Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Microstructural Characterization of Cofired Tungsten-Metallized High-Alumina Electronic Substrates

Microstructural characterization of a high-Al₂O₃ substrate containing cofired thick-film tungsten metallization, with particular emphasis on the metal/ceramic interface, was conducted. The substrate contained tabular Al₂O₃ grains surrounded by a continuous calcium magnesium aluminum silicate glass containing particles of monoclinic ZrO₂ and reduced rutile (TiO_{2- x} ). The metal/ceramic adhesion was caused by mechanical interlocking between the W and Al₂O₃ grains by the glass phase which penetrated the porous W layers during sintering; there was no interfacial reaction or diffusion zone. The mechanical properties of the W metallization did not limit interfacial strength. Heat treatments of the substrate at 1400 K in air and under vacuum resulted in the devitrification of the intergranular glass. The most abundant devitrification product was anorthite (CaAl₂Si₂O₈), accompanied by magnesium aluminate titanate, magnesium aluminate spinel, α-cristobalite (SiO₂), and α-cordierite (Mg₂Al₄Si₅O₁₈). In addition, small rutile particles precipitated within the Al₂O₃ grains.     

Serotonin and serotonin receptors in the central auditory system

Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.     

Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects

CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. OBJECTIVE: To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS: Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. SETTING: University-based medical centers and affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. RESULTS: The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS: Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.     

The multi-agent programming contest from 2005–2010

The Multi-Agent Programming Contest is an annual international event on programming multi-agent systems: Teams of agents participate in a simulated cooperative scenario. It started in 2005 and is organised in 2010 for the sixth time. The contest is an attempt to stimulate research in the area of multi-agent system development and programming by (i) identifying key problems in the field and (ii) collecting suitable benchmarks that can serve as milestones for testing multi-agent programming languages, platforms and tools. This article provides a short history of the contest since it started and reports in more detail on the cows and cowboys scenario implemented for the 2008, 2009 and 2010 contest editions. We briefly discuss the underlying technological background and conclude with a critical discussion of the experiences and lessons learned.     

A Lack of Insight: An Experimental Analysis of R&D Managers’ Decision Making in Innovation Portfolio Management

This study analyses the decision to exploit an innovation project and investigates differences in individuals’ evaluations of project attributes in the context of innovation project portfolio management. A conjoint field experiment was used to collect data on exploitation decisions made by 126 research and development (R&D) managers to test how managers evaluate specific project attributes in the context of innovation project portfolio management. I analyse the relative power and popularity of profitability, strategy, uncertainty and social dimensions of the portfolio while R&D managers exploit an innovation project. Moreover, using social judgement theory, I analyse actual exploitation processes (i.e., the innovation attributes an R&D manager considers while he or she is making an exploitation decision) and self‐reported decision‐making attributes (i.e., managers’ self‐reported data). The data underline that R&D managers value specific project attributes more and others less, and therefore find disparities in innovation project portfolio decision making. Based on this study's results, decision makers are better able to reflect and understand the influence of specific project attributes. Therefore, they should investigate established decision‐making processes which can help them to improve portfolio performance.     

Model checking multi-agent systems with logic based Petri nets

We introduce a class of Petri nets, simple logic Petri nets (SLPN), that are based on logical expressions. We show how this type of nets can be efficiently mapped into logic programs with negation: the corresponding answer sets describe interleaved executions of the underlying nets (Theorem 1). The absence of an answer set indicates a deadlock situation. We also show how to correctly model and specify AgentSpeak agents and multi-agent systems with SLPN’s (Theorem 2). Both theorems allow us to solve the task of model checking AgentSpeak multi-agent systems by computing answer sets of the obtained logic program with any ASP system.     

Segmentation of microcalcifications in mammograms

A systematic method for the detection and segmentation of microcalcifications in mammograms is presented. It is important to preserve size and shape of the individual calcifications as exactly as possible. A reliable diagnosis requires both rates of false positives as well as false negatives to be extremely low. The proposed approach uses a two-stage algorithm for spot detection and shape extraction. The first stage applies a weighted difference of Gaussians filter for the noise-invariant and size-specific detection of spots. A morphological filter reproduces the shape of the spots. The results of both filters are combined with a conditional thickening operation. The topology and the number of the spots are determined with the first filter, and the shape by means of the second. The algorithm is tested with a series of real mammograms, using identical parameter values for all images. The results are compared with the judgement of radiological experts, and they are very encouraging. The described approach opens up the possibility of a reproducible segmentation of microcalcifications, which is a necessary precondition for an efficient screening program.     

Measurement of thrombus formation on intravascular catheters

War is a complex social situation due to the interplay of multiple factors. Economical and political ones are of utmost importance, but human attitudes and motivations must be also taken into account. Being desirable to modify human transactions in such a way that they do not interfere with the basic right of everyone to a condition of physical and mental well-being, war must be abolished. The author contends that an understanding of behaviour through Psychology can be helpful in that aim. Aggression is considered the principal psychological cause of war. It is worth while to differentiate between aggression as an instrument for attaining a special end, and as pure hostility. Only in the first form, it is held here, does it play an important role in war. Psychogists must deal also with a wide range of states of mind that can be "served" by aggression: feelings of inferiority or insecurity, fear, greed, projections, compensations, rationalizations, etc. Scientific approach is not the only one Physiology brings to war prevention. It is equally important the wide dissemination of its conclusions among the general public. Information on the dynamics that prompt people to decide war would make it easier to control. This applies not only to political or military leaders, but also to civil populations. Concerning those two possible contributions of psychologists, scientific and educative, it is suggested the extensive use of psychodramatic techniques. Their richness lie in the lifelike experiences they convey to the participants, and particular aptitude to promote changes of attitudes. Investigation and information on the psychological processes related to war should be undertaken by international organizations of social scientists, acting simultaneously in several countries. Some of the initial steps they could further: 1) that prevention of war be a current subject matter in psychological courses; 2) that the World Health Organization take interest in this subject; 3) that psychologists participate in international political and economical bodies in order to clarify the psychological factors leading to war.