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Search Results: 1 - 10 of 220 matches for " Gottfried Konecny "
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Amplification Target ADRM1: Role as an Oncogene and Therapeutic Target for Ovarian Cancer
Marlena S. Fejzo,Lee Anderson,Erika M. von Euw,Ondrej Kalous,Nuraly K. Avliyakulov,Michael J. Haykinson,Gottfried E. Konecny,Richard S. Finn,Dennis J. Slamon
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms14023094
Abstract: Approximately 25,000 ovarian cancers are diagnosed in the U.S. annually, and 75% are in the advanced stage and largely incurable. There is critical need for early detection tools and novel treatments. Proteasomal ubiquitin receptor ADRM1 is a protein that is encoded by the ADRM1 gene. Recently, we showed that among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification and was significantly upregulated with respect to stage, recurrence, and metastasis. Its overexpression correlated significantly with shorter time to recurrence and overall survival. Array-CGH and microarray expression of ovarian cancer cell lines provided evidence consistent with primary tumor data that ADRM1 is a 20q13 amplification target. Herein, we confirm the ADRM1 amplicon in a second ovarian cancer cohort and define a minimally amplified region of 262 KB encompassing seven genes. Additionally, using RNAi knock-down of ADRM1 in naturally amplified cell line OAW42 and overexpression of ADRM1 via transfection in ES2, we show that (1) ADRM1 overexpression increases proliferation, migration, and growth in soft agar, and (2) knock-down of ADRM1 results in apoptosis. Proteomic analysis of cells with ADRM1 knock-down reveals dysregulation of proteins including CDK-activating kinase assembly factor MAT1. Taken together, the results indicate that amplified ADRM1 is involved in cell proliferation, migration and survival in ovarian cancer cells, supporting a role as an oncogene and novel therapeutic target for ovarian cancer.
Relational Verification of Programs with Integer Data
Filip Konecny
Information Sciences and Technologies Bulletin of the ACM Slovakia , 2013,
Abstract: This work presents novel methods for verication of reachabilityand termination properties of programs that manipulateunbounded integer data. Most of these methodsare based on acceleration techniques which compute transitiveclosures of program loops.Firtly, we present an algorithm that accelerates severalclasses of integer relations and show that the new methodperforms up to four orders of magnitude better than theprevious ones. On the theoretical side, our frameworkprovides a common solution to the acceleration problemby proving that the considered classes of relations are periodic.Subsequently, we introduce a semi-algorithmic reachabilityanalysis technique that tracks relations between variablesof integer programs and applies the proposed accelerationalgorithm to compute summaries of proceduresin a modular way. Next, we present an alternative approachto reachability analysis that integrates predicateabstraction with our acceleration techniques to increasethe likelihood of convergence of the algorithm. We evaluatethese algorithms and show that they can handlea number of complex integer programs where previousapproaches failed.Finally, we study the termination problem for severalclasses of program loops and show that it is decidable.Moreover, for some of these classes, we design a polynomialtime algorithm that computes the exact set ofprogram congurations from which non-terminating runsexist. We further integrate this algorithm into a semialgorithmicmethod that analyzes termination of integer programs, and show that the resulting technique can verifytermination properties of several non-trivial integerprograms.
PTIME Computation of Transitive Closures of Octagonal Relations
Filip Konecny
Computer Science , 2014,
Abstract: Computing transitive closures of integer relations is the key to finding precise invariants of integer programs. In this paper, we study difference bounds and octagonal relations and prove that their transitive closure is a PTIME-computable formula in the existential fragment of Presburger arithmetic. This result marks a significant complexity improvement, as the known algorithms have EXPTIME worst case complexity.
Inherited trombophilic states and pulmonary embolism
Filip A. Konecny
Journal of Research in Medical Sciences , 2009,
Abstract: Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital-associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short. In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention. KEYWORDS: Inherited thrombophilic states, venous thromboembolism, pulmonary embolism.
Massive pulmonary embolism: the predisposing and complicating factors, its current diagnostic approaches and critical importance of early diagnostic physical exam
Filip A. Konecny
Journal of Research in Medical Sciences , 2006,
Abstract: Massive pulmonary embolism (MPE) often leads to circulation collapse, a form of shock. The process is set off by thrombus or multiple thrombi dislodgement followed by a rapid perfusion insufficiency of pulmonary arterial system. Patients experience severe hypotension with diastolic and systolic failure with an acute tricuspid regurgitation. On many occasions, release of an obstruction is unattainable and death is occurring frequently within one hour of presentation. A key reported source of MPE is its occurrence as a complication of deep vein thrombosis (DVT). While long-term immobilization and surgery are both directly associated with MPE, others such as previous DVT, malignancy, infectious lung and heart diseases, family thrombophilia, lower limb paralysis and pregnancy have to be considered as risk factors mainly due to its silent nature. Predisposing and complicating risks should be addressed by an early diagnostic physical exam. The clinician might offer a wide variety of diagnostic approaches, combining techniques into algorithms to better deal with the embolism severity. Multiple patient life-style changes and decisions to adhere to the proposed plan should be built up on patient-physician team effort. KEY WORDS: Massive pulmonary embolism, predisposing factors, current diagnostic approaches.
Pulmonary Embolism and vascular injury: What is the role of thrombin?
Filip A Konecny
Journal of Research in Medical Sciences , 2007,
A model of massive pulmonary embolism, development and characterization The pre-clinical steps forward and details of the progress
Filip A. Konecny
Journal of Research in Medical Sciences , 2008,
Abstract: BACKGROUND: Massive pulmonary embolism (MPE) is in most cases an unpredictable, life-threatening lung injury. In order to test this shock and its natural sequence, MPE animal model was established. Based on previous models, discussed within the article framework, this model was designed to closely narrate clinical pulmonary embolism. METHODS: MPE was induced by a single injection of minced radioactive blood thrombi into an internal jugular vein. Thrombi were prepared from the autologous blood of each animal. Using rabbit model allowed sampling and recording additional data necessary for better analysis. Clotting additives were used for rapid clot stabilization. Clot was stabilized at room temperature for one hour and separated into micro-emboli of comparable size prior to the intravenous injection. A radioactive tracer, I-125 labeled rabbit fibrinogen, was added into thrombi to measure dynamic lung thrombiturnover. RESULTS: Thrombolysis dynamic efficacy was characterized by presence of high statistical significant difference (P < 0.001) found between released radioactive I-125 fibrin degradation products (FDPs) at 10 minutes and all others FDP time points until 60 minutes. Pulmonary thrombolysis was characterized by measuring residual radioactivity of the lungs at 10 and 60 minutes and was found statistically significant (P < 0.05) during the period of 50 minutes. For the purpose of model validation, systemic blood pressure, measured in carotid artery, significantly increased from the baseline point 47 mmHg to 80 mmHg at the first 10 minutes. Enormous mechanical thrombus injury of lung vasculature was depicted by MSB staining. CONCLUSIONS: This MPE model contains a set of important and original patho-physiological data mimicking the fundamental characteristics of this shock situation in humans, which enhances the understanding of MPE, and leads to better characterization of this critical clinical condition. KEYWORDS: Massive pulmonary embolism, animal model, thrombolysis dynamic efficacy.
Complete relations on fuzzy complete lattices
Jan Konecny,Michal Krupka
Computer Science , 2015,
Abstract: We generalize the notion of complete binary relation on complete lattice to residuated lattice valued ordered sets and show its properties. Then we focus on complete fuzzy tolerances on fuzzy complete lattices and prove they are in one-to-one correspondence with extensive isotone Galois connections. Finally, we prove that fuzzy complete lattice, factorized by a complete fuzzy tolerance, is again a fuzzy complete lattice.
Plummer-Vinson syndrome
Gottfried Novacek
Orphanet Journal of Rare Diseases , 2006, DOI: 10.1186/1750-1172-1-36
Abstract: Plummer-Vinson syndrome, PVSPaterson-Kelly syndromePaterson-Brown Kelly syndromeSideropenic dysphagiaPlummer-Vinson syndrome is defined by the classic triad of dysphagia, iron-deficiency anemia and esophageal webs. Even though the syndrome is very rare nowadays, its recognition is important because it identifies a group of patients at increased risk of squamous cell carcinoma of the pharynx and the esophagus.The syndrome eponym has been frequently discussed [1,2]. The most used name is Plummer-Vinson syndrome, named after Henry Stanley Plummer (1874–1936) and Porter Paisley Vinson (1890–1959) who were physicians on the staff of the Mayo Clinic. In 1912, Plummer reported a series of patients with long-standing iron deficiency anemia, dysphagia and spasm of the upper esophagus without anatomic stenosis, which was described as hysterical [3]. In 1919 Vinson reported another case of 'angulation' of the esophagus and attributed the first description of this entity to the earlier report of Plummer [4]. Some years later he published a series of patients with dysphagia who were successfully treated with the passage of bougies; most of the patients were women [5].Another term is Paterson-Kelly syndrome, named after Donald Ross Paterson (1863–1939) and Adam Brown-Kelly (1865–1941), both British laryngologists, who published their findings independently in 1919 [6,7]. They were the first to describe the characteristic clinical features of the syndrome. Paterson gave the fullest description but without reference to anemia. He was also the first to draw attention to an association with post-cricoid carcinoma. Brown-Kelly not only described the signs and symptoms of the condition, but also considered anemia.Exact data about incidence and prevalence of the syndrome are not available. In the first half of the 20th century Plummer-Vinson syndrome seemed to be common in Caucasians of Northern countries, particularly among middle-aged women [8]. Nowadays, it is extremely rare. In a se
Continental USA Travel Tracks
Gottfried Hogh
Solstice : Electronic Journal of Geography and Mathematics , 2004,
Abstract: The link to the fulltext on a current website is given below. Should that link fail to work, please go to this persistent URL and download the associated file for this issue. http://deepblue.lib.umich.edu/handle/2027.42/58219While you are there, take a look around and see if there are other issues and documents that are related to your interests!
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