gebhart/patrepeval huggingface dataset:
Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial–mesenchymal transition of cancer cells (2013)

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ-SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFβ-TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5β1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFβ1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFβ-TAK1 and TGFβ-SMAD pathways is pivotal for TGFβ1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.
Dissecting mechanisms underlying the pathogenesis of eosinophilic esophagitis (HYP6P.263) (2014)

Abstract Eosinophilic esophagitis (EoE) is an allergic disease characterized by esophageal eosinophilia, inflammation, and dysfunction. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent need to identify new pathways that could be targeted to treat EoE. Recently, EoE was associated with a gain-of-function polymorphism in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation and peripheral basophilia. However, how TSLP and basophils might contribute to the development of eosinophil responses during EoE remains unknown. Here, we employed a new murine model of EoE-like disease to investigate the role of TSLP and basophils in promoting esophageal eosinophil responses. Development of esophageal eosinophil responses was dependent on TSLP-elicited basophils, and antibody-mediated neutralization of TSLP or depletion of basophils ameliorated established esophageal eosinophilia. In addition, we examined how sort-purified human basophils influence eosinophil responses in vitro. Finally, elevated TSLP levels and exaggerated basophil responses observed in esophageal biopsies from EoE patients correlated with eosinophil responses. Together, these data indicate that TSLP-elicited basophil responses may play a key role in mediating eosinophil responses in EoE, suggesting that the TSLP-basophil axis could represent a new and promising therapeutic target to treat this disease.
DETERMINATION OF THE OUTFLOW VALVE OPENING AREA OF THE AIRCRAFT CABIN PRESSURIZATION SYSTEM (2005)

The cabin pressure control system continuously monitors the ground and flight modes of the airplane (climb, cruise, or descent) as well as holding patterns at various altitudes. It uses this information to allow air to escape continuously from the airplane by further opening or closing the outflow valve. Thus, the cabin internal pressure is controlled by modulating the exhaust airflow through the escape valve (outflow valve). As the airplane changes altitude, the outflow valve repositions itself to allow more or less air to escape. While the external ambient pressure is equivalent to the altitude of 36,000 ft, the cabin pressure is maintained at approximately 8,000 ft due to the physiological human requirements (mainly the respiratory needs). This leads a high differential pressure between the cabin and the external environment implying in more intense structural efforts to the fuselage. The outflow valve is constantly being positioned to maintain cabin pressure as close to sea level as practical, without exceeding a predetermined cabin-to-outside pressure differential. In this context, this work focuses on the determination of the outflow valve opening area of the aircraft cabin pressurization system for ground and flight schedules, considering: (i) the inflow supplied by the air-conditioning packs; (ii) cabin leakages and (iii) the pressure change rate. The cabin leakage is modelled using the orifice compressible flow theory and the inflow rate is constant (determined by the cabin ventilation requirements). Results are obtained using a typical aircraft flight mission (schedule).
Digital model of TiO 2 memristor for field‐programmable gate array (2014)

A digital model which imitates the behaviour of a TiO 2 memristor as a new block in Alter DSP Builder is proposed in this Letter. The proposed model can be used as an independent memristor unit working with other units for designing memristor circuits based on field‐programmable gate array. The accuracy of the digital model is confirmed not only by simulations, but also by hardwire experiments.
Failure-cause analysis: fossil-fired boilers, pressure parts. Final report (1981)

Root-cause failure analyses were conducted to determine the reason for high forced-outage rates attributed to boiler-pressure-part failures in four medium-sized fossil-fired electricity generating units. Those analyses were conducted not only to identify the reasons for the high forced-outage rates in the four boilers selected for study, which are discussed in detail in this report, but also to identify areas where research studies directed toward the solution of specific failure problems related to boiler pressure parts could be expected to increase the availability of both existing and future medium-sized fossil-fired units. Twenty-four such areas were identified, six related to analyzing causes of component falures, nine related to improving equipment or operating procedures, and nine related to increasing fundamental knowledge of factors causing boiler tube degradation. The systematic problem-solving approach used in conducting the root-cause analyses is described in sufficient detail to allow utilities to apply similar techniques, if desired, for analyzing failures of other power plant equipment.
pH‐stat fed‐batch process to enhance the production of cis, cis‐muconate from benzoate by Pseudomonas putida KT2440‐JD1 (2011)

Pseudomonas putida KT2440-JD1 is able to cometabolize benzoate to cis, cis-muconate in the presence of glucose as growth substrate. P. putida KT2440-JD1 was unable to grow in the presence of concentrations above 50 mM benzoate or 600 mM cis, cis-muconate. The inhibitory effects of both compounds were cumulative. The maximum specific uptake rate of benzoate was higher than the specific production rate of cis, cis-muconate during growth on glucose in the presence of benzoate, indicating that a benzoate derivative accumulated in the cells, which is likely to be catechol. Catechol was shown to reduce the expression level of the ben operon, which encodes the conversion of benzoate to cis, cis-muconate. To prevent overdoses of benzoate, a pH-stat fed-batch process for the production of cis, cis-muconate from benzoate was developed, in which the addition of benzoate was coupled to the acidification of the medium. The maximum specific production rate during the pH-stat fed-batch process was 0.6 g (4.3 mmol) g dry cell weight(-1) h(-1), whereas 18.5 g L(-1) cis, cis-muconate accumulated in the culture medium with a molar product yield of close to 100%. Proteome analysis revealed that the outer membrane protein H1 was upregulated during the pH-stat fed-batch process, whereas the expression of 10 other proteins was reduced. The identified proteins are involved in energy household, transport, translation of RNA, and motility.
Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson’s disease (2022)

We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors. Furthermore, stress-induced autophagy resulted in an age-dependent accumulation of macroautophagic structures. Finally, we show that these impairments in patient-derived DA neurons leads to an accumulation of phosphorylated alpha-synuclein, the classical hallmark of PD pathology. This pathological phenotype is absent in neurons generated from induced pluripotent stem cells from the same patients. Taken together, our results show that direct neural reprogramming can be used for obtaining patient-derived DA neurons, which uniquely function as a cellular model to study age-related pathology relevant to idiopathic PD.
An Analytical Approach to the Design of Multiple Mode Rectangular Cavity Waveguide Filters (2017)

The multiple mode rectangular cavity structure with square corner cuts is revisited. An attempt to predict the physical dimensions of the cavity for dual mode second-order and triple mode third-order filters is made. Analytic expressions are formed to be used in the design process. The classical triple mode cavity filter structure is altered to give a finite frequency transmission zero either in the lower or upper sideband of the center frequency. The concept is illustrated with example designs. A novel additive manufacturing technique is used to fabricate a selected filter structure. The experimental results are in agreement with the expectations.
Rare earth elements (REE) in biology and medicine (2020)

Abstract This survey reports on topics that were presented at the workshop on “Challenges with Rare Earth Elements. The Periodic Table at work for new Science &amp; Technology” hold at the Academia dei Lincei in November 2019. The herein reported materials refer to presentations dealing with studies and applications of rare earth elements (REE) in several areas of Biology and Medicine. All together they show the tremendous impact REE have in relevant fields of living systems and highlight, on one hand, the still existing knowledge gap for an in-depth understanding of their function in natural systems as well as the very important role they already have in providing innovative scientific and technological solutions in a number of bio-medical areas and in fields related to the assessment of the origin of food and on their manufacturing processes. On the basis of the to-date achievements one expects that new initiatives will bring, in a not too far future, to a dramatic increase of our understanding of the REE involvement in living organisms as well as a ramp-up in the exploitation of the peculiar properties of REE for the design of novel applications in diagnostic procedures and in the set-up of powerful medical devices. This scenario calls the governmental authorities for new responsibilities to guarantee a continuous availability of REE to industry and research labs together with providing support to activities devoted to their recovery/recycling.
Hydrogenation of Phenol in Supercritical Carbon Dioxide Catalyzed by Palladium Supported on Al‐MCM‐41: A Facile Route for One‐Pot Cyclohexanone Formation (2009)

Abstract The hydrogenation of phenol has been carried out in supercritical carbon dioxide (scCO 2 ) under very mild reaction conditions at the temperature of 50 °C over palladium supported Al‐MCM‐41 (metal loading ∼1%). This palladium catalyst is shown to be highly active and promotes the selective formation of cyclohexanone (∼98%), an industrially important compound, in a “one‐pot” way. The effects of different variables like carbon dioxide and hydrogen pressure, reaction time and also silica/alumina ratio of the MCM‐41 support along with palladium dispersion are presented and discussed. The pressure effect of carbon dioxide is significantly prominent in terms of conversion and cyclohexanone selectivity. Moreover, the silica/alumina ratio was also found to be an important parameter to enhance the effectiveness of the catalyst as it exhibits a remarkable increase in phenol conversion from 20.6% to 98.4% as the support changes from only silica MCM‐41 to Al‐MCM‐41. A plausible mechanism for the hydrogenation of phenol to cyclohexanone over the palladium catalyst has been proposed. The proposition is validated by transition state calculations using density functional theory (DFT), which reveal that cyclohexanone is a favorable product and stabilized by &lt;19 kcal mol −1 over cyclohexanol in scCO 2 medium. Under similar reaction conditions, phenol hydrogenation was also carried out with rhodium, supported on Al‐MCM‐41. In contrast to the palladium catalyst, a mixture of cyclohexanone (57.8%) and cyclohexanol (42.2%) was formed. Detailed characterization by X‐ray diffraction and transmission electron microscopy confirmed the presence of metal nanoparticles (palladium and rhodium) between 10–20 nm. Both the catalysts exhibit strikingly different product distributions in solventless conditions compared to scCO 2 . This method can also be successfully applied to the other hydroxylated aromatic compounds.
A Particle Detector Based on a Double Barrier Josephson Junction (2005)

We analyze the performance of a particle detector based on a double-barrier Nb/Al/AlOx/Al/AlOx/Al/Nb junction where the Al trapping layer is embedded between two insulating AlO/sub x/ barriers. Within this layer, a very sharp Andreev bound state (ABS) level E/sub 0/ is formed. Because of a very long recombination time, the charge amplification factor is expected to be 10-100 times larger in the double-barrier detector compared to ordinary single-barrier devices. The double barrier detector also has much higher idle-state subgap resistance at low temperatures. Because the middle Al quasiparticle trap layer is separated from the adjacent layers by two insulating tunneling barriers, the proximity effect is minimized. This provides much better alignment between the maximum of nonequilibrium quasiparticle distribution function and the maximum in the electron density of states. All the factors listed result in much higher sensitivity and the energy resolution of the double barrier Nb-based STJ as compared to their single-barrier analogs.
γ radiation induced self-assembly of fluorescent molecules into nanofibers: a stimuli-responsive sensing (2015)

γ radiation causes self-assembly of sensor molecules into a nanofibril structure, enabling stimuli-responsive sensing based on fluorescence and photoconductivity modulation.
Alterations of autophagic and innate immune responses by the Crohn’s disease-associated ATG16L1 mutation (2022)

Crohn's disease (CD) is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines. These pro-inflammatory cytokines are produced by macrophages and dendritic cells (DCs) upon sensing the intestinal microbiota by the pattern recognition receptors (PRRs). Impaired activation of PRR-mediated signaling pathways is associated with chronic gastrointestinal inflammation, as shown by the fact that loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene increase the risk of CD development. Autophagy is an intracellular degradation process, during which cytoplasmic nutrients and intracellular pathogens are digested. Given that impaired reaction to intestinal microbiota alters signaling pathways mediated by PRRs, it is likely that dysfunction of the autophagic machinery is involved in the development of CD. Indeed, the loss-of-function mutation T300A in the autophagy related 16 like 1 (ATG16L1) protein, a critical regulator of autophagy, increases susceptibility to CD. Recent studies have provided evidence that ATG16L1 is involved not only in autophagy, but also in PRR-mediated signaling pathways. ATG16L1 negatively regulates pro-inflammatory cytokine responses of macrophages and DCs after these cells sense the intestinal microbiota by PRRs. Here, we discuss the molecular mechanisms underlying the development of CD in the T300A <i>ATG16L1</i> mutation by focusing on PRR-mediated signaling pathways.
Validation of Heat-Flux Predictions on the Outer Air Seal of a Transonic Turbine Blade (2003)

It is desirable to accurately predict the heat load on turbine hot section components within the design cycle of the engine. Thus, a set of predictions of the heat flux on the blade outer air seal of a transonic turbine is here validated with time-resolved measurements obtained in a single-stage high-pressure turbine rig. Surface pressure measurements were also obtained along the blade outer air seal, and these are also compared to three-dimensional, Reynolds-averaged Navier-Stokes predictions. A region of very high heat flux was predicted as the pressure side of the blade passed a fixed location on the blade outer air seal, but this was not measured in the experiment. The region of high heat flux was associated both with very high harmonics of the blade-passing event and a discrepancy between predicted and measured time-mean heat-flux levels. Further analysis of the predicted heat flux in light of the experimental technique employed in the test revealed that the elevated heat flux associated with passage of the pressure side might be physical. Improvements in the experimental technique are suggested for future efforts.
The Relationship Between Hemoglobin A1C in Youth With Type 1 Diabetes and Chaos in the Family Household (2013)

This study demonstrated the relationship of family environment and glycemic control for youth with T1DM. The findings highlight the need to individually assess the youth's home environment to promote diabetes management and care during clinic visits.
Impact of All-Terrain Vehicle Accidents on Pediatric Patient Outcomes at an Appalachian Children’s Hospital (2022)

Introduction The use of all-terrain vehicles (ATVs) has become increasingly popular as an outdoor recreational activity among people living in the United States, particularly in areas such as the southeast. There are significant risks involved with riding ATVs, especially in the pediatric population, due to lack of training and experience. The purpose of this study was to evaluate the outcomes of pediatric patients involved in ATV-associated accidents. Methods This study is a retrospective review of 98 pediatric patients ages 15 years and younger involved in ATV accidents who were admitted to a pediatric hospital between January 2015 and December 2020. Outcomes, including types of injuries sustained, length of hospital stay, length of ICU stay, and injury severity score (ISS) were analyzed between age groups (0-5, 6-10, and 11-15). Results The mean hospital stay across all age groups was 1.7 ± 1.9 days, mean ICU stay was 3.8 ± 4.0 days, and mean injury severity score (ISS) was 5.9 ±4.8. The 11-15-year-old age group had a significantly longer hospital stay and higher ISS scores compared to both of the younger age groups (0-5 and 6-10 years old). There was no difference in ICU days between the age groups. Orthopedic injuries were the most common type of injury, occurring in 55% of all patients, followed by head injuries in 29% of patients, and spinal fractures in 2% of patients. The most common orthopedic fracture in the 11-15-year-old group was tibia/fibula, while humerus fractures were the most common type of fracture in the 0-5 and 6-10 year age groups. Orthopedic procedures were required in 35% of all included patients. There was no statistically significant difference in types of injuries and types of fractures sustained between each group. Chest injuries, including pneumothorax, lung contusions, and rib fractures, occurred most often in the older age group 11-15 years (n=65). Those who experienced chest injuries had a higher ISS, although it was not statistically significant (p=0.06) compared to those who did not have chest injuries. There was no difference in hospital or ICU length of stay in patients with chest injuries. Conclusions The results of this study demonstrate the outcomes of pediatric patients admitted for ATV accidents at a rural Appalachian pediatric hospital and provide an overview of the most common injuries involved in this trauma mechanism. Pediatric patients aged 11-15 years of age involved in ATV accidents are at risk for longer hospital length of stay and higher ISS compared to younger age groups. Additionally, patients ages 11-15 were more susceptible to chest injuries following ATV accidents. The results of this study will be used to develop a standardized trauma protocol for the management of this specific trauma mechanism in the pediatric population based on common injury patterns among each age group.
HIF1A induces expression of the WASF3 metastasis‐associated gene under hypoxic conditions (2012)

The WASF3 (WAVE3) gene is an important mediator of cell motility, invasion and metastasis and is expressed at high levels in some advanced stage tumors. In our survey of breast cancer cells, we now demonstrate that exposure to hypoxic conditions increases WASF3 expression levels in MDA231, SKBR3 and MCF7 cells. The WASF3 promoter region contains HIF1A response elements (HRE). ChIP assays demonstrate that HIF1A binds to these HRE elements in the promoter region, and luciferase reporter assays using the WASF3 gene minimal promoter shows that hypoxia results in its upregulation. Phosphorylation of WASF3 is required for its ability to affect invasion and increased phosphoactivation of WASF3 is also seen in cells challenged with hypoxia. These cells also show increased motility in the scratch wound assay. Cells in which WASF3 has been knocked down show no response to hypoxia as expected, implicating the specificity of the hypoxic response to WASF3. Overall, these experiments demonstrate WASF3 is a HIF1A-regulated gene and suggests a mechanism to explain the observation of elevated expression of WASF3 in advanced stage tumors.