11 research outputs found

    Management-Employee Buyouts in Hungary and Poland

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    This paper is part of a project whic began in December 1994 and consists of research focusing on legal and institutional aspects of privatization as well as the courses and outcomes of privatization processes under way in the countries of Central and Eastern Europe. The specific issue this paper focuses on is management-employee buyouts in Hungary and Poland.management-employee buyouts, transition, Poland, Hungary

    Efficiency of different marker systems for genotype fingerprinting and for genetic diversity studies in barley (Hordeum vulgare L.)

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    AbstractGenetic relationships between 38 barley genotypes were determined with the aid of 36 RAPD, 54 STS and 26 SSR markers. The dendrogram groups showed high coincidence with growth habit and ear type. There were significant correlations between the Jaccard coefficients obtained using the matrices of each single marker type and their combined matrix. When the varieties were grouped using markers with above-average Polymorphic Information Content (PIC) values, the same groups were obtained as when using all markers, outlining their usefulness for estimating diversity between the varieties. Three RAPD or four SSR primers were sufficient to distinguish all the barley varieties from each other. The applicability of the various types of primers differed. The STS markers could best be used for estimating relationships between the varieties and the SSR markers for distinguishing genotypes from each other, while RAPD markers could be employed both for estimating the relationships between varieties and for variety identification

    Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

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    Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/ results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. Lay abstract: Head and neck cancers often have a poor treatment outcome. In order to study the response of the tissue, a miniaturized culture system has been developed to keep a small piece of tumor alive. In the current study, we show that small pieces of cancer tissue can be maintained in the system, using tissue structure and viability of single cells as a guide. In future work, patient equivalent treatments can be applied to these microculture systems to investigate individual patient tumor responses, which could help to guide treatment selection

    A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform

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    © 2019 The Author(s). Background: Though the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or 'precision' medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies. Methods: Human thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 μm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting). Results: Maintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p < 0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated on-chip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period. Conclusions: The described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time

    The Use of Tissue-on-Chip Technology to Focus the Search for Extracellular Vesicle miRNA Biomarkers in Thyroid Disease

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    Citation: Haigh, T.; Beattie, H.; Wade, M.A.; England, J.; Kuvshinov, D.; Karsai, L.; Greenman, J.; Green, V. The Use of Tissue-on-Chip Technology to Focus the Search for Extracellular Vesicle miRNA Biomarkers in Thyroid Disease. Int. J. Mol. Sci. 2024, 25, 71. Abstract: Small extracellular vesicles (sEVs) contain microRNAs (miRNAs

    Lack of cyclophilin D protects against the development of acute lung injury in endotoxemia.

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    Sepsis caused by LPS is characterized by an intense systemic inflammatory response affecting the lungs, causing acute lung injury (ALI). Dysfunction of mitochondria and the role of reactive oxygen (ROS) and nitrogen species produced by mitochondria have already been proposed in the pathogenesis of sepsis; however, the exact molecular mechanism is poorly understood. Oxidative stress induces cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT), leading to organ failure in sepsis. In previous studies mPT was inhibited by cyclosporine A which, beside CypD, inhibits cyclophilin A, B, C and calcineurin, regulating cell death and inflammatory pathways. The immunomodulatory side effects of cyclosporine A make it unfavorable in inflammatory model systems. To avoid these uncertainties in the molecular mechanism, we studied endotoxemia-induced ALI in CypD-/- mice providing unambiguous data for the pathological role of CypD-dependent mPT in ALI. Our key finding is that the loss of this essential protein improves survival rate and it can intensely ameliorate endotoxin-induced lung injury through attenuated proinflammatory cytokine release, down-regulation of redox sensitive cellular pathways such as MAPKs, Akt, and NF-kappaB and reducing the production of ROS. Functional inhibition of NF-kappaB was confirmed by decreased expression of NF-kappaB-mediated proinflammatory genes. We demonstrated that impaired mPT due to the lack of CypD reduces the severity of endotoxemia-induced lung injury suggesting that CypD specific inhibitors might have a great therapeutic potential in sepsis-induced organ failure. Our data highlight a previously unknown regulatory function of mitochondria during inflammatory response

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    Interview with Laszlo Karsai - January 10, 2016

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    Interview Themes: 0:41 Family origins, Elek Karsai (b. 1922), Holocaust, survival of father in Buda in 1944; 2:00 Holocaust in family history; 3:20 1983 – Starts research on Hungarian Gypsy Holocaust; 5:00 Elek Karsai’s Holocaust stories, his work on Szálasi’s trial; 7:00 Ph.D. dissertation on the nationality question and Marxism, criticizes Marx and Engels; 8:00 1978-79: his paper published in Magyar Filozófiai Szemle, identifies as a right-wing dissident at Szeged University; 10:00 Publications on the Holocaust; 11:00 Elek Karsai’s political trajectory, 1940s, finished rabbinical seminary, then became social democrat, then communist; starts his career as sociology professor around Sándor Szalai; After Szalai’s conviction he works as an archivist at the National Archives; 15:00 Father rejoins the communist party in the early 1960s; 16:00 Karsai’s articles in Beszélő in 1980s, in which he criticized Tamás Krausz and László Béládi; 20:00 Parallels between the leftist and liberal generations of intellectuals that came of age in 1945 and 1989: missed opportunities and the experience of having “screwed up”; 22:00 Elek Karsai's documentary book on 1944/1945 Sorsforduló, protest by Czechoslovak embassy, book triggered political scandal, Soviet communist party initiates censorship of L. K.; 24:00 Elek Karsai nominated as director of Trade Union Archive; 28:00 Sociology as a discipline in late 1940s, József Szigeti, István Király; 34:00 Fear as a defining experience of his father; 35:00 László Karsai’s mother and grandmother, Emma Lederer; 40:00 Grandmother and politics, Mihály Babits, Antonio Widmar, László Hárs; 44:00 Political convictions of the women in his family; Mother worked at the Hungarian Television, travel to Cannes; 49:00 Reading complete works of Marx and Engels; 51:00 1956 Revolution as taboo, disillusionment with communism in late 1950s; 56:00 Elek Karsai’s radio show; 58:00 Protest of Hungarian writers at the UN; 1:00:00 Exposure to anti-Communist literature in Paris in early 1980s, 1956 literature; 1:03:00 1956 Revolution, Tibor Méray – Tamás Aczél, Tisztító vihar; 1:07:00 Expulsion from Szeged University; 1:12:00 History and historiography of the Holocaust; 1:16:00 Historian as public intellectual in Hungary; 1:17:00 Mistakes of the generation of 1989, Viktor Orbán, similar to Franz Joseph and János Kádár as “father figure” for Hungarians, corruption; 1:22:00 The crisis of liberal democracy; 1:28:00 Hungarian Jews and the migrant crisis, György Konrád, Hungarian Jews and politics after 1989; 1:33:00 Migrant crisis, Muslim minorities from North Africa and the Middle EastInterview with László Karsai, Professor of History at Szeged University in Hungary. The interview was conducted in Budapest, Hungary on January 10, 2016. László Karsai specializes in the history of the Holocaust and anti-Semitism in Hungary. He has also written on the nationality question in France and on the Gypsy Holocaust in Hungary. His publications include: A cigánykérdés Magyarországon 1919-1945. Út a cigány Holocausthoz [The Gypsy Question in Hungary 1919-1945. Toward the Gypsy Holocaust] (1992), as well as with many works, including a book on the nationalities question in Belgium (Flamandok és vallonok, 1986), and a biography of the Hungarian Arrow Cross leader, Ferenc Szálasi (Szálasi Ferenc - Politikai életrajz, 2016). He also compiled and edited two extensive volumes of primary sources: one of anti-Semitic writings and another of writings against anti-Semitism in Hungary. Special thanks to Máté Rigó, Cornell University Ph.D. student, for preparing an inventory of the interview.1_ynrpj3a

    Recent Advances in Multi-paradigm Modeling

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    Model-Based Design of complex software systems is an activity that requires the use of different modeling formalisms, with different perspectives of the system, to cover all relevant aspects of the system, to avoid over-design, to employ manageable models and to support system integration. The comprehensive use of models in design has created a set of challenges beyond those of supporting one isolated design task. In particular, the need to combine, couple, and integrate models at different levels of abstraction and in different formalisms is posing a set of specific problems that must be tackled. Multi-Paradigm Modeling is precisely the research field to focus on developing an appropriate set of concepts and tools to address the challenge of integrating models of different aspects of a software system specified using different formalisms and eventually at different levels of abstraction. This paper summarizes the results of the 3rd Workshop on Multi-Paradigm Modeling: Concepts and Tools. Fulltext Previe
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