Основні проблеми розвитку українського газового ринку на сучасному етапі

Successful implementation of an enterprise strategy, the reorganization of an enterprise, the successful enterprise-wide adoption of a new enterprise resource planning system, or simply being able to manage the daily operations at an enterprise in general are all common examples of organizational actions that are strongly interrelated with the achievement of goals related to these actions. From the research as presented in this paper, it becomes clear that it is not elementary to clearly formulate goals and to understand how to achieve them. In two use scenarios, it is described how the executive board of a mid-sized bank in Germany wants to achieve their overall goal to increase the bank appraisal. The first scenario deals with determining who is responsible for goal creation and accomplishment, while the second scenario deals with describing a concrete goal system. A domain-specific modelling language (DSML) for designing goal models is proposed that provides solutions for requirements that are derived from the described scenarios. This DSML is coined the ‘goal modelling language’ (GoalML), which enables the development of goal models from multiple perspectives in order to relate goals with their context and vice versa

Depression and Personality: The Impact of Personality Dysfunction on Quality and Severity of Depressive Symptoms and the moderating Role of Culture

Background: This dissertation project aims to help clarify to what extent – and under which circumstances – different forms of personality dysfunction affect the clinical presentation and severity of depression. Borderline Personality Disorder (BPD) is counted among the most severe forms of personality pathology (Hooley, Cole, & Gironde, 2012). Furthermore, there is literature describing distinct characteristics of depression experience in BPD patients (see Silk, 2010). Nevertheless, several issues with regard to “borderline-depression” remain unclear. In addition, Klein and colleagues (2009) suggested that future research should identify moderators of the personality-mood relationship. Hence, another focus of this project lies on the degree to which the relationship between personality and depression varies by cultural context. Methods: The first study provides a systematic review of depression quality, and a meta-analysis of depression severity in BPD patients compared to those with depressive disorders (DeDs). Based on a systematic literature search, 26 studies were identified for systematic review and 35 studies were included for meta-analysis. The review focused on different forms of depressive symptoms, affective impairment, self-evaluation, and negative interpersonal experiences. Besides overall group differences, the meta-analysis also examined different potential moderators of effect sizes. The second study employs ambulatory assessment methodology to explore affective instability and reactivity in 20 patients with major depressive disorder and BPD (MDD+BPD-group), and 21 patients with depression only (MDD-group). Participants reported on current affect, daily events, and attribution of affective states to events five times per day over a seven-day period. Study three compares the implications of personality dysfunction for depression severity in Chile and Germany. 30 Chilean and 30 German women matched for age and depression severity completed the Self-Construal Scale, Center for Epidemiological Studies Depression Scale, Depressive Experiences Questionnaire, and an inventory assessing overall personality functioning (OPD-Structure Questionnaire). Results: Findings of study one indicate that depression quality in BPD is characterized by higher anger/hostility and self-criticism. There was no difference in depression severity between BPD and DeD groups, and a high level of heterogeneity. Moderator analyses revealed lower depression severity in BPD patients without comorbid DeDs, but higher severity in BPD patients with comorbid DeDs compared to depressed controls. Results of study two do not indicate higher affective instability in the MDD+BPD-group. Depressed patients with BPD reported less subjectively perceived affective reactivity, while actual associations between events and affect were not different between groups, except for one finding: In MDD+BPD patients, overall mood was lower after being alone. In study three, culture moderated the relationship between dependency and depression, with higher dependency predicting higher depression in German but not in Chilean women. Self-criticism and impaired personality functioning were positively related to depression in both countries. Discussion: Results suggest high variability in depression severity across BPD patients, point toward the consideration of comorbid DeDs, and lend partial support to a BPD-specific depression quality. Furthermore, findings from ambulatory assessment question affective instability and suggest impaired attribution of mood changes and less tolerance of being alone as specific for depression in BPD. The intercultural comparison indicates that the adaptiveness of dependency seems to vary across cultures, while the implications of negative self-evaluation and broader concepts of personality dysfunction might be more universal. Main limitations of the current project lie in small sample sizes (studies two and three) and the cross-sectional research designs of studies one and three

Status epilepticus enhances depotentiation after fully established LTP in an NMDAR-Dependent but GluN2B-independent manner

N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here,we testedwhether LFS-inducedDP is also altered in pathologicalGluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit-specific blocker Ro 25-6981 (1 M) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor-dependence, we applied the NMDA receptor antagonist D-AP5 (50 M) prior to LFS and observed that DPwas abolished in both control and post- SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS-DP clearly requiredNMDA receptor activation, GluN2B-containingNMDA receptors were not involved in this formof depotentiatio

Status epilepticus enhances depotentiation after fully established LTP in an NMDAR-Dependent but GluN2B-independent manner

N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here,we testedwhether LFS-inducedDP is also altered in pathologicalGluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit-specific blocker Ro 25-6981 (1 M) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor-dependence, we applied the NMDA receptor antagonist D-AP5 (50 M) prior to LFS and observed that DPwas abolished in both control and post- SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS-DP clearly requiredNMDA receptor activation, GluN2B-containingNMDA receptors were not involved in this formof depotentiatio

Deep brain stimulation for movement disorder treatment: Exploring frequency-dependent efficacy in a computational network model

A large scale computational model of the basal ganglia (BG) network is proposed to describes movement disorder including deep brain stimulation (DBS). The model of this complex network considers four areas of the basal ganglia network: the subthalamic nucleus (STN) as target area of DBS, globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus (THA). Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities can be derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities switch from normal conditions to parkinsonian. Simulating DBS on the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.Comment: 40 pages, 16 figure

NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-termpotentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-primingwas diminishedwhen applied in the presence of themetabotropic glutamate receptor antagonists (RS)- -methylserine-O-phosphate (MSOP) and (RS)--methyl-4-carboxyphenylglycine (MCPG).Moreover,whenHFMSwas delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 M), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity

NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-termpotentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-primingwas diminishedwhen applied in the presence of themetabotropic glutamate receptor antagonists (RS)- -methylserine-O-phosphate (MSOP) and (RS)--methyl-4-carboxyphenylglycine (MCPG).Moreover,whenHFMSwas delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 M), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity

Characterization of defined sulfated heparin-like oligosaccharides by electrospray ionization ion trap mass spectrometry

Glycosaminoglycans (GAG) as long, unbranched polysaccharides are major components of the extracellular matrix. Many studies provided additional evidence of a specific binding between mediators and sulfated GAG, at which the sulfation code-which means the number and positions of sulfate groups along the polysaccharide chain-plays an important role. GAG from natural sources are very inhomogeneous regarding their sulfation patterns and molecular weight. Additionally, there is a high risk of contamination. This results in a growing interest in the careful characterization of native GAG and the synthesis of artificial GAG. Additionally, chemically oversulfated GAG analogues show many favorable properties. However, the structural characterization of these carbohydrates by mass spectrometry remains challenging. One significant problem is the sulfate loss during the ionization, which increases with the number of sulfate residues. We used the sulfated pentasaccharide fondaparinux as model substance to optimize sample preparation and measurement conditions, compared different established desalination methods and already existing protocols for sulfated oligosaccharides, and investigated their impact on the quality of the mass spectra. After optimization of the measurement conditions, we could establish a gentle and fast protocol for the mass spectrometry characterization of (fully) sulfated, artificial GAG-like oligosaccharides with minimized sulfate loss in the positive and negative ion mode. Here, the negative ion mode was more sensitive in comparison with the positive one, and fondaparinux species with sulfate loss were not detectable under the optimized conditions in the positive ion mode

The microbiota and autoimmunity: their role in thyroid autoimmune diseases

Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject

Possible Consequences for TGF-β1 Signaling

Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet. Examining the interaction of all components of the TGF-β1:receptor complex with sHA by surface plasmon resonance, we could show that highly sulfated HA (sHA3) blocks binding of TGF-β1 to its TGF-β receptor-I (TβR-I) and -II (TβR-II). However, sequential addition of sHA3 to the TβR-II/TGF-β1 complex led to a significantly stronger recruitment of TβR-I compared to a complex lacking sHA3, indicating that the order of binding events is very important. Molecular modeling suggested a possible molecular mechanism in which sHA3 could potentially favor the association of TβR-I when added sequentially. For the first time bioactivity of TGF-β1 in conjunction with sHA was investigated at the receptor level. TβR-I and, furthermore, Smad2 phosphorylation were decreased in the presence of sHA3 indicating the formation of an inactive signaling complex. The results contribute to an improved understanding of the interference of sHA3 with TGF-β1:receptor complex formation and will help to further improve the design of functional biomaterials that interfere with TGF-β1-driven skin fibrosis