C-H aktivace deazapurinovych heterocyklu

Direct C-H borylations of 7-deazapurines (7H-pyrrolo[2,3-d]pyrimidine) were developed at position 8 using B2pin2 and Ir catalysis. The obtained boronates were efficiently applied in the Suzuki cross-couplings with aryl halides and other functional group transformations to give diverse 6-substituted 8-aryl-7-deazapurine derivatives. Furthermore, I was also interested in the synthesis of biologically relevant 8-aryl-7- deazaadenines and -7-deazahypoxanthines. As the direct C-H borylation of 7- deazaadenines was unsuccessful and the borylation/Suzuki reaction of 6-chloro-7- deazapurine gave only low yield (20%) of the desired 8-aryl derivative, I focused on the one-pot borylation/arylation of SEM-protected 6-methylsulfanyl- or 6-methoxy-7- deazapurines. The one-pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine base, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were successfully converted to 8-halo- or 8-trifluoromethyl-7- deazapurine derivatives. While the 7-deazahypoxantine analogues were almost entirely inactive, most of the 8-subtituted 6-methoxy-7-deazapurine and 7-deazaadenines bases showed significant cytostatic activities. Also a general...Nejprve byla vyvinuta přímá C-H borylace 7-deazapurinů (7H-pyrrolo[2,3- d]pyrimidin) v poloze 8 za použití B2pin2 a Ir katalýzy. Takto získané boronáty byly efektivně využity v Suzukiho cross-coupling reakci s arylhalogenidy a jiné další transformace vedly ke vzniku různě 6-substituovaným 8-aryl-7-deazapurinům. Následným cílem práce byla syntéza potencionálně biologicky aktivních 8-aryl-7-deazaadeninů a -7-deazahypoxantinů. Vzhledem k tomu, že přímá C-H borylace 7-deazaadeninů nebyla úspěšná a "one-pot" borylace/Suzukiho reakce 6-chlor-7-deazapurinu poskytovala pouze nízký výtěžek (20%) tíženého 8-arylovaného derivátu, zaměřil jsem se na borylaci/arylaci SEM-chráněného 6- methylsulfanyl nebo 6-methoxy-7-deazapurinu. Borylace/Suzukiho reakce byla následována buď demethylací a deprotekcí za vzniku deazahypoxantinové báze, nebo oxidací sulfidu na sulfon, aminací a odstranění chránící skupiny za vzniku deazaadeninů. Kromě toho byly boronáty úspěšně převedeny na 8-halogen- nebo 8-trifluormethyl-7-deazapurinové deriváty. Zatímco 7-deazahypoxantinové analogy byly téměř úplně neaktivní, většina z 8- subtituovaných 6-methoxy-7-deazapurinů a 7- deazaadeninů měla cytostatický účinek v mikromolární koncentraci. Dále byla vyvinuta mědí katalyzovaná C-H sulfenylace purinů, 7-deaza- a 9- deazapurinů...Department of Organic ChemistryKatedra organické chemieFaculty of SciencePřírodovědecká fakult

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Background and purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

Testování nástrojů pro měření vibrací v automobile

This work is specialized on testing of several sensors for measurement vibration, that be applicable for measurement on vehicles also behind running. These sensors are connected to PC and universal mobile measuring system cRIO (National Instruments) with analog I/O module for measurement vibration, that is described in diploma work: [JURÁNEK 2008]. This system has upped mechanical and heat imunity, small proportions and is therefore acceptable also measurement behind ride vehicles. It compose from two head parts. First is measuring part, composite from instruments cRIO. First part is controlled and monitored by PDA there is connected of wireless (second part hereof system). To system cRIO is possible connect sensors by four BNC connector or after small software change is possible add sensor to other analog modul cRIO. Here will be test several different types of accelerometers (USB sensor company Phidgets, MEMS sensor company Freescale, piezoresistiv and Delta Tron accelerometers company Brüel&Kjær). These sensors is attach to stiff board, board is attach to vibrator and excite by proper signal. Testing will realized with reference to using for measurement in cars. Results will be compared with professional signal analyser LabShop pulse from company Brüel&Kjær.Tato práce je zaměřena na ověření několika snímačů pro měření vibrací, které jsou použitelné pro měření na vozidlech i za provozu. Tyto snímače jsou připojeny k přenosnému univerzálnímu měřicímu systému cRIO (National Instruments) s IO moduly pro měření vibrací, který je blíže popsán v diplomové práci:[JURÁNEK 2008]. Tento systém má zvýšenou mechanickou a tepelnou odolnost, malé rozměry a je proto vhodný i k měření za jízdy vozidla. Skládá se ze dvou hlavních částí. První je měřicí část, složena ze zařízení cRIO. Tato první část je ovládána a monitorována pomocí bezdrátově připojeného PDA, které tvoří druhou část tohoto systému. Je možné zde připojit snímače pomoci čtyř BNC konektorů nebo také po úpravě software lze připojit snímač k jinému analogovému modulu cRIO. Skupinu testovaných snímačů tvoří několik různých typů akcelerometrů (USB snímače značky Phidgets, MEMS snímače značky Freescale, piezoresistivní a Delta Tron akcelerometry značky Brüel&Kjær). Tyto snímače budou uchyceny na tuhé desce připevněné k vibrátoru a rozkmitány vhodným signálem. Testování bude prováděno s ohledem na použití pro měření v automobilech. Výsledky budou porovnány s profesionálním signálovým analyzátorem LabShop Pulse od firmy Brüel&Kjær

C-H activations of deazapurine heterocycles

Direct C-H borylations of 7-deazapurines (7H-pyrrolo[2,3-d]pyrimidine) were developed at position 8 using B2pin2 and Ir catalysis. The obtained boronates were efficiently applied in the Suzuki cross-couplings with aryl halides and other functional group transformations to give diverse 6-substituted 8-aryl-7-deazapurine derivatives. Furthermore, I was also interested in the synthesis of biologically relevant 8-aryl-7- deazaadenines and -7-deazahypoxanthines. As the direct C-H borylation of 7- deazaadenines was unsuccessful and the borylation/Suzuki reaction of 6-chloro-7- deazapurine gave only low yield (20%) of the desired 8-aryl derivative, I focused on the one-pot borylation/arylation of SEM-protected 6-methylsulfanyl- or 6-methoxy-7- deazapurines. The one-pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine base, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were successfully converted to 8-halo- or 8-trifluoromethyl-7- deazapurine derivatives. While the 7-deazahypoxantine analogues were almost entirely inactive, most of the 8-subtituted 6-methoxy-7-deazapurine and 7-deazaadenines bases showed significant cytostatic activities. Also a general..

C-H activations of deazapurine heterocycles

Direct C-H borylations of 7-deazapurines (7H-pyrrolo[2,3-d]pyrimidine) were developed at position 8 using B2pin2 and Ir catalysis. The obtained boronates were efficiently applied in the Suzuki cross-couplings with aryl halides and other functional group transformations to give diverse 6-substituted 8-aryl-7-deazapurine derivatives. Furthermore, I was also interested in the synthesis of biologically relevant 8-aryl-7- deazaadenines and -7-deazahypoxanthines. As the direct C-H borylation of 7- deazaadenines was unsuccessful and the borylation/Suzuki reaction of 6-chloro-7- deazapurine gave only low yield (20%) of the desired 8-aryl derivative, I focused on the one-pot borylation/arylation of SEM-protected 6-methylsulfanyl- or 6-methoxy-7- deazapurines. The one-pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine base, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were successfully converted to 8-halo- or 8-trifluoromethyl-7- deazapurine derivatives. While the 7-deazahypoxantine analogues were almost entirely inactive, most of the 8-subtituted 6-methoxy-7-deazapurine and 7-deazaadenines bases showed significant cytostatic activities. Also a general..

Testing of Tools for Measurement Vibration in Car

This work is specialized on testing of several sensors for measurement vibration, that be applicable for measurement on vehicles also behind running. These sensors are connected to PC and universal mobile measuring system cRIO (National Instruments) with analog I/O module for measurement vibration, that is described in diploma work: [JURÁNEK 2008]. This system has upped mechanical and heat imunity, small proportions and is therefore acceptable also measurement behind ride vehicles. It compose from two head parts. First is measuring part, composite from instruments cRIO. First part is controlled and monitored by PDA there is connected of wireless (second part hereof system). To system cRIO is possible connect sensors by four BNC connector or after small software change is possible add sensor to other analog modul cRIO. Here will be test several different types of accelerometers (USB sensor company Phidgets, MEMS sensor company Freescale, piezoresistiv and Delta Tron accelerometers company Brüel&Kjær). These sensors is attach to stiff board, board is attach to vibrator and excite by proper signal. Testing will realized with reference to using for measurement in cars. Results will be compared with professional signal analyser LabShop pulse from company Brüel&Kjær

Intravenous Thrombolysis in Posterior versus Anterior Circulation Stroke: Clinical Outcome Differs Only in Patients with Large Vessel Occlusion

The safety and efficacy of intravenous thrombolysis (IVT) are well established in anterior circulation stroke (ACS) but are much less clear for posterior circulation stroke (PCS). The aim of this study was to evaluate the occurrence of parenchymal hematoma (PH) and 3-month clinical outcomes after IVT in PCS and ACS. In an observational, cohort multicenter study, we analyzed data from ischemic stroke patients treated with IVT prospectively collected in the SITS (Safe Implementation of Treatments in Stroke) registry in the Czech Republic between 2004 and 2018. Out of 10,211 patients, 1166 (11.4%) had PCS, and 9045 (88.6%) ACS. PH was less frequent in PCS versus ACS patients: 3.6 vs. 5.9%, odds ratio (OR) = 0.594 in the whole set, 4.4 vs. 7.8%, OR = 0.543 in those with large vessel occlusion (LVO), and 2.2 vs. 4.7%, OR = 0.463 in those without LVO. At 3 months, PCS patients compared with ACS patients achieved more frequently excellent clinical outcomes (modified Rankin scale [mRS] 0–1: 55.5 vs. 47.6%, OR = 1.371 in the whole set and 49.2 vs. 37.6%, OR = 1.307 in those with LVO), good clinical outcomes (mRS 0–2: 69.9 vs. 62.8%, OR = 1.377 in the whole set and 64.5 vs. 50.5%, OR = 1.279 in those with LVO), and had lower mortality (12.4 vs. 16.6%, OR = 0.716 in the whole set and 18.4 vs. 25.5%, OR = 0.723 in those with LVO) (p < 0.05 in all cases). In PCS versus ACS patients, an extensive analysis showed a lower risk of PH both in patients with and without LVO, more frequent excellent and good clinical outcomes, and lower mortality 3 months after IVT in patients with LVO

Biotic threats to garden monuments: algae, cyanobacteria and invasive plant species

Chateau, city parks and gardens are perceived as harmonious parts of the landscape. Unfortunately, even these areas have to face various threats, and they can be a threat to the surrounding environment. The exhibition /catalogue presents a look at the organisms that threaten parks. These threats cover unwelcomed invaders covering invasive plants and small microorganisms in the soil, on facades, statues or in water. On the other hand, some species that are intentionally brought to the parks can be risky not only the gardens themselves but also their surroundings