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GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.Swindell krzysztof bojanowski Mark S.Kindy Raymond M.W.Chau Dorothy Ko Heritage College of Osteopathic Medicine Ohio UniversityAthensOHUSA Sunny BioDiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAMC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug GM604(GM6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by GM6(FDR<0.10).Early(6 h)responses included up-regulation of Notch and hedgehog signaling components,with increased expression of developmental genes mediating neurogenesis and axon *** GM6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment(FDR<0.10),which were known to function in neurogenesis,axon guidance and the intrinsic apoptosis ***:Our findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECM modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease RNA-seq Transcriptome

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Factors determining changes in the network of marked hiking trails in the Sudetes

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Journal of Mountain Science 2024年第4期21卷 1075-1099页

作者： krzysztof KOŁODZIEJCZYK Department of Regional Geography and Tourism Institute of Geography and Regional DevelopmentFaculty of Earth Sciences and Environmental ManagementUniversity of WroclawNo.1Uniwersytecki Square50-137 WroclawPoland

Hiking trails are a basic type of tourist infrastructure,which,on the one hand,make areas available for tourist traffic,and on the other hand,can contribute to the protection of the natural environment(if they are well designed and maintained).Owing to the variety of performed functions,their designation is determined by several factors:natural,technical,economic,*** of trails change *** aim of this article is to determine exactly what factors influence transformations within the hiking trail networks and what is their *** this end,three study areas in the Sudetes were analysed:one on the Polish side of the Sudetes-the Table(Stołowe)Mountains,and two on the Czech side-the rock town near the village of Sloup vČechách and the central part of Zlatohorská*** analysis of changes in the shape of the networks over time was carried out,as well as surveys of institutions that were responsible for or influenced these *** areas are characterised by a significant level of changes in the trail *** the factors influencing these changes,the tourist attractiveness of the area,the resilience of the environment,the intensity of tourism traffic,the environmental transformations associated with it,the history of tourism development and land ownership changes should be considered the most *** each stage of forming networks,the key factor should be tourists’needs,including the desire to escape the urbanised *** this reason,trails should avoid roads with artificial(hard)surfaces and heavy automobile traffic.

关键词： Hiking trails Trail networks Graphs Tourist traffic Sudetes

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The Generalized Stackelberg Equilibrium of the Two-Person Stopping Game

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Journal of the Operations Research Society of China 2024年第1期12卷 155-168页

作者： Marek Skarupski krzysztof J.Szajowski Faculty of Pure and Applied Mathematics Wroclaw University of Science and Technology50-370WrocƚawDolonoslaskiePoland

In modeling the bilateral selection of states of the process,Dynkin(Dokl Akad Nauk USSR 185:241–288,1969)proposed a two-person game in which players use stopping moments as *** purpose of this work is to present a model of the game in which the players have different information about the process itself,as well as various laws to stop the process and accept its *** game model uses the stochastic process apparatus,in particular,the ability to create different filters for the same *** sets of stopping moments based on different filters are not identical,which allows us to model different sets of strategies for *** show that the follower,by observing the behavior of a rational leader,can recover information that is lost due to the lack of complete observation of the state of the *** the competition of two opponents for the maximum of the ***,one of whom has access to full information and the other only knows their relative ranks,we found the generalized Stackelberg *** the priority of a player observing the relative ranks is less than 50%,then that player modifies his strategy based on the behavior of the second *** a player with full information,information about the behavior of the player observing the relative ranks is useless.

关键词： No-zero-sum game Optional stopping Equilibrium Filtration

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Advancing emergency preparedness in a postpandemic world:global collaboration and innovative approaches for hospitals

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Emergency and Critical Care Medicine 2024年第3期4卷 103-104页

作者： krzysztof Goniewicz Dennis G.Barten Department of Security Studies Polish Air Force UniversityDęblinPoland Department of Emergency Medicine VieCuri Medical CenterVenlothe Netherlands

As the world transitions into a postpandemic era,hospitals and healthcare systems must adapt their emergency management plans to address the unique challenges that *** upon the previous Hospital Emergency Management Plan^([1])during the coronavirus disease 2019 pandemic,this commentary offers updated and novel suggestions for emergency preparedness,emphasizing the need for international coordination and the implementation of innovative strategies.

关键词： innovative prepare global

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Crossover to PDT after the unsuccessful micropulse laser treatment of central serous chorioretinopathy

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Advances in Ophthalmology Practice and Research 2024年第1期4卷 32-38页

作者： Maciej Gawęcki krzysztof Kicinski Andrzej Grzybowski Dobry Wzrok Ophthalmological Clinic 80-822GdanskPoland Department of Ophthalmology Pomeranian Hospitals in Wejherowo84-200WejherowoPoland Institute for Research in Ophthalmology Foundation for Ophthalmology DevelopmentPoznanPoland

Purpose:Subthreshold micropulse laser(SML)and photodynamic therapy(PDT)are among the most effective therapeutic modalities applied to central serous chorioretinopathy(CSCR).This study aimed to evaluate the ef-ficacy and durability of PDT in CSCR cases unresponsive to at least two SML ***:The study included 26 consecutive eyes of 24 patients(21 males and three females)with chronic *** all cases,a lack of reduction in subretinal fluid(SRF)levels was noted after at least two consecutive SML *** parameters of best corrected visual acuity(BCVA)and spectral domain optical coherence tomog-raphy(SD-OCT)were evaluated at baseline and 1,3 and 12 months ***:The mean duration of symptoms in the group was 53.81±39.48 months,the mean age of the patients was 49.26±12.91 years,and the mean subfoveal choroidal thickness(SFCT)was 572.11±116.21 *** resorption of SRF was observed in 21 out of 26 eyes(80.77%)at 1 month and sustained in 18 cases(69.23%)at 12 *** 12 months,in the sustained group,BCVA improved significantly from 0.39±0.18 to 0.19±0.2 logMAR(P=0.01),central subfoveal thickness(CST)reduced from 316.44±75.83 mm to 197.67±22.99 mm(P<0.0001),and SFCT reduced from 579.28 mm to 446.78 mm(P<0.0001).Conclusions:PDT provides the opportunity for the successful treatment of CSCR unresponsive to SML *** are possible even in cases with a long duration of symptoms and significant alterations in retinal ***,PDT should be considered for patients with prominently increased choroidal thickness.

关键词： Photodynamic therapy Subthreshold micropulse laser Central serous chorioretinopathy Sybretinal fluid

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Prediction of the Photofading of Selected Derivatives of 5-(4-X-Phenylazo)-3-Cyano-1-(H or Ethyl)-6-Hydroxy-4-Methyl-2-Pyridone: Theoretical Studies, Comparison of AM1 and PM3 Methods

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Computational Chemistry 2024年第2期12卷 25-56页

作者： krzysztof Wojciechowski Lucjan Szuster Institute of Environmental Engineering and Building Installations Lodz University of Technology d Poland Institute of Leather Industry d Poland

We analysed the photooxidation reaction in the electro-(1O2) and nucleophilic (O2•−) reaction of 2-pyridone azo derivatives. First, we calculated the energy (enthalpies) of tautomers formation, which is a measure of durability and the probability of their formation. We performed the light fastness calculations of the monoazopyridone dyes. Using the semi-empirical methods of quantum chemistry AM1 and PM3, the reactivity indicators of superdelocalisability (SrE(N)) and the electron density distribution in ground state on the highest occupied HOMO orbital and the lowest unoccupied excited state LUMO in 2-pyridone phenylazo derivatives were calculated. Superdelocalisability coefficients enable the stability to oxidising agents of various chemical molecules depending on the tautomeric forms in which they may occur. The results of the electron density calculations at the HOMO and LUMO boundary orbitals allow to determine the tendency to electrophilic attack with singlet oxygen 1O2 or nucleophilic attack of the superoxide anion O2•−on a specific atom in the molecule. The structure of the dyes was optimised with MM+, MD and AM1 or PM3 until a constant energy value was achieved with a convergence criterion of 0.01 kcal/mol.

关键词： Photochemical Degradation AM1 and PM3 Methods Boundary Orbitals Electron Densities Electrophilic and Nucleophilic Reaction HOMO and LUMO Orbitals

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The g-factor measurement as an ultimate test for nuclear chirality

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Frontiers of physics 2024年第3期19卷 1-10页

作者： Ernest Grodner Michał Kowalczyk Julian Srebrny Leszek Próchniak Chrystian Droste Jan Kownacki Maciej Kisieliński krzysztof Starosta Takeshi Koike National Centre for Nuclear Research 05-540ŚwierkPoland Heavy Ion Laboratory University of WarsawPasteura 5a02-093 WarsawPoland Faculty of Physics University of WarsawPasteura 502-093 WarsawPoland Simon Fraser University 8888 University Drive BurnabyB.C.Canada V5A 1S6 Department of Physics Tohoku UniversitySendaiMiyagi 980-8577Japan

We present results of a series of experiments aimed at finding the most direct fingerprints of a phenomenon of nuclear chirality. These experiments brought a detailed knowledge of the so called partner bands in 132La, 128Cs and 126Cs including absolute values of E2 and M1 transition probabilities obtained through the DSA (Doppler Shift Attenuation) method. Considering the indirect character of observables such as energies and transition rates we proposed measurement of the g-factor of a chosen state as a direct, ultimate test of chirality. Our experiment on the bandhead of partner bands in 128Cs showed feasibility of this approach. Measured value of the g-factor which suggests non-chiral character of this state leads to another puzzle in the chirality studies — how the chirality emerges with increasing spin of levels along a partner band.

关键词： nuclear chirality electromagnetic transitions electromagnetic moments level lifetimes

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Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy Alexandra Kovar Teresa S Jones krzysztof J Wikiel Edward L Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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Influence of processing history on microstructure， mechanical properties， and electrical conductivity of Cu-0.7Mg alloy

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Transactions of Nonferrous Metals Society of China 2024年

作者： Alireza KALHOR Kinga RODAK Marek TKOCZ Bartosz CHMIELA Ivo SCHINDLER ?ukasz POLOCZEK krzysztof RADWA?SKI Hamed MIRZADEH Marian KAMPIK Faculty of Materials Engineering， Silesian University of Technology V?B – Technical University of Ostrava， Faculty of Materials Science and Technology Materials Research Group， ?ukasiewicz Upper Silesian Institute of Technology School of Metallurgy and Materials Engineering， College of Engineering， University of Tehran Faculty of Electrical Engineering， Silesian University of Technology

The effects of forward extrusion as well as extrusion combined with reversible torsion (KoBo extrusion)， followed by additional deformation via the MaxStrain module of the Gleeble thermomechanical simulator， on the microstructure， mechanical properties， and electrical conductivity of a Cu-0.7Mg (wt.%) alloy， were investigated in this work. The simulation results highlighted the critical influence of processing history in determining the equivalent strain distribution. The sample subjected to forward extrusion at 400 ℃and subsequent MaxStrain processing (FM sample)， possessed 76% lower grain size compared to the sample processed solely with MaxStrain (AM sample). Likewise， the KoBo-extruded and MaxStrain-processed sample (KM sample) exhibited 66% smaller grain size compared to the AM sample. Tensile test results revealed that the AM， FM， and KM samples， respectively， possessed 251%， 288%， and 360% higher yield strength， and 95%， 121%， and 169% higher tensile strength compared to the initial annealed alloy， as a result of grain refinement as well as deformation strengthening. Finally， the electrical conductivity measurements revealed that AM， FM， and KM samples， respectively， possessed electrical conductivity values of 37.9， 35.6， and 32.0 (MS/m)， which， considering their mechanical properties， makes them eligible to be categorized as high-strength and high-conductivity copper alloys.

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Bone graft incorporation failure with inappropriate limb load transfer can lead to aseptic acetabular loosening of metal-on-metal prosthesis: A case report

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World Journal of Orthopedics 2024年第7期15卷 668-674页

作者： RafałStanisław Domagalski Bogdan Dugiełło Sonia Rokicka Szymon Czech RafałSkowroński Dominika Rokicka Marta Patrycja Wróbel krzysztof Strojek Tomasz Stołtny District Hospital of Orthopaedics and Trauma Surgery in PiekaryŚląskie PiekaryŚląskie 41-940Poland District Railway Hospital Medical University of SilesiaKatowice 40-760Poland Faculty of Medicine Medical University of GdańskGdańsk 80-210Poland “ALFA”Orthopaedics and Traumatology Center Białystok 15-763Poland Department of Internal Medicine Diabetology and Cardiometabolic DisordersFaculty of Medical Sciences ZabrzeMedical University of SilesiaZabrze 41-800Poland

BACKGROUND Aseptic acetabular loosening can result from various factors that can be categorized into groups:patient-related,surgeon-related and *** present a case of a 63-year-old patient who at first underwent a total hip arthro-plasty(THA)using a metal-on-metal bearing due to hip ***-up visits revealed no complications after the *** years after the THA,acetabular component loosening occurred due to subsequent trauma of the opposite hip,necessitating a revision THA using a ceramic-on-ceramic *** SUMMARY We aim to illustrate a rare case where the primary reason for undergoing THA revision was not only incomplete bone graft incorporation but also improper limb load *** the revision arthroplasty,a 9-year follow-up visit revealed improvements in all evaluation measures on questionnaire compared to the state before surgery:Harris Hip Score(before surgery:15;after surgery:95),Western Ontario and McMaster Universities Arthritis Index(before surgery:96;after surgery:0),and Visual Analogue Scale(before surgery:10;after surgery:1).CONCLUSION Opposite-hip trauma caused a weight transfer to the limb after a THA *** process led to a stress shielding effect,resulting in acetabular component loosening.

关键词： Acetabular loosening Limb load Stress shielding effect Revision hip arthroplasty Case report

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