Upnp-Based Discovery And Management Of Hypervisors And Virtual Machines

The paper introduces a Universal Plug and Play based discovery and management toolkitthat facilitates collaboration between cloud infrastructure providers and users. The presentedtools construct a unified hierarchy of devices and their management-related services, thatrepresents the current deployment of users’ (virtual) infrastructures in the provider’s (physical)infrastructure as well as the management interfaces of respective devices. The hierarchycan be used to enhance the capabilities of the provider’s infrastructure management system.To maintain user independence, the set of management operations exposed by a particulardevice is always defined by the device owner (either the provider or user)

Low-basicity 5-HT7 receptor agonists synthesized using the van Leusen multicomponent protocol

A series of 5-aryl-1-alkylimidazole derivatives was synthesized using the van Leusen multicomponent reaction. The chemotype is the first example of low-basicity scaffolds exhibiting high affinity for 5-HT7 receptor together with agonist function. The chosen lead compounds 3-(1-ethyl-1H-imidazol-5-yl)-5- iodo-1H-indole (AGH-107, 1o, Ki 5-HT7=6nM, EC50=19nM, 176-fold selectivity over 5-HT1AR) and 1e (5-methoxy analogue, Ki 5-HT7=30nM, EC50=60nM) exhibited high selectivity over related CNS targets, high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures. A rapid absorption to the blood, high blood-brain barrier permeation and a very high peak concentration in the brain (Cmax=2723 ng/g) were found for 1o after i.p. (5mg/kg) administration in mice. The compound was found active in novel object recognition test in mice, at 0.5, 1 and 5mg/kg. Docking to 5-HT7R homology models indicated a plausible binding mode which explain the unusually high selectivity over the related CNS targets. Halogen bond formation between the most potent derivatives and the receptor is consistent with both the docking results and SAR. 5-Chlorine, bromine and iodine substitution resulted in a 13, 27 and 89-fold increase in binding affinities, respectively, and in enhanced 5-HT1AR selectivity

Edukuje i promuje : Festiwal Sacrum Profanum świetnie odgrywa swą rolę

Gazeta Wyborcza. - 2012, nr 218 (18 IX), dod. Kraków, s.

Muzeum PRL-u czy Nowej Huty?

Gazeta Wyborcza. - 2011, nr 29 (5-6 II), dod. Kraków, s.

Stężenie VEGF-A, sVEGFR-2 i galektyny-3 w surowicy pacjentek z rakiem piersi nie koreluje ze stopniem zaawansowania klinicznego, wielkością guza ani skutecznością chemioterapii okołooperacyjnej

INTRODUCTION: Tumor angiogenesis is regulated by numerous cytokines and growth factors, with vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR-2), and galectin-3, playing a significant role in the process. There are conflicting data concerning changes in serum VEGF, sVEGFR-2 and galectin-3 levels in breast cancer (BC) patients during the course of the disease and chemotherapy (CTH). This study aimed to assess the serum levels of VEGF-A, sVEGFR-2, and galectin-3 in women starting adjuvant and neoadjuvant therapy for BC, and their changes during the treatment. MATERIAL AND METHODS: This single-center study enrolled 98 women with non-metastatic BC, including 56 who started adjuvant therapy and 42 preoperative (neoadjuvant/induction) CTH. The serum levels of VEGF-A, sVEGFR-2, and galectin-3 were assessed at the beginning of CTH and after 2 subsequent months. RESULTS: There were no significant differences in the serum levels of VEGF-A, sVEGFR-2, and galectin-3 between patients starting adjuvant and preoperative therapy. In addition, there was no correlation between the serum levels and the clinical stage of BC. During CTH, a significant increase in VEGF-A, sVEGFR-2, and galectin-3 was noted, however, without a predictive significance for obtaining complete pathological response (pCR) both for the initial levels and changes in the serum levels. CONCLUSIONS: The serum levels of VEGF-A, sVEGFR-2, and galectin-3 do not correlate with the clinical stage or tumor size in patients with non-metastatic BC. The baseline levels of VEGF-A, sVEGFR-2 and galectin-3, and the observed increase in the serum levels of VEGF-A and sVEGFR-2 during CTH do not predict its efficacy.WSTĘP: Angiogeneza nowotworowa jest procesem regulowanym przez wiele cytokin i czynników wzrostu, spośród których znaczącą rolę odgrywają czynnik wzrostu śródbłonka naczyń (vascular endothelial growth factor – VEGF), drugi rozpuszczalny receptor dla śródbłonkowego czynnika wzrostu (soluble vascular endothelial growth factor recep-tor 2 – sVEGFR-2) i galektyna-3. Dane literaturowe dotyczące oceny zmian stężenia VEGF, sVEGFR-2 oraz galekty-ny-3 w trakcie chemioterapii (chemotherapy – CTH) raka piersi (breast cancer – BC) są niejednoznaczne. Celem niniej-szej pracy była analiza stężenia VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy pacjentek z rakiem piersi, rozpoczynających adjuwantową i neoadjuwantową chemioterapię oraz ocena zmian stężenia tych cytokin w trakcie leczenia. MATERIAŁ I METODY: Jednoośrodkowe badanie objęło 98 pacjentek z miejscowo zaawansowanym rakiem piersi, w tym 56 poddanych adjuwantowej i 42 neoadjuwantowej terapii. Stężenie VEGF-A, sVEGFR-2 i galektyny-3 w surowicy krwi oceniono na początku leczenia oraz po 2 miesiącach terapii. WYNIKI: Nie stwierdzono istotnych różnic pomiędzy stężeniami VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy pacjentek poddanych adjuwantowej i neoadjuwantowej chemioterapii. Nie wykazano również zależności między stężeniem tych cytokin w surowicy a stopniem zaawansowania klinicznego raka piersi. W trakcie przedoperacyjnej chemio-terapii odnotowano znaczące zwiększenie stężenia VEGF-A, sVEGFR-2 i galektyny-3, jednakże zarówno wyjściowe stężenia cytokin, jak i zmiany w czasie nie miały znaczenia predykcyjnego dla uzyskania całkowitej odpowiedzi pato-ogicznej. WNIOSKI: Stężenia VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy nie korelują ze stopniem zaawansowania klinicznego ani masą nowotworu u pacjentek z miejscowo zaawansowanym rakiem piersi. Wyjściowe stężenia VEGF-A, sVEGFR-2 i galektyny-3 oraz zaobserwowany wzrost stężeń tych cytokin w surowicy w trakcie chemioterapii nie mają wartości predykcyjnej dla jej skuteczności

Laparoscopic Living Donor Nephrectomy—Single-Center Initial Experience

(1) Background: Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total laparoscopic approach offers decreased postoperative pain, less incisional morbidity, and a shorter recovery time. (2) Methods: We present the results of a series of 43 laparoscopic donor nephrectomies performed in a single center. The procedures were performed in a systematic approach with transperitoneal access using four ports. The main renal artery and vein were ligated using a linear stapler fixed with an alternate triple row of titanium staples. The specimen was extracted in an endoscopic bag through an additional incision. (3) Results: All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.73 min. In all recipients, immediate kidney allograft function was observed. (4) Conclusions: Total laparoscopic living donor nephrectomy is a safe procedure. It was performed successfully in all cases with a short surgical time, low morbidity, and 0% mortality

Laparoscopic Living Donor Nephrectomy—Single-Center Initial Experience

(1) Background: Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total laparoscopic approach offers decreased postoperative pain, less incisional morbidity, and a shorter recovery time. (2) Methods: We present the results of a series of 43 laparoscopic donor nephrectomies performed in a single center. The procedures were performed in a systematic approach with transperitoneal access using four ports. The main renal artery and vein were ligated using a linear stapler fixed with an alternate triple row of titanium staples. The specimen was extracted in an endoscopic bag through an additional incision. (3) Results: All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.73 min. In all recipients, immediate kidney allograft function was observed. (4) Conclusions: Total laparoscopic living donor nephrectomy is a safe procedure. It was performed successfully in all cases with a short surgical time, low morbidity, and 0% mortality

N-skatyltryptamines - dual 5-HT6R/D2R ligands with antipsychotic and procognitive potential

A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT(1A), 5-HT(2A), 5-HT(6), and D(2) receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D(2) receptor antagonists with additional 5-HT(6)R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT(6)R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT(6)R agonists was more ambiguous—in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D(2)R antagonist function combined with 5-HT(6)R agonism, and mixed D(2)/5-HT(6)R antagonists in murine models of psychosis

Funnel metadynamics and behavioral studies reveal complex effect of D2AAK1 ligand on anxiety-like processes

Anxiety is a troublesome symptom for many patients, especially those suffering from schizophrenia. Its regulation involves serotonin receptors, targeted e.g. by antipsychotics or psychedelics such as LSD. 5-HT(2A) receptors are known for an extremely long LSD residence time, enabling minute doses to exert a long-lasting effect. In this work, we explore the changes in anxiety-like processes induced by the previously reported antipsychotic, D2AAK1. In vivo studies revealed that the effect of D2AAK1 on the anxiety is mediated through serotonin 5-HT(1A) and 5-HT(2A) receptors, and that it is time-dependent (anxiogenic after 30 min, anxiolytic after 60 min) and dose-dependent. The funnel metadynamics simulations suggest complicated ligand-5HT(2A)R interactions, involving an allosteric site located under the third extracellular loop, which is a possible explanation of the time-dependency. The binding of D2AAK1 at the allosteric site results in a broader opening of the extracellular receptor entry, possibly altering the binding kinetics of orthosteric ligands