Ultra-high resolution mass separator—Application to detection of nuclear weapons tests

A Penning trap-based purification process having a resolution of about 1 ppm is reported. In this context, we present for the first time a production method for the most complicated and crucially important nuclear weapons test signature, ^133mXe. These pure xenon samples are required by the Comprehensive Nuclear-Test-Ban Treaty Organization to standardize and calibrate the worldwide network of xenon detectors.     

Synthesis and preclinical characterization of [64Cu]NODAGA-MAL-exendin-4 with a Nε-maleoyl-l-lysyl-glycine linkage

IntroductionRenal localization of high radioactivity levels during targeted imaging compromises tissue visualization in the kidney region and limits diagnostic accuracy. Radioiodinated antibody fragments with a renal enzyme-cleavable N^ε-maleoyl-l-lysyl-glycine (MAL) linkage demonstrated low renal radioactivity levels in mice, from early postinjection times. This study tested the hypothesis whether a ⁶⁴Cu-labeled NODAGA-exendin-4 peptide with a MAL linkage ([⁶⁴Cu]NODAGA-MAL-exendin-4) could decrease kidney radioactivity levels in rats, compared to a [⁶⁴Cu]NODAGA-exendin-4 reference, without impairing the radioactivity levels in the target tissue.MethodsNODAGA-MAL-exendin-4 was synthesized in a two-phase approach using solid support to prepare maleoyl-derivatized NODAGA followed by Michael addition to cysteine-derivatized exendin-4 in solution. Radiolabeling was performed in buffered aqua with [⁶⁴Cu]CuCl₂, which was produced via the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction. The in vitro and in vivo stability, lipophilicity, and distribution kinetics in major rat organs for [⁶⁴Cu]NODAGA-MAL-exendin-4 were studied and compared to [⁶⁴Cu]NODAGA-exendin-4. Labeling of pancreatic islets was assessed using autoradiography.ResultsNODAGA-MAL-exendin-4 was synthesized, with an overall yield of 9%, and radiolabeled with ⁶⁴Cu with high specific radioactivity. Serum incubation studies showed high stability for [⁶⁴Cu]NODAGA-MAL-exendin-4. Similar tissue distribution kinetics was observed for [⁶⁴Cu]NODAGA-MAL-exendin-4 and [⁶⁴Cu]NODAGA-exendin-4, with high kidney radioactivity levels.ConclusionsThe incorporated MAL linkage in [⁶⁴Cu]NODAGA-MAL-exendin-4 was unable to reduce kidney radioactivity levels, compared to [⁶⁴Cu]NODAGA-exendin-4. The applicability of metabolizable linkages in the design of kidney-saving exendin-4 analogs requires further investigation.     

Problem-based learning in clinical practice: employment and education as development partners

In this project tutorial small group working sessions of problem-based learning were carried out in the long-term care practice period of nursing students. The purpose was to describe nursing students’ learning when tutorial work was carried out during their first clinical practice period. The students had one PBL cycle during their four weeks’ clinical practice consisting of two tutorial sessions where clinical mentors and the teacher worked together as tutors. The students were pre-tested before the clinical practice and post-tested afterwards using a questionnaire. The questionnaire had been used in pilot projects during 2004–2005. Altogether, 40 nursing students participated in the study. There were statistically significant differences between pre- and post-test in “PBL-learning skills” (p < 0.001) and “interaction with old patients” (p < 0.001). The means of items “Interested in work in long-term care” and “Own attitude towards long-term care” had increased between pre- and post-test. In conclusion it can be suggested that carrying out tutorials in nursing students’ clinical practice is beneficial.     

Phyllotactic patterning of gerbera flower heads

Phyllotaxis, the distribution of organs such as leaves and flowers on their support, is a key attribute of plant architecture. The geometric regularity of phyllotaxis has attracted multidisciplinary interest for centuries, resulting in an understanding of the patterns in the model plants Arabidopsis and tomato down to the molecular level. Nevertheless, the iconic example of phyllotaxis, the arrangement of individual florets into spirals in the heads of the daisy family of plants (Asteraceae), has not been fully explained. We integrate experimental data and computational models to explain phyllotaxis in Gerbera hybrida. We show that phyllotactic patterning in gerbera is governed by changes in the size of the morphogenetically active zone coordinated with the growth of the head. The dynamics of these changes divides the patterning process into three phases: the development of an approximately circular pattern with a Fibonacci number of primordia near the head rim, its gradual transition to a zigzag pattern, and the development of a spiral pattern that fills the head on the template of this zigzag pattern. Fibonacci spiral numbers arise due to the intercalary insertion and lateral displacement of incipient primordia in the first phase. Our results demonstrate the essential role of the growth and active zone dynamics in the patterning of flower heads.

The most common type of phyllotaxis—spiral phyllotaxis—is observed across the plant kingdom from algae to angiosperms (1). Its distinctive feature is the arrangement of organs in left- and right-winding spirals called (contact) parastichies (2). At the remarkable intersection of biology and mathematics, the numbers of parastichies are typically two consecutive elements of the Fibonacci sequence 1, 2, 3, 5, 8, 13, 21, 34, 55,....The development of phyllotactic patterns has been the subject of extensive experimental and theoretical studies (3–7). It is particularly well understood, down to the molecular level, in Arabidopsis and tomato (8, 9). In these plants, organ primordia emerge sequentially at the periphery of a dome-shaped meristem located at the tip of a growing shoot, giving rise to a spiral pattern with low parastichy numbers, e.g., 3/5 in the flowering shoot of Arabidopsis (10). In contrast, florets in the heads of the Asteraceae family are arranged in patterns with much higher parastichy numbers, up to 89/144 in the sunflower (11). As observed by Kuhlemeier (12), the development of these patterns has not been fully understood.The seminal idea behind explanations of phyllotaxis is due to Hofmeister (13), who proposed that new primordia emerge at locations that are sufficiently distant from the primordia formed earlier. Snow and Snow (14, 15) refined this hypothesis by postulating that new primordia are inserted as soon as space becomes available for them within the growing apical meristem. The resulting process is commonly abstracted as an iterative addition—also referred to as accretion (16, 17) or stacking (7, 18)—of new elements at the distal boundary of a spiral lattice (Fig. 1A). van Iterson (19) showed that, if the circumference of this lattice compared to the size of the added organs gradually increases, the number of parastichies will progress according to the Fibonacci sequence. This observation lies at the base of current theories explaining the prevalence of Fibonacci numbers in phyllotaxis, cf. refs. 7 and 20–22. In the flower heads of some species in the Aster family, however, patterns with relatively high Fibonacci parastichy numbers emerge outside the context of a gradually built-up lattice (Fig. 1B). Previous attempts to capture this process required an a priori assumption of the golden divergence angle between consecutive primordia (23–25) or produced whorls rather than spirals (26), leaving open the question of how the observed patterns arise.Open in a separate windowFig. 1.Problem position and the model system. (A) Example of a spiral phyllotactic lattice. Bracts in the flower head of Cirsium vulgare (common thistle) are arranged into a circular lattice that originates at the stem, possibly continuing the pattern of leaves, and extends by the addition of new elements at its distal boundary. The development of such patterns is largely understood. Image credit: Jouko Rikkinen, University of Helsinki/Finnish Biodiversity Information Facility, licensed under CC BY-NC 4.0 (B) The arrangement of bracts in gerbera. A pattern with a relatively high Fibonacci number of visible parastichies (13) is not preceded by a lattice. The development of such patterns has remained an open problem. (C and D) Gerbera head morphology. (C) Longitudinal section of the head. The head resembles a solitary flower, but comprises three types of florets (ray, trans, and disk) attached to a receptacle and surrounded by bracts. (D) The disk florets are arranged in a spiral phyllotactic pattern, with parastichies (representatives highlighted) occurring in Fibonacci numbers. (Scale bars: 1 cm.)Looking for an explanation, we selected Gerbera hybrida as a model plant due to its susceptibility to genetic transformation. A mature gerbera head comprises 600 to 700 individual florets of three different types, attached to a large receptacle (∼1.5 cm in diameter) surrounded by 80 to 90 leaflike involucral bracts (Fig. 1C). The florets are arranged in spirals (Fig. 1D), with up to 34/55 parastichies near the head rim. The head is supported by a leafless stem (scape), which may appear in a terminal or lateral position in the shoot (SI Appendix, Fig. S1). In the latter case, the scape constitutes the whole growth axis, which suggests that the phyllotactic pattern in the heads develops de novo. The separation of the head from the vegetative part of the plant and the large number of parastichies add to the usefulness of gerbera as a model system for studying phyllotaxis.     

Monitoring of multiple myeloma and bone marrow fibrosis with aminoterminal propeptide of type III collagen (PIIINP)

Bone marrow fibrosis is known in myelomatosis and depends on the extent of plasma cell infiltration. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) has previously been reported to reflect fibrogenesis in the marrow in myelofibrosis. Here we followed 15 consecutive patients with newly diagnosed multiple myeloma with repeated PIIINP measurements during treatment with intermittent courses of melphalan and prednisolone. PIIINP was found to change with clinical behaviour of the disease, nonresponders and patients with recurrent disease having elevated values and the values in responders decreasing to the normal level or remaining there. Collagen fibres in plasma cell infiltrates of biopsies from bone marrow or skeletal tumours of these patients stained heavily with antibodies against PIIINP. Our results suggest that PIIINP works as a noninvasive indicator of bone marrow fibrogenesis. In multiple myeloma PIIINP is a sensitive, but not specific marker of disease course.     

Integration of reproductive meristem fates by a SEPALLATA-like MADS-box gene

Reproductive transition, inflorescence architecture, meristem patterning, and floral organ identity have been studied as distinct research areas in plant science. By using the ornamental plant Gerbera, we demonstrate that all of these keystone aspects of reproductive meristematic fate are integrated genetically by a single SEPALLATA-like MADS-box gene from a functional class designated previously as "floral homeotic" or "organ identity." This extended regulatory network has not been elaborated in the model plant systems, which have a floral design and inflorescence-determinacy state that obscures these relationships.     

Evaluation of salmon calcitonin treatment in bone metastases from breast cancer--a controlled trial

Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions.