bluuebunny/crossref_metadata_2025_split huggingface dataset:
Welded joints of offshore fixed platforms for the extraction of oil, gas and other minerals on shelf
Authors: Starokon I V 
Published: April 2020

Abstract
The world is actively developing offshore mineral deposits (oil, gas, coal, steel and other minerals). Offshore fixed platforms are actively used for offshore production. During operation, these platforms are subject to various impacts (wave, wind, etc.), which leads to the occurrence of alternating stresses. Current AC voltages activate fatigue processes in welded joints. Therefore, the knowledge of the peculiarities of the stress state of the welded joints of offshore platforms is the key to understanding the fatigue processes taking place in them. Nowadays various theories offer different understanding of the stresses acting in a welded joint. For example, the strength theory does not take into account the presence of “hot spots” in the welded joint, assuming a uniform distribution of stresses on the welding seam. The influence of static load on the general picture of the stress state in the welded joint was also investigated. As a result of the carried out researches the location of points with the greatest concentration of pressure, influence of thicknesses, diameters and an angle of interface of connected elements is established. The calculations showed that the sharper the angle of connection of the branch to the main pipe, the lower the value of stress concentration coefficients. Stresses acting in the welded joint also increase in case of increase in the diameter and wall thickness of the offshore platform columns. The analysis of the results of the computer model showed that the greatest contribution to the stress state of the platform is the tensile force and bending moment outside the plane, which indicates that the points with the highest stress concentration will be the points located in the direction of the wave beam.
Study of deformations of building structures thin-walled elements by the method of moire strips
Authors: Yemets V N , Kalmova M A , Akhmedov A D 
Published: April 2020

Abstract
The article deals with the application of one of the experimental optical-geometric methods which is the method of moire strips with a reflected grid (according to the Ligtenberg scheme) to the study of I-beam corrugated beams with different wall configurations of constant thickness, rigidly fixed on one side and free on the other (console). The bending deformation process was observed from the action of a concentrated force at the free end with the gradual loading at different intervals of the applied force action. A model of a beam made of low-modulus material (plexiglass) with two types of wall profile: wavy and triangular was tested. The modeling process of the studied beams was developed. Virtual technique of moire patterns formation with the subsequent computer processing by standard programs was applied. The analysis of the deflections along the beam length depending on the load is given and deflections graphs are constructed in comparison with the theoretical calculation for models with corrugated and flat walls (standard I-beam).
Esterified Hyaluronic Acid Matrix in Lower Extremity Reconstruction With Exposed Tendon and Bone: A Retrospective Review
Authors: Kozusko Steven D , Hassouba Mahmoud , Hill David M , Liu Xiangxia , Dadireddy Kalyan , Velamuri Sai R 
Published: April 2020

Abstract
Lower extremity wounds with exposed bone and tendon often need coverage to allow the underlying tissue to regenerate prior to skin graft. The surgeon is limited in his or her choices to augment tissue regeneration in these types of complicated cases; for instance, autologous skin should not be placed on exposed bone or tendon and is at risk for contracture when placed over the joints. Therefore, novel technologies are necessary to provide a scaffolding for tissue to regenerate and allow for a successful graft. One such technology is an esterified hyaluronic acid matrix (eHAM), which can provide a proper scaffold for endothelial cell migration and aid in angiogenesis. The eHAM is made of two layers: a layer of hyaluronic acid covered with a silicone layer. In this retrospective chart review, we describe our usage of eHAM to provide scaffolding for tissue regeneration prior to grafting in 15 cases of complicated lower extremity wounds with exposed bone and tendon. The average patient age was 45.8 years, and all patients had multiple medical comorbidities, such as poorly controlled diabetes mellitus, hypertension, and nicotine addiction. Patient wound types were diverse, including traumatic wounds, chronic diabetic foot ulcers, and thermal or electric burns. Thirteen of the 15 cases were treated successfully with eHAM. In these cases, definitive coverage with split-thickness skin grafting was effective and limb salvage was successful. In the 13 successful cases, the mean time to split-thickness skin graft was 22.9 ± 7.0 days. All patients continue to do well at follow-up (ranging from 6 to 48 weeks), with minimal complications reported. Given the success rate with eHAM in this challenging population, we conclude that eHAM can be a treatment option for similar cases.
When brain stimulation backfires: the effects of prefrontal cortex stimulation on impulsivity
Authors: Bell Sarah Beth , Turner Brian , Sawaki Lumy , DeWall Nathan 
Published: April 2020

Abstract
Transcranial direct current stimulation (tDCS) can sometimes cause the opposite of its intended effect. These reverse effects may be related in part to individual differences in personality and neurochemistry. Previous studies have demonstrated that dopamine levels can impact the effects of tDCS. In the present study, 124 healthy participants took the UPPS impulsive behavior scale. Participants then underwent a single, randomized anodal or sham tDCS session on the prefrontal cortex. While the effects of tDCS were still active, they performed the Stop Signal Task, a measure of state impulsivity. tDCS was associated with increased errors on this task in people who had higher scores on the UPPS in two facets of impulsivity that correlate with dopamine levels. tDCS had no effects on people who are low in trait impulsivity. These results suggest that the reverse effects of tDCS could be associated with inter-individual differences in personality and neurochemistry.
Multi‐omics approach identifies differences between cranial and spinal motor neuron – A step towards understanding ALS
Authors: Maity Shuvadeep , An Disi , Randleman Justin , Iannitelli Dylan , Mazzoni Esteban , Vogel Christine 
Published: April 2020

Amyotrophic Lateral Sclerosis (ALS) is an adult‐onset fatal neurodegenerative disease with a selective, highly progressive loss of both spinal and upper motor neurons. However, cranial motor neurons are much less sensitive and survive until the late stages of the disease. The inability of the cells to respond appropriately to Endoplasmic Reticulum (ER) stress is thought to be one of the major reasons for the ALS progression. ER stress is a condition that arises after the accumulation of misfolded proteins inside the ER and activates a repertoire of transcriptional and translational events collectively called unfolded protein response (UPR). In the context of ALS progression, the dynamics of transcriptomics and proteomic profile over time in the presence of ER stress conditions are poorly understood. Here, we established a condition where ER stress shows differential vulnerability of stem cell derived cranial (CrMN) and spinal motor (SpMN) neurons. Using high throughput quantitative omics approaches, we quantified >8,200 genes over time and found that subtle expression changes influence several pathways that are essential for cranial and spinal motor neuron function. We demonstrate that pathways related to overall protein turnover differ in these two cell lines. Specifically, we identified expression differences in Rab proteins that have not been recognized to‐date. These Rab proteins affect synaptic recycling, endocytic sorting, and autophagic flux. Further, we discovered a novel link between the core proteasome and endocytic pathways that potentially help CrMN to turn over proteins more efficiently than SpMN. Combined, these results illustrate new insights into the complex behavior and subtle differences between two motor neuron cell lines and provide new avenues towards therapeutic intervention.Support or Funding InformationNational Institute of General Medical Sciences (R01 GM113237), National Institute of General Medical Sciences (1R35GM127089‐01), Project ALS (A13‐0416)
NEIL2 plays a critical role in limiting inflammation and preserving genomic integrity in H. pylori‐infected gastric epithelial cells
Authors: Sayed Ibrahim M. , Sahan Ayse Z. , Venkova Tatiana , Chakraborty Anirban , Reyes Victor , Mukhopadhyay Dibyabrata , Pinchuk Irina , Beswick Eileen , Ghosh Pradipta , Hazra Tapas K. , Das Soumita 
Published: April 2020

The accumulation of Helicobacter pylori infection‐ induced DNA damage in gastric epithelial cells is a risk factor for developing gastric cancer; however, the underlying mechanisms remain poorly understood. Here we report that suppression of the DNA repair enzyme NEIL2 is one such mechanism via which H. pylori infection may fuel the accumulation of DNA damage during the initiation and progression of gastric cancers (GCs). We found that NEIL2 was significantly downregulated upon H. pylori infection both in vitro and in human gastric biopsies. The H. pylori infection‐induced downregulation of NEIL2 is specific, as Campylobacter jejuni has no such effect. Using gastric organoids isolated from the murine and human stomach in co‐culture studies with live microbes, mimicking the infected stomach lining, we found that H. pylori infection was associated with proinflammatory cytokines release; this response was more pronounced in Neil2 knock out (KO) mouse cells compared to wild type (WT) cells suggesting that NEIL2 suppresses inflammation under physiological conditions. In vivo studies in mice showed that despite a lower bacterial load, as determined by UreB expression, DNA damage was significantly higher in Neil2 KO mice compared to WT mice. Interestingly, after infection with H. pylori, Neil2 KO mice has higher inflammation and epithelial cell damage compared to WT cells. Taken together, our data suggest that downregulation of NEIL2 is a plausible way of how H. pylori infection derails DNA damage repair mechanisms and initiates GCs.Support or Funding InformationThis work was supported, in whole or in part, by National Institute of Health Grants: DK107585 and DK099275 (to SD); R01 NS073976 (to TH).
Inhibition of P2X4 purinoceptor reduces growth of the cerebral aneurysm
Authors: Fukuda Miyuki , Fukuda Shunichi , Suzuki Takashi , Niwa Youko , Hasegawa Koji , Shimatsu Akira , Tsukahara Tetsuya 
Published: April 2020

BackgroundRupture of a cerebral aneurysm is a major cause of life‐threatening subarachnoid hemorrhage. However, there are no effective therapeutic drugs for the treatment of aneurysms, partly because the pathogenesis of the aneurysm remains unresolved. Although chronic inflammation of the cerebral arterial wall plays an important role in aneurysm formation, it is not clear what triggers the inflammation. We previously reported that inhibition of the endothelial shear stress sensor, P2X4 purinoceptor, significantly reduces mRNA expressions of known inflammatory contributors to aneurysm formation, leading to suppression of aneurysm induction. We examined here whether inhibition of P2X4 has any influence on cerebral aneurysm ‘growth’ or not.MethodsSprague‐Dawley rats were subjected to cerebral aneurysm‐generating surgery with ligation of unilateral common carotid artery and renal hypertension. P2X4 purinoceptor inhibitor, paroxetine (8 mg/kg/day) was administered to rats. Three weeks after the surgery, the aneurysm size was examined with light microscopy, and protein expressions of contributors to aneurysm formation using Western blotting.ResultsThe cerebral aneurysm‐inducing surgery induced an aneurysm in 100% of rats 2 weeks after the surgery. Application of paroxetine from 2 weeks after surgery led to a significant reduction in aneurysm size in the rats sacrificed 3 weeks after aneurysm‐inducing surgery (p=0.0145), indicating that paroxetine suppressed enlargement of formed aneurysms. The protein expression levels of known inflammatory contributors to aneurysm formation (MCP‐1, IL1ß, TNFα, iNOS, and COX‐2) were all significantly elevated in the rats that underwent the aneurysm‐inducing surgery compared to the non‐surgical group, and the values in the surgical group were all significantly decreased by paroxetine administration.ConclusionThe data suggest that P2X4 is required for the cerebral aneurysm growth. Enhanced shear stress‐associated hemodynamic stress on the vascular endothelium may trigger the cerebral aneurysm enlargement. Since paroxetine has been used for human as an antidepressant, clinical use of this P2X4 purinoceptor inhibitor is expected as a novel therapy for cerebral aneurysms.Support or Funding InformationThis work was supported by the Japan Agency for Medical Research and Development (AMED) under grant no. JP15gm0810006h0301, a JSPS KAKENHI grant (no. 15K10323), and The Shimizu Foundation for Immunology and Neuroscience.
ZEBRAFISH AS MODELS OF TYROSINE KINASE‐DRIVEN CANCER
Authors: Medishetty Raghavender , Challa Anil , Rao C. Mallukarjuna , Chatti Kiranam 
Published: April 2020

The protein kinase gene family encodes proteins involved in several essential functions, with cell growth and migration being essential outcomes. Mutations in kinases underlie a broad range of diseases, primarily inflammation and cancer. Tyrosine kinase inhibitors (TKIs) in particular, are successfully used as a targeted therapy for cancer and inflammation‐driven disorders. Current unmet needs include addressing the adverse effects of TKIs, the emergence of resistance, and the necessity of newer TKIs. Experiments using accessible animal models such as zebrafish can help address these needs. Zebrafish studies can help in efficient characterization of toxicological and pharmacological effects of inhibition using known or potential TKIs, via the combination of phenotypic and molecular analysis. The recent application of CRISPR‐Cas9 further enables the development of genetically engineered cancer models in zebrafish. Following our previous work showing conservation of zebrafish tyrosine kinases compared to humans, we are now studying the effects of chemical or genetic tyrosine kinase modulation in zebrafish.To identify the phenotypic endpoints of tyrosine kinase inhibition in zebrafish, we selected a few drugs approved by the USFDA for treating cancer and inflammation‐related disorders in humans. We evaluated phenotypic effects including adverse effects to identify NOELs and detectable and consistent phenotypic endpoints of such compounds in zebrafish. These effects provide a basis to evaluate novel TKI compounds. Further, tyrosine kinase genes involved in inflammation and cancer were selected for targeted genetic modification in zebrafish using CRISPR Cas9. Our initial data demonstrate the development of MET (HGFR) homozygous mutant zebrafish and the phenotypes associated with this mutant. Detailed characterization of this mutant including molecular analysis is under way. The characteristics of this mutant provide the basis to identify MET‐specific inhibitors. Development of zebrafish models carrying oncogenic TK mutants, and detailed characterization of the effects of TKIs in zebrafish are ongoing.In summary, our work is focussed on identifying TKI treatment‐related phenotypes in zebrafish, and generation of TK‐crispant zebrafish as cancer models.Support or Funding InformationDepartment of Biotechnology and the Indian Council of Medical Research, Govt. of India
Impaired Tricellular Tight Junctions Open the Barrier for Lipopolysaccharide Uptake
Authors: Krug Susanne M. , Lee In-Fah M. , Weiß Franziska , Hu Jia-Chen E. , Fromm Michael , Schulzke Jörg D. 
Published: April 2020

Lipopolysaccharides (LPS) are essential membrane components of most Gram‐negative bacteria and several pathologies have been linked to LPS‐induced inflammation. However, understanding the mechanisms of intestinal uptake of LPS is still at its beginning. Uptake is thought to happen either via toll‐like‐receptor‐4‐induced phagocytosis or via paracellular passage. In ulcerative colitis (UC), the paracellular barrier formed by tight junctions (TJ) is impaired and tricellulin, a protein of the tricellular TJ of importance for regulation of paracellular macromolecule passage, is downregulated.We hypothesize that a sole reduction in tricellulin expression leads to enhanced antigen uptake with the consequence that LPS is passing the intestinal epithelium via the tricellular TJ.For analyzing this, we generated clones of intestinal epithelial cell monolayers HT‐29/B6 at different tricellulin knockdown levels and measured the permeability for LPS. The passage of LPS through the tricellular TJ was visualized using a dedicated fluorescence microscopical technique. We then analyzed the capability of passaged LPS to stimulate immune cells and by that to induce inflammation. For this, we added LPS apically to the monolayers containing different levels of tricellulin and co‐cultured them with basolaterally located macrophages. Passing LPS should stimulate these after passage. The basolateral medium thus containing secreted cytokines was added to otherwise uninvolved HT‐29/B6 cells and the effect on transepithelial resistance (TER) was monitored.Using concentrations of LPS which were below to affect the epithelial barrier of HT‐29/B6 cells, at a decreased level of tricellulin of 50% the permeability for LPS was three times higher than in controls (shTric50: 2.09±0.56 × 10−9 cm/s; control: 0.70±0.13 × 10−9 cm/s; n=7, p=0.03). Although the permeability was quite low in absolute terms, LPS passage in shTric50 was sufficient to stimulate macrophages to secrete cytokines. This was not the case for cells with high tricellulin expression. TER of HT‐29/B6 cells treated with the supernatants of the macrophages of the co‐culture with LPS‐incubated controls did not change.We conclude that reduced tricellulin levels allow for paracellular passage of LPS via tricellular TJs and thereby may stimulate immune cells supporting inflammatory processes as happening in UC. This signifies a new pathomechanistic pathway for LPS‐induced inflammation.Support or Funding InformationSupported by DFG GRK 2318 and DFG TRR 241
Computed Cell‐Cell Interactions Correlate with Physical Location of Cells in C. elegans
Authors: Armingol Erick , Joshi Chintan , Baghdassarian Hratch Matthew , Shamie Isaac , Lewis Nathan 
Published: April 2020

Behaviors, functions and phenotypes of multicellular organisms are shaped by the coordination of cellular activities and properties. Those cellular activities and properties depend on activation of cell‐cell communication pathways and proper intercellular interactions amongst cells. The most important factors that influence how cells communicate and interact are localization of cells in the organism, expression levels of membrane proteins and secreted proteins. We sought to understand how intercellular interactions may be shaped by cell proximity, by analyzing protein‐protein interactions that could lead cell‐cell communication and interaction. We evaluated cell‐cell communication in C. elegans by integrating single‐cell RNA‐seq data and a list of ligand‐receptor pairs. To assess the potential of interaction, we computed a cell‐cell interaction (CCI) score that captures the number of ligand‐receptor pairs that are active between two cells versus the active ligands or receptors in each of those cells. We used this approach for every cell pair in the transcriptomics data. To associate the CCI score to the physical location of cells we used a published 3D‐map of cells to create a distance matrix among cell pairs. Afterwards, we calculated a correlation score between CCI score and physical distance of cell pairs. The score was used as an objective function to be maximized as ligand‐receptor pairs were randomly dropped from the list by a genetic algorithm (GA). Subsequently, a permutation analysis was run to evaluate the extent of significance of the ligand‐receptor pairs that were selected to maximize the correlation. To understand the role of those protein‐protein interactions, we performed a functional analysis on the list obtained by the GA. From these analyses, we obtained a negative spearman correlation between CCI scores and physical distances, showing that the protein‐protein interactions obtained by the GA capture properties of 3D‐location of cells and their potential of interaction given their proximity to certain cells. In addition, functional analysis of enriched ligand‐receptor pairs gave us more insights about the role that they could have given the cell locations. Our approach of computing CCI scores will facilitate data‐driven discoveries such as detecting key ligand‐receptor pairs for given properties or phenotypes of cells, and in the case of C. elegans, demonstrates that physical location of cells may be predicted by molecular signatures associated with the proteins mediating the interactions.Support or Funding InformationThis work was supported by the Keck Foundation, and scholarship awards from Becas Chile (CONICYT) and the Fulbright Commission.
Protective effects of Gallic acid against COPD linked inflammation and emphysema
Authors: Singla Esha , Naura Amarjit Singh 
Published: April 2020

Chronic Obstructive Pulmonary Disorder (COPD) is a chronic inflammatory disease, currently affecting around 328 million people worldwide. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti‐oxidant and anti‐inflammatory activities. The aim of the present work was to investigate the beneficial effects of Gallic acid against COPD linked inflammation and emphysema by utilizing Elastase (ET) and Cigarette smoke (CS) based mouse model(s) of the disease. Male Balb/c mice were treated with ET (1U/mouse) or exposed to CS (9 cigarettes/day for 4 days). GA administration was started 7 days (daily) prior to induction of injury with ET or CS exposure. Broncho‐alveolar lavage was analysed for inflammatory cells and pro‐inflammatory cytokines. Lung homogenate was assessed for oxidative stress related biochemical parameters. Further, lung tissue was subjected to semi‐quantitative RT‐PCR, Immunoblotting and histological analysis. Our data showed that GA treatment suppressed the ET induced recruitment of inflammatory cells particularly neutrophils as well as myeloperoxidase activity in lungs at 24 hrs post injury. Reduction in the inflammatory cells was associated with subdued production of pro‐inflammatory cytokines namely IL‐1β, TNF‐α and IL‐6. Additionally, GA normalized the ET induced redox imbalance in the lungs towards normal as reflected by levels of ROS, MDA, GSH and protein carbonyls. Further, GA treatment blunted the ET induced phosphorylation of p65NF‐kB and its inhibitor IκBα along with down‐regulation of mRNA expression of NF‐kB dependent pro‐inflammatory factors including IL‐1β, TNF‐α, MIP‐2, KC and GCSF. Moreover, GA suppressed the CS induced influx of neutrophils and macrophages along with blunted gene expression of pro‐inflammatory cytokines TNF‐α, MIP‐2 and KC. Finally, histological analysis of lungs at 21 days after elastase administration showed that the phytochemical blocks the development of emphysema by restoring the balance between matrix metallo‐proteinases and their inhibitor(s). Overall, our data shows that GA effectively modulates pulmonary inflammation and emphysema associated with COPD pathogenesis in mice and thus may offer a new/alternative treatment strategies in the area.Support or Funding InformationFinancial support from Department of Biotechnology, Government of India (BT/PR17968/MED/122/33/2016 and BT/RLF/Re‐entry/36/2012), UGC‐SAP and Senior Research Fellowship from Indian Council of Medical Research (ICMR), India