at wave 1 and wave 2 separated by an interval of 2 years and from wave 2 assessment and informant interviews, and included medical, psychiatric and ADL items and interviewers' own observations. The sample (N = 42) was derived from the first year of the wave 2 assessments, potential dementia cases entering consecutively while presumed normals were selected randomly. Informants were available in 30. Agreement on diagnosis and type of dementia improved with increasing information, particularly from informants, but remained poor regarding severity. The number of cases of dementia, defined operationally, increased from 10 to 12 and uncertain cases fell from eight to six, but no respondent initially diagnosed as a dementia case was rediagnosed as a non-case, or vice versa. Dementia type changed from agreement about Alzheimer's disease to agreement about vascular dementia in one case. Operational and algorithmic diagnoses showed good agreement. Causes of disagreement, the role of vignettes and the relevance of the results for population surveys are discussed.