Recruiting future neuroscientists: what asking the recruits can teach us.

Many different strategies are used to recruit students into scientific research careers, including neuroscience research. These strategies are rarely based on knowledge about students; instead, activities are selected based on their ease of implementation. The goal of the LEARN Project is to encourage high school students into mental health science research using the theme of learning and memory. One intervention the authors developed is five Web-based biographies introducing students to contemporary neuroscientist role models studying learning and memory. To guide the design of this intervention, the authors created a survey to determine where students obtain career information and who and what influences their career selection. In a convenience sample of 124 students, the authors found that almost all students use the Internet for information about careers, in addition to consulting family members and teachers. Students' career selections are influenced most by family members, teachers, and people already in the field. The most important factors students look for in their future career are money, fun, and a good match between current interests and future careers. The data affirm the value of outreach efforts that go beyond students to include a broader audience of parents and teachers who play a critical role in career selection.     

Dodecon,das lösliche Hämagglutinin bei allen Adenoviren der Untergruppe II

Zusammenfassung Die Sedimentationsraten der kompletten löslichen Hämagglutinine der Adenoviren wurden bei 16 Prototypen der Untergruppe II im Saccharose-Gradienten bestimmt. Die Werte waren für alle Viren ähnlich (65±10S). Dies bedeutet, daß die strukturellen Komponenten ebenfalls identisch sein dürften, also Dodecon (1).

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Dodecon, the soluble hemagglutinin present in all adenovirus types of subgroup II

Summary The sedimentation rate of the soluble complete hemagglutinins of 16 prototype adenoviruses of subgroup II were determined by means of sucrose gradient centrifugation. The rates were similar for all types (65±10S), thus indicating that the structural components may also be identicali.e. dodecon (1).

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Durchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Flow cytometric analysis of cell proliferation dynamics in the B cell compartment of the mouse

Using a method which allows simultaneous flow cytometric detectionof cell surface markers and 5-bromo-2'-deoxyuridine (BrdU) incorporation,the distribution and proliferative behavior of B lineage subpopulationswas studied in intact adult mice. In the bone marrow we coulddefine two subsets of B cells on the basis of differential expressionof the pan-B cell marker B220 and of membrane-associated µand immunoglobulin heavy chains. B220^dullµ^+– Bcells were found to emerge from rapidly dividing cells and probablyrepresent B cells recently generated from B220^dullµ^–pie-B cells. In contrast, oniy few, If any, of the B220^brightµ⁺⁺B cells were labeled with BrdU after a period of 8 days, suggestingthat these cells represent long-lived B cells residing in thebone marrow. Analysis of BrdU-Incorporation into splenic B cellsshowed that only 20% of these cells had gone through cell divisionduring the preceding 8 days. Almost none of the B cells in theperitoneum, a large fraction of which belongs to the Ly1 B subset,were labeled with BrdU over a period of 7 days in 8-month-oldanimals.     

Dosimetric characteristics of a new unshielded silicon diode and its application in clinical photon and electron beams

Shielded p-silicon diodes, frequently applied in general photon-beam dosimetry, show certain imperfections when applied in the small photon fields occurring in stereotactic or intensity modulated radiotherapy (IMRT), in electron beams and in the buildup region of photon beam dose distributions. Using as a study object the shielded p-silicon diode PTW 60008, well known for its reliable performance in general photon dosimetry, we have identified these imperfections as effects of electron scattering at the metallic parts of the shielding. In order to overcome these difficulties a new, unshielded diode PTW 60012 has been designed and manufactured by PTW Freiburg. By comparison with reference detectors, such as thimble and plane-parallel ionization chambers and a diamond detector, we could show the absence of these imperfections. An excellent performance of the new unshielded diode for the special dosimetric tasks in small photon fields, electron beams and build-up regions of photon beams has been observed. The new diode also has an improved angular response. However, due to its over-response to low-energy scattered photons, its recommended range of use does not include output factor measurements in large photon fields, although this effect can be compensated by a thin auxiliary lead shield.     

Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a nonsedating benzodiazepine derivative that exhibits broad spectrum cytotoxicity against human solid tumor cell lines and potently inhibits farnesylation of the H-ras and K-ras oncogenic proteins. This report describes the initial Phase I clinical trial of the compound. The main objective of the study was to determine the dose-limiting toxicities and the maximum tolerated dose of BMS-214662 when administered as a single dose i.v. over 1 h every 21 days to patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients with advanced solid tumors and adequate organ function were eligible for the study. The dose was escalated according to a modified Fibonacci schedule after evaluating groups of at least three patients for toxicity during the first cycle of therapy at each dose level. Pharmacokinetic and pharmacodynamic studies were performed after administration of the two initial doses. RESULTS: The dose of BMS-214662 was escalated from 36 to 225 mg/m(2) through 5 intermediate dose levels in a total of 44 patients. Dose-limiting toxicities occurred in 3 of the 13 (23%) patients during the first cycle of treatment with 225 mg/m(2), consisting of grade 3 nausea/vomiting in 2 patients and grade 3 diarrhea in another patient. In addition, four of these patients experienced reversible grade 3 transaminitis, which was not considered to be dose-limiting. At the recommended dose for Phase II studies, 200 mg/m(2), the most common side effects were reversible transaminitis, nausea, and vomiting. Although there were no objective responses, one patient with pancreatic cancer continues to receive treatment more than 3.5 years after entering the study. BMS-214662 exhibited linear pharmacokinetics and had a mean biological half-life of 1.55 +/- 0.27 h and a total body clearance of 21.8 +/- 10.8 liters/h/m(2), with a low apparent volume of distribution at steady state (31.5 +/- 12.9 liters/m(2)). In patients treated with the recommended Phase II dose, the mean maximum plasma concentration of the drug was 6.57 +/- 2.94 microg/ml, and farnesyltransferase activity in peripheral blood mononuclear cells decreased to a nadir of 10.5 +/- 6.4% of baseline at the end of the infusion but fully recovered within 24 h. CONCLUSIONS: BMS-214662 can be delivered safely as a single 1-h i.v. infusion at a dose that results in pronounced inhibition of farnesyltransferase activity in peripheral blood mononuclear cells. However, the duration of enzyme inhibition was transient, recovering in parallel with the decline in plasma concentrations of this rapidly eliminated drug. Because indications of anticancer activity were observed in several patients, further optimization of the administration schedule for this promising new compound is warranted.     

Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.