Beurteilung der Lungengesundheit von Schweinen aus verschiedenen ökologischen Haltungssystemen mittels BAL und Lungenhistologie

Im vorliegenden Forschungsvorhaben wurde die Lungengesundheit von Schweinen in Abhängigkeit von verschiedenen Haltungs- und Managementbedingungen beschrieben. Die Untersuchung erfolgte an Mastschweinen verschiedener Herkünfte (konventionell – ökologischer Tiefstreustall – Stall nach EU-Öko-VO – Freilandhaltung) und an Tieren unterschiedlichen Alters. In der konventionellen Schweinemast handelte es sich hierbei um Ferkel, Läufer und Mastschweine derselben Herkunft, in der ökologischen Schweinemast um Läufer, Mastschweine und XXL-Schweine von jeweils zwei Beständen. Letztere Untersuchung diente vor allem der Abbildung möglicher Effekte von Unterschieden im betrieblichen und Hygienemanagement auf die Tiergesundheit in den beiden ökologischen Beständen. Der Gesundheitszustand der Tiere mit Betonung des Lungenbefundes wurde über Schlachtkörperuntersuchungen, bronchoalveoläre Lavage (BAL) und histologische Untersuchung makroskopisch auffälliger Lungenbefunde erfasst. Allgemein wurde festgestellt, dass die Tiere im Zeitverlauf und in Abhängigkeit von den Haltungsbedingungen Zeichen einer zunehmenden entzündlichen Veränderung im Bereich der Atemwege zeigten (BAL: prozentuale Reduktion der Makrophagen bei gleichzeitigem relativen Anstieg der Lymphozyten). Die histologische Untersuchung wies auf ein unterschiedlich ausgeprägtes v.a. viral bedingtes infektiöses Geschehen hin, das möglicherweise durch eine in unterschiedlichem Ausmaß bestehende irritative Schädigung der Atemwege gefördert wurde. Sowohl bei Untersuchung der Mastschweine als auch bei Probenahme bei unterschiedlich alten Tieren wurde deutlich, dass den Managementfaktoren (Entwurmung, Impfstatus, Hygiene) eine bedeutende Rolle im Hinblick auf den Gesundheitszustand zukommt. Im negativen Fall führte dieser Effekt dazu, dass die Anzahl auffälliger Befunde trotz vergleichsweiser guter Stallluftqualität (sehr) hoch war. Neben baulich-technischen Faktoren kommt folglich dem Management eine sehr große Bedeutung zu

Врахування вітчизняних умов при використанні закордонних Z-моделей прогнозування банкрутства

The green cw laser presented in this work is realized by means of a Pr:YLF crystal emitting at 523 nm that is pumped by a blue GaN laser diode in an extremely short resonator. With a 500 mW-diode a laser has been achieved with M2 = 1, a slope of 40 % and an output power of 140mW with an absorbed pump power of 410 mW which results in an electrooptical efficiency of 6.5 %. Despite the reduced overlap with a 1 W-diode the output power rises to 290 mW with an absorbed pump power of 850 mW and the M2 increases only slightly. Based on these results a compact laser package has been accomplished using a monolithic micro optics for the beam shaping of the diode light and joining all components with a low-shrinkage adhesive on a common base plate. In a first test of the alignment strategy a laser with an output power of 92 mW has been achieved by means of the 500 mW pump power

Оптимізація макрологістичних мереж

We report on a Laser source, emitting in the mid-IR spectral range. A mode-locked Nd: YVO Laser is used as a pump Laser, followed by two nonlinear frequency conversion steps (OPG, DFG). The broad-band output beam is tunable between 9 ?m and 13 ?m, with average powers up to 10 mW. Further extension of the tuning range is possible

Fragen des Arbeits-, Tier- und Umweltschutzes bei der Schweinemast in verschiedenen Systemen unter besonderer Berücksichtigung mikrobieller Belastungen

Vor dem Hintergrund häufiger Atemwegserkrankungen bei Schweinen und landwirtschaftlich Beschäftigten war es das Ziel eines interdisziplinären Verbundprojektes, Belastungen von Mensch, Tier und Umwelt in ökologischen und konventionellen Haltungssystemen für die Schweinemast zu erfassen. Die Untersuchungen wurden in zwei konventionellen (Stall A, B) (BVT-Stall, 50% reduzierter Schlitzanteil, Zwangsbelüftung) und zwei ökologischen Ställen durchgeführt: Stall C (Praxisstall: Tiefstreu, freie Fenster-Lüftung), Stall D (Praxisstall: EU-Öko-VO, Trauf-First-Lüftung). Über 2 Mastperioden (je 3 Messungen; kalte / warme Jahreszeit) wurden die Parameter erfasst: luftgetragene Endotoxine, Schimmelpilze, Bakterien mit Differenzierung, arbeitsmedizinische Staubfraktionen, Materialproben, Staubfraktion PM10, NH3, CO2 und CH4, Lufttemperatur, Luftfeuchte. Die Beschreibung der Tiergesundheit erfolgte über serologische (Mycoplasmen, PRRS-, Influenza-A- und Circo-Virus) und koprologische (Parasitenbefall) Analysen und über Schlachtkörper- und Organbefundungen (Lunge, Pleura, Perikard, Leber). Am Beispiel der Endotoxin-Konzentration wurden die z.T. sehr hohen biologischen Belastungen deutlich: Stall C (Median: 14.495 EU/m3), Stall A/B (5.544 EU/m3), Stall D (2.876 EU/m3). Personengetragene Messungen führten zu deutlich höheren Werten. Die CO2- und NH3-Konzentrationen lagen in allen Ställen im Durchschnitt deutlich unter dem Grenzwert von 3000 ppm bzw. 20 ppm. In Stall C und D war die CH4-Konzentration allerdings höher als in Stall A/B (oberer Bereich der Literaturangaben). Auffällige Lungenbefunde fanden sich bei ca. 45% der untersuchten Schlachttiere, unabhängig vom Haltungssystem; parasitäre Leberveränderungen wurden ausschließlich in den Ställen C und D ermittelt. Die Untersuchungsergebnisse unterstreichen die Bedeutung der Ausführung, Dimensionierung und Regelung des Lüftungssystems sowie die Sauberkeit bzw. Hygiene und insbesondere das Betriebsmanagement im Stall und ihre Schlüsselrolle hinsichtlich der Freisetzungsmengen von Schadstoffen sowie der Tiergesundheit. Demgegenüber kommt der Klassifizierung der Haltungsumwelt durch die Einteilung in Haltungssystemen nur eine geringe Aussagekraft zu

Multi-minicore Disease

Abstract Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown. Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD due to dominant RYR1 mutations, reflecting the common genetic background. Pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but likely to involve altered excitability and/or changes in calcium homeoestasis; calcium-binding motifs within the selenoprotein N protein also suggest a possible role in calcium handling. The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy; muscle MRI may aid genetic testing as patterns of selective muscle involvement are distinct depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of malignant hyperthermia susceptibility in RYR1-related forms. In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor.</p

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Fixed bobbin friction stir welding of marine grade aluminium.

PROBLEM - The bobbin friction stir welding (BFSW) process has potential benefits for welding thin sheet aluminium alloy. The main benefits of friction stir welding over conventional thermal welding processes are minimisation of energy usage, no need for consumables, potential for good weld quality without porosity, no fumes, minimal adverse environmental effects (green), minimal waste (lean), and reduced threats to personal health and safety. The BFSW process has further advantages over conventional friction stir welding (CFSW) in the reduction of welding forces, faster welding, and less fixturing. It is especially attractive to industries that join thin sheet material, e.g. boat-building. The industrial need for this project arose from the desire to apply the technology at a ship manufacturing company, INCAT located in Hobart, Tasmania, Australia. However there are peculiar difficulties with the specific grade of material used in this industry, namely thin sheet aluminium Al6082-T6. Early efforts with a portable friction stir welding machine identified the process to have low repeatability and reproducibility, i.e. process-instability. There are a large number of process variables and situational factors that affect weld quality, and many of these are covert. This is also the reason for divergent recommendations in the literature for process settings. PURPOSE - The main purpose of this research was to identify covert variables and better understand their potentially adverse effects on weld quality. Therefore, this thesis investigated the hidden variables and their interactions. Developing this knowledge is a necessity for making reliable and repeatable welds for industrial application. APPROACH - An explorative approach that focused on the functional perspective was taken. An extensive empirical testing programme was undertaken to identify the variables and their effects. In the process a force platform and BFSW tools were designed and built. A variety of machine platforms were used, namely portable friction stir welding, manual milling machine and computer numerical control (CNC) milling machine. The trials were grouped into 14 test plans. These are tool shoulder gap, spindle and travel speed, tool features, machines, tool fixation, machinery, welding direction, plate size (width and dimension), support insulation, tool materials, substrate properties and fixation. For the welded plates besides visual inspection of the weld, current, force, and temperature were measured. The Fourier transform was used to analyse the frequency response of machines. Also the welded samples were tested to the maritime standards of Det Norske Veritas (DNV). A number of relationships of causality were identified whereby certain variables affected weld quality. A model was developed to represent the proposed causality using the IDEF0 systems engineering method. FINDINGS - From these trials six main variables have been identified. These are tool features, spindle speed, travel speed, shoulder gap compression, machine variability, tool and substrate fixation. A rigid system is required for a consistent weld results. Under this condition, full pin features (threads and flats) need to be used to balance the adverse effects of individual features. It has been shown that fabricated bobbin tools with sharp edges can cause cuts and digging thus this feature should be avoided. Additionally, the substrate should have continuous interaction with the tool so the shoulder interference needs to be fixed and well-controlled. It is found that the compression generated by the shoulder towards the substrate helps material grabbing for better tool-substrate interaction. It is also shown that tool entry causes ejection of material and hence an enduring mass deficit, which manifests as a characteristic tunnel defect. The new explanation of the formation, origin and location of this defect has been explained. Material transportation mechanisms within the weld have been elucidated. It is also found that the role of the travel speed is not only to control heat generation but also for replacing the deficit material. Additionally, heat supplied to the weld depends not only on thickness, but also the width of the plate. Different types of machine cause an interaction in the material flow through their controller strategies. Jerking motion can occur at a slow travel speed, which also alters the way material is being transported. The Fourier transform (FFT) has been used to identify the characteristics of good and bad BFSW welds. This has the potential to be expanded for real-time process control. IMPLICATIONS - Tool deflection and positioning, material flow and availability are identified as affecting weld quality through stated mechanisms. The impact is even more severe when involving thin-plate aluminium. For the industry to successfully adopt this technology the process typically needs tight control of shoulder gap, tool strength and stiffness, feature fabrication, substrate and tool fixation. Additionally spindle and travel speed need to be adjusted not only based on the type of materials and thickness, but also the width, type of machine and method of tool entry. ORIGINALITY - New data are presented, which lead to new insights into the welding mechanics, production settings, material transportation and weld defects for BFSW on thin sheet material. The conventional idea that the welding tool has a semi-steady interaction with the substrate is not supported. Instead the interaction is highly dynamic, and this materially affects the weld-quality, especially in the difficult-to-weld material under examination. Factors such as shoulder gap, tool and substrate fixation compliance and machine types emerge as variables that need to be given attention in the selection of process parameters. The causal relationships have been represented in a conceptual model using an IDEF0 system approach. This study has made several original contributions to the body of knowledge. First is the identification of previously hidden variables that effect weld formation for the fixed gap BFSW process. The second contribution is a new way of understanding the material transportation mechanics within the weld. This includes the flow around the pin in the plane of the weld, the vertical transportation of material up the pin, the formation of turbulent-like knit lines at the advancing side, and the formation of tunnel defects. Also included here is a new understanding of how material deficit arises at tool entry and exit, and from flash/chips, and how this contributes to the tunnel weld defect. In addition, new understandings of the role of feed rate have been identified. Related to the material transportation, the work has also identified the importance of an interference fit between the substrate and tool. A third contribution is the identification of the dynamic interaction between tool and substrate. This identifies the important role rigidity plays. Associated with this is the identification of frequency characteristics of the motors under load. The fourth contribution is identification of the specific process settings for the difficult-to-weld material of AL6082-T6. The fifth contribution is the development of a novel method of fabricating bobbin friction stir welding tools as embodied in a patent application

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area

Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment