A New Hand-Held Microsystem Architecture for Biological Analysis

This paper presents a hand-held microsystem based on new fully integrated magnetoresistive biochips for biomolecular recognition (DNA hybridization, antibody antigen interaction, etc.). Magnetoresistive chip surfaces are chemically treated, enabling the immobilization of probe biomolecules such as DNA or antibodies. Fluid handling is also integrated in the biochip. The proposed microsystem not only integrates the biochip, which is an array of 16times16 magnetoresistive sensors, but it also provides all the electronic circuitry for addressing and reading out each transducer. The proposed architecture and circuits were specifically designed for achieving a compact, programmable and portable microsystem. The microsystem also integrates a hand-held analyzer connected through a wireless channel. A prototype of the system was already developed and detection of magnetic nanoparticles was obtained. This indicates that the system may be used for magnetic label based bioassays     

Granular Reasoning Using Zooming In & Out: Part 2. Aristotle's Categorical Syllogism

The concept of granular computing is applied to Aristotle's categorical syllogism. Such kind of reasoning is called granular reasoning in this paper. For the purpose, two operations called zooming in & out are introduced to reconstruct granules of possible worlds.     

Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats

PURPOSE: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (Tmax), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. METHODS: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature > 42 degrees C). RESULTS: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0.05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. CONCLUSIONS: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.     

Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)^y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.     

An investigation of methods of pileup rejection for 2-D array detectors employed in high resolution PET

Two methods of rejecting pileup events in 2-D array detectors used in positron emission tomography (PET) are investigated. Since the methods are based on different physical properties, they were investigated separately and in combination. Method one is based on the fact that valid events in the 2-D array detector occur only in a limited pulseheight range for each detector element, and by rejecting events outside these energy ranges, many of the pileup events can be rejected. Method two is based on the fact that most pileup event pairs have a time differential, which will cause a difference in the shape of the signal which increases the rise time of an integrated signal or the crossover time of a bipolar signal from a shaping amplifier. Method two proved to be somewhat better than method one. However, the ideal system would most likely use both methods simultaneously.     

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.     

Agents’ model of uncertainty

Multi-agent systems play an increasing role in sensor networks, software engineering, web design, e-commerce, robotics, and many others areas. Uncertainty is a fundamental property of these areas. Agent-based systems use probabilistic and other uncertainty models developed earlier without explicit consideration of agents. This paper explores the impact of agents on uncertainty models and theories. We compare two methods of introducing agents to uncertainty theories and propose a new theory called the agent-based uncertainty theory (AUT). We show advantages of AUT for advancing multi-agent systems and for solving an internal fundamental question of uncertainty theories, that is identifying coherent approaches to uncertainty. The advantages of AUT are that it provides a uniform agent-based representation and an operational empirical interpretation for several uncertainty theories such as rough set theory, fuzzy sets theory, evidence theory, and probability theory. We show also that the introduction of agents to intuitionist uncertainty formalisms can reduce their conceptual complexity. To build such uniformity the AUT exploits the fact that agents as independent entities can give conflicting evaluations of the same attribute. The AUT is based on complex aggregations of crisp (non-fuzzy) conflicting judgments of agents. The generality of AUT is derived from the logical classification of types (orders) of conflicts in the agent populations. At the first order of conflict, the two agent populations are disjoint and there is no interference of logic values assigned to any statement p and its negation by agents. The second order of conflict models superposition (interference) of logic values for overlapping agent populations where an agent assigns conflicting logic values (true, false) to the same attribute simultaneously.

Deleting files in the Celeste peer-to-peer storage system

Celeste is a robust peer-to-peer object store built on top of a distributed hash table (DHT). Celeste is a working system, developed by Sun Microsystems Laboratories. During the development of Celeste, we faced the challenge of complete object deletion, and moreover, of deleting “files” composed of several different objects. This important problem is not solved by merely deleting meta-data, as there are scenarios in which all file contents must be deleted, e.g., due to a court order. Complete file deletion in a realistic peer-to-peer storage system has not been previously dealt with due to the intricacy of the problem — the system may experience high churn rates, nodes may crash or have intermittent connectivity, and the overlay network may become partitioned at times. We present an algorithm that eventually deletes all file contents, data and meta-data, in the aforementioned complex scenarios. The algorithm is fully functional and has been successfully integrated into Celeste.