68 research outputs found
mRNA Abundance of Neurogenic Factors Correlates with Hearing Capacity in Auditory Brainstem Nuclei of the Rat
No full textNeural stem cells (NSCs) have previously been described up to the adult stage in the rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. A better understanding of molecular factors affecting NSCs and neurogenesis is of interest as they represent potential targets to treat the cause of neurologically based hearing disorders. The role of genes affecting NSC development and neurogenesis in CN over time on hearing capacity has remained unclear. This study investigated the mRNA abundance of genes influencing NSCs and neurogenesis in rats’ CN over time. The CN of rats on postnatal days 6, 12, and 24 were examined. Real-time quantitative polymerase chain reaction arrays were used to compare mRNA levels of 84 genes relevant to NSCs and neurogenesis. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected in the rat CN. Additionally, crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. The results of this work should contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway
Engineering of cartilage tissue constructs in a 3-dimensional perfusion bioreactor culture system under controlled oxygen tension
No full textThe most relevant results generated in this thesis can be summarized as follow:
· Adult human articular chondrocytes (AHAC) from elderly individuals expanded in culture
medium supplemented with the growth factors TGFβ-1, FGF-2 and PDGF and subsequently
cultured in 3-d pellets had an enhanced chondrogenic capacity when exposed to more
physiological (i.e. 5%) oxygen levels.
· In correlation with the enhanced tissue forming capacity of AHAC from elderly donors under
low oxygen tension, the mRNA expression levels of selective matrix degrading enzymes
were reduced as compared to conventional in vitro oxygen culture condition.
· We developed an integrated bioreactor system, which streamlines within a single device the
phases of perfusion cell seeding and prolonged perfusion culture of cell seeded scaffolds in
vitro.
· The culturing of uniformly seeded adult human articular chondrocytes under direct perfusion,
where cells are continuously exposed to a normoxic range of oxygen levels, can maintain a
uniform distribution of viable cells throughout thick porous scaffolds as compared to
statically cultured constructs.
· The culturing of constructs uniformly seeded with adult human articular chondrocytes under
a more physiological range of oxygen resulted in a higher chondrogenic differentiation as
compared to culture under normoxic levels. Anyhow, this effect was less pronounced as
compared to statically cultured cell constructs or micromass cell pellets, possibly due to the
flow induced shear forces.
· Reduced perfusion flow rates applied to chondrocytes on porous scaffolds significantly
induced more cartilaginous tissue in the presents of low vs. high oxygen levels. However the
effects of low oxygen were not as marked as in pellet culture
Making Dead Letters Live: Strategies to Improve the Effectiveness of EU Legislation in Central and Eastern Europe
No full textAs many empirical studies have shown, non-compliance with EU legislation has already been a significant phenomenon within the EU15. With the accession of twelve new Member States since 2004, all of which had to align their legal and administrative systems to the acquis communautaire within a very short time frame, the compliance issue has become even more pressing. Against this background, it is the aim of this paper to take a closer look at how four new Member States from Central and Eastern Europe fare in implementing EU legislation and how possible compliance problems could be remedied in the future. The paper presents findings from a comparative project on the transposition, enforcement and application of EU legislation from the fields of working time and equal treatment in the Czech Republic, Hungary, Slovakia and Slovenia. The results show that while transposition performance is relatively good, all four countries are marked by significant problems in application and enforcement. On the basis of intense focus group sessions involving practitioners from the four countries, the paper presents a set of strategies to improve the current state of affairs and concludes with some remarks on the chances for these options to be actually put into practice in the new Member States
Analysis of neural stem cells of the rat inferior colliculus in the course of time
No full textNeural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use.Neuronale Stammzellen wurden kürzlich im unteren Colliculus inferior (CI) identifiziert. Diese Zellen sind von besonderem Interesse, da es keine therapeutischen Optionen für geschädigte neuronale Strukturen gibt. Ziel dieses Forschungsprojekts ist es, das neurogene Potenzial im CI der Ratte von den ersten postnatalen Tagen bis zum Erwachsenenalter zu untersuchen. Der CI von Ratten vom 6. bis zum 48. postnatalen Tag wurde mit Neurosphären-Assays und histologischen Schnitten untersucht. In frei schwimmenden CI-Zellkulturen bildeten sich Neurosphären bei Tieren vom frühen postnatalen Alter bis zum Erwachsenenalter. Die Menge der gebildeten Neurosphären nahm im höheren Alter ab und stieg mit der Anzahl der Zelllinienpassagen. Die Zellen in den Neurosphären und die histologischen Schnitte zeigten eine positive Färbung mit neuronalen Stammzell-Markern (Doublecortin, Sox-2, Musashi-1, Nestin und Atoh1). Dissoziierte Einzelzellen aus den Neurosphären differenzierten und wurden positiv für die neuralen Abstammungsmarker β-III-Tubulin, GFAP und MBP angefärbt. Darüber hinaus wurden neuronalen Stammzell-Marker (Doublecortin, Sox-2, CDK5R1 und Ascl-1) mittels qRT-PCR untersucht. Zusammenfassend lässt sich sagen, dass ein neurogenes Potenzial im CI der Ratte von den frühen postnatalen Tagen bis zum Erwachsenenalter nachgewiesen und bewertet wurde. Die Identifizierung von neuronalen Stammzellen im CI der Ratte und ihre altersspezifischen Merkmale tragen zu einem besseren Verständnis der Entwicklung und der Plastizität der Hörbahn bei und könnten für eine therapeutische Nutzung aktiviert werden
The Exchange Rate and Canadian Inflation Targeting
No full textThe author provides a non-technical explanation of the role played by the exchange rate in Canada's inflation-targeting monetary policy. He reviews the motivation for inflation targeting and describes the monetary transmission mechanism. Though the exchange rate is an integral component of the transmission mechanism, the author explains why it is not a target for monetary policy. He provides a simple taxonomy for exchange rate movements, distinguishing between movements associated with direct shocks to aggregate demand and those unrelated to such direct shocks. He explains the importance to monetary policy of determining the cause of any given movement in the exchange rate, and of determining the net effect on aggregate demand. The author also describes Canadian monetary policy during the 2003-04 period, a time when the Canadian dollar appreciated sharply against the U.S. dollar.Exchange rates; Inflation targets; Monetary policy implementation
Active Cancellation of TS Instabilities in Compressible Flows Using a Closed-Loop Controller
No full textAbstract only
The propagation of light in a turbulent atmosphere
No full textThis report describes the instrumentation which is currently being utilized at the Oregon Graduate Center in a study of atmospheric turbulence effects on the long-range propagation of visible and infrared laser beams, with independent measurements of the turbulence parameters. The specially designed instrumentation includes portions of an Analog Computer; a special Differential Thermometer; a Laser Modulator; and auxiliary meteorological instruments; which were developed by the author. Sample experimental results are given in the report
The role of additional radiotherapy for primary central nervous system lymphoma
No full textPrior to the introduction of the chemotherapeutic agent methotrexate, radiotherapy was the sole, first-line option for the treatment of individuals with primary central nervous system lymphoma (PCNSL), Now that methotrexate is available, the role of radiotherapy in the treatment of PCNSL has been called into question. Although various studies suggest promising results with regard to overall and progression-free survival with the use of chemotherapeutic regimens alone as well as in combination with radiotherapy, no evidence-based standard regimen has yet been defined.; The objective of this review was to assess and summarise the evidence available regarding the efficacy and tolerability of radiotherapy in addition to chemotherapy in the treatment of immunocompetent individuals with PCNSL.; We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 01.2014), MEDLINE from January 1950 to February 2014 and conference proceedings from 2005 to 2013. ; We included randomised controlled trials (RCTs) comparing chemotherapy plus radiotherapy with chemotherapy alone in individuals with PCNSL. Outcomes defined in this review were overall survival, progression-free survival, response to treatment, adverse events, treatment related mortality and quality of life. We excluded trials in which the chemotherapy regimen differed between treatment arms, trials in which fewer than 80% of participants had PCNSL or those recruiting immunocompromised individuals with PCNSL.; Two review authors independently screened the results of the search strategies for eligibility for this review. Both assessed risk of bias. Where relevant data was unavailable, we contacted the investigator by email.; Of the 556 potentially relevant studies only two met the inclusion criteria. One of those was excluded as the trial was abandoned prematurely and reported only preliminary results. The only analysed trial enrolled 551 participants receiving first-line chemotherapy (methotrexate) followed by whole brain radiotherapy (WBR) or receiving chemotherapy only (methotrexate followed by cytarabine in case of incomplete response). In this non-inferiority trial, the intention-to-treat (ITT) population consisted of 411 participants and the per-protocol (PP) population of 318 participants. We judged the potential for risk of bias in this open-label study as moderate.The estimated effect of chemotherapy plus WBR on survival was similar to that with chemotherapy alone but due to a wide CI we could not rule out the superiority of either therapy. This applied to both the ITT population (HR 1.01, 95% CI 0.79 to 1.30; P = 0.94) and the PP population (HR 1.06, 95% CI 0.80 to 1.40; P = 0.71) (moderate-quality evidence). Due to the low number of participants and a risk of detection bias we found low-quality evidence for an improvement in progression-free survival in participants in the ITT population receiving WBR in addition to chemotherapy (HR 0.79, 95% CI 0.63 to 0.99; P = 0.041). An improvement in PFS was also observed with WBR plus chemotherapy in participants in the PP population, but the CI was slightly wider and the result not significant (HR 0.82,95% CI 0.64 to 1.07; P = 0.14). Treatment-related mortality and health-related quality of life were not evaluated. Treatment-related neurotoxicity was assessed clinically in 79 participants, revealing signs of neurotoxicity in 49% of those receiving chemotherapy plus radiotherapy and in 26% of those receiving chemotherapy only (RR 1.85, 95% CI 0.98 to 3.48; P = 0.054) (very-low-quality evidence).; In summary, the currently available evidence (one RCT) is not sufficient to conclude that WBR plus chemotherapy and chemotherapy alone have similar effects on overall survival in people with PCNSL. The findings suggest that the addition of radiotherapy (WBR) to chemotherapy may increase progression-free survival, but may also increase the incidence of neurotoxicity compared to chemotherapy only (methotrexate monotherapy). As the role of chemoradiotherapy in the treatment of PCNSL remains unclear, further prospective, randomised trials are needed before definitive conclusions can be drawn
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