In 2018,the pan-Janus kinase(JAK)inhibitor tofacitinib was launched for the treatment of ulcerative colitis(UC).Although tofacitinib has proven efficacious in patients with active UC,it failed in patients with Crohn’...In 2018,the pan-Janus kinase(JAK)inhibitor tofacitinib was launched for the treatment of ulcerative colitis(UC).Although tofacitinib has proven efficacious in patients with active UC,it failed in patients with Crohn’s disease(CD).This finding strongly hints at a different contribution of JAK signaling in both entities.Here,we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription(STAT)pathway and inflammatory bowel diseases(IBD).In particular,we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD,highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD.Finally,we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.展开更多
AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. T...AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (CulZn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION: Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.展开更多
AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetra...AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.展开更多
The authors investigate the long-term dynamics of the three-dimensional Navier- Stokes-Voight model of viscoelastic incompressible fluid. Specifically, upper bounds for the number of determining modes are derived for ...The authors investigate the long-term dynamics of the three-dimensional Navier- Stokes-Voight model of viscoelastic incompressible fluid. Specifically, upper bounds for the number of determining modes are derived for the 3D Navier-Stokes-Voight equations and for the dimension of a global attractor of a semigroup generated by these equations. Viewed from the numerical analysis point of view the authors consider the Navier-Stokes-Voight model as a non-viscous (inviscid) regularization of the three-dimensional Navier-Stokes equations. Furthermore, it is also shown that the weak solutions of the Navier-Stokes- Voight equations converge, in the appropriate norm, to the weak solutions of the inviscid simplified Bardina model, as the viscosity coefficient v →0.展开更多
The primary objective of this study was to design and size a sustainable sanitation solution for the Ndiebene Gandiol 1 school located in the eponymous commune in northern Senegal. Field investigations led to the coll...The primary objective of this study was to design and size a sustainable sanitation solution for the Ndiebene Gandiol 1 school located in the eponymous commune in northern Senegal. Field investigations led to the collection of wastewater samples. Their analysis revealed specific pollutant loads, including loads of BOD5 3.6966 kgO<sub>2</sub>/day and COD of 12.8775 kgO<sub>2</sub>/day, which were central to the design phase. Following a rigorous assessment of the existing sanitation infrastructure, constructed wetland (CWs) emerged as the most appropriate ecological solution. This system, valued for its ability to effectively remove contaminants, was tailored to the specific needs of the site. Consequently, the final design of the filter extends over 217.16 m<sup>2</sup>, divided into two cells of 108.58 m<sup>2</sup> each, with dimensions of 12.77 m in length and 8.5 m in width. The depth of the filtering medium is approximately 0.60 m, meeting the standards while ensuring maximized purification. Typha, an indigenous and prolific plant known for its purification abilities, was selected as the filtering agent. Concurrently, non-crushed gravel was chosen for its proven filtration capacity. This study is the result of a combination of scientific rigor and design expertise. It provides a holistic view of sanitation for Ndiebene Gandiol. The technical specifications and dimensions of the constructed wetland filter embody an approach that marries indepth analysis and practical application, all aimed at delivering an effective and long-lasting solution to the local sanitation challenges. By integrating precise scientific data with sanitation design expertise, this study delivers a holistic solution for Ndiebene Gandiol. The detailed dimensions and specifications of the constructed wetland filter reflect a methodology that combines meticulous analysis with practical adaptation, aiming to provide an effective and sustainable response to the challenges of rural and school sanitation in the northern region of Senegal.展开更多
The existing knowledge regarding the interfacial forces,lubrication,and wear of bearings in real-world operation has significantly improved their designs over time,allowing for prolonged service life.As a result,self-...The existing knowledge regarding the interfacial forces,lubrication,and wear of bearings in real-world operation has significantly improved their designs over time,allowing for prolonged service life.As a result,self-lubricating bearings have become a viable alternative to traditional bearing designs in industrial machines.However,wear mechanisms are still inevitable and occur progressively in self-lubricating bearings,as characterized by the loss of the lubrication film and seizure.Therefore,monitoring the stages of the wear states in these components will help to impart the necessary countermeasures to reduce the machine maintenance downtime.This article proposes a methodology for using a long short-term memory(LSTM)-based encoder-decoder architecture on interfacial force signatures to detect abnormal regimes,aiming to provide early predictions of failure in self-lubricating sliding contacts even before they occur.Reciprocating sliding experiments were performed using a self-lubricating bronze bushing and steel shaft journal in a custom-built transversally oscillating tribometer setup.The force signatures corresponding to each cycle of the reciprocating sliding motion in the normal regime were used as inputs to train the encoder-decoder architecture,so as to reconstruct any new signal of the normal regime with the minimum error.With this semi-supervised training exercise,the force signatures corresponding to the abnormal regime could be differentiated from the normal regime,as their reconstruction errors would be very high.During the validation procedure for the proposed LSTM-based encoder-decoder model,the model predicted the force signals corresponding to the normal and abnormal regimes with an accuracy of 97%.In addition,a visualization of the reconstruction error across the entire force signature showed noticeable patterns in the reconstruction error when temporally decoded before the actual critical failure point,making it possible to be used for early predictions of failure.展开更多
Embryo cryopreservation(CP) has became a very important part of the clinical use of in vitro fertilization. Oocyte CP offers more advantages compared with embryo freezing with regard to less ethical, legal and moral...Embryo cryopreservation(CP) has became a very important part of the clinical use of in vitro fertilization. Oocyte CP offers more advantages compared with embryo freezing with regard to less ethical, legal and moral problems. However, the efficiency of this procedure is still low, which prevents its clinical application in wide range. The aim of our paper is to review the basic principles, technical and safety aspects and current status of oocyte cryopreservation in human assisted reproduction.展开更多
This research paper defines the theoretical foundations and computational implementation of a non-conventional modeling and simulation methodology,inspired by the needs of problem solving for biological,agricultural,a...This research paper defines the theoretical foundations and computational implementation of a non-conventional modeling and simulation methodology,inspired by the needs of problem solving for biological,agricultural,aquacultural and environmental systems.The challenging practical problem is to develop a framework for automatic generation of causally right and balance-based,unified models that can also be applied for the effective coupling amongst the various(sophisticated field-specific,sensor data processing-based,upper level optimization-driven,etc.)models.The scientific problem addressed in this innovation is to develop Programmable Process Structures(PPS)by combining functional basis of systems theory,structural approach of net theory and computational principles of agent based modeling.PPS offers a novel framework for the automatic generation of easily extensible and connectible,unified models for the underlying complex systems.PPS models can be generated from one state and one transition meta-prototypes and from the transition oriented description of process structure.The models consist of unified state and transition elements.The local program containing prototype elements,derived also from the meta-prototypes,are responsible for the case-specific calculations.The integrity and consistency of PPS architecture are based on the meta-prototypes,prepared to distinguish between the conservation-laws-based measures and the signals.The simulation is based on data flows amongst the state and transition elements,as well as on the unification based data transfer between these elements and their calculating prototypes.This architecture and its AI language-based(Prolog)implementation support the integration of various field-and task-specific models,conveniently.The better understanding is helped by a simple example.The capabilities of the recently consolidated general methodology are discussed on the basis of some preliminary applications,focusing on the recently studied agricultural and aquacultural cases.展开更多
Methionine(Met)is an essential and first limiting amino acid in the poultry diet that plays a significant role in chicken embryonic development and growth.The present study examined the effect of in ovo injection of D...Methionine(Met)is an essential and first limiting amino acid in the poultry diet that plays a significant role in chicken embryonic development and growth.The present study examined the effect of in ovo injection of DL-Met and L-Met sources and genotypes on chicken embryonic-intestinal development and health.Fertilized eggs of the two genotypes,TETRA-SL layer hybrid(TSL)—commercial layer hybrid and Hungarian Partridge colored hen breed(HPC)—a native genotype,were randomly distributed into four treatments for each genotype.The treatment groups include the following:1)control non-injected eggs(NoIn);2)saline-injected(SaIn);3)DL-Met injected(DLM);and 4)L-Met injected(LM).The in ovo injection was carried out on 17.5 d of embryonic development;after hatching,eight chicks per group were sacrificed,and the jejunum was extracted for analysis.The results showed that both DLM and LM groups had enhanced intestinal development as evidenced by increased villus width,villus height,and villus area(P<0.05)compared to the control.The DLM group had significantly reduced crypt depth,glutathione(GSH)content,glutathione S-transferase 3 alpha(GST3),occludin(OCLN)gene expression and increased villus height to crypt depth ratio in the TSL genotype than the LM group(P<0.05).The HPC genotype has overexpressed insulin-like growth factor 1(IGF1)gene,tricellulin(MD2),occludin(OCLN),superoxide dismutase 1(SOD1),and GST3 genes than the TSL genotype(P<0.05).In conclusion,these findings showed that in ovo injection of Met enhanced intestinal development,and function,with genotypes responding differently under normal conditions.Genotypes also influenced the expression of intestinal antioxidants,tight junction,and growth-related genes.展开更多
Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined...Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined to a single functional region of the brain.Here,we demonstrate a novel technique,termed the multiarea two-photon real-time in vivo explorer(MATRIEX),that allows the user to target multiple functional brain regions distributed within a zone of up to 12mm in diameter,each with a field of view(FOV)of ~200μm in diameter,thus performing two-photon Ca2+imaging with single-cell resolution in all of the regions simultaneously.For example,we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex,primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states.A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances(>1 mm)both laterally and axially but that are imaged by a single conventional laser scanning device.In particular,the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself.Thus,the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.展开更多
We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from...We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from the angle of the mandible to the upper mediastinum.Disruption of the thymic descent can result in ectopically/abnormally localised islets of accessory thymic tissue,which may undergo cystic changes,as described in a case report by Sun et al.This anatomical variation of the thymus may be clinically misinterpreted as a neoplasm or other congenital anomalies as a branchial cyst,lymphatic malformation or cystic hygroma.The present editorial focuses on the challenge of establishing a diagnosis of ectopically localised tissue of thymus often presented as a lateral cervical mass,especially in the case of cystic variation/degeneration of this thymic tissue.We summarise hypotheses on the origin of such congenital cervical thymic cysts from the point of view of evolutionary history and embryology.We also discuss lesser-known facts about the anatomy,histopathology and developmental biology of the thymus as one of the most enigmatic organs in the human body.展开更多
AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis. METHODS: Pancreatitis was...AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis. METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2×100μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK. RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-κB (NF-κB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress. CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.展开更多
Functional surfaces in relative contact and motion are prone to wear and tear,resulting in loss of efficiency and performance of the workpieces/machines.Wear occurs in the form of adhesion,abrasion,scuffing,galling,an...Functional surfaces in relative contact and motion are prone to wear and tear,resulting in loss of efficiency and performance of the workpieces/machines.Wear occurs in the form of adhesion,abrasion,scuffing,galling,and scoring between contacts.However,the rate of the wear phenomenon depends primarily on the physical properties and the surrounding environment.Monitoring the integrity of surfaces by offline inspections leads to significant wasted machine time.A potential alternate option to offline inspection currently practiced in industries is the analysis of sensors signatures capable of capturing the wear state and correlating it with the wear phenomenon,followed by in situ classification using a state-of-the-art machine learning(ML)algorithm.Though this technique is better than offline inspection,it possesses inherent disadvantages for training the ML models.Ideally,supervised training of ML models requires the datasets considered for the classification to be of equal weightage to avoid biasing.The collection of such a dataset is very cumbersome and expensive in practice,as in real industrial applications,the malfunction period is minimal compared to normal operation.Furthermore,classification models would not classify new wear phenomena from the normal regime if they are unfamiliar.As a promising alternative,in this work,we propose a methodology able to differentiate the abnormal regimes,i.e.,wear phenomenon regimes,from the normal regime.This is carried out by familiarizing the ML algorithms only with the distribution of the acoustic emission(AE)signals captured using a microphone related to the normal regime.As a result,the ML algorithms would be able to detect whether some overlaps exist with the learnt distributions when a new,unseen signal arrives.To achieve this goal,a generative convolutional neural network(CNN)architecture based on variational auto encoder(VAE)is built and trained.During the validation procedure of the proposed CNN architectures,we were capable of identifying acoustics signals corresp展开更多
AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis ...AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test. RESULTS: The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION: The results of the current study show that carriage of the +49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.展开更多
Road traffic congestion has become an everyday phenomenon in today's cities all around the world.The reason is clear:at peak hours,the road network operates at full capacity.In this way,growing traffic demand cann...Road traffic congestion has become an everyday phenomenon in today's cities all around the world.The reason is clear:at peak hours,the road network operates at full capacity.In this way,growing traffic demand cannot be satisfied,not even with traffic-responsive signal plans.The external impacts of traffic congestion come with a serious socio-economic cost:air pollution,increased travel times and fuel consumption,stress,as well as higher risk of accidents.To tackle these problems,a number of European cities have implemented reduced speed limit measures.Similarly,a general urban speed limit measure is in preparatory phase in Budapest,Hungary.In this context,a complex preliminary impact assessment is needed using a simulated environment.Two typical network parts of Budapest were analyzed with microscopic traffic simulations.The results revealed that speed limits can affect traffic differently in diverse network types indicating that thorough examination and preparation works are needed prior to the introduction of speed limit reduction.展开更多
Rapidly solidified Al100-x-Cux alloys (x = 5, 10, 15, 25, 35 wt%) were prepared and analyzed. High cooling rate increased the Cu solubility in α-AI matrix. The influence of the cooling rate on Cu solubility extensi...Rapidly solidified Al100-x-Cux alloys (x = 5, 10, 15, 25, 35 wt%) were prepared and analyzed. High cooling rate increased the Cu solubility in α-AI matrix. The influence of the cooling rate on Cu solubility extension in AI was experimentally simulated. Thus the pouring was performed in metallic die and by melt spinning-low pressure (MS- LP) technique. Melt processing by liquid quenching was performed using a self-designed melt spinning set-up which combined the cooling technology of a melt jet on the spinning disc with the principle of the mold feeding from low pressure casting technology. The thickness of the melt-spun ribbons was in the range of 30-70 μm. The cooling rate provided by MS-LP was within 105-106 K/s after the device calibration. The obtained alloys were characterized from structural, thermal and mechanical point of view. Optical microscopy and scanning electron microscopy were employed for the microstructural characterization which was followed by X-ray analysis. The thermal properties were evaluated by dilatometric and differential scanning calorimetric measurements. Vickers microhardness measurements were performed in the study. In the case of the hypereutectic alloy with 35 wt% Cu obtained by MS-LP method, the microhardness value increased by 45% compared to the same alloy obtained by gravity casting method. This was due to the extended solubility of the alloying element in the α-AI solid solution.展开更多
The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies.Over the past decades,rapid development and affordability of molecular tools have tremendously improved i...The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies.Over the past decades,rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats.Yet,in spite of the progress of molecular methods,knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging.In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels.Combining the information from previous efforts such as FUNGuild and FunFun together with involvement of expert knowledge,we reannotated 10,210 and 151 fungal and Stramenopila genera,respectively.This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera,designed for rapid functional assignments of environmental stud-ies.In order to assign the trait states to fungal species hypotheses,the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences.On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1%dissimilarity threshold.展开更多
High entropy alloys(HEAs)based on transition metals display rich magnetic characteristics,however attempts on their application in energy efficient technologies remain scarce.Here,we explore the magnetocaloric applica...High entropy alloys(HEAs)based on transition metals display rich magnetic characteristics,however attempts on their application in energy efficient technologies remain scarce.Here,we explore the magnetocaloric application for a series of Mn_(x)Cr_(0.3)Fe_(0.5)Co_(0.2)Ni_(0.5)Al_(0.3)(0.8<x<1.1)HEAs by integrated theoretical and experimental methods.Both theory and experiment indicate the designed HEAs have the Curie temperature close to room temperature and is tunable with Mn concentration.A non-monotonic evolution is observed for both the entropy change and the relative cooling power with changing Mn concentration.The underlying atomic mechanism is found to primarily emerge from the complex impact of Mn on magnetism.Advanced magnetocaloric properties can be achieved by tuning Mn concentration in combination with controlling structural phase stability for the designed HEAs.展开更多
文摘In 2018,the pan-Janus kinase(JAK)inhibitor tofacitinib was launched for the treatment of ulcerative colitis(UC).Although tofacitinib has proven efficacious in patients with active UC,it failed in patients with Crohn’s disease(CD).This finding strongly hints at a different contribution of JAK signaling in both entities.Here,we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription(STAT)pathway and inflammatory bowel diseases(IBD).In particular,we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD,highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD.Finally,we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.
基金Supported by the Hungarian Scientific Research Fund (T042589).
文摘AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (CulZn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION: Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.
基金Supported by the National Research Foundation (OTKA) T30735 and T042589
文摘AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.
基金supported by the Scientific and Research Council of Turkey (No.106T337)the ISF Grant (No.120/6)+1 种基金the BSF Grant (No.2004271)the National Science Foundation (Nos.DMS-0504619,DMS-0708832)
文摘The authors investigate the long-term dynamics of the three-dimensional Navier- Stokes-Voight model of viscoelastic incompressible fluid. Specifically, upper bounds for the number of determining modes are derived for the 3D Navier-Stokes-Voight equations and for the dimension of a global attractor of a semigroup generated by these equations. Viewed from the numerical analysis point of view the authors consider the Navier-Stokes-Voight model as a non-viscous (inviscid) regularization of the three-dimensional Navier-Stokes equations. Furthermore, it is also shown that the weak solutions of the Navier-Stokes- Voight equations converge, in the appropriate norm, to the weak solutions of the inviscid simplified Bardina model, as the viscosity coefficient v →0.
文摘The primary objective of this study was to design and size a sustainable sanitation solution for the Ndiebene Gandiol 1 school located in the eponymous commune in northern Senegal. Field investigations led to the collection of wastewater samples. Their analysis revealed specific pollutant loads, including loads of BOD5 3.6966 kgO<sub>2</sub>/day and COD of 12.8775 kgO<sub>2</sub>/day, which were central to the design phase. Following a rigorous assessment of the existing sanitation infrastructure, constructed wetland (CWs) emerged as the most appropriate ecological solution. This system, valued for its ability to effectively remove contaminants, was tailored to the specific needs of the site. Consequently, the final design of the filter extends over 217.16 m<sup>2</sup>, divided into two cells of 108.58 m<sup>2</sup> each, with dimensions of 12.77 m in length and 8.5 m in width. The depth of the filtering medium is approximately 0.60 m, meeting the standards while ensuring maximized purification. Typha, an indigenous and prolific plant known for its purification abilities, was selected as the filtering agent. Concurrently, non-crushed gravel was chosen for its proven filtration capacity. This study is the result of a combination of scientific rigor and design expertise. It provides a holistic view of sanitation for Ndiebene Gandiol. The technical specifications and dimensions of the constructed wetland filter embody an approach that marries indepth analysis and practical application, all aimed at delivering an effective and long-lasting solution to the local sanitation challenges. By integrating precise scientific data with sanitation design expertise, this study delivers a holistic solution for Ndiebene Gandiol. The detailed dimensions and specifications of the constructed wetland filter reflect a methodology that combines meticulous analysis with practical adaptation, aiming to provide an effective and sustainable response to the challenges of rural and school sanitation in the northern region of Senegal.
基金This work was funded by the Austrian COMET Program(project InTribology,No.872176)via the Austrian Research Promotion Agency(FFG)and the Provinces of Niederosterreich and Vorarlberg,and has been carried out within the Austrian Excellence Centre of Tribology(AC2T research GmbH).
文摘The existing knowledge regarding the interfacial forces,lubrication,and wear of bearings in real-world operation has significantly improved their designs over time,allowing for prolonged service life.As a result,self-lubricating bearings have become a viable alternative to traditional bearing designs in industrial machines.However,wear mechanisms are still inevitable and occur progressively in self-lubricating bearings,as characterized by the loss of the lubrication film and seizure.Therefore,monitoring the stages of the wear states in these components will help to impart the necessary countermeasures to reduce the machine maintenance downtime.This article proposes a methodology for using a long short-term memory(LSTM)-based encoder-decoder architecture on interfacial force signatures to detect abnormal regimes,aiming to provide early predictions of failure in self-lubricating sliding contacts even before they occur.Reciprocating sliding experiments were performed using a self-lubricating bronze bushing and steel shaft journal in a custom-built transversally oscillating tribometer setup.The force signatures corresponding to each cycle of the reciprocating sliding motion in the normal regime were used as inputs to train the encoder-decoder architecture,so as to reconstruct any new signal of the normal regime with the minimum error.With this semi-supervised training exercise,the force signatures corresponding to the abnormal regime could be differentiated from the normal regime,as their reconstruction errors would be very high.During the validation procedure for the proposed LSTM-based encoder-decoder model,the model predicted the force signals corresponding to the normal and abnormal regimes with an accuracy of 97%.In addition,a visualization of the reconstruction error across the entire force signature showed noticeable patterns in the reconstruction error when temporally decoded before the actual critical failure point,making it possible to be used for early predictions of failure.
文摘Embryo cryopreservation(CP) has became a very important part of the clinical use of in vitro fertilization. Oocyte CP offers more advantages compared with embryo freezing with regard to less ethical, legal and moral problems. However, the efficiency of this procedure is still low, which prevents its clinical application in wide range. The aim of our paper is to review the basic principles, technical and safety aspects and current status of oocyte cryopreservation in human assisted reproduction.
文摘This research paper defines the theoretical foundations and computational implementation of a non-conventional modeling and simulation methodology,inspired by the needs of problem solving for biological,agricultural,aquacultural and environmental systems.The challenging practical problem is to develop a framework for automatic generation of causally right and balance-based,unified models that can also be applied for the effective coupling amongst the various(sophisticated field-specific,sensor data processing-based,upper level optimization-driven,etc.)models.The scientific problem addressed in this innovation is to develop Programmable Process Structures(PPS)by combining functional basis of systems theory,structural approach of net theory and computational principles of agent based modeling.PPS offers a novel framework for the automatic generation of easily extensible and connectible,unified models for the underlying complex systems.PPS models can be generated from one state and one transition meta-prototypes and from the transition oriented description of process structure.The models consist of unified state and transition elements.The local program containing prototype elements,derived also from the meta-prototypes,are responsible for the case-specific calculations.The integrity and consistency of PPS architecture are based on the meta-prototypes,prepared to distinguish between the conservation-laws-based measures and the signals.The simulation is based on data flows amongst the state and transition elements,as well as on the unification based data transfer between these elements and their calculating prototypes.This architecture and its AI language-based(Prolog)implementation support the integration of various field-and task-specific models,conveniently.The better understanding is helped by a simple example.The capabilities of the recently consolidated general methodology are discussed on the basis of some preliminary applications,focusing on the recently studied agricultural and aquacultural cases.
基金awarded a Stipendium Hungaricum Scholarship for Ph.D.studiesthe support of the OTKA grant(K139021)
文摘Methionine(Met)is an essential and first limiting amino acid in the poultry diet that plays a significant role in chicken embryonic development and growth.The present study examined the effect of in ovo injection of DL-Met and L-Met sources and genotypes on chicken embryonic-intestinal development and health.Fertilized eggs of the two genotypes,TETRA-SL layer hybrid(TSL)—commercial layer hybrid and Hungarian Partridge colored hen breed(HPC)—a native genotype,were randomly distributed into four treatments for each genotype.The treatment groups include the following:1)control non-injected eggs(NoIn);2)saline-injected(SaIn);3)DL-Met injected(DLM);and 4)L-Met injected(LM).The in ovo injection was carried out on 17.5 d of embryonic development;after hatching,eight chicks per group were sacrificed,and the jejunum was extracted for analysis.The results showed that both DLM and LM groups had enhanced intestinal development as evidenced by increased villus width,villus height,and villus area(P<0.05)compared to the control.The DLM group had significantly reduced crypt depth,glutathione(GSH)content,glutathione S-transferase 3 alpha(GST3),occludin(OCLN)gene expression and increased villus height to crypt depth ratio in the TSL genotype than the LM group(P<0.05).The HPC genotype has overexpressed insulin-like growth factor 1(IGF1)gene,tricellulin(MD2),occludin(OCLN),superoxide dismutase 1(SOD1),and GST3 genes than the TSL genotype(P<0.05).In conclusion,these findings showed that in ovo injection of Met enhanced intestinal development,and function,with genotypes responding differently under normal conditions.Genotypes also influenced the expression of intestinal antioxidants,tight junction,and growth-related genes.
基金supported by the“100-Talents Program for Elite Engineers”of the CAS(H.J.)the Key Scientific Research Equipment Development Project of the CAS(Super-resolution Microscopy Systems and Key Components,ZDYZ2013-1)+3 种基金the“1000-Talents Program for Young Scholars”of China(X.C.)grants from the Ministry of Science and Technology of China(“973 Program”:2015CB759500,2018YFA0109600)the National Natural Science Foundation of China(61705251,81671106,81771175,31700933,81721001)the China Postdoctoral Science Foundation(2018M632374).
文摘Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined to a single functional region of the brain.Here,we demonstrate a novel technique,termed the multiarea two-photon real-time in vivo explorer(MATRIEX),that allows the user to target multiple functional brain regions distributed within a zone of up to 12mm in diameter,each with a field of view(FOV)of ~200μm in diameter,thus performing two-photon Ca2+imaging with single-cell resolution in all of the regions simultaneously.For example,we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex,primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states.A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances(>1 mm)both laterally and axially but that are imaged by a single conventional laser scanning device.In particular,the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself.Thus,the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.
文摘We point out the issue of differential diagnosis regarding the finding of ectopically localised thymic tissue(a thymic cyst)in the neck.Thymic tissue can be found anywhere along its developmental tract of descent,from the angle of the mandible to the upper mediastinum.Disruption of the thymic descent can result in ectopically/abnormally localised islets of accessory thymic tissue,which may undergo cystic changes,as described in a case report by Sun et al.This anatomical variation of the thymus may be clinically misinterpreted as a neoplasm or other congenital anomalies as a branchial cyst,lymphatic malformation or cystic hygroma.The present editorial focuses on the challenge of establishing a diagnosis of ectopically localised tissue of thymus often presented as a lateral cervical mass,especially in the case of cystic variation/degeneration of this thymic tissue.We summarise hypotheses on the origin of such congenital cervical thymic cysts from the point of view of evolutionary history and embryology.We also discuss lesser-known facts about the anatomy,histopathology and developmental biology of the thymus as one of the most enigmatic organs in the human body.
基金the postdoctoral fellowship of the Hungarian Ministry of Educationthe National Research Foundations (OTKA) grants T30735,T042589 and TS049817
文摘AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis. METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2×100μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK. RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-κB (NF-κB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress. CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.
基金This work was funded by the Austrian COMET Program(project InTribology,No.872176)via the Austrian Research Promotion Agency(FFG)the Provinces of Niederösterreich and Vorarlberg and has been carried out within the Austrian Excellence Centre of Tribology(AC2T Research GmbH)Experiments were carried out within the framework of a project funded by the government of Lower Austria(No.K3-F-760/001-2017).
文摘Functional surfaces in relative contact and motion are prone to wear and tear,resulting in loss of efficiency and performance of the workpieces/machines.Wear occurs in the form of adhesion,abrasion,scuffing,galling,and scoring between contacts.However,the rate of the wear phenomenon depends primarily on the physical properties and the surrounding environment.Monitoring the integrity of surfaces by offline inspections leads to significant wasted machine time.A potential alternate option to offline inspection currently practiced in industries is the analysis of sensors signatures capable of capturing the wear state and correlating it with the wear phenomenon,followed by in situ classification using a state-of-the-art machine learning(ML)algorithm.Though this technique is better than offline inspection,it possesses inherent disadvantages for training the ML models.Ideally,supervised training of ML models requires the datasets considered for the classification to be of equal weightage to avoid biasing.The collection of such a dataset is very cumbersome and expensive in practice,as in real industrial applications,the malfunction period is minimal compared to normal operation.Furthermore,classification models would not classify new wear phenomena from the normal regime if they are unfamiliar.As a promising alternative,in this work,we propose a methodology able to differentiate the abnormal regimes,i.e.,wear phenomenon regimes,from the normal regime.This is carried out by familiarizing the ML algorithms only with the distribution of the acoustic emission(AE)signals captured using a microphone related to the normal regime.As a result,the ML algorithms would be able to detect whether some overlaps exist with the learnt distributions when a new,unseen signal arrives.To achieve this goal,a generative convolutional neural network(CNN)architecture based on variational auto encoder(VAE)is built and trained.During the validation procedure of the proposed CNN architectures,we were capable of identifying acoustics signals corresp
基金Supported by the grants of Hungarian Science Foundation (OTKA T 0495X9)Hungarian Ministry of Health (ETT 497/2006)by the National Office for Research and Technology, "Pazmany Peter" program. (RET- II 08/2005)
文摘AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test. RESULTS: The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION: The results of the current study show that carriage of the +49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.
基金supported by the National Laboratory for Autonomous Systems fund of the Hungarian Ministry for Innovation and Technology(2019-2.1.7-ERA-NET-2021-00019).
文摘Road traffic congestion has become an everyday phenomenon in today's cities all around the world.The reason is clear:at peak hours,the road network operates at full capacity.In this way,growing traffic demand cannot be satisfied,not even with traffic-responsive signal plans.The external impacts of traffic congestion come with a serious socio-economic cost:air pollution,increased travel times and fuel consumption,stress,as well as higher risk of accidents.To tackle these problems,a number of European cities have implemented reduced speed limit measures.Similarly,a general urban speed limit measure is in preparatory phase in Budapest,Hungary.In this context,a complex preliminary impact assessment is needed using a simulated environment.Two typical network parts of Budapest were analyzed with microscopic traffic simulations.The results revealed that speed limits can affect traffic differently in diverse network types indicating that thorough examination and preparation works are needed prior to the introduction of speed limit reduction.
基金supported by the Sectoral Operational Programme Human Resources Development(SOP HRD)ID59321 financed from the European Social Fundsupported by the Romanian Government
文摘Rapidly solidified Al100-x-Cux alloys (x = 5, 10, 15, 25, 35 wt%) were prepared and analyzed. High cooling rate increased the Cu solubility in α-AI matrix. The influence of the cooling rate on Cu solubility extension in AI was experimentally simulated. Thus the pouring was performed in metallic die and by melt spinning-low pressure (MS- LP) technique. Melt processing by liquid quenching was performed using a self-designed melt spinning set-up which combined the cooling technology of a melt jet on the spinning disc with the principle of the mold feeding from low pressure casting technology. The thickness of the melt-spun ribbons was in the range of 30-70 μm. The cooling rate provided by MS-LP was within 105-106 K/s after the device calibration. The obtained alloys were characterized from structural, thermal and mechanical point of view. Optical microscopy and scanning electron microscopy were employed for the microstructural characterization which was followed by X-ray analysis. The thermal properties were evaluated by dilatometric and differential scanning calorimetric measurements. Vickers microhardness measurements were performed in the study. In the case of the hypereutectic alloy with 35 wt% Cu obtained by MS-LP method, the microhardness value increased by 45% compared to the same alloy obtained by gravity casting method. This was due to the extended solubility of the alloying element in the α-AI solid solution.
基金Estonian Science Foundation grants PSG136,PRG632,PUT1170the University of Tartu(PLTOM20903)the European Regional Development Fund(Centre of Excellence EcolChange).
文摘The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies.Over the past decades,rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats.Yet,in spite of the progress of molecular methods,knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging.In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels.Combining the information from previous efforts such as FUNGuild and FunFun together with involvement of expert knowledge,we reannotated 10,210 and 151 fungal and Stramenopila genera,respectively.This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera,designed for rapid functional assignments of environmental stud-ies.In order to assign the trait states to fungal species hypotheses,the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences.On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1%dissimilarity threshold.
基金supported by the Swedish Research Council(2015-5335 and 2017-06474)the Swedish Foundation for Strategic Research (S14-0038 and SM16-0036)+3 种基金the Swedish Foundation for International Cooperation in Research and Higher Education(CH2015-6292)the Swedish Energy Agency,the Hungarian Scientific Research Fund (OTKA 128229)the Carl Tryggers Foundationsupport from the Swedish Energy Agency (Energimyndigheten),ST and UPP and e SSENCE
文摘High entropy alloys(HEAs)based on transition metals display rich magnetic characteristics,however attempts on their application in energy efficient technologies remain scarce.Here,we explore the magnetocaloric application for a series of Mn_(x)Cr_(0.3)Fe_(0.5)Co_(0.2)Ni_(0.5)Al_(0.3)(0.8<x<1.1)HEAs by integrated theoretical and experimental methods.Both theory and experiment indicate the designed HEAs have the Curie temperature close to room temperature and is tunable with Mn concentration.A non-monotonic evolution is observed for both the entropy change and the relative cooling power with changing Mn concentration.The underlying atomic mechanism is found to primarily emerge from the complex impact of Mn on magnetism.Advanced magnetocaloric properties can be achieved by tuning Mn concentration in combination with controlling structural phase stability for the designed HEAs.