189 research outputs found

    Using adapted primary science literature to enhance argumentation and reasoning skills in middle school students

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    Adapted primary literature is literature adapted from primary scientific literature for the purpose of using it with school age students. The process begins with teachers finding an appropriate primary scientific literature article, written by scientists for scientists, and rewriting the article to meet the reading level and understanding of the students being taught. In the newly created article, a teacher focuses only on the part of the original article that is important to the students learning and the writer may add background information, graphics, or edit existing graphics to make them more student friendly. The goal of this project is to create guidelines for the creation of adapted primary literature articles, to use those guidelines to create adapted primary literature, and to then incorporate these articles into storylines

    Biomarkers of HIV-1 associated dementia: proteomic investigation of sera

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    Background: New, more sensitive and specific biomarkers are needed to support other means of clinical diagnosis of neurodegenerative disorders. Proteomics technology is widely used in discovering new biomarkers. There are several difficulties with in-depth analysis of human plasma/ serum, including that there is no one proteomic platform that can offer complete identification of differences in proteomic profiles. Another set of problems is associated with heterogeneity of human samples in addition intrinsic variability associated with every step of proteomic investigation. Validation is the very last step of proteomic investigation and it is very often difficult to validate potential biomarker with desired sensitivity and specificity. Even though it may be possible to validate a differentially expressed protein, it may not necessarily prove to be a valid diagnostic biomarker. Results: In the current study we report results of proteomic analysis of sera from HIV-infected individuals with or without cognitive impairment. Application of SELDI-TOF analysis followed by weak cation exchange chromatography and 1-dimensional electrophoresis led to discovery of gelsolin and prealbumin as differentially expressed proteins which were not detected in this cohort of samples when previously investigated by 2-dimensional electrophoresis with Difference Gel Electrophoresis technology. Conclusion: Validation using western-blot analysis led us to conclude that relative change of the levels of these proteins in one patient during a timeframe might be more informative, sensitive and specific than application of average level estimated based on an even larger cohort of patients

    Protezione ambientale o ampliamento aeroportuale? Il principio di full Jurisdiction nell’ordinamento austriaco

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    Austria è un paese piuttosto piccolo, primo di particolare importanza globale. Cionondimeno, l’esperienza austrica in materia di full jurisdiction delle corti amministrative può risultare interessante per due ordini di ragioni. In primo luogo, l’Austria ha recentemente (cinque anni orsono) cambiato radicalmente il proprio sistema processuale amministrativo. In secondo luogo, una recente pronuncia giudiziale ha destato l’attenzione non solo dei giuristi ma anche dell’opinione pubblica provocando un accesi dibattito: nel Febbraio del 2017, la Corte Amministrativa Federale ha disposto l’annullamento del provvedimento di ampliamento dell’aeroporto di Vienna, provocando l’indignazione non solo del management aeroportuale, ma anche del ceto imprenditoriale e di una parte del mondo politico. Questo caso dimostra molto bene che le corti amministrative che operano in full jurisdiction possono ricevere maggiore pubblicità delle corti di cassazione. Già nel Giugno 2017, solo quattro mesi dopo, la Corte Costituzionale ha ribaltato la decisione del giudice amministrativo, riformando la decisione di bloccare i lavori di ampliamento dell’aeroporto, stabilendo che la Corte Federale Amministrativa avesse gravemente violato la legge agendo arbitrariamente. Il contributo, prende spunto dalla citata vicenda, per evidenziare quanto delicata sia la comprensione del ruolo e dei limiti del principio di full jurisdiction a fronte di decisioni amministrative connotate elevato tasso di politicità. Austria is a rather small country without much global importance. Nevertheless, for the topic of full jurisdiction of administrative courts it may be interesting for two reasons. First, Austria radically changed its system of administrative jurisdiction five years ago. Second, I can recount a recent case, which still attracts public attention and even now provokes heated debates: in February 2017, the Federal Administrative Court stopped the expansion of the Vienna airport and thus provoked an outrage not only of the airport management, but also of the business and some parts of the political sector in general. This case demonstrates very well that administrative courts with full jurisdiction have more publicity than the mere courts of cassation. Already in June 2017, which means only four months after the court’s ruling, the Constitutional Court decided in favor of the airport and annulled the contested decision. The Constitutional Court held that the federal administrative court had gravely misapplied the law and thereby acted arbitrarily. Therefore, a couple of things may be learned from this case example. The essay, inspired by the aforementioned affair, highlights how problematic is the understanding of role and the limitations of the principle of full jurisdiction in case of administrative decisions characterized by political nature.  Parole chiave: Austria – processo amministrativo – casistica giurisprundenziale - full jusrisdiction – ruolo – limitiKeywords: Austria – administrative jurisdiction – case law- full jusrisdiction – role – limits

    Immunoreactivity of anti-gelsolin antibodies: implications for biomarker validation

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    <p>Abstract</p> <p>Background</p> <p>Proteomic-based discovery of biomarkers for disease has recently come under scrutiny for a variety of issues; one prominent issue is the lack of orthogonal validation for biomarkers following discovery. Validation by ELISA or Western blot requires the use of antibodies, which for many potential biomarkers are under-characterized and may lead to misleading or inconclusive results. Gelsolin is one such biomarker candidate in HIV-associated neurocognitive disorders.</p> <p>Methods</p> <p>Samples from human (plasma and CSF), monkey (plasma), monocyte-derived macrophage (supernatants), and commercial gelsolin (recombinant and purified) were quantitated using Western blot assay and a variety of anti-gelsolin antibodies. Plasma and CSF was used for immunoaffinity purification of gelsolin which was identified in eight bands by tandem mass spectrometry.</p> <p>Results</p> <p>Immunoreactivity of gelsolin within samples and between antibodies varied greatly. In several instances, multiple bands were identified (corresponding to different gelsolin forms) by one antibody, but not identified by another. Moreover, in some instances immunoreactivity depended on the source of gelsolin, e.g. plasma or CSF. Additionally, some smaller forms of gelsolin were identified by mass spectrometry but not by any antibody. Recombinant gelsolin was used as reference sample.</p> <p>Conclusions</p> <p>Orthogonal validation using specific monoclonal or polyclonal antibodies may reject biomarker candidates from further studies based on misleading or even false quantitation of those proteins, which circulate in various forms in body fluids.</p

    Opposing regulation of endolysosomal pathways by long-acting nanoformulated antiretroviral therapy and HIV-1 in human macrophages.

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    BACKGROUND: Long-acting nanoformulated antiretroviral therapy (nanoART) is designed to improve patient regimen adherence, reduce systemic drug toxicities, and facilitate clearance of human immunodeficiency virus type one (HIV-1) infection. While nanoART establishes drug depots within recycling and late monocyte-macrophage endosomes, whether or not this provides a strategic advantage towards viral elimination has not been elucidated. RESULTS: We applied quantitative SWATH-MS proteomics and cell profiling to nanoparticle atazanavir (nanoATV)-treated and HIV-1 infected human monocyte-derived macrophages (MDM). Native ATV and uninfected cells served as controls. Both HIV-1 and nanoATV engaged endolysosomal trafficking for assembly and depot formation, respectively. Notably, the pathways were deregulated in opposing manners by the virus and the nanoATV, likely by viral clearance. Paired-sample z-scores, of the proteomic data sets, showed up- and down- regulation of Rab-linked endolysosomal proteins. NanoART and native ATV treated uninfected cells showed limited effects. The data was confirmed by Western blot. DAVID and KEGG bioinformatics analyses of proteomic data showed relationships between secretory, mobility and phagocytic cell functions and virus and particle trafficking. CONCLUSIONS: We posit that modulation of endolysosomal pathways by antiretroviral nanoparticles provides a strategic path to combat HIV infection

    Opposing regulation of endolysosomal pathways by long-acting nanoformulated antiretroviral therapy and HIV-1 in human macrophages.

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    BACKGROUND: Long-acting nanoformulated antiretroviral therapy (nanoART) is designed to improve patient regimen adherence, reduce systemic drug toxicities, and facilitate clearance of human immunodeficiency virus type one (HIV-1) infection. While nanoART establishes drug depots within recycling and late monocyte-macrophage endosomes, whether or not this provides a strategic advantage towards viral elimination has not been elucidated. RESULTS: We applied quantitative SWATH-MS proteomics and cell profiling to nanoparticle atazanavir (nanoATV)-treated and HIV-1 infected human monocyte-derived macrophages (MDM). Native ATV and uninfected cells served as controls. Both HIV-1 and nanoATV engaged endolysosomal trafficking for assembly and depot formation, respectively. Notably, the pathways were deregulated in opposing manners by the virus and the nanoATV, likely by viral clearance. Paired-sample z-scores, of the proteomic data sets, showed up- and down- regulation of Rab-linked endolysosomal proteins. NanoART and native ATV treated uninfected cells showed limited effects. The data was confirmed by Western blot. DAVID and KEGG bioinformatics analyses of proteomic data showed relationships between secretory, mobility and phagocytic cell functions and virus and particle trafficking. CONCLUSIONS: We posit that modulation of endolysosomal pathways by antiretroviral nanoparticles provides a strategic path to combat HIV infection

    Developing Accelerator Mass Spectrometry Capabilities for Anthropogenic Radionuclide Analysis to Extend the Set of Oceanographic Tracers

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    Recent major advances in Accelerator Mass Spectrometry (AMS) at the Vienna Environmental Research Accelerator (VERA) regarding detection efficiency and isobar suppression have opened possibilities for the analysis of additional long-lived radionuclides at ultra-low environmental concentrations. These radionuclides, including 233^{233}U, 135^{135}Cs, 99^{99}Tc, and 90^{90}Sr, will become important for oceanographic tracer application due to their generally conservative behavior in ocean water. In particular, the isotope ratios 233^{233}U/236^{236}U and 137^{137}Cs/135^{135}Cs have proven to be powerful fingerprints for emission source identification as they are not affected by elemental fractionation. Improved detection efficiencies allowed us to analyze all major long-lived actinides, i.e., 236^{236}U, 237^{237}Np, 239,240^{239,240}Pu, 241^{241}Am as well as the very rare 233^{233}U, in the same 10 L water samples of a depth profile from the northwest Pacific Ocean. For this purpose, a simplified and very flexible chemical purification procedure based on extraction chromatography (a single UTEVA® column) was implemented which can be extended by a DGA® column for Am purification. The procedure was validated with the reference materials IAEA-381/385. With the additional increase in ionization efficiency expected for the extraction of actinides as fluoride molecules from the AMS ion source, a further reduction of chemical processing may become possible. This method was successfully applied to an exemplary set of air filter samples. In order to determine the quantitative 237^{237}Np concentration reliably, a 236^{236}Np spike material is being developed in collaboration with the University of Tsukuba, Japan. Ion-Laser Interaction Mass Spectrometry (ILIAMS), a novel technique for the efficient suppression of stable isobaric background, has been developed at VERA and provides unprecedented detection sensitivity for the fission fragments 135^{135}Cs, 99^{99}Tc, and 90^{90}Sr. The corresponding setup is fully operational now and the isobar suppression factors of >105^{5} achieved, in principle, allow for the detection of the mentioned radionuclides in the environment. Especially for 90^{90}Sr analysis, this new approach has already been validated for selected reference materials (e.g., IAEA-A-12) and is ready for application in oceanographic studies. We estimate that a sample volume of only (1-3) L ocean water is sufficient for 90^{90}Sr as well as for 135^{135}Cs analysis, respectively

    Increased mesiotemporal delta activity characterizes virtual navigation in humans

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    Hippocampal theta or rhythmic slow activity (RSA) occurring during exploratory behaviors and rapid-eye-movement (REM) sleep is a characteristic and well-identifiable oscillatory rhythm in animals. In contrast, controversy surrounds the existence and electrophysiological correlates of this activity in humans. Some argue that the human hippocampal theta occurs in short and phasic bursts. On the contrary, our earlier studies provide evidence that REM-dependent mesiotemporal RSA is continuous like in animals but instead of the theta it falls in the delta frequency range. Here we used a virtual navigation task in 24 epilepsy patients implanted with foramen ovale electrodes. EEG was analyzed for 1-Hz wide frequency bins up to 10 Hz according to four conditions: resting, non-learning route-following, acquisition and recall. We found progressively increasing spectral power in frequency bins up the 4 Hz across these conditions. No spectral power increase relative to resting was revealed within the traditional theta band and above in any of the navigation conditions. Thus the affected frequency bins were below the theta band and were similar to those characterizing REM sleep in our previous studies providing further indication that it is delta rather than theta that should be regarded as a human analogue of the animal RSA

    ケンポウ ジツムカ ト シテノ ハンス ケルゼン

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    ハンス・ケルゼンは、多くの学的分野において、すなわち法哲学および法社会学と同様に法理論において傑出した業績を有しており、これは国際法と同様に憲法の分野でもそうである。学者としての彼の計り知れない意義は、彼が法実務においても意義深い役割を果たしたことを忘れさせてしまう。本稿は、憲法におけるハンス・ケルゼンの実務活動に着目し、彼が、起草者(Legist)、コンメンタールの執筆者(Kommentator)そして裁判官(Richter)として、どのように活動したかを明らかにする。起草者(Ⅱ.)としての彼は、オーストリア連邦憲法の作成に際してすべてを取り仕切る中心人物だったのであり、これによって政治的決定は適切な形式でもたらされ、政党間の紛争は妥協案によって解決することができた。コンメンタールの執筆者(Ⅲ.)としての彼は、伝統的な司法活動と距離をとって、憲法法律の構造をはっきりさせること、組織上の枠条件を描写すること、手続技術上の進行をくまなく照らすこと、その他には解決のための決定を下すことなしに、解釈についての様々な選択肢を明らかにすることにとどまった。これに対して、憲法裁判所における裁判官(Ⅳ.)としての彼の役割は、完全に異なるものであった。彼は、文言に執着せず、第一義的には体系的かつ目的論的に論拠づけを行ったのであり、また彼は自らの判事としての役割を、新興の民主制を擁護しそしてそれを促進するよう努める政治的職務と理解していた。最後に(Ⅴ.)本稿は、ハンス・ケルゼンの実務上の働きが彼の法理論上の業績をどのように豊かにしたのかを取り上げる。翻訳磯村, 晃/
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