Highly diastereoselective synthesis of substituted pyrrolidines using a sequence of azomethine ylide cycloaddition and nucleophilic cyclization

Abstract: Although cycloadditions of azomethine ylides usually give mixtures of endo/exo adducts, we successfully tuned the mechanistic path of a new reaction cascade to afford substituted pyrrolidines in high yields and diastereomeric purity. This was achieved by forcing the demetalation of tin- or silicon-substituted iminium ions, followed by azomethine ylide cycloaddition and nucleophilic cyclization. Structural complexity is thus built rapidly in a fully controlled one-pot reaction cascade

The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis by a H+-Activated, Na+-Dependent Ionic Shift in Esophageal Cells

Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells develop resistance to bile acid-induced cell death. To understand how bile acids induce apoptosis resistance we first need to identify the molecular pathways that initiate apoptosis in response to bile acid exposure. In this study we examined the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role of Na+/H+ exchanger (NHE) and Na+ influx in esophageal cells. In vitro studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA (0.2 mM -0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic acidification. Fluorescence microscopy in conjunction with atomic absorption spectrophotometry demonstrated that this effect on lysosomes correlated with influx of Na+, subsequent loss of intracellular K+, an increase of Ca2+ and apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of NHE, prevented Na+, K+ and Ca2+ changes and caspase 3/7 activation induced by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na+ levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On the contrary, DCA-induced cell death was inhibited by medium with low a Na+ concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with or without EIPA. Severe tissue damage and caspase-3 activation was observed after DCA treatment, but EIPA almost fully prevented this response. In summary, NHE-mediated Na+ influx is a critical step leading to DCA-induced apoptosis. Cells tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our data suggests that suppression of NHE by endogenous or exogenous inhibitors may lead to apoptosis resistance during GI tumorigenesis

Navigating through a document-centered electronic medical record: a mock-up based on WWW technology.

Current WWW technology facilitates the development of "hypertext" applications. A hospital-wide study of users' requirements in France led to a document-centered approach to the patient Electronic Medical Record (EMR). In order to refine such a specification, and taking advantage of WWW technology, we have developed a running mock-up of a document-based EMR from an actual paper-based patient record. Synthesis documents were added and linked to original replicated paper documents to form a hypertextual EMR. The mock-up has been presented to health care professional boards to gather their remarks and wishes, and then enhanced accordingly. The current version reflects (part of) their requirements for an EMR, and is presented in this paper

Personality characteristics and profiles of Greek elementary teachers using the sixteen personality factor questionnaire (16PF)

Empirical evidence indicates that a teacher's personality influences the classroom climate, students' behaviors, and their interpersonal relationships. Although the effect of a teacher's personality on students' psychological well-being has long been stressed in many studies, very little is known about the actual personality characteristics of Greek in-service teachers. The purpose of this study was to allocate the characteristics that best describe the personality of Greek elementary school teachers (according to the 16 Cattellian primary factors). Our study belongs in the broader research field aiming at describing and understanding the possible foundations of teachers' behavior. The sample consisted of 138 elementary teachers, who completed a standardized Greek version of the 16PF. Our statistical analysis of one-sample t-test along with an effect size calculation revealed that certain personality characteristics described the Greek elementary teacher and clearly distinguishes them from the normative group of the Greek population. Elementary teachers appear to be quite submissive, cautious, with a tendency to oppose or postpone change. They also scored a low tolerance level against fear and arousal, and high tension levels. Elementary teachers seem to respond to events, ideas, and experiences more with feeling than with thinking and find it difficult to control their feelings, which results in getting upset easily. They also seem to pay little attention to how they may appear to others and generally do what they feel like doing. Elementary teachers also scored low on aspiration level. Possible implications of the results are discussed with reference to students' psychological well-being. ©Freund Publishing House Ltd

Users' evaluation of OncoDoc, a breast cancer therapeutic guideline delivered at the point of care.

Despite the dissemination of computer-based "clinical practice guidelines" as decision support systems, low practical compliance rates are still observed. The reason commonly invoked is that such recommendations, suited to average patients, are not rules for all the patients. Rather than providing automatic decision support, OncoDoc allows the clinician to operationalize the implemented breast cancer therapeutic expertise through his hypertextual reading of the knowledge base. In this way, he has the opportunity to interpret the information provided in the context of his patient therefore controlling his categorization to the closest appropriate "average patient". After a four-month real-life experimentation of the system, a survey was conducted among the users. The observed compliance, significantly higher than the best figures found in the literature, and the clinicians objective and subjective evaluation of the system reinforced the implementation choices adopted in OncoDoc

Developing an unpaved road assessment system for practical deployment with high-resolution optical data collection using a helicopter UAV

The need of local governments and transportation agencies to periodically asses the condition of unpaved roads in a cost-effective manner with rapid response times has lead to interest in the use of UAVs (Unmanned Aerial Vehicles) and remote sensing technologies. Currently these assessments are done through visual inspections with agency staff making occasional spot measurements. An unpaved road assessment system was developed to address these issues while at the same time providing a more accurate means of characterizing distresses and determining the roads condition for inspectors. This system uses a single-rotor UAV with a Digital Single-lens Reflex (DSLR) camera to capture overlapping imagery of unpaved roads. The UAV is equipped with a full combination GPS plus IMU (Inertial Measurement Unit) that allows it to fly predetermined waypoints with great stability while at the same time allowing the pilot the ability to take over at any time. Collected imagery is analyzed to locate road distresses. The imagery is run through a Structure From Motion (SfM) algorithm that generates a 3D model of the road surface from which additional condition information can be characterized. This system is easily transported and rapidly deployable to sections of unpaved roads for assessment

System models of IR diffractive optical systems based on a coherence theroretic framework

Diffractive optical systems in the Infrared (IR) wavelength regime are being re-examined for remote sensing applications. A pupil-plane adaptive coded aperture can enable a fine resolution, wide field of view sensor system without mechanical scanning. Due to the relatively long wavelengths, coded aperture systems in the IR have unique issues in regards to e.g. X-ray coded apertures. These include diffraction effects, wavelength dependence of optical elements, off axis aberrations due to thick screens, etc. In this paper, we provide a general system model framework based on partial coherence theory that enables us to explore many of the technical challenges in IR diffractive imaging. This paper develops the general theory and shows examples of issues that impact the optical transfer function (OTF) and impulse response of these types of architectures