Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling.

In-Vessel Penetrator -käärmerobotin mallinnus ADAMS-ohjelmistolla

Työn tavoitteena oli muodostaa virtuaaliprototyyppi fuusioreaktorin huollossa käytettävästä IVP-robotista. Työssä mallinnettiin robotin mekaniikka joustavana sekä toimilaitteiden ja käyttöjen dynaamiset ominaisuudet valmistajien esitietojen ja mitoitustietojen perusteella. Käyttöjen ja mekaniikan mallit yhdistettiin ADAMS-ohjelmistossa. Mekaanisten joustojen mallinnuksessa sekä verifioinnissa käytettiin apuna ANSYS –ohjelmistoa. Virtuaaliprototyypin toimivuudesta varmistuttiin vertaamalla sitä robotin suunnittelutietoihin ja fyysiseen prototyyppiin. Robotin ohjauksessa käytettävän P-säätäjän vaikutusta tutkittiin eri vahvistuksen arvoilla sekä verrattiin mekaanisia vasteita fyysisen prototyypin dynaamisiin testeihin. Esimerkkinä robotin käyttäytymisestä todellisessa tilanteessa simuloitiin sen ajoa reaktoriin. Toteutetun simulointimallin todettiin vastaavan rakenteeltaan sekä siinä esiintyvien voimien osalta suunnitelmien mukaista konstruktiota. Käytetyillä parametreilla se toteutti hyvin robotille asetetut nopeusvaatimukset.

GATA2 is required for lymphatic vessel valve development and maintenance.

Heterozygous germline mutations in the zinc finger transcription factor GATA2 have recently been shown to underlie a range of clinical phenotypes, including Emberger syndrome, a disorder characterized by lymphedema and predisposition to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). Despite well-defined roles in hematopoiesis, the functions of GATA2 in the lymphatic vasculature and the mechanisms by which GATA2 mutations result in lymphedema have not been characterized. Here, we have provided a molecular explanation for lymphedema predisposition in a subset of patients with germline GATA2 mutations. Specifically, we demonstrated that Emberger-associated GATA2 missense mutations result in complete loss of GATA2 function, with respect to the capacity to regulate the transcription of genes that are important for lymphatic vessel valve development. We identified a putative enhancer element upstream of the key lymphatic transcriptional regulator PROX1 that is bound by GATA2, and the transcription factors FOXC2 and NFATC1. Emberger GATA2 missense mutants had a profoundly reduced capacity to bind this element. Conditional Gata2 deletion in mice revealed that GATA2 is required for both development and maintenance of lymphovenous and lymphatic vessel valves. Together, our data unveil essential roles for GATA2 in the lymphatic vasculature and explain why a select catalogue of human GATA2 mutations results in lymphedema.

NG2 glia are required for vessel network formation during embryonic development.

The NG2(+) glia, also known as polydendrocytes or oligodendrocyte precursor cells, represent a new entity among glial cell populations in the central nervous system. However, the complete repertoire of their roles is not yet identified. The embryonic NG2(+) glia originate from the Nkx2.1(+) progenitors of the ventral telencephalon. Our analysis unravels that, beginning from E12.5 until E16.5, the NG2(+) glia populate the entire dorsal telencephalon. Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain. NG2(+) glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls. Absence of NG2(+) glia drastically affects the vascular development leading to severe reduction of ramifications and connections by E18.5. By revealing a novel and fundamental role for NG2(+) glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains.

Novel Robot Solutions for Carrying out Field Joint Welding and Machining in the Assembly of the Vacuum Vessel of ITER

It is necessary to use highly specialized robots in ITER (International Thermonuclear Experimental Reactor) both in the manufacturing and maintenance of the reactor due to a demanding environment. The sectors of the ITER vacuum vessel (VV) require more stringent tolerances than normally expected for the size of the structure involved. VV consists of nine sectors that are to be welded together. The vacuum vessel has a toroidal chamber structure. The task of the designed robot is to carry the welding apparatus along a path with a stringent tolerance during the assembly operation. In addition to the initial vacuum vessel assembly, after a limited running period, sectors need to be replaced for repair. Mechanisms with closed-loop kinematic chains are used in the design of robots in this work. One version is a purely parallel manipulator and another is a hybrid manipulator where the parallel and serial structures are combined. Traditional industrial robots that generally have the links actuated in series are inherently not very rigid and have poor dynamic performance in high speed and high dynamic loading conditions. Compared with open chain manipulators, parallel manipulators have high stiffness, high accuracy and a high force/torque capacity in a reduced workspace. Parallel manipulators have a mechanical architecture where all of the links are connected to the base and to the end-effector of the robot. The purpose of this thesis is to develop special parallel robots for the assembly, machining and repairing of the VV of the ITER. The process of the assembly and machining of the vacuum vessel needs a special robot. By studying the structure of the vacuum vessel, two novel parallel robots were designed and built; they have six and ten degrees of freedom driven by hydraulic cylinders and electrical servo motors. Kinematic models for the proposed robots were defined and two prototypes built. Experiments for machine cutting and laser welding with the 6-DOF robot were carried out. It was demonstrated that the parallel robots are capable of holding all necessary machining tools and welding end-effectors in all positions accurately and stably inside the vacuum vessel sector. The kinematic models appeared to be complex especially in the case of the 10-DOF robot because of its redundant structure. Multibody dynamics simulations were carried out, ensuring sufficient stiffness during the robot motion. The entire design and testing processes of the robots appeared to be complex tasks due to the high specialization of the manufacturing technology needed in the ITER reactor, while the results demonstrate the applicability of the proposed solutions quite well. The results offer not only devices but also a methodology for the assembly and repair of ITER by means of parallel robots.

Surface chemistry of fibres and vessel elements in chemical and recycled pulps

Den viktigaste råvaran i papperstillverkning är pappersmassa. Massan innehåller (ved)fibrer men också finmaterial och andra typers (ved)celler, så som kärlceller. Hur dessa komponenter beter sig under arkformationen i pappersmaskinen eller hur de bidrar till egenskaperna hos det färdiga pappret avgörs till stor del av massakomponenternas ytkemiska sammansättning, fysiska struktur och mängden joniserbara grupper på ytan. I denna avhandling studerades ytegenskaperna hos fraktionerade kemiska massor och returfibermassor med avancerade analystekniker. Rester av avfärgningskemikalier identifierades på både returfibrer och på kärlceller. Dessa kan påverka arkformationen och arkstyrkan på returfiberpapper. Kärlcellernas cellväggsstruktur visade sig skilja sig från fibrernas. Resultaten kan främja utvecklingen av returfiberprosessen och användningen av kärlcellsrika lövvedsmassor.

Characterization of fiber and vessel elements in pulp suspension images

The thesis is related to the topic of image-based characterization of fibers in pulp suspension during the papermaking process. Papermaking industry is focusing on process control optimization and automatization, which makes it possible to manufacture highquality products in a resource-efficient way. Being a part of the process control, pulp suspension analysis allows to predict and modify properties of the end product. This work is a part of the tree species identification task and focuses on analysis of fiber parameters in the pulp suspension at the wet stage of paper production. The existing machine vision methods for pulp characterization were investigated, and a method exploiting direction sensitive filtering, non-maximum suppression, hysteresis thresholding, tensor voting, and curve extraction from tensor maps was developed. Application of the method to the microscopic grayscale pulp images made it possible to detect curves corresponding to fibers in the pulp image and to compute their morphological characteristics. Performance of the method was evaluated based on the manually produced ground truth data. An accuracy of fiber characteristics estimation, including length, width, and curvature, for the acacia pulp images was found to be 84, 85, and 60% correspondingly.

Integration of cooking and vacuum cooling of carrots in a same vessel

Cooked vegetables are commonly used in the preparation of ready-to-eat foods. The integration of cooking and cooling of carrots and vacuum cooling in a single vessel is described in this paper. The combination of different methods of cooking and vacuum cooling was investigated. Integrated processes of cooking and vacuum cooling in a same vessel enabled obtaining cooked and cooled carrots at the final temperature of 10 ºC, which is adequate for preparing ready-to-eat foods safely. When cooking and cooling steps were performed with the samples immersed in boiling water, the effective weight loss was approximately 3.6%. When the cooking step was performed with the samples in boiling water or steamed, and the vacuum cooling was applied after draining the boiling water, water loss ranged between 15 and 20%, which caused changes in the product texture. This problem can be solved with rehydration using a small amount of sterile cold water. The instrumental textural properties of carrots samples rehydrated at both vacuum and atmospheric conditions were very similar. Therefore, the integrated process of cooking and vacuum cooling of carrots in a single vessel is a feasible alternative for processing such kind of foods.

Genetics of inherited small vessel diseases – in search of a novel small vessel disease and modifiers of the clinical course of CADASIL

The genetic and environmental risk factors of vascular cognitive impairment are still largely unknown. This thesis aimed to assess the genetic background of two clinically similar familial small vessel diseases (SVD), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) and Swedish hMID (hereditary multi-infarct dementia of Swedish type). In the first study, selected genetic modifiers of CADASIL were studied in a homogenous Finnish CADASIL population of 134 patients, all carrying the p.Arg133Cys mutation in NOTCH3. Apolipoprotein E (APOE) genotypes, angiotensinogen (AGT) p.Met268Thr polymorphism and eight NOTCH3 polymorphisms were studied, but no associations between any particular genetic variant and first-ever stroke or migraine were seen. In the second study, smoking, statin medication and physical activity were suggested to be the most profound environmental differences among the monozygotic twins with CADASIL. Swedish hMID was for long misdiagnosed as CADASIL. In the third study, the CADASIL diagnosis in the Swedish hMID family was ruled out on the basis of genetic, radiological and pathological findings, and Swedish hMID was suggested to represent a novel SVD. In the fourth study, the gene defect of Swedish hMID was then sought using whole exome sequencing paired with a linkage analysis. The strongest candidate for the pathogenic mutation was a 3’UTR variant in the COL4A1 gene, but further studies are needed to confirm its functionality. This study provided new information about the genetic background of two inherited SVDs. Profound knowledge about the pathogenic mutations causing familial SVD is also important for correct diagnosis and treatment options.

Captain Lewis Warrington and others : memorial of Lewis Warrington, Captain in the U.S. Navy, (in behalf of himself and the officers and crew of the U.S. sloop-of-war Peacock); praying that the one half of the proceeds of the Epervier and goods which went into the officers and crew of said vessel, it having been decreed to them by the United States court as captors. April 26, 1848.--

Caption title.

Lymphatic vessel function in atherosclerosis

L'athérosclérose est une maladie inflammatoire chronique caractérisée par l'accumulation de cholestérol dans la paroi artérielle et associée à une réponse immunitaire anormale dans laquelle les macrophages jouent un rôle important. Récemment, il a été démontré que les vaisseaux lymphatiques jouent un rôle primordial dans le transport inverse du cholestérol (Martel et al. JCI 2013). L’objectif global de mon stage de maîtrise a été de mieux caractériser la dysfonction lymphatique associée à l’athérosclérose, en étudiant de plus près l’origine physiologique et temporelle de ce mauvais fonctionnement. Notre approche a été d’étudier, depuis l’initiation de l’athérosclérose jusqu’à la progression d’une lésion athérosclérotique tardive, la physiologie des deux constituants principaux qui forment les vaisseaux lymphatiques : les capillaires et collecteurs lymphatiques. En utilisant comme modèle principal des souris Ldlr-/-; hApoB100+/+, nous avons pu démontrer que la dysfonction lymphatique est présente avant même l’apparition de l’athérosclérose, et que cette dysfonction est principalement associée avec un défaut au niveau des vaisseaux collecteurs, limitant ainsi le transport de la lymphe des tissus périphériques vers le sang. De plus, nous avons démontré pour la première fois l’expression du récepteur au LDL par les cellules endothéliales lymphatiques. Nos travaux subséquents démontrent que ce défaut de propulsion de la lymphe pourrait être attribuable à l’absence du récepteur au LDL, et que la dysfonction lymphatique observée précocement dans l’athérosclérose peut être limitée par des injections systémiques de VEGF (vascular endothelial growth factor) –C. Ces résultats suggèrent que la caractérisation fonctionnelle de la capacité de pompage des vaisseaux collecteurs serait une condition préalable à la compréhension de l'interaction entre la fonction du système lymphatique et la progression de l'athérosclérose. Ultimement, nos travaux nous ont amené à considérer de nouvelles cibles thérapeutiques potentielles dans la prévention et le traitement de l’athérosclérose.

Indian Law on Control of Vessel Sourced Pollution in Maritime Ports

Maritime ports are inevitable for India’s economic development. The very existence and sustainable development of ports depend on clean port environment. There is a notion that shipping is an over regulated industry. But in India, it is being operated under sub- standard conditions, raising crucial issues of environmental pollution in the country’s ports. The negative impacts of vessel sourced pollution on the eco-fragile coastal peninsula can be detrimental to the living conditions, health and interests of the coastal population. It can disturb marine life and imbalance the aquatic ecosystem. The present study analyses control of vessel sourced pollution in Indian ports from an economic and ecological perspective. The study investigates legal reasons behind the weak control, regulation and monitoring over vessel sourced pollution in Indian ports. The loopholes in the legal system are identified and suggestion made to implement stronger enforcement. Unless, vessel operations are properly regulated in ports, the trade and economic prospects of India will be jeopardized.

Quantification of the probability of containment failure caused by an in-vessel steam explosion for the Sizewell B PWR

AEA Technology has provided an assessment of the probability of α-mode containment failure for the Sizewell B PWR. After a preliminary review of the methodologies available it was decided to use the probabilistic approach described in the paper, based on an extension of the methodology developed by Theofanous et al. (Nucl. Sci. Eng. 97 (1987) 259–325). The input to the assessment is 12 probability distributions; the bases for the quantification of these distributions are discussed. The α-mode assessment performed for the Sizewell B PWR has demonstrated the practicality of the event-tree method with input data represented by probability distributions. The assessment itself has drawn attention to a number of topics, which may be plant and sequence dependent, and has indicated the importance of melt relocation scenarios. The α-mode failure probability following an accident that leads to core melt relocation to the lower head for the Sizewell B PWR has been assessed as a few parts in 10 000, on the basis of current information. This assessment has been the first to consider elevated pressures (6 MPa and 15 MPa) besides atmospheric pressure, but the results suggest only a modest sensitivity to system pressure.