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Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157,L-NAME and L-arginine

World Journal of Gastroenterology 2018年第48期24卷 5462-5476页

作者： Domagoj Drmic Mariam Samara Tinka Vidovic dominik malekinusic Marko Antunovic Borna Vrdoljak Jelena Ruzman Marija Milkovic Perisa Katarina Horvat Pavlov Jerusha Jeyakumar Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb

AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system *** Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.

关键词： BPC 157 perforated cecum L-arginine L-NAME vessels rats

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Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

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World Journal of Gastroenterology 2017年第48期23卷 8465-8488页

作者： Antonija Duzel Josipa Vlainic Marko Antunovic dominik malekinusic Borna Vrdoljak Mariam Samara Slaven Gojkovic Ivan Krezic Tinka Vidovic Zdenko Bilic Mario Knezevic Marko Sever Nermin Lojo Antonio Kokot Marijan Kolovrat Domagoj Drmic Jaksa Vukojevic Tamara Kralj Katarina Kasnik Marko Siroglavic Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb Medical Faculty J.J.Strossmayer University of Osijek OsijekCroatia Rudjer Boskovic Institute Department of Molecular Medicine

AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157,L-NAME,L-arginine(alone/combined),saline] was bath at the blood deprived colon segment. During reperfusion,medication was BPC 157 or saline. We recorded(USB microscope camera) vessel presentation through next 15 min of ischemic colitis(ICrats) or reperfusion(removed ligations)(IC + RL-rats);oxidative stress as MDA(increased(IC-and IC + RLrats)) and NO levels(decreased(IC-rats);increased(IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction(OB)] for 3 d(IC + OBrats),then received BPC 157 bath. RESULTS Commonly,in colon segment(25 mm,2 ligations on left colic artery and vein,3 arcade vessels within ligated segment),in IC-,IC + RL-,IC + OB-rats,BPC 157(10 μg/kg) bath(1 m L/rat) increased vessel presentation,inside/outside arcade interconnections quickly reappeared,mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME(5 mg) and L-arginine(100 mg). MDA-and NO-levels were normal in BPC 157 treated IC-rats and IC + RLrats. In addition,on day 10,BPC 157-treated IC + OBrats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects;the treated colon segment was of normal diameter,and only small adhesions were *** BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

关键词： Ischemic colitis Blood flow rescue Collaterals BPC 157 L-NAME L-arginine Oxidative stress NO Rats

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Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

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World Journal of Hepatology 2020年第5期12卷 184-206页

作者： Marijan Kolovrat Slaven Gojkovic Ivan Krezic dominik malekinusic Borna Vrdoljak Katarina Kasnik Kovac Tamara Kralj Domagoj Drmic Ivan Barisic Katarina Horvat Pavlov Andreja Petrovic Antonija Duzel Mario Knezevic Ivan Mirkovic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUND The Pringle maneuver[portal triad obstruction(PTO)]provides huge disturbances during ischemia and even more thereafter in ***,a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion ***,BPC 157,as a cytoprotective agent,successfully resolved vessel occlusions in rats(ischemic colitis;deep vein thrombosis,superior anterior pancreaticoduodenal vein;bile duct cirrhosis)through rapid collateral vessel recruitment to circumvent vessel ***,medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively,at various time points during *** To introduce BPC 157 therapy against pringle *** In deeply anesthetised rats,the portal triad was clamped up for 30 *** then underwent reperfusion for either 15 min or 24 ***[(10μg,10 ng/kg)regimens,administered as a single challenge]picked(a)ischemia,PTO period[at 5 min before(ip)or at 5 or 30 min of ligation time(as a bath to PTO)]or(b)reperfusion,post-PTO period[at 1 or 15 min(bath during surgery)or 24 h(ip)reperfusion-time].We provided gross,microscopy,malondialdehyde,serum enzymes,electrocardiogram,portal,caval,and aortal pressure,thrombosis and venography *** BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude,S1Q3T3 QRS pattern and tachycardia).Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein)as the adequate shunting immediately affected disturbed *** hypertension and severe aortal hypotension during PTO,as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO)or completely abrogated(reperfusion);thrombosis in portal vein tributaries and inferior caval vein o

关键词： BPC 157 Pringle maneuver Rats Portal hypertension Caval hypertension Ischemia

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Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157,L-NAME and L-arginine in rats

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2020年第5期11卷 93-109页

作者： Lidija Berkopic Cesar Slaven Gojkovic Ivan Krezic dominik malekinusic Helena Zizek Lovorka Batelja Vuletic Andreja Petrovic Katarina Horvat Pavlov Domagoj Drmic Antonio Kokot Josipa Vlainic Sven Seiwerth Predrag Sikiric Department of Pharmacology School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia Institute Ruder Boskovic Zagreb 10000Croatia

BACKGROUND After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats,there is failed vasculature,and finally,increased adhesion *** hypothesized that unlike nitric oxide(NO)-agents,L-NAME and/or L-arginine,the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects(“vascular recruitment”)means attenuated bowel adhesion formation and NO-and malondialdehyde(MDA)-tissue *** To focused on the bowel adhesion and the therapy with the BPC 157,its most and application of *** Along with defect creation,medication was(1)during surgery,once,at 1 min after defect creation as an abdominal bath(1 mL/rat),BPC 157(10μg/kg,10 ng/kg,1 mL/rat),an equivolume of saline,L-NAME(5 mg/kg),L-arginine(200 mg/kg)alone and/or ***,medication was(2)intraperitoneally once daily,first application at 30 min after surgery,last application 24 h before assessment at d 7 or d *** a postponed therapy to preexisting adhesion(3),BPC 157(10μg/kg,10 ng/kg intraperitoneally,1 mL/rat)was given once daily since d *** recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect,which occurs ***,also applied as post-treatment,BPC 157 creates attenuated adhesions,minimal or no ***,NO-agents have diverse initial and final effects:The initial weakening of blood vessel disappearance and finally,severe worsening of adhesions(LNAME)vs the initial weakening of blood vessel disappearance and finally,attenuation of adhesions formation(L-arginine),which counteract each other response given ***,BPC 157 maintains its beneficial effect also when given with NO-agents(L-NAME+BC 157;L-arginine+BPC 157;L-NAME+L-arginine+BPC 157).Finally,with respect to the increased NO-and MDAvalues-adhesion tissue formation relation,unlike diverse effect of the NO-agents,the BPC 157 application effect regularly

关键词： Abdominal wall defect Adhesions BPC 157 Vascular recruitment Nitric oxide-agents Rats

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Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in ratsPentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

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World Journal of Gastrointestinal Pathophysiology 2020年第1期11卷 1-19页

作者： Slaven Gojkovic Ivan Krezic Borna Vrdoljak dominik malekinusic Ivan Barisic andreja Petrovic Katarina Horvat Pavlov Marijan Kolovrat Antonija Duzel Mario Knezevic Katarina Kasnik Kovac Domagoj Drmic Lovorka Batelja Vuletic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of ZagrebZagreb 10000Croatia

BACKGROUND Recently,as a possible therapy resolving solution,pentadecapeptide BPC 157 therapy,has been used in alleviating various vascular occlusion *** 157 was previously reviewed as novel mediator of Robert cytoprotection and endothelium protection in the stomach,and gut-brain axis,beneficial therapy in gastrointestinal tract,with particular reference to vascular recruitment,ulcerative colitis and tumor cachexia,and other tissues *** we raised new hypothesis about BPC 157 therapy in the Budd-Chiari syndrome in rats,rapid bypassing of the suprahepatic inferior caval vein occlusion,and rats recovery with the active and effective pharmacotherapy *** To investigate Budd-Chiari syndrome model(inferior caval vein suprahepatic occlusion)resolution,since BPC 157 resolves various rat vascular *** We assessed the activated bypassing pathways between the inferior and superior caval veins and portocaval shunt,counteracted caval/portal hypertension,aortal hypotension,venous/arterial thrombosis,electrocardiogram disturbances,liver and gastrointestinal lesions(i.e.,stomach and duodenum hemorrhages,in particular,congestion).Rats with suprahepatic occlusion of the inferior vena cava by ligation were medicated at 1 min,15 min,24 h,or 48 h *** consisted of 10μg/kg BPC 157,10 ng BPC 157 or 5 m L/kg saline,administered once as an abdominal bath or intragastric *** and microscopic observations were made,in addition to assessments of electrical activity of the heart(electrocardiogram),portal and caval hypertension,aortal hypotension,thrombosis,hepatomegaly,splenomegaly and ***,levels of nitric oxide,malondialdehyde in the liver and serum enzymes were *** BPC 157 counteracted increased P wave amplitude,tachycardia and ST-elevation,i.e.,right heart failure from acute thrombotic coronary *** bypassing pathway of the inferior vena cava-azygos(hemiazygos)vein-superior

关键词： BPC 157 Budd Chiari syndrome Portal/caval hypertension

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Context-aware reinforcement learning for cooling operation of data centers with an Aquifer Thermal Energy Storage

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Energy and AI 2024年第3期17卷 233-246页

作者： Lukas Leindals Peter Grønning dominik Franjo Dominković Rune Grønborg Junker Department of Applied Mathematics and Computer Science Technical University of DenmarkDenmark

Data centers are often equipped with multiple cooling units. Here, an aquifer thermal energy storage (ATES) system has shown to be efficient. However, the usage of hot and cold-water wells in the ATES must be balanced for legal and environmental reasons. Reinforcement Learning has been proven to be a useful tool for optimizing the cooling operation at data centers. Nonetheless, since cooling demand changes continuously, balancing the ATES usage on a yearly basis imposes an additional challenge in the form of a delayed reward. To overcome this, we formulate a return decomposition, Cool-RUDDER, which relies on simple domain knowledge and needs no training. We trained a proximal policy optimization agent to keep server temperatures steady while minimizing operational costs. Comparing the Cool-RUDDER reward signal to other ATES-associated rewards, all models kept the server temperatures steady at around 30 °C. An optimal ATES balance was defined to be 0% and a yearly imbalance of −4.9% with a confidence interval of [−6.2, −3.8]% was achieved for the Cool 2.0 reward. This outperformed a baseline ATES-associated reward of 0 at −16.3% with a confidence interval of [−17.1, −15.4]% and all other ATES-associated rewards. However, the improved ATES balance comes with a higher energy consumption cost of 12.5% when comparing the relative cost of the Cool 2.0 reward to the zero reward, resulting in a trade-off. Moreover, the method comes with limited requirements and is applicable to any long-term problem satisfying a linear state-transition system.

关键词： Data centers ATES Smart energy systems Reinforcement learning Delayed rewards

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Towards an enhanced understanding of the particle size effect on conversion/alloying lithium-ion anodes

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Materials Futures 2024年第1期3卷 150-164页

作者： Jakob Asenbauer dominik Horny Mayokun Olutogun Katrin Schulz Dominic Bresser Helmholtz Institute Ulm(HIU) 89081 UlmGermany Karlsruhe Institute of Technology(KIT) 76021 KarlsruheGermany Institute for Applied Materials(IAM) Karlsruhe Institute of Technology(KIT)76131 KarlsruheGermany Karlsruhe University of Applied Sciences 76133 KarlsruheGermany

Conversion/alloying materials(CAMs)represent a potential alternative to graphite as a Li-ion anode active material,especially for high-power *** far,however,essentially all studies on CAMs have been dealing with nano-sized particles,leaving the question of how the performance(and the de-/lithiation mechanism in general)is affected by the particle ***,we comparatively investigate four different samples of Zn_(0.9)Co_(0.1)O with a particle size ranging from about 30 nm to a few *** results show that electrodes made of larger particles are more susceptible to fading due to particle displacement and particle *** results also show that the conversion-type reaction in particular is affected by an increasing particle size,becoming less reversible due to the formation of relatively large transition metal(TM)and alloying metal nanograins upon lithiation,thus hindering an efficient electron transport within the initial particle,while the alloying contribution remains essentially *** generality of these findings is confirmed by also investigating Sn_(0.9)Fe_(0.1)O_(2) as a second CAM with a substantially greater contribution of the alloying reaction and employing Fe instead of Co as a TM dopant.

关键词： particle size conversion alloying anode lithium-ion battery

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The transcription factor HSFA7b controls thermomemory at the shoot apical meristem by regulating ethylene biosynthesis and signaling in Arabidopsis

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Plant Communications 2024年第3期5卷 47-61页

作者： Sheeba John Federico Apelt Amit Kumar Ivan FAcosta dominik Bents Maria Grazia Annunziata Franziska Fichtner Caroline Gutjahr Bernd Mueller-Roeber Justyna J.Olas University of Potsdam Institute of Biochemistry and BiologyKarl-Liebknecht-Straße 24-25Haus 2014476 PotsdamGermany Max Planck Institute of Molecular Plant Physiology Am Muehlenberg 114476 PotsdamGermany Laboratory of Molecular Biology Wageningen University6700 AP Wageningenthe Netherlands Center of Plant Systems Biology and Biotechnology(CPSBB) 14 St.Knyaz Boris 1 Pokrastitel Str.4023 PlovdivBulgaria Present address:Institute of Plant Biochemistry Heinrich Heine University DusseldorfUniversit€atsstr.140225 DusseldorfGermany Leibniz Institute of Vegetable and Ornamental Crops Theodor-Echtermeyer-Weg 114979 GroßbeerenGermany

The shoot apical meristem(SAM)is responsible for overall shoot growth by generating all aboveground *** research has revealed that the SAM displays an autonomous heat stress(HS)memory of a previous non-lethal HS *** the importance of the SAM for plant growth,it is essential to determine how its thermomemory is mechanistically ***,we report that HEAT SHOCK TRAN-SCRIPTION FACTOR A7b(HSFA7b)plays a crucial role in this process in Arabidopsis,as the absence of functional HSFA7b results in the temporal suppression of SAM activity after *** found that HSFA7b directly regulates ethylene response at the SAM by binding to the promoter of the key ethylene signaling gene ETHYLENE-INSENSITIVE 3 to establish ***,we demonstrated that HSFA7b regulates the expression of ETHYLENE OVERPRODUCER 1(ETO1)and ETO1-LIKE 1,both of which encode ethylene biosynthesis repressors,thereby ensuring ethylene homeostasis at the *** together,these results reveal a crucial and tissue-specic role for HSFA7b in thermomemory at the Arabidopsis SAM.

关键词： ethylene response heat stress adaptation shoot apical meristem SAM thermopriming thermomemory

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Exploring the Characteristics of Data Breaches: A Descriptive Analytic Study

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Journal of Information Security 2024年第2期15卷 168-195页

作者： dominik Molitor Aditya Saharia Viju Raghupathi Wullianallur Raghupathi Gabelli School of Business Fordham University New York USA Brooklyn College The City University of New York New York USA

Data breaches have massive consequences for companies, affecting them financially and undermining their reputation, which poses significant challenges to online security and the long-term viability of businesses. This study analyzes trends in data breaches in the United States, examining the frequency, causes, and magnitude of breaches across various industries. We document that data breaches are increasing, with hacking emerging as the leading cause. Our descriptive analyses explore factors influencing breaches, including security vulnerabilities, human error, and malicious attacks. The findings provide policymakers and businesses with actionable insights to bolster data security through proactive audits, patching, encryption, and response planning. By better understanding breach patterns and risk factors, organizations can take targeted steps to enhance protections and mitigate the potential damage of future incidents.

关键词： Cyber Security Information Security Data Breaches Descriptive Analytics Privacy Visualization Visual Analytics

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No generality in biodiversity-productivity relationships along elevation in temperate and subtropical forest landscapes

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Forest Ecosystems 2024年第3期11卷 255-265页

作者： Jiayun Zou Yahuang Luo Rupert Seidl dominik Thom Jie Liu Lisa Geres Tobias Richter Linjiang Ye Wei Zheng Liangliang Ma Jie Song Kun Xu Dezhu Li Lianming Gao Sebastian Seibold Ecosystem Dynamics and Forest Management Research Group School of Life SciencesTechnical University of MunichHans-Carl-von-Carlowitz-Platz 285354FreisingGermany State Key Laboratory of Plant Diversity and Specialty Crops Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100China Berchtesgaden National Park Doktorberg 683471Germany Gund Institute for Environment University of Vermont617 Main StreetBurlingtonVT 1105405USA Faculty of Biological Sciences Institute for EcologyEvolution and DiversityConservation BiologyGoethe University FrankfurtFrankfurt am MainGermany University of Chinese Academy of Sciences Beijing10049China TUD Dresden University of Technology Forest ZoologyPienner Str.701737TharandtGermany

An improved understanding of biodiversity-productivity relationships(BPRs)along environmental gradients is crucial for effective ecosystem management and biodiversity *** stress-gradient hypothesis suggests that BPRs are stronger in stressful environments compared to more favorable ***,there is limited knowledge regarding the variation of BPRs along elevational gradients and their generality across different *** study how BPRs change with elevation,we harnessed inventory data on 6,431 trees from152 plots surveyed twice in eight to ten year intervals in mountain forests of temperate Europe and subtropical *** quantified the relationship between aboveground productivity and different biodiversity measures,including taxonomic,functional,and phylogenetic *** elucidate the processes underlying BPRs,we studied the variation of different functional traits along elevation across *** found no general pattern of BPRs across landscapes and *** were neutral for all biodiversity measures in temperate forests,and negative for taxonomic and functional diversity in subtropical *** were largely congruent between taxonomic,functional and phylogenetic *** found only weak support for the stress-gradient hypothesis,with BPRs turning from negative to positive(effect not significant)close to the tree line in subtropical *** temperate forests,however,elevation patterns were strongly modulated by species identity effects as influenced by specific *** effect of traits such as community-weighted mean of maximum plant height and wood density on productivity was congruent across *** study highlights the context-dependence of BPRs across elevation gradients and *** traits are key modulating factors of BPRs and should be considered more explicitly in studies of the functional role of ***,our findings highlight that potential trade-offs be

关键词： Biodiversity-ecosystem functioning Climate mitigation Elevation gradients Forest management Forest productivity Functional traits Nature conservation Phylogenetic diversity

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