Use of learning-logs in high school pre-algebra classes to improve mastery of rational numbers and linear equations for high-risk minority students

The purpose of this study was to determine whether there was a relationship in the use of learning-logs to traditional or current math instruction in secondary school pre-algebra classes to improve the mastery of single-variable equations by high-risk minority students

Modification of Daunorubicin-GnRH-III Bioconjugates With Oligoethylene Glycol Derivatives to Improve Solubility and Bioavailability for Targeted Cancer Chemotherapy

Daunorubicin-GnRH-III bioconjugates have recently been developed as drug delivery systems with potential applications in targeted cancer chemotherapy. In order to improve their biochemical properties, several strategies have been pursued: (1) incorporation of an enzymatic cleavable spacer between the anticancer drug and the peptide-based targeting moiety, (2) peptide modification by short chain fatty acids or (3) attachment of two anticancer drugs to the same GnRH-III derivative. Although these modifications led to more potent bioconjugates, a decrease in their solubility was observed. Here we report on the design, synthesis and biochemical characterization of daunorubicin-GnRH-III bioconjugates with increased solubility, which could be achieved by incorporating oligoethylene glycol-based spacers in their structure. First, we have evaluated the effect of an oligoethylene glycol-based spacer on the solubility, enzymatic stability/degradation, cellular uptake and in vitro cytostatic effect of a bioconjugate containing only one daunorubicin attached through a GFLG tetrapeptide spacer to the GnRH-III targeting moiety. Thereafter, more complex compounds containing two copies of daunorubicin, GFLG spacers as well as Lys(nBu) in position 4 of GnRH-III were synthesized and biochemically characterized. Our results indicated that all synthesized oligoethylene glycol-containing bioconjugates had higher solubility in cell culture medium than the unmodified analogs. They were degraded in the presence of rat liver lysosomal homogenate leading to the formation of small drug containing metabolites. In the case of bioconjugates containing two copies of daunorubicin, the incorporation of oligoethylene glycol-based spacers led to increased in vitro cytostatic effect on MCF-7 human breast cancer cells

Flavin-Dependent Monooxygenases from N-oxygenating Arctiids

Pflanzen, die Pyrrolizidinalkaloide (PAs) synthetisieren, verfügen durch die PAs über eine effektive chemische Abwehr gegen nicht angepasste Herbivoren. Aus der Familie der Arctiiden (Bärenspinner) sind eine Reihe von Arten bekannt, deren Raupen PA-haltige Pflanzen fressen können. Dabei können die angepassten Arctiiden diese Pflanzen nicht nur als Nahrungsressource nutzen sondern vielmehr die in den Pflanzen enthaltenen PAs aufnehmen, speichern und zur Verteidigung gegen eigene Fraßfeinde einsetzen. Bei Tyria jacobaeae (Arctiidae) konnte das für diese Anpassung essentielle Enzym die Senecionin N-Oxygenase (SNO) identifiziert werden. Die SNO, eine Flavin-abhängige Monooxygenase (FMO), katalysiert die N-Oxygenierung von tertiären PAs in das korrespondierende N-Oxid. Mit Hilfe von degenerierten Primern wurden aus Proben von den Arctiiden Grammia geneura, Arctia caja und Arctia villica, für die eine N-Oxygenierung nachgewiesen werden konnte, cDNA-Klone identifiziert, die aufgrund der Sequenzidentitäten den Flavin-abhängigen Monooxygenasen zugeordnet werden konnten. Dabei lassen sich die Sequenzen der identifizierten cDNA-Klone in zwei Gruppen einteilen. Die FMO-Sequenz von G. geneura, die eine hohe Übereinstimmung zur bereits gut charakterisierten SNO von T. jacobaeae aufweist, wurde heterolog in E. coli exprimiert. Zur Bestimmung der enzymatischen Aktivität wurde ein Meßverfahren mit radioaktiv markierten Senecionin (PA) eingesetzt. Für das heterolog exprimierte Protein konnte eine N-Oxygenierung des tertiären Senecionins nachgewiesen werden. Das heterolog exprimierte Enzym von G. geneura konnte als Pyrrolizidinalkaloid N-oxygenierendes Enyzm als Pyrrolizidinalkaloid N-Oxygenase (PNO) identifiziert werden. Die Ergebnisse legen nahe, dass die Arctiiden über zwei verschiedene Gruppen von Flavin-abhängigen Monooxygenasen verfügen. Die SNO von T. jacobaeae, die PNO von G. geneura und mutmaßlich auch die identifizierten Sequenzen von A. caja und A. villica gehören hier zu einer Gruppe von Flavin-abhängigen Monooxygenasen den PNOs, die für die Entgiftung von PAs die zentrale Rolle spielen. Die Funktion der potentiell zweiten Gruppe von FMOs ist bislang nicht bekannt.Plants which synthesize pyrrolizidinalkaloids (PAs) have an effective chemical defence against non adapted herbivores. From some species of the arctiids (Lepidoptera) it is well kown that the caterpillars are feeding on PA-containing plants. These species are not only able to cope with plant derived PAs but also to accumulate them for their own defense against predators. The responsible enzym for this adaptation the Senecionine N-oxygenase (SNO) from Tyria jacobaeae (arctiid moth) was identified. The SNO a flavin-dependent monooxygenase (FMO) catalyses the formation of the non-toxic PA N-oxides from the protoxic tertiary PAs. After comparison of cDNA clones other kown FMOs from insect with the SNO from T. jacobaeae degenerated primers were constructed. From probes of the arctiids Grammia geneura, Arctia caja and Arctia villica some cDNA clones could be identified which have a high sequence conformity to other flavin-dependent monooxygenases. The identified cDNA clones could divided into two groups. The cDNA clone which was identified from G. genuera has a high conformity to the SNO from T. jacobaeae. The identified cDNA clone from G. geneura was expressed heterologous in E. coli. For the measurement of enzymatic activity an enzymatic test system with the radioactiv labelled PA Senecionine was established. The testing of the expressed protein shows the PA N-oxide formation from tertiäry PA. Thus the heterologous expressed enzyme from G. geneuera is an pyrrolizidine alkaloid N-oxygenating enzyme further called as pyrrolizidine alkaloid N-oxygenase (PNO). Presumably the arctiid moths have two groups of FMOs. The SNO from T. jacobaeae, the PNO from G. genuera and presumably the cDNA clones form A. caja and A. villica belong to a group of FMOs called the pyrrolizidine alkaloid N-oxygenases (PNOs) which are basically responsible for the detoxification of protoxic PAs. The function of the supposed second group of FMOs remains unkown

Anxiety, inhibition and the prefrontal cortex

This dissertation investigates the impact of trait anxiety and anxiety sensitivity on emotional and behavioural inhibition in healthy subjects. An aversive fear-conditioning and extinction design was employed to study the influence of trait anxiety on the neurobiology of emotional inhibition using fMRI. A Go/ Nogo-task was selected to examine the impact of trait anxiety and anxiety sensitivity on the electrophysiology of response inhibition using EEG. Our findings emphasize the role of the prefrontal cortex and the ACC in inhibition and anxiety. In the first experiment, trait anxiety was related to impaired fear extinction. Neurobiologically, hypo-activation of the PFC and hyper-activation of the amygdala have been observed. The second experiment yielded enhanced response inhibition and anxiety-related hyper-activation of the PFC. Thus, anxiety is related to deficits in behavioural and emotional inhibition

Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines

Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). Results: During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. Conclusions: Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets

Serotonergic, brain volume and attentional correlates of trait anxiety in primates.

Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders.This research was supported by a Medical Research Programme Grant (G0901884) from the Medical Research Council UK (MRC) to Angela Roberts, and a PhD studentship from MRC and final-term funding from Trinity College, Cambridge, UK to Yevheniia Mikheenko.This is the author accepted manuscript. The final version is available from NPG at http://www.nature.com/npp/journal/v40/n6/full/npp2014324a.htm

Employee Behaviour as a Possible Corporate System Vulnerability when Implementing Digitalisation in Smart Cities

Digitizing processes to improve the citizen centered performance is one of the key challenges for Smart Cities (Radchenko, 2023) This paper contends that, whilst resolving those challenges, the implemented strategies could cause undesired outcomes. Also, this intersects significantly with urban planning considerations, as it involves the integration of digital technologies, including infrastructure, service and governance. At first glance, innovative digital technologies might render more transparent processes saving time and money for organizations. However, people, too often, disregard the threats associated with them. The latter can be classified in external and internal threats. Interestingly, companies feel threatened more by the internal ones since they cannot entirely be eliminated (Boce, 2023). In more detail, the importance of the topic emerges from the following research gap: “From the general point of view of companies, there are no real structures for security management. Also, they do not design policies that will minimize internal threats, they have not yet understood the importance and influence of man as a threatening factor…” (Boce, 2023, p.76). The research addresses the general question of how employee behavior contributes to internal vulnerabilities affecting the security and compliance governance of digitalization implementations in a Smart City context? The aim of this research in progress is to address this ‘human threat’ via a comprehensive systematic literature review and a consecutive empirical research design

Coated Blade Spray Ion Mobility Spectrometry

Coated blade spray (CBS) is a microextraction technology with blades that serve as both the extraction device and the electrospray ionization (ESI) emitter. CBS is designed for easy and rapid extraction of analytes in complex matrices as well as ESI directly from the blade. The technology selectively enriches the components of interest on a coated metal blade. The coating consists of a selective polymer. So far, CBS has only been coupled with mass spectrometry but never with ion mobility spectrometry (IMS), where ions are separated and detected based on their ion mobility in a drift gas under the influence of an electric field, while instrumentation is compact and easy to operate so that the advantages of CBS can be particularly well exploited. Therefore, this work focuses on coupling CBS with our previously described ESI-IMS. The ion mobility spectrometer has a drift length of only 75 mm and provides a high resolving power of RP = 100. In this work, preliminary measurements of CBS-IMS are presented. In particular, the detection of benzodiazepines and ketamine in drinks and the pesticide isoproturon in water samples is shown to demonstrate the feasibility of CBS-IMS

Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending o