Alternative Tasks for the Teaching and the Learning of functions: analysis of an intervention in the High School

In this paper we focus on the application of two mathematical alternative tasks to the teaching and learning of functions with high school students. The tasks were elaborated according to the following methodological approach: (i) Problem Solving and/or mathematics investigation and (ii) a pedagogical proposal, which defends that mathematical knowledge is developed by means of a balance between logic and intuition. We employed a qualitative research approach (characterized as a case study) aimed at analyzing the didactic pedagogical potential of this type of methodology in high school. We found that tasks such as those presented and discussed in this paper provide a more significant learning for the students, allowing a better conceptual understanding, becoming still more powerful when one considers the social-cultural context of the students.

Sequence and Copy Number Analyses of HEXB Gene in Patients Affected by Sandhoff Disease: Functional Characterization of 9 Novel Sequence Variants

Sandhoff disease (SD) is a lysosomal disorder caused by mutations in the HEXB gene. To date, 43 mutations of HEXB have been described, including 3 large deletions. Here, we have characterized 14 unrelated SD patients and developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay to investigate the presence of large HEXB deletions. Overall, we identified 16 alleles, 9 of which were novel, including 4 sequence variation leading to aminoacid changes [c.626C>T (p.T209I), c.634C>A (p.H212N), c.926G>T (p.C309F), c.1451G>A (p.G484E)] 3 intronic mutations (c.1082+5G>A, c.1242+1G>A, c.1169+5G>A), 1 nonsense mutation c.146C>A (p.S49X) and 1 small in-frame deletion c.1260_1265delAGTTGA (p.V421_E422del). Using the new MLPA assay, 2 previously described deletions were identified. In vitro expression studies showed that proteins bearing aminoacid changes p.T209I and p.G484E presented a very low or absent activity, while proteins bearing the p.H212N and p.C309F changes retained a significant residual activity. The detrimental effect of the 3 novel intronic mutations on the HEXB mRNA processing was demonstrated using a minigene assay. Unprecedentedly, minigene studies revealed the presence of a novel alternative spliced HEXB mRNA variant also present in normal cells. In conclusion, we provided new insights into the molecular basis of SD and validated an MLPA assay for detecting large HEXB deletions.

Trasmission and Reflection (ATR)Far-Infrared Spectroscopy Applied in the Analysis of Cultural Heritage Materials

FIR spectroscopy is an alternative way of collecting spectra of many inorganic pigments and corrosion products found on art objects, which is not normally observed in the MIR region. Most FIR spectra are traditionally collected in transmission mode but as a real novelty it is now also possible to record FIR spectra in ATR (Attenuated Total Reflectance) mode. In FIR transmission we employ polyethylene (PE) for preparation of pellets by embedding the sample in PE. Unfortunately, the preparation requires heating of the PE in order to produces at transparent pellet. This will affect compounds with low melting points, especially those with structurally incorporated water. Another option in FIR transmission is the use of thin films. We test the use of polyethylene thin film (PETF), both commercial and laboratory-made PETF. ATR collection of samples is possible in both the MIR and FIR region on solid, powdery or liquid samples. Changing from the MIR to the FIR region is easy as it simply requires the change of detector and beamsplitter (which can be performed within a few minutes). No preparation of the sample is necessary, which is a huge advantage over the PE transmission method. The most obvious difference, when comparing transmission with ATR, is the distortion of band shape (which appears asymmetrical in the lower wavenumber region) and intensity differences. However, the biggest difference can be the shift of strong absorbing bands moving to lower wavenumbers in ATR mode. The sometimes huge band shift necessitates the collection of standard library spectra in both FIR transmission and ATR modes, provided these two methods of collecting are to be employed for analyses of unknown samples. Standard samples of 150 pigment and corrosion compounds are thus collected in both FIR transmission and ATR mode in order to build up a digital library of spectra for comparison with unknown samples. XRD, XRF and Raman spectroscopy assists us in confirming the purity or impurity of our standard samples. 24 didactic test tables, with known pigment and binder painted on the surface of a limestone tablet, are used for testing the established library and different ways of collecting in ATR and transmission mode. In ATR, micro samples are scratched from the surface and examined in both the MIR and FIR region. Additionally, direct surface contact of the didactic tablets with the ATR crystal are tested together with water enhanced surface contact. In FIR transmission we compare the powder from our test tablet on the laboratory PETF and embedded in PE. We also compare the PE pellets collected using a 4x beam condenser, focusing the IR beam area from 8 mm to 2 mm. A few samples collected from a mural painting in a Nepalese temple, corrosion products collected from archaeological Chinese bronze objects and samples from a mural paintings in an Italian abbey, are examined by ATR or transmission spectroscopy.

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

Novel organic semiconductors and their applications in electronics

The main goals of this thesis were the design, synthesis, and characterization of novel organic semiconductors, together with their applications in electronics, such as OFETs, OPVs, and OLEDs. The results can be summarized as follows:rn1. In chapter II, two novel angular n-type molecules were presented. Their different alkyl chains play a pivotal role in the molecular orientation relative to surface. One molecule with longer branched chains is tilted with respect to the substrate, thereby resulting in poor device performance, while the other adopt an edge-on orientation with an OFET electron mobility of 0.01 cm2 V-1 s-1.rn2. In chapter III, fused bis-benzothiadiazoles with different molecular geometries, namely linear benzoquinone-fused bis(benzothiadiazole) and V-shaped sulfone-fused bis(benzothiadiazole), were shown. This work not only contributes to the diversity of electron acceptors based on bis-benzothiadiazole moieties, but also highlights the important role of molecular shape for the solid-state packing of organic conjugated materials. In chapter IV, we demonstrated the synthesis of layered acceptors via dimerization of thiadiazole end-capped acenes. Interestingly, they feature huge differences in their photophysical properties. One compound showed a new strong emission in the near-infrared region introduced by the aggregation effect. The planosymmetric compound featured intramolecular excimer (IEE) fluorescence in solution. rn3. In chapter V and VI, we have demonstrated the synthesis of novel spiro-bifluorene based asymmetric and symmetric cruciform electron acceptors with dicyanovinylene substitutions. The solar cells based on PTB7:asymmetric acceptor yields the highest PCE of 0.80%. Such results demonstrate for the first time that dicyanovinylene substituted acceptor could be an alternative to fullerene-based acceptors. rn4. In chapter VII, two novel blue-emitting compounds were shown, which consist of dihydroindenofluorenyl units and ladder-type poly-p-phenylene groups, respectively. The two novel cruciform rigid compounds present not only excellent thermal and electrochemical stability but also high PLQYs. Through analysis of their triplet energy levels, both molecules can be served as hosts for other normal fluorescent or phosphorescent materials.rn

Preventing erosion with novel agents

Objectives: This in vitro study aimed to investigate the protective effect of four commercial novel agents against erosion. Methods: Ninety human molars were distributed into 9 groups, and after incubation in human saliva for 2 h, a pellicle was formed. Subsequently, the specimens were submitted to demineralization (orange juice, pH 3.6, 3 min) and remineralization (paste slurry containing one of the tested novel agents, 3 min) cycles, two times per day, for 4 days. The tested agents were: (1) DenShield Tooth; active ingredient: 7.5% W/W NovaMin® (calcium sodium phosphosilicate); (2) Nanosensitive hca; active ingredient: 7.5% W/W NovaMin®; (3) GC Tooth Mousse; active ingredient: 10% Recaldent™ (CPP-ACP); (4) GC MI Paste Plus; active ingredients: 10% Recaldent™, 900 ppm fluoride. Two experimental procedures were performed: in procedure 1, the tested agents were applied prior to the erosive attack, and in procedure 2 after the erosive attack. A control group receiving no prophylactic treatment was included. Surface nanohardness (SNH) of enamel specimens was measured after pellicle formation and after completion of daily cyclic treatment. Results: SNH significantly decreased at the end of the experiment for all groups (p < 0.05). In both procedures, there was no statistically significant difference between the control group and those treated with paste slurries (p > 0.05). In addition, the changes in SNH (ΔSNH = SNHbaseline − SNHfinal) did not show statistically significant difference between both procedures (p > 0.05). Conclusion: Tooth erosion cannot be prevented or repaired by these novel agents, regardless of fluoride content.

Rationales for the Bernese approaches in acetabular surgery

PURPOSE: To present two new approaches to acetabular surgery that were established in Berne, and which aim at enhanced visualization and anatomical reconstruction of acetabular fractures. METHOD: The trochanteric flip osteotomy allows for surgical hip dislocation, and was introduced as a posterior approach for acetabular fracture management involving the posterior column and wall. For acetabular fractures predominantly involving the anterior column and the quadrilateral plate, the Pararectus approach is described. RESULTS: Full exposure of the hip joint, as provided by the trochanteric flip osteotomy, facilitates anatomical reduction of acetabular or femoral head fractures and safe positioning of the anterior column screw in transverse or T-shaped fractures. Additionally, the approach enables osteochondral transplantation as a salvage procedure for severe chondral femoral head damage and osteoplasty of an associated inadequate offset at the femoral head-neck junction. The Pararectus approach allows anatomical restoration with minimal access morbidity, and combines advantages of the ilioinguinal and modified Stoppa approaches. CONCLUSIONS: Utilization of the trochanteric flip osteotomy eases visualization of the superior aspect of the acetabulum, and enables the evaluation and treatment of chondral lesions of the femoral head or acetabulum and labral tears. Displaced fractures of the anterior column with a medialized quadrilateral plate can be addressed successfully through the Pararectus approach, in which surgical access is associated with minimal morbidity. However, long-term results following the two presented Bernese approaches are needed to confirm that in the treatment of complex acetabular fractures the rate of poor results in almost one-third of all cases (as currently yielded using traditional approaches) might be reduced by the utilization of the presented novel approaches.

Novel mutation in OTC gene causes neonatal death in twin brothers

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. OTC locus is located in the short arm of X-chromosome. Authors report a case of a woman who gave birth to monozygotic male twins who later died because of severe neonatal-onset hyperammonaemic encephalopathy caused by a novel mutation of OTC gene. Post-mortem liver biopsy was taken from the second twin; afterwards, blood was drawn from the mother for examination. DNA sequence data showed that the mother was a carrier of the same novel mutation that was previously detected in the case of her son. In OTC deficiency, detection of female carriers is important for genetic counselling and eventual prenatal diagnosis.

Narrated PowerPoints and Audio Podcasts in Clinical Teaching: One Clerkship's Experience

Introduction: Clinical medical education is increasingly utilizing novel technological approaches in order to supplement traditional lecture-based didactics. The Neurology Core Clerkship at Baylor College of Medicine is a four week required course taken by clinical medical students. Given the large amount of information to be disseminated in a short period of time, part of the didactic material has been provided online in the form of narrated PowerPoint files or lecture audio tracks along with stand-alone PowerPoint files. The narrated files are generated using the native PowerPoint narration function while the stand-alone audio files are created as MP3 format files using an inexpensive digital recording device. [See PDF for complete abstract]

Controlling New Media (without the Law)

The purpose of this paper is to explore some emerging modes of control that are evolving wholly or partially outside conventional media law. We focus in particular on the entirely novel mechanisms of control enabled through code and technology in general. We compare these new models with traditional regulatory bodies and their decision-making processes and, making reference to the values and interests that are embedded in the design of mediating technologies, ask whether the new tools of control are appropriate for achieving public policy objectives in a complex new-and-old media landscape, or whether in fact they introduce some dangers.

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides

We present the synthesis of the two novel nucleosides iso-tc-T and bcen-T, belonging to the bicyclo-/tricyclo-DNA molecular platform. In both modifications the torsion around C6’–C7’ within the carbocyclic ring is planarized by either the presence of a C6’–C7’ double bond or a cyclopropane ring. Structural analysis of these two nucleosides by X-ray analysis reveals a clear preference of torsion angle γ for the gauche orientation with the furanose ring in a near perfect 2’-endo conformation. Both modifications were incorporated into oligodeoxynucleotides and their thermal melting behavior with DNA and RNA as complements was assessed. We found that the iso-tc-T modification was significantly more destabilizing in duplex formation compared to the bcen-T modification. In addition, duplexes with complementary RNA were less stable as compared to duplexes with DNA as complement. A structure/affinity analysis, including the already known bc-T and tc-T modifications, does not lead to a clear correlation of the orientation of torsion angle γ with DNA or RNA affinity. There is, however, some correlation between furanose conformation (N- or S-type) and affinity in the sense that a preference for a 3’-endo like conformation is associated with a preference for RNA as complement. As a general rule it appears that Tm data of single modifications with nucleosides of the bicyclo-/tricyclo-DNA platform within deoxyoligonucleotides are not predictive for the stability of fully modified oligonucleotides.

Synthesis and cellular characterization of novel isoxazolo- and thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth and death

Coumarins are extensively studied anticoagulants that exert additional effects such as anticancerogenic and even anti-inflammatory. In order to find new drugs with anticancer activities, we report here the synthesis and the structural analysis of new coumarin derivatives which combine the coumarin core and five member heterocycles in hydrazinylidene-chroman-2,4-diones. The derivatives were prepared by derivatization of the appropriate heterocyclic amines which were used as electrophiles to attack the coumarin ring. The structures were characterized by spectroscopic techniques including IR, NMR, 2D-NMR and MS. These derivatives were further characterized especially in terms of a potential cytotoxic and apoptogenic effect in several cancer cell lines including the breast and prostate cancer cell lines MCF-7, MDA-MB-231, PC-3, LNCaP, and the monocytic leukemia cell line U937. Cell viability was determined after 48 h and 72 h of treatment with the novel compounds by MTT assay and the 50% inhibitory concentrations (EC50 values) were determined. Out of the 8 novel compounds screened for reduced cell viability, 4c, 4d and 4e were found to be the most promising and effective ones having EC50 values that were several fold reduced when compared to the reference substance 4-hydroxycoumarin. However, the effects were cancer cell line dependent. The breast cancer MDA-MB-231 cells, the prostate cancer LNCaP cells, and U937 cells were most sensitive, MCF-7 cells were less sensitive, and PC-3 cells were more resistant. Reduced cell viability was accompanied by increased apoptosis as shown by PARP-1 cleavage and reduced activity of the survival protein kinase Akt. In summary, this study has identified three novel coumarin derivatives that in comparison to 4-hydroxycoumarin have a higher efficiency to reduce cancer cell viability and trigger apoptosis and therefore may represent interesting novel drug candidates

The TIM translocase in T. brucei contains Rhomboid-like proteins that are essential for mitochondrial protein import

The parasitic protozoon Trypanosoma brucei is one of the earliest branching eukaryotes that have mitochondria capable of oxidative phosphorylation. Their protein import systems are of similar complexity yet different composition than those in other eukaryotes. To elucidate the composition of the trypanosomal translocase of the inner mitochondrial membrane (TIM) we performed CoIPs of epitope-tagged TbTim17 and two other candidates in combination with SILAC-based quantitative mass spectrometry. This led to the identification of ten candidates for core TIM subunits. Eight of them were present in the previously determined inner membrane proteome and four show homology to small Tim chaperones. Three candidates, a trypanosomatid-specific 42 kDa protein (Tim42) and two putative orthologues of inactive rhomboid proteases were analyzed further. All three proteins are essential in both life cycle stages and their ablation results in a strong protein import defect in vivo and in vitro. Blue native PAGE revealed their presence in a high molecular weight complex. Unlike anticipated, trypanosomes have a highly complex TIM translocase that has extensively been redesigned. None of the three novel TIM subunits has ever been associated with mitochondrial protein import. Two of them belong to the rhomboid protease family, a member of which recently has been implicated in the ERAD translocation system. This suggests an exciting analogy between protein translocases of mitochondria and the ER.