Effects of diclofenac, L-NAME, L-Arginine, and pentadecapeptide BPC 157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 hour-short-bowel rats

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

AIM: To counteract/reveal celecoxib-induced toxicity and NO system involvement. ----- METHODS: Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. ----- RESULTS: This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). ----- CONCLUSION: BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement

Radiooznačeni peptidi v nuklearni medicini

Nuklearna medicina pri obravnavi onkoloških bolnikov omogoča slikovni prikaz oziroma lokalizacijo tumorjev, ciljano zdravljenje ter spremljanje uspešnosti zdravljenja. Visoko specifične radiooznačene peptidne učinkovine lahko izkoristimo za ciljanje tumorskih celic, ki imajo na svoji površini prekomerno izražene receptorje za te učinkovine. Enako peptidno učinkovino lahko radiooznačimo tako z diagnostičnimi kot terapevtskimi radionuklidi, kar nam omogoča personaliziran pristop pri obravnavi bolnikov. V preglednem članku opisujemo dva sistema teranostičnih parov, ki jih v nuklearni medicini uporabljamo za diagnosticiranje ter zdravljenje tumorjev. Klasičen primer takšnih teranostičnih parov so radiooznačeni analogi somatostatina, ki se rutinsko uporabljajo v diagnostiki ter zdravljenju nevroendokrinih tumorjev (NET) s prekomerno izraženimi receptorji za somatostatin. Po drugi strani pa so radiooznačeni analogi minigastrina, ki se vežejo na receptorje za holecistokinin-2, primerni za diagnostiko medularnega raka ščitnice (MTC), za njihovo varno zdravljenje pa še potekajo klinična preskušanja

From preclinical development to clinical application : kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

Introduction A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04) after labelling with 111In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze-dried formulation of the precursor CP04 for a first multi-centre clinical trial with 111In-CP04 in MTC patients. Materials and methods The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 μg) were prepared and radiolabelled with 111In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. Results Use of ascorbic acid buffer (pH 4.5) allowed freeze-drying of the kit formulation with satisfactory pellet-formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met11-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 μg formulation. The final formulations contained 10 or 50 μg CP04, 25 mg ascorbic acid, 0.5 mg gentisic acid and 5 mg l-methionine. The radiolabelling performed by incubation of 200-250 MBq 111InCl3 at 90°C for 15 min resulted in reproducible radiochemical purity (RCP) > 94%. Kit-stability was proven for > 6 months at + 5°C and at + 25°C. The radiolabelled product was stable for > 4 h at + 25°C. Conclusion A kit formulation to prepare 111In-CP04 for clinical application was developed, showing high stability of the kit as well as high RCP of the final product

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen

COORDINATED VOLTAGE CONTROL IN DISTRIBUTION NETWORKS WITH DISTRIBUTED GENERATION VARIOUS REACTIVE POWER OPTIONS

Doktorska disertacija sega na področje kakovosti električne energije in pametnih distribucijskih omrežij v elektroenergetiki. V prvem poglavju so predstavljeni glavni pojmi in smernice v elektroenergetiki. V Sloveniji in svetu se poraba energije neprenehoma zvišuje. Tako je lahko pričakovati, da bomo leta 2035 porabili približno 36 % več energije kot leta 2000. Od tega se bo najbolj povečala raba električne energije, do leta 2035 za približno 70 %, največjo rast pa se pričakuje v državah v razvoju. Med večjimi izzivi, s katerimi se bo Evropa morala soočiti v prihodnjem desetletju, so poleg gospodarske krize, tudi energetski izzivi. Konkurenčnost našega gospodarstva je močno odvisna od zanesljive oskrbe z energijo: varna, zanesljiva, trajnostna in cenovno sprejemljiva energetska oskrba je ključna pri gospodarskih in strateških interesih Evropske zveze kot globalne igralke. Ta dejstva vodijo v razvoj nove dobe v elektroenergetiki in jo lahko povzamemo z besedno zvezo »pametna omrežja«. V tem poglavju je razložena točna definicija pametnih omrežij in njegovih gradnikov. Poudarek je tudi na razpršenih virih (RV), kot krivcih za probleme, ki se pojavljajo v omrežju. Opisana in nakazana je tudi nadaljnja smer razvoja distribucijskih omrežij v Sloveniji, skupaj z novimi tehnologijami. V celotnem poglavju bralec dobi hiter in nazoren vpogled v trenutno in bodoče stanje v elektroenergetiki. Tehnološki razvoj, kateremu smo priča v zadnjem desetletju, je omogočil prihod novih tehnologij, ki so gradniki pametnih omrežij. Za njihovo uspešno delovanje je potrebno usklajeno delovanje vseh njegovih delov, tako obstoječih, kot novih: klasičnih proizvodnih enot, razpršenih virov, komunikacijskih in informacijskih tehnologij (IKT), delujočo regulacijo virov z možnostjo upravljanja porabe, naprav močnostne elektronike, sistemov naprednega daljinskega merjenja itd. V drugem poglavju so predstavljene vse ključne tehnologije in tudi koncepti regulacije virov in bremen v pametnih omrežjih. Najprej so predstavljene tehnologije proizvodnje električne energije, to so male hidroelektrarne, vetrne elektrarne, sončne elektrarne, kogeneracijske elektrarne ipd. Nato so na kratko predstavljeni tudi električni stroji za proizvodnjo iz razpršenih virov, to so asinhronski generator, sinhronski generator in močnostni pretvorniki. Predstavljeni so tudi povsem novi elementi, ki jih do sedaj v distribucijskih omrežjih nismo srečevali, to so regulacijski SN/NN transformator, ki lahko spreminja napetostno stopnjo med obratovanjem, hranilniki energije (baterije, črpalne elektrarne, vztrajniki, …). Da distribucijskemu omrežju sploh lahko rečemo »pametno« omrežje, mora imeti vzpostavljen sistem informacijskih in komunikacijskih tehnologij. IKT so eden ključnih gradnikov pametnih omrežji. Polna uresničitev koncepta pametnega omrežja zahteva IKT povezave do vsakega elementa v elektroenergetskem sistemu (EES), torej mora vključevati elemente proizvodnje, prenosa, distribucije in segati tudi do vsakega končnega odjemalca. V tem poglavju so na kratko predstavljene potrebe in rešitve, ki so izvedljive in uporabne v pametnih omrežjih. Nadzor in upravljanje velikega števila priključnih mest (odjemalcev in proizvajalcev) zahteva razvoj posebnih IKT rešitev. Na koncu poglavja sta predstavljena še dva koncepta vodenja razpršenih virov in bremen, to sta upravljanje s porabo in virtualna elektrarna, ki je skupek razpršenih virov, vodenih iz skupnega centra za nadzor, ki nastopajo na trgu kot ena velika elektrarna. Eden glavnih problemov, ki jih prinašajo razpršeni viri, so težave z napetostjo. Razpršeni viri lahko vzdolž voda, zaradi injekcije delovne moči, dvignejo napetostni nivo preko zakonsko dovoljene meje, kar lahko povzroči poškodbe naprav, priklopljenih na omrežje, omrežja samega in tudi izpad napajanja, kar ima za posledico finančno breme. V doktorski disertaciji največ pozornosti posvečamo ravno problematiki vzdrževanja ustreznega napetostnega profila. V tretjem poglavju je problem porasta napetosti opisan z uporabo enačb, ki ponazarjajo realne razmere v omrežju. Opisan je klasičen način regulacije napetosti, ki pa kmalu ne bo več zadosten. Tradicionalna rešitev omenjene težave bi bila ojačenje elektroenergetskega omrežja z dodatnimi vodi in transformatorji oz. s povečanjem presekov vodnikov in s tem predimenzioniranjem omrežja. Takšne rešitve so sicer zanesljive, vendar so zaradi okoljevarstvenih razlogov, zakonskih omejitev in tudi cene, v večini primerov izredno draga in ekonomsko neupravičena rešitev. Eden od alternativnih pristopov je na splošno tehnološki pristop, kar pomeni, da se z minimalnimi vlaganji v omrežje izkoristi nove možnosti regulacije, kjer sistem to dopušča. V svetu se že pojavljajo razne ekonomsko ugodne rešitve, ki pa ne prinašajo trajnostne rešitve in poljubne optimizacije v omrežjute rešitve so predstavljene v nadaljevanju. Do nedavnega, so razpršeni viri delovali s konstantnim faktorjem moči (cos= 1). Torej niso sodelovali pri regulaciji napetosti. Glede na to, da je ravno razpršena proizvodnja glavni krivec za poraste napetosti, je prav, da za to prevzamejo določeno odgovornost in obvezno sodelujejo pri sistemskih storitvah. Zadnjih nekaj let se že pojavljajo ideje in zahteve v tej smeri. Tako so bila v Sloveniji leta 2011 sprejeta navodila za priključevanje razpršene proizvodnje, kjer je bila določena statična Q(U) karakteristika za razpršeno proizvodnjota so podrobneje predstavljena v tem poglavju. Na podlagi lokalne meritve napetosti in trenutne proizvodnje delovne moči razpršenega vira, se določi koliko jalove moči mora proizvajati razpršeni vir. V elektroenergetiki se za opis realnih naprav pogosto uporablja ekvivalenten model vezja. Z uporabo teh modelov lahko, raje kot da s fizičnim testiranjem na terenu ali laboratoriju, njihovo obnašanje opišemo z matematičnimi enačbami. V četrtem poglavju je zato predstavljeno modeliranje elementov, ki so uporabljeni v simulacijah. To so bremena, razpršeni viri, vodi in transformatorji. Posebno pozornost smo namenili modeliranju bremen na NN strani. Pri analizi VN in SN omrežij lahko obremenitvene diagrame bremen (in generatorjev) opišemo s tipičnimi krivuljami, ki podajajo pričakovan odjem v določenem času. Analiza NN omrežja pa zahteva povsem drugačen pristop. Odjem na tem napetostnem nivoju je praviloma povsem naključen. Zato je potrebno za analize razmer v NN omrežjih uporabiti stohastične modele uporabnikov. Nadalje, smo preučili zmožnost uporabe metode Monte Carlo za ocenjevanje dovoljene količine razpršenih virov v NN omrežju. Dandanes načrtovanje omrežij poteka tako, da načrtovalec predpostavi maksimalno porabo in nato izračuna pretoke moči. Če je katerikoli izmed kriterijev prekoračen, je potrebno omrežje ojačiti z dodatnimi vodi ali transformatorji. Zaradi okoljskih vidikov, zakonskih omejitev, cene in uvajanja novih elementov v omrežje, tak pristop ni več zadosten. Načrtovanje je potrebno nadgraditi na višjo stopnjo, ki bo omogočala boljši izkoristek sistema. Zaradi stohastične narave NN omrežij, se zdi najbolj primeren statističen pristop. Začetna ideja statističnega pristopa načrtovanja predpostavlja, da je izvedba simulacij in načrtovanje glede na najslabše možne razmere v omrežju, preveč pesimistično. Opisana je metoda za načrtovanje NN omrežij z visoko stopnjo razpršene proizvodnje, ki ima za osnovo pristop na podlagi Monte Carlo metode in statistične analize podatkov. Z naključnimi vzorci in ponavljanjem poskusov lahko predvidevamo oz. napovemo kakšne bodo napetostne razmere v prihodnosti. Na podlagi teh podatkov lahko izberemo najboljše, oz. najcenejše rešitve in jih pravočasno umestimo v plan razvoja omrežja. Rezultat metode so krivulje, ki podajajo verjetnost nastopa neustreznih napetostnih razmer, kot funkcija inštalirane moči razpršenih virov. Metodo se da smiselno uporabiti tudi v SN omrežju. V okviru doktorske naloge je bilo analizirano tudi delovanje več optimizacijskih metod, ki služijo kot podlaga za izdelavo novih algoritmov vodenja in načrtovanja v pametnih omrežjih. Izsledki so predstavljeni v petem poglavju. Algoritmi slonijo na dejstvu, da bo večina distribucijskega omrežja v naslednjih desetih letih pokrita z meritvami v realnem času. Merjeni podatki iz pametnih števcev služijo kot vhodni parametri za koordiniran nadzor napetosti. Ta se izvaja v skupnem centru vodenja. Kot izhodni parameter tega algoritma, so nove obratovalne točke generatorjev in napetostna stopnja regulacijskega transformatorja v RTP. Regulacijski algoritem je izdelan tako, da omogoča vzpostavitev trga z jalovo močjo. Razpršeni viri podajo svoje ponudbe, nato pa algoritem izvede optimizacijo in poda nove obratovalne točke za razpršene vire, da so obratovalni stroški najmanjši. S tem pristopom pridobijo vsi akterji v omrežju. Najprej je predstavljena analiza razmer ob pogoju, da vsi razpršeni viri obratujejo z enakim tg. Če razpršeni viri delujejo po principu statične karakteristike, morajo viri, ki so bolj oddaljeni od razdelilne transformatorske postaje (RTP) vzdolž izvoda, proizvajati oz. porabljati več jalove moči, kot tisti na začetku izvoda, kar ima za posledico hitrejše staranje naprav (pretvornikov) in potrebno predimenzioniranje naprav. Ena izmed možnosti, ki se ponuja, je uporaba enotnega oz. skupnega tg za vse generatorje v omrežju. Tg je razmerje med generatorjevo trenutno proizvodnjo jalove in delovne moči in se lahko interpretira kot obdavčitev generatorjev z jalovo močjo. Z izvedbo simulacij je narejena popolna analiza obratovalnih razmer v primeru takšnega obratovanja. Nadalje smo analizirali razmere, pri čemer pustimo, da se cene na trgu same izoblikujejo. Dodatno pa je potrebno, ko je kriterijska funkcija definirana, izbrati ustrezno metodo, s katero bomo iskali optimalno rešitev. Problem, ki ga moramo rešiti je problematičen zato, ker je vpliv na izgube nelinearen. Optimizacija enega generatorja vpliva na izgube v celem omrežju. Njihov vpliv pa je različen za vsak generator posebej. Dejstvo, da so izgube v vejah nelinearna funkcija injekcij moči v vozliščih, otežuje reševanje optimizacijskega problema. Z majhnimi injekcijami jalove moči v postopku minimizacije izgub, lahko ta problem lineariziramo. Predstavljena je optimizacijska metoda, ki izrablja dejstvo, da so v pametnem omrežju razpršeni viri med seboj komunikacijsko povezani in da jim je poznana topologija omrežja. Generator lahko spremeni svojo izhodno moč samo tako, da za en korak zmanjša ali zveča izhodno moč. Na ta način algoritem izračuna prihranke moči za oba primera za vse generatorje in nato določi kateri generator bo spremenil svojo izhodno moč v trenutni iteraciji. Po določenem številu iteracij oz. izračunih pretokov moči, se algoritem ustali v določeni delovni točki. S tem pristopom, se problem minimizacije izgub razdeli na več manjših problemov, ki jih je lažje in hitreje rešiti. Izhodi algoritma so nove obratovalne točke generatorjev, ki se jih razpošlje mednje. Če je v omrežju velika količina razpršenih virov, algoritem v ta namen upošteva tudi faktorje občutljivosti in tako tudi v izrednih razmerah določi najcenejšo angažiranost razpršenih virov. Nadalje sta predstavljeni še dve metodi za iskanje optimalne točke obratovanja. Zelo opevana metoda v znanstvenih člankih je uporaba genetskih algoritmov. Logika, na kateri bazirajo, je ta, da naj bi bili procesi v naravi zaradi evolucije najbolj optimalni. Populacija osebkov se skozi generacije razmnožuje in razvija po načelu naravne selekcije, tako preživijo samo najboljši osebki, ki tudi lažje najdejo partnerja za razmnoževanje. Slabši posamezniki znotraj populacije bodo imeli manj možnosti za razmnoževanje in bodo skozi več generacij izginili. Če obnašanje narave opišemo z matematičnimi enačbami, lahko razvijemo uporabno optimizacijsko metodo. Druga metoda, zopet evolucijska, pa je metoda iskanja kukavice oz. metoda kukavičjega gnezda. Raziskave obnašanja živali so pokazale, da se nekatere obnašajo po določenem vzorcu, ki je tipičen za Lévijev let, ki ga oponaša kukavica pri podtikanju jajc. Kukavica išče najbolj primerno gnezdo, da odloči jajce in s tem poveča verjetnost, da potomec preživi. Matematiki so na podlagi tega razvili novo optimizacijsko metodo. Metoda kukavičjega gnezda je relativno nova in ker je publikacij v strokovni literaturi malo, smo jo uporabili kot način za optimiziranje kriterijskih funkcij pri analizi delovanja distribucijskih omrežij. Rezultate pa smo primerjali z ostalimi metodami. Njena prednost je tudi enostavna implementacija. V šestem poglavju smo delovanje novih regulacijskih metod preverili na modelu dveh omrežij. Prvo omrežje je srednjenapetostno in drugo nizkonapetostno, kjer je upoštevana stohastična narava uporabnikov. Najprej so uporabljene najbolj preproste regulacijske metode in nato kompleksnejše. Vsi rezultati so na koncu zbrani v tabeli in ponazorjeni grafično za lažjo primerjavo. Kot omenjeno, smo se v doktorski disertaciji dotaknili tudi problematike načrtovanja NN omrežja. Rezultati podajajo verjetnost, da bomo pri določeni inštalirani moči razpršenih virov imeli težave z napetostjo. Metoda veliko obeta, z njenim nadaljnjim razvojem in dopolnitvami je pričakovati, da bo dobila mesto znotraj bodočih metod načrtovanja omrežij. V sedmem poglavju sledi zaključek, kjer so opisane najpomembnejše ugotovitve doktorske disertacije.Doctoral dissertation extends the scope of power quality and smart distribution networks in power engineering. The first section presents the key concepts and guidelines in power engineering. The world power consumption is increasing. Thus, we can expect that we will spend in 2035 approximately 36 % more energy than in 2000, of which the electricity consumption will increase the most, for about 70 %. The largest growth is expected in developing countries. Among the major challenges that Europe will have to face in the coming decade in addition to the economic crisis is the energy crisis. Competitiveness of our economy is heavily dependent on energy security: safe, secure, sustainable and cheap energy supply is crucial to the economic and strategic interests of the European Union as global player. These facts lead to the development of a new era in electricity and can be summarized by the phrase »smart grid«. This chapter explains the exact definition of smart grids and its building blocks. The emphasis is also on distributed power sources as the culprit for the problems that occur in the network. Also further direction of distribution networks development, along with new technologies in Slovenia is presented. Throughout the chapter the reader gets a quick and vivid insight into the current and future situation in the electricity sector. Technological progress, which we have witnessed in the last decade, has enabled the arrival of new technologies, which are the building blocks of smart grids. Their successful operation requires harmonized operation of all its parts, both - existing and the new ones: production units, distribution sources, information and communication technologies (ICT), functional control of distributed generation with the possibility of power management, power electronic devices, advanced remote measurement systems, etc.. The second chapter presents the key technologies and concepts of power sources and load control in smart grids. Firstly, the power production technologies are presented, i.e. small hydro power plants, wind farms, solar power plants, cogeneration plants etc. Then the electric machines, used in distribution generation, to produce electricity are presented, such as induction generator, synchronous generator and power converters. New elements, which haven\u27t been used in distribution networks until now, are presented. These are MV/LV OLTC transformer, energy storage (batteries, pumped power plants, flanges …). The distribution network cannot become smart grid if the communication and information technologies are not established. ICT is one of the key building blocks of smart grids. Full realization of the concept of smart grids requires ICT links to each element in the electric power system, so it should include elements of power generation, transmission, and distribution and extend up to the end of each client. In this chapter, the most practical and useful ICT technologies for smart grids are presented. Control and management of a large number of connection points (customers and suppliers) requires the development of specific ICT solutions. Finally, the chapter presents two concept of managing distribution generation loads, namely demand-side management, and virtual power plant, which is a set of distributed generation, managed from a common control center, which appears in the electricity market as one big power plant. One of the main problems posed by distributed generation is related to the voltage rise. Distributed generation can along the feeder, because of the injection of active power, raise the voltage offer the statutory defined limits, which can cause damage to the devices connected to the network, the network itself and the loss of power, resulting in a financial burden. In this doctoral thesis, most attention is paid exactly to the problem of maintaining adequate voltage profile. The third section describes the voltage rise problem using the equations that represent real network conditions. Classical approach of voltage control, which will soon no longer be sufficient, is presented. The traditional solution in these problems would be reinforcing the network with additional transformers and by increasing the conductor’s cross-sections and thus oversizing the networks. Such solutions are reliable, however, due to environmental considerations, legal constraints and also price, in most cases, very expensive and economic unjustified solution. One of the alternative approaches is in general, technological approach, which means that with the minimum investments in the network new control possibilities are exploited where this is possible. In the world there are already new low-costs solutions emerging, which do not bring any sustainable solutions at these time. Until recently, the distributed generation operated with constant power factor (cos= 1). This means that they did not participate in the voltage control. Given that distributed generation is the main culprit for the voltage rise problemsit is fair that they also take some responsibility for this and participate in the voltage control. Over the last few years there have already been few ideas in this direction. Slovenia, for example, issued guidelines for connection of distributed generation where static Q(U) characteristic for distributed generation are prescribed. On the basis of local voltage measurements and active power output, their reactive power output is determined. To describe real electrical devices equivalent circuit model is commonly used. By using these models, rather than by physical testing in the field or laboratory, their behavior can be described by mathematical equations. In the fourth chapter modeling of the elements that are used in in the simulations is presented. These are loads, distributed generation, lines and transformers. Special attention is paid to the modeling of loads on LV side. In the analysis of HV and MV networks typical load diagrams can be used. Analysis of LV networks, however, requires a completely different approach. Consumption on this voltage level is usually completely random. Therefore, it is necessary for the analysis of the LV networks to use stochastic load models. Furthermore, the use of statistical method Monte Carlo is considered when evaluating allowed amount of distributed generation in the LV network. Nowadays, network planning takes place so that the maximum consumption is assumed and then power-flow calculated. If any of the criteria is exceeded, it is necessary to strengthen the network with additional lines or transformers. Due to environmental concerns, legal restrictions, prices and the introduction of new elements in the network, this approach is no longer sufficient. Planning should be upgraded to the next level, which will allow better utilization of the system. Due to the stochastic nature of the LV networks, statistical approach seems most appropriate. The basic idea of statistical approach of planning assumes that the planning for the worst possible conditions in the network is too pessimistic. That is why statistical approach using Monte Carlo method is presented. With random samples and repetition of experiments voltage situation in the future can be predicted with desirable level of accuracy. Based on the results we can choose the best or the cheapest solutions and fit them into the network development plan. The results of the method are curves that give the probability of inadequate voltage conditions as a function of hosting capacity. Method can be easily applied to MV network analysis. The thesis analyses also the functioning of several optimization methods that serve as the basis for the creation of new control algorithms to be used in smart grids. The results are presented in the fifth chapter. Firstly, analysis of the network situation where all the generation operates with the same tan is presented. If a customer lives far away from the substation, where voltage deviations are more frequent, the inverters will have to inject or consume more reactive power than for those located in areas where the voltage deviations are minor. Also their location may change depending on how the entire distribution system is configured. As retail customers typically have no choice where they are located along the feeder, it seems inappropriate that they are required to produce or consume a large amount of reactive power and hence, tak

Příklad e-learningové komunity v celoživotním vzdělávání učitelů tělesné výchovy An example of an e-learning community for lifelong learning by physical education teachers

Současn&eacute; trendy ve světě i v EU vykazuj&iacute; zvy&scaron;uj&iacute;c&iacute; se počet skupin, vzděl&aacute;vaj&iacute;c&iacute;ch se prostřednictv&iacute;m e-learningu, tzv. e-learningov&yacute;ch komunit. Tento př&iacute;spěvek představuje prvn&iacute; takovouto e-learningovou komunitu ve Slovinsku, a to v oblasti pedagogick&eacute; praxe studentů &ndash; "Sportfolio.si".<br />Pedagogov&eacute;, studenti sportu, profesoři a mentoři na &scaron;kol&aacute;ch v r&aacute;mci e-learningov&eacute; komunity spolupracuj&iacute; a propojuj&iacute; tak "teorii a praxi". V r&aacute;mci e-komunity a pomoc&iacute; blogů (weblogů) mohou uživatel&eacute; sd&iacute;let př&iacute;klady nejlep&scaron;&iacute;ch postupů a z&iacute;sk&aacute;vat, rozv&iacute;jet a sd&iacute;let tak profesn&iacute; kompetence v oblasti tělesn&eacute; v&yacute;chovy. Potvrzuj&iacute; tak my&scaron;lenku, že "vlastn&iacute; vědomosti lze rozv&iacute;jet t&iacute;m, že je sd&iacute;l&iacute;me s ostatn&iacute;mi".<br />Takov&eacute; jsou rovněž trendy v EU, kter&aacute; od pedagogů požaduje neust&aacute;le přej&iacute;mat nov&eacute; role (kompetence) a měnit či opou&scaron;tět někter&eacute; role dř&iacute;věj&scaron;&iacute;. Pedagogov&eacute; se tud&iacute;ž mus&iacute; neust&aacute;le starat o vlastn&iacute; osobnostn&iacute; a profesn&iacute; rozvoj. Pomoc&iacute; tzv. celoživotn&iacute;ho vzděl&aacute;v&aacute;n&iacute; se pedagogov&eacute; st&aacute;vaj&iacute; ned&iacute;lnou souč&aacute;st&iacute; "uč&iacute;c&iacute; se společnosti" neboli společnosti vědomostn&iacute;, kter&aacute; představuje jeden ze z&aacute;sadn&iacute;ch c&iacute;lů evropsk&eacute; politiky v oblasti v&yacute;chovy a vzděl&aacute;v&aacute;n&iacute;, kter&eacute;ho m&aacute; b&yacute;t dosaženo do roku 2010.<br />V budoucnosti by e-learningov&eacute; komunity mohly představovat &uacute;činnou oporu při celoživotn&iacute;m vzděl&aacute;v&aacute;n&iacute; učitelů tělesn&eacute; v&yacute;chovy a podpořit rozvoj sportů v&scaron;ech typů a měř&iacute;tek. The contemporary trends in the world and in the EU indicate an increase in the number of e-learning communities. This paper presents an example of the first learning community in Slovenia in the field of practical pedagogical training for students, the "Sportfolio.si".<br />The Faculty, sport students, professors, and the mentors at schools cooperate within the e-learning community and in this way interconnect "theory and practice". Within the e-community and by using blogs (web logs), users can share "examples of the best practice" and therefore gain, develop, and share professional competencies in the field of physical education – they are proving the idea that "you can develop your own knowledge if you share it with others".<br />These are also the trends in the EU which require teachers to continuously adopt new roles (competencies), and to change or abandon some of their earlier ones. Teachers must therefore permanently arrange for their own personal and professional development. With so called lifelong learning, teachers are becoming an important integral part of the "learning society" or the society of knowledge, which represents one of the fundamental goals of the European policies in the field of education and training to be achieved by the year 2010.<br />In the future, e-learning communities could provide an efficient source of support for the lifelong learning of physical education teachers and promote the development of sport of all types and dimensions

Minimization of losses in smart grids using coordinated voltage control

This article deals with the influence of distributed generation (DG) on distribution line losses with respect to voltage profile. The article focuses on the development of a control strategy to minimize the grid losses and assure fairness regarding reactive power contributions. As retail customers typically have no choice where they are located along a feeder, it seems unfair that only some of them bear all the burden and responsibility for the voltage rise. On the basis of new technologies, which are capable of fast communication and data processing, a new control system has been proposed that combines classical centralized and local control. The heart of the control system is a load-flow algorithm, which estimates the voltage drop using a modeled network. Different control solutions were evaluated by means of computer simulations. The simulated network is an actual Slovenian medium-voltage distribution network which covers a large area with diverse feeders and thus gives relatively general results