1,691 research outputs found

    Making the transition to curriculum integration: a curriculum design in middle level schools

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    The purpose of this dissertation was to investigate middle level teachers\u27 transitional process as they move from an interdisciplinary/multidisciplinary curricular format to curriculum integration. This study was designed to identify key stakeholders in this transitional process and determine the role each played, and to identify and investigate the key steps and obstacles along the way. The primary participants in this study were identified as teachers in the process of transitioning to a curriculum integration model. They and two other teachers on their five-teacher team, five students, three parents and the school principal were interviewed. Teacher interviews were most extensive, delving into their philosophical beliefs about teaching and learning, as well as details of their practice. Students and parents shared their thoughts and feelings about student involvement in planning curriculum and the school\u27s principal elaborated on the role of leadership in curriculum change. Other qualitative data gathering techniques used in this study included on-site visits and analysis of curriculum-related documents, including curriculum unit guidelines, assessment tools and lists generated in student brainstorming sessions. A cross-case analysis was used to group answers to the same question looking for similar or different responses. Five themes emerged related to the philosophical beliefs and guiding principles of the two primary teachers in this study: a) commitment to trusting student/teacher relationships, student involvement in curriculum planning, and democratic process in the classroom are cornerstones to enacting curriculum integration, b) this curriculum requires teachers to think in an integrative manner, c) integrative thinking and child-centered teaching can be learned, d) to bring about significant curriculum change, leadership is necessary at multiple levels, and e) team configuration can facilitate or complicate curriculum integration. The findings of this study also reveal a number of benefits to curriculum integration, including: the motivational value that results from the ownership students feel when they are involved in curriculum planning, the constructive nature of learning which is enhanced by emphasizing connections across the curriculum, the need for students to become responsible and accountable for their own learning ,and the effectiveness of cooperative learning and peer teaching

    High-Redshift Metals. II. Probing Reionization Galaxies with Low-Ionization Absorption Lines at Redshift Six

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    We present a survey for low-ionization metal absorption line systems towards 17 QSOs at redshifts z_em=5.8-6.4. Nine of our objects were observed at high resolution with either Keck/HIRES or Magellan/MIKE, and the remainder at moderate resolution with Keck/ESI. The survey spans 5.3 < z_abs < 6.4 and has a pathlength interval \Delta X=39.5, or \Delta z=8.0. In total we detect ten systems, five of which are new discoveries. The line-of-sight number density is consistent with the combined number density at z~3 of DLAs and sub-DLAs, which comprise the main population of low-ionization systems at lower redshifts. This apparent lack of evolution may occur because low ionization systems are hosted by lower-mass halos at higher redshifts, or because the mean cross section of low-ionization gas at a given halo mass increases with redshift due to the higher densities and lower ionizing background. The roughly constant number density notably contrasts with the sharp decline at z > 5.3 in the number density of highly-ionized systems traced by C IV. The low-ionization systems at z~6 span a similar range of velocity widths as lower-redshift sub-DLAs but have significantly weaker lines at a given width. This implies that the mass-metallicity relation of the host galaxies evolves towards lower metallicities at higher redshifts. These systems lack strong Si IV and C IV, which are common among lower-redshift DLAs and sub-DLAs. This is consistent, however, with a similar decrease in the metallicity of the low- and high-ionization phases, and does not necessarily indicate a lack of nearby, highly-ionized gas. The high number density of low-ionization systems at z~6 suggests that we may be detecting galaxies below the current limits of i-dropout and Ly-alpha emission galaxy surveys. These systems may therefore be the first direct probes of the `typical' galaxies responsible for hydrogen reionization.Comment: 15 pages, 15 figures, submitted to Ap

    3D printing of tablets using inkjet with UV photoinitiation

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    Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalised manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41 mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector

    Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development.

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    Cellular ATP is mainly generated through mitochondrial oxidative phosphorylation, which is dependent on mitochondrial DNA (mtDNA). We have previously demonstrated the importance of oocyte mtDNA for porcine and human fertilization. However, the role of nuclear-encoded mitochondrial replication factors during oocyte and embryo development is not yet understood. We have analyzed two key factors, mitochondrial transcription factor A (TFAM) and polymerase gamma (POLG), to determine their role in oocyte and early embryo development. Competent and incompetent oocytes, as determined by brilliant cresyl blue (BCB) dye, were assessed intermittently during the maturation process for TFAM and POLG mRNA using real-time RT-PCR, for TFAM and POLG protein using immunocytochemistry, and for mtDNA copy number using real-time PCR. Analysis was also carried out following treatment of maturing oocytes with the mtDNA replication inhibitor, 2',3'-dideoxycytidine (ddC). Following in vitro fertilization, preimplantation embryos were also analyzed. Despite increased levels of TFAM and POLG mRNA and protein at the four-cell stage, no increase in mtDNA copy number was observed in early preimplantation development. To compensate for this, mtDNA appeared to be replicated during oocyte maturation. However, significant differences in nuclear-encoded regulatory protein expression were observed between BCB(+) and BCB(-) oocytes and between untreated oocytes and those treated with ddC. These changes resulted in delayed mtDNA replication, which correlated to reduced fertilization and embryonic development. We therefore conclude that adherence to the regulation of the timing of mtDNA replication during oocyte maturation is essential for successful embryonic development

    Effect of acute and chronic sunitinib treatment on cardiac function and CaMKII

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    Calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac contractile function and dysfunction and may be an unwanted secondary target for anti-cancer drugs such as sunitinib and imatinib that have been reported to alter cardiac performance. This study aimed to determine whether anti-cancer kinase inhibitors may affect CaMKII activity and expression when administered in vivo

    3D extrusion printing of high drug loading immediate release paracetamol tablets

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    The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-Ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 seconds and release of most of the drug within 5 minutes. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards

    Making tablets for delivery of poorly soluble drugs using photoinitiated 3D inkjet printing

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    © 2019 In this study, we investigate the viability of three-dimensional (3D) inkjet printing with UV curing to produce solid dosage forms containing a known poorly soluble drug, carvedilol. The formulation consists of 10 wt% carvedilol, Irgacure 2959, and a photocurable N-vinyl-2-pyrrolidone (NVP) and poly(ethylene glycol) diacrylate matrix, with the intention of forming an amorphous solid solution for release of carvedilol. Characterization of the printed tablets showed that the drug is an amorphous state and indicated hydrogen bonding interactions between the drug and cross-linked matrix. Several simple geometries (ring, mesh, cylinder, thin film) were printed, and the surface area to volume ratio of the prints was estimated. Over 80% carvedilol release was observed for all printed tablet geometries within ten hours. The release behaviour of carvedilol was fastest for the thin films, followed by the ring and mesh geometries, and slowest in the cylindrical forms. More rapid release was correlated to an increased surface area to volume ratio. This is the first study to implement 3D UV inkjet to make solid dispersion tablets suitable for poorly soluble drugs. Results also demonstrate that high drug-loaded tablets with a variety of release profiles can successfully be accessed with the same UV-curable inkjet formulation by varying the tablet geometry

    Extrusion 3D printing of paracetamol tablets from a single formulation with tunable release profiles through control of tablet geometry

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    An extrusion based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring, and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (>80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation, breaking force and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia. X-Ray Powder Diffraction, Differential Scanning Calorimetry, and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities

    Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma

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    Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH

    Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

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    In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development
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