Duszpasterstwo ksi����y diecezjalnych oraz kapelan��w wojskowych w latach 1919-1939 na terenie Okr��gu Korpusu nr VII

Wydzia�� Historyczny

Konspiracja i podziemie zbrojne w Wielkopolsce 1945-1949. Powstanie, rozw��j i rozbicie przez aparat bezpiecze��stwa

Wydzia�� Historyczny

Zinstytucjonalizowane sieci wsp����dzia��ania mi��dzygminnego w Polsce

Podstawowym problemem badawczym rozprawy doktorskiej mgra Bart��omieja Ko��suta jest powstawanie i funkcjonowanie zinstytucjonalizowanych sieci wsp����dzia��ania mi��dzygminnego w Polsce. W pracy skoncentrowano si�� na realizacji pi��ciu najwa��niejszych cel��w poznawczych. Dotycz�� one: 1. identyfikacji zinstytucjonalizowanych sieci wsp����dzia��ania mi��dzygminnego w Polsce wed��ug stanu na koniec 2014 roku, 2. typologii funkcjonalnej zidentyfikowanych sieci, 3. pr��by wyja��nienia przyczyn powstawania sieci w okresie 1990-2014, 4. weryfikacji wybranych czynnik��w usieciowienia gmin, 5. pr��by oceny przydatno��ci wybranych teorii instytucjonalnych w wyja��nianiu przyczyn powstawania i funkcjonowania sieci. W rozprawie wykorzystano szereg metod i technik badawczych, m. in. metod�� analizy tre��ci, statystyczne miary wsp����zmienno��ci (wsp����czynnik phi Yule���a, iloraz szans, wsp����czynnik korelacji liniowej Pearsona). W procesie identyfikacji sieci przeanalizowano ponad 2,5 tys. dokument��w i opracowa��, korzystaj��c przy tym z kilkudziesi��ciu, r����nego rodzaju baz danych. Wyniki przeprowadzonych bada�� empirycznych pozwoli��y tak��e dokona�� oceny przydatno��ci teorii instytucjonalnych (m. in. instytucjonalizmu wyboru racjonalnego, instytucjonalizmu socjologicznego oraz instytucjonalizmu historycznego) w wyja��nianiu przyczyn powstawania i funkcjonowania sieci. Zrealizowana rozprawa jest pierwszym tak kompleksowym i pog����bionym opracowaniem geograficznego wymiaru zinstytucjonalizowanej wsp����pracy mi��dzygminnej w Polsce.

Integrated Chest Image Analysis System "BU-MIA"

We introduce "BU-MIA," a Medical Image Analysis system that integrates various advanced chest image analysis methods for detection, estimation, segmentation, and registration. BU-MIA evaluates repeated computed tomography (CT) scans of the same patient to facilitate identification and evaluation of pulmonary nodules for interval growth. It provides a user-friendly graphical user interface with a number of interaction tools for development, evaluation, and validation of chest image analysis methods. The structures that BU-MIA processes include the thorax, lungs, and trachea, pulmonary structures, such as lobes, fissures, nodules, and vessels, and bones, such as sternum, vertebrae, and ribs.

Automatic 3D Registration of Lung Surfaces in Computed Tomography Scans

We developed an automated system that registers chest CT scans temporally. Our registration method matches corresponding anatomical landmarks to obtain initial registration parameters. The initial point-to-point registration is then generalized to an iterative surface-to-surface registration method. Our "goodness-of-���t" measure is evaluated at each step in the iterative scheme until the registration performance is sufficient. We applied our method to register the 3D lung surfaces of 11 pairs of chest CT scans and report promising registration performance.

Characterisation of the role of Fas in intestinal inflammation and cancer

Background: The role of Fas (CD95) and its ligand, Fas ligand (FasL/CD95L), is poorly understood in the intestine. Whilst Fas is best studies in terms of its function in apoptosis, recent studies suggest that Fas ligation may mediate additional, non-apoptotic functions such as inflammation. Toll like Receptors (TLRs) play an important role in mediating inflammation and homeostasis in the intestine. Recent studies have shown that a level of crosstalk exists between the Fas and TLR signalling pathways but this has not yet been investigated in the intestine. Aim: The aim of this study was to evaluate potential cross-talk between TLRs and Fas/FasL system in intestinal cancer cells. Results: Treatment with TLR4 and TLR5 ligands, but not ligands for TLR2 and TLR9 increased the expression of Fas and FasL in intestinal cancer cells in vitro. Consistent with this, expression of Fas and FasL was reduced in the distal colon tissue from germ-free (GF), TLR4 and TLR5 knock-out (KO) mice but was unchanged in TLR2KO tissue, suggesting that intestinal cancer cells display a degree of specificity in their ability to upregulate Fas and FasL expression in response to TLR ligation. Expression of both Fas and FasL was significantly reduced in TRIF KO tissue, indicating that signalling via TRIF by TLR4 and TLR5 agonists may be responsible for the induction of Fas and FasL expression in intestinal cancer cells. In addition, modulating Fas signalling using agonistic anti-Fas augmented TLR4 and TLR5-mediated tumour necrosis factor alpha (TNF��) and interleukin 8 (IL)-8 production by intestinal cancer cells, suggesting crosstalk occurs between these receptors in these cells. Furthermore, suppression of Fas in intestinal cancer cells reduced the ability of the intestinal pathogens, Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL-8, suggesting that Fas signalling may play a role in intestinal host defence against pathogens. Inflammation is known to be important in colon tumourigenesis and Fas signalling on intestinal cancer cells has been shown to result in the production of inflammatory mediators. Fas-mediated signalling may therefore play a role in colon cancer development. Suppression of tumour-derived Fas by 85% led to a reduction in the tumour volume and changes in tumour infiltrating macrophages and neutrophils. TLR4 signalling has been shown to play a role in colon cancer via the recruitment and activation of alternatively activated immune cells. Given the crosstalk seen between Fas and TLR4 signalling in intestinal cancer cells in vitro, suppressing Fas signalling may enhance the efficacy of TLR4 antagonism in vivo. TLR4 antagonism resulted in smaller tumours with fewer infiltrating neutrophils. Whilst Fas downregulation did not significantly augment the ability of TLR4 antagonism to reduce the final tumour volume, Fas suppression may augment the anti-tumour effects of TLR4 antagonism as neutrophil infiltration was further reduced upon combinatorial treatment. Conclusion: Together, this study demonstrates evidence of a new role for Fas in the intestinal immune response and that manipulating Fas signalling has potential anti-tumour benefit.

Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis.

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.

A strategy to advance the evidence base in palliative medicine: formation of a palliative care research cooperative group.

BACKGROUND: Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping. METHODS: A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care. RESULTS: The resulting Palliative Care Research Cooperative (PCRC) agreed on a set of core principles: active, interdisciplinary membership; commitment to shared research purposes; heterogeneity of participating sites; development of research capacity in participating sites; standardization of methodologies, such as consenting and data collection/management; agile response to research requests from government, industry, and investigators; focus on translation; education and training of future palliative care researchers; actionable results that can inform clinical practice and policy. Consensus was achieved on a first collaborative study, a randomized clinical trial of statin discontinuation versus continuation in patients with a prognosis of less than 6 months who are taking statins for primary or secondary prevention. This article describes the formation of the PCRC, highlighting processes and decisions taken to optimize the cooperative group's success.

Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2.

BACKGROUND: The lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR), highly expressed in brown adipose tissue (BAT), yet their impact on adipocyte function and metabolism remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: PRLR knockout (KO) newborn mice were phenotypically characterized in terms of thermoregulation and their BAT differentiation assayed for gene expression studies. Derived brown preadipocyte cell lines were established to evaluate the molecular mechanisms involved in PRL signaling on BAT function. Here, we report that newborn mice lacking PRLR have hypotrophic BAT depots that express low levels of adipocyte nuclear receptor PPARgamma2, its coactivator PGC-1alpha, uncoupling protein 1 (UCP1) and the beta3 adrenoceptor, reducing mouse viability during cold challenge. Immortalized PRLR KO preadipocytes fail to undergo differentiation into mature adipocytes, a defect reversed by reintroduction of PRLR. That the effects of the lactogens in BAT are at least partly mediated by Insulin-like Growth Factor-2 (IGF-2) is supported by: i) a striking reduction in BAT IGF-2 expression in PRLR KO mice and in PRLR-deficient preadipocytes; ii) induction of cellular IGF-2 expression by PRL through JAK2/STAT5 pathway activation; and iii) reversal of defective differentiation in PRLR KO cells by exogenous IGF-2. CONCLUSIONS: Our findings demonstrate that the lactogens act in concert with IGF-2 to control brown adipocyte differentiation and growth. Given the prominent role of brown adipose tissue during the perinatal period, our results identified prolactin receptor signaling as a major player and a potential therapeutic target in protecting newborn mammals against hypothermia.

Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice.

Morphine induces antinociception by activating mu opioid receptors (muORs) in spinal and supraspinal regions of the CNS. (Beta)arrestin-2 (beta)arr2), a G-protein-coupled receptor-regulating protein, regulates the muOR in vivo. We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. To determine the general applicability of the (beta)arr2-muOR interaction in other neuronal systems, we have, in the present study, tested (beta)arr2 knock-out ((beta)arr2-KO) mice using the warm water tail-immersion paradigm, which primarily assesses spinal reflexes to painful thermal stimuli. In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Interestingly, however, after a delayed onset, they do ultimately develop morphine tolerance, although to a lesser degree than the wild-type (WT) controls. In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. These findings provide in vivo evidence that the muOR is differentially regulated in diverse regions of the CNS. Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent.

Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice.

The reinforcing and psychomotor effects of morphine involve opiate stimulation of the dopaminergic system via activation of mu-opioid receptors (muOR). Both mu-opioid and dopamine receptors are members of the G-protein-coupled receptor (GPCR) family of proteins. GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of beta(arrestins), which prevents further receptor-G-protein coupling. Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. However, whether abrogating muOR desensitization affects the reinforcing and psychomotor properties of morphine has remained unexplored. In the present study, we examined this question by assessing the effects of morphine and cocaine on locomotor activity, behavioral sensitization, conditioned place preference, and striatal dopamine release in beta(arr2) knock-out (beta(arr2)-KO) mice and their wild-type (WT) controls. Cocaine treatment resulted in very similar neurochemical and behavioral responses between the genotypes. However, in the beta(arr2)-KO mice, morphine induced more pronounced increases in striatal extracellular dopamine than in WT mice. Moreover, the rewarding properties of morphine in the conditioned place preference test were greater in the beta(arr2)-KO mice when compared with the WT mice. Thus, beta(arr2) appears to play a more important role in the dopaminergic effects mediated by morphine than those induced by cocaine.

NEGLECTED CELLO REPERTOIRE OF TWENTIETH CENTURY ENGLISH COMPOSERS

In the Twentieth Century, the proliferation of cellists and the exceptional development of cello techniques, combined with composers' acceptance of the challenges by these developments, led many British composers to contribute to the enrichment of the cello concert repertoire. A great number of compositions written for the cello in the Twentieth Century England have been long neglected. In comparison with their other works in the genres of concerto, symphony, and opera, works for cello by prominent Twentieth Century English composers Elgar, Walton, and Britten are relatively unknown, except for Elgar's cello concerto. There are also many lesser-known composers like Delius, Bax, Bridge, and Clarke, who flourished in the fmt half of the century, but eventually became disregarded. Some reasons for this neglect may be as follows: the reluctant attitude toward new trends in the English musical establishment around the turn of the century; a lack of readily available editions of these composers' compositions; an over-abundance of fine composers at one time; and lastly, an overly individualistic approach to the music restricting a general public appreciation and recognition. Encountering a recording of the Walton cello concerto prompted me to further study the neglected Twentieth Century English cello repertoire. Many works of the above-mentioned composers still have not been fully valued in the cello repertoire. For this reason, the purpose of this project was to inspire cellists to learn and broaden as well as to appreciate the beauty of the Twentieth Century cello literature. As part of the doctoral performance project, three recitals featuring the works by six English composers were performed. My collaborator in all three recitals was pianist Eunae KO. The fmt recital included the Sonata for cello and piano by Frank Bridge and the Concerto by William Walton. The second recital was comprised of relatively unknown cello works: Sonatina in D major by Arnold Bax, Romance by Frederick Delius, and the Sonata Op. 40 by Rebecca Clarke. The third recital consisted of Folk-Tale by Arnold Bax and the Symphony for Cello and Orchestra Op. 68 by Benjamin Britten.

TWENTIETH CENTURY VARIATIONS ON BORROWED THEMES

Mergers and acquisitions are words that are usually associated with the modern business world. Such joint efforts toward improvement, however, existed long before our time, in the form of musical partnerships. It was not unusual for composers to share in each other's works, borrowing themes and recreating them to generate new meanings; in the process, new masterpieces were often created. My performance project, Twentieth Century Variations on Borrowed Themes, explores the fruits of such labor. The main objective of this project is to demonstrate how certain composers of the twentieth century have taken famous themes and used them to create variations, imbuing their own creative ideas, musical styles and pianistic challenges. This objective was accomplished by performing three recorded public recitals. These programs consisted of early to late twentieth century pieces that are based on borrowed themes, either in theme and variations form, fantasia form, paraphrase form, or transformal variation form. I have selected the pieces based on their artistic merits and technical challenges, thus allowing me to grow as a pianist and artist. In addition, I wanted to choose some pieces that are rarely performed, as I believe the public delights in hearing unfamiliar gems. The first recital consisted of the music of two legendary pianists: Variations on a Theme of Chopin by Rachmaninoff and Goldberg Variations by BachIBusoni. The second program featured Grand Fantasy on Gershwin's Porgy and Bess by Earl Wild, Sonatina No. 6 (Fantasy on Bizet 's "Carmen") by Busoni, and Rhapsody on a Theme by Paganini, op.43 by Rachmaninoff. Some unusual and seldom-performed pieces, as well as a familiar favorite, were spotlighted in the third recital. The pieces performed on this program were John Rea's Twenty-one Transformal Variations on the "Kindersznen " by Robert Schumann (Las Meninas), Muczynski's Desperate Measures (Paganini Variations), Busoni's Elegie No. 3 (Turandot 's room), and Rhapsodie Espagnole by LisztIBuson. These composers artfully breathed new life into the material borrowed from others, and in the process, the "borrowed" themes became undoubtedly and uniquely their own music.

beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.

The two widely coexpressed isoforms of beta-arrestin (termed beta arrestin 1 and 2) are highly similar in amino acid sequence. The beta-arrestins bind phosphorylated heptahelical receptors to desensitize and target them to clathrin-coated pits for endocytosis. To better define differences in the roles of beta-arrestin 1 and 2, we prepared mouse embryonic fibroblasts from knockout mice that lack one of the beta-arrestins (beta arr1-KO and beta arr2-KO) or both (beta arr1/2-KO), as well as their wild-type (WT) littermate controls. These cells were analyzed for their ability to support desensitization and sequestration of the beta(2)-adrenergic receptor (beta(2)-AR) and the angiotensin II type 1A receptor (AT(1A)-R). Both beta arr1-KO and beta arr2-KO cells showed similar impairment in agonist-stimulated beta(2)-AR and AT(1A)-R desensitization, when compared with their WT control cells, and the beta arr1/2-KO cells were even further impaired. Sequestration of the beta(2)-AR in the beta arr2-KO cells was compromised significantly (87% reduction), whereas in the beta arr1-KO cells it was not. Agonist-stimulated internalization of the AT(1A)-R was only slightly reduced in the beta arr1-KO but was unaffected in the beta arr2-KO cells. In the beta arr1/2-KO cells, the sequestration of both receptors was dramatically reduced. Comparison of the ability of the two beta-arrestins to sequester the beta(2)-AR revealed beta-arrestin 2 to be 100-fold more potent than beta-arrestin 1. Down-regulation of the beta(2)-AR was also prevented in the beta arr1/2-KO cells, whereas no change was observed in the single knockout cells. These findings suggest that sequestration of various heptahelical receptors is regulated differently by the two beta-arrestins, whereas both isoforms are capable of supporting receptor desensitization and down-regulation.