The success of locoregional, low-dose recombinant interleukin-2 therapy in tumor-bearing mice is dependent on the time of rIL-2 administration

The most common chromosomal aberrations in myelodysplastic syndromes (MDS) are complete or partial loss of chromosomes 5 and 7, and trisomy 8. To identify genes important in the pathogenesis of this disease that could be associated with these gross chromosomal defects, we have employed the differential display PCR (DDPCR) procedure developed by Liang and Pardee. This method allows simultaneous comparison of several cDNA sources for the presence of differentially expressed genes. Polymorphonuclear cells (PMNs) from two MDS patients, containing a 5q deletion or a trisomy 8, and three healthy controls were used. Initial screening resulted in the identification of five and three partial cDNA sequences, respectively that were either differentially expressed in both patient samples or in individual patients, as compared with the controls. The authenticity of aberrant expression was verified by reanalyzing the same primer combinations on newly prepared cDNA. Differential expression of the three remaining fragments was subsequently checked on a larger panel of MDS patients, using amplicon-specific primer sets. These were obtained by cloning and sequencing of the fragments. For one partial cDNA (DC3), the original expression pattern, i.e., decreased expression in individual MDS patients, was confirmed. These results demonstrate the utility of the DDPCR procedure to isolate differentially expressed sequences in primary patient samples where the availability of cells is a limiting factor.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

The psychosomatic network: foundations of mind-body medicine

Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in brain structures associated with emotional processing, and throughout many organ systems. This finding supported neuropeptides as biochemical substrates of emotion, and the neuropeptide-receptor network as a parasynaptic system crossing traditional brain-body boundaries. The medical relevance of these findings was affirmed by psychoneuroimmunology research: neuropeptides help to regulate immunocyte trafficking, there is bidirectional communication between nervous and immune system components, immunocytes produce neuropeptides, and nerve cells produce immune-associated cytokines. In the past decade, the concept of a unified psychosomatic network has been strengthened by animal and human research demonstrating relationships between behavior and neuropeptide-mediated regulation of immune functions. Research on emotional expression or disclosure in healthy human subjects as well as in cancer and HIV-positive patients has shown significant positive correlations with clinically relevant immune functions and/or positive health outcomes. Psychosocial interventions emphasizing emotional expression or active coping have evidenced survival benefits in breast cancer and melanoma. These findings suggest that emotional expression generates balance in the neuropeptide-receptor network and a functional healing system. Emotional expression is also a marker for psychospiritual vitalization, and further research should evaluate links between energy-based models of health and neuropeptide-receptor-based models under the rubric of an informational paradigm.     

Tomographic reconstruction from experimentally obtained cone-beam projections

Direct reconstruction in three dimensions for two-dimensional projection data has been achieved by cone-beam reconstruction techniques. In this paper explicit formulas for a cone-beam convolution and back-projection reconstruction algorithm are given in a form which can be easily coded for a computer. The algorithm is justified by analyzing tomographic reconstructions of a uniformly attenuating sphere from simulated noisy projection data. A particular feature of this algorithm is the use of a one-dimensional rather than two-dimensional convolution function, greatly speeding up the reconstruction. The technique is applicable however large the cone angle of data capture and correctly reduces to the pure fan-beam reconstruction technique in the central section of the cone. The method has been applied to data captured on a cone-beam CT scanner designed for bone mineral densitometry.     

An Objective Method to Prioritize Socio‐Environmental Water Management Tradeoffs Using Multi‐Criteria Decision Analysis

Rivers provide many social and environmental services that benefit humanity. A critical role of water mangers is to prioritize water allocation options that trade off socio‐economic and hydro‐ecological benefits in rivers. Methods for multi‐criteria decision analysis (MCDA) provide a structured and systematic manner for researchers to aid in this process. In this paper, we describe a new MCDA method that prioritizes large multi‐dimensional sets of tradeoffs to support well‐informed water management in rivers. The method was developed based on an environmental flows planning study in the Goulburn‐Broken River catchment, Victoria, Australia. A combined simulation and heuristic optimization procedure was previously integrated into a hydrological catchment network model. That process resulted in a large set of viable daily water allocation schedules that traded off long‐term irrigation and hydro‐ecological benefits at the catchment outlet. We provided new guidance procedures to identify priority tradeoffs that can be used in stakeholder deliberations and catchment decision‐making. Our MCDA method included combined multi‐dimensional ordination and cluster analysis to spread the water allocation alternatives onto a two‐dimensional plane to discover alternatives with similar criteria tradeoffs. A geometric distance‐based method was performed on the full set of alternatives and on the identified clusters to rank the alternatives in accordance with minimizing the distance of the alternatives to an ideal but non‐feasible reference point in multi‐dimensional space. This method complements the use of elicitation procedures when water manager or other stakeholder interaction is not an option or when objectivity is desired. Copyright © 2016 John Wiley & Sons, Ltd.     

The adsorption and decomposition of carbon dioxide on polycrystalline copper

The interaction of carbon dioxide with polycrystalline copper has been studied by radiolabelling techniques using {14-C} carbon dioxide, and by temperature programmed desorption. It is showninter alia, that: carbon dioxide is weakly adsorbed at the clean surface; that this acts as precursor which, on activation, produces adsorbed carbon monoxide and surface oxygen; and that this oxidised copper surface then adsorbs carbon dioxide more strongly yielding a state which can be hydrogenated first to formate, and thereafter to methanol.     

Optics clustered to output unique solutions: a multi-laser facility for combined single molecule and ensemble microscopy

Optics clustered to output unique solutions (OCTOPUS) is a microscopy platform that combines single molecule and ensemble imaging methodologies. A novel aspect of OCTOPUS is its laser excitation system, which consists of a central core of interlocked continuous wave and pulsed laser sources, launched into optical fibres and linked via laser combiners. Fibres are plugged into wall-mounted patch panels that reach microscopy end-stations in adjacent rooms. This allows multiple tailor-made combinations of laser colours and time characteristics to be shared by different end-stations minimising the need for laser duplications. This setup brings significant benefits in terms of cost effectiveness, ease of operation, and user safety. The modular nature of OCTOPUS also facilitates the addition of new techniques as required, allowing the use of existing lasers in new microscopes while retaining the ability to run the established parts of the facility. To date, techniques interlinked are multi-photon/multicolour confocal fluorescence lifetime imaging for several modalities of fluorescence resonance energy transfer (FRET) and time-resolved anisotropy, total internal reflection fluorescence, single molecule imaging of single pair FRET, single molecule fluorescence polarisation, particle tracking, and optical tweezers. Here, we use a well-studied system, the epidermal growth factor receptor network, to illustrate how OCTOPUS can aid in the investigation of complex biological phenomena.     

Verification of Knowledge Assets in Electronic Repositories: Expert- and Community-Governance

Two mechanisms that verify knowledge contributions in electronic repositories are expert-governance and community-governance. Our goal is to examine repository users' perceptions of the conditions under which these mechanisms verify knowledge contributions. Qualitative data show that perceived credibility of experts, perceived ownership of content, and experts' (meticulous) execution of governance functions are salient for expert-governance, and the perceived involvement of community members, and community members' (continuous and collective) execution of governance functions are important for community-governance.     

A model to predict land susceptibility to wind erosion in western Queensland,Australia

This paper describes the development and validation of the Australian Land Erodibility Model (AUSLEM), designed to predict land susceptibility to wind erosion in western Queensland, Australia. The model operates at a 5 × 5 km spatial resolution on a daily time-step with inputs of grass and tree cover, soil moisture, soil texture and surficial stone cover. The system was implemented to predict land erodibility, i.e. susceptibility to wind erosion, for the period 1980–1990. Model performance was evaluated using cross-correlation analyses to compare trajectories of mean annual land erodibility at selected locations with trends in wind speed and observational records of dust events and a Dust Storm Index (DSI). The validation was conducted at four spatial length scales from 25 to 150 km using windows to represent potential dust source areas centered on and positioned around eight meteorological stations within the study area. The predicted land erodibility had strong correlations with dust-event frequencies at half of the stations. Poor correlations at the other stations were linked to the inability of the model to account for temporal changes in soil erodibility, and comparing trends in the land erodibility of regions with dust events whose source areas lie outside the regions of interest. The model agreement with dust-event frequency trends was found to vary across spatial scales and was highly dependent on land type characteristics around the stations and on the types of dust events used for validation.     

Plate beamsplitter to produce multiple equal-intensity beams

The design of a plate beamsplitter to produce multiple beams of equal intensity is presented. Multiple beams of equal intensity can be obtained from a plate by varying the reflectances of the front and back surfaces. The application for which we designed the plate beamsplitter was a fourbeam multiplexed galvanometric scanner for a confocal scanning microscope. Multiplexing with four beams increases the effective optical scanning rate (and therefore the confocal imaging rate) to four times the electromechanical scanning rate of the galvanometrically driven mirrors.