Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial Notch Signaling Regulates the Function of the Retinal Pigment Epithelial Barrier via EC Angiocrine Signaling

The outer blood–retina barrier (oBRB), comprises tightly connected retinal pigment epithelium (RPE) cells, Bruch’s membrane, and choroid blood vessels, and is essential for retinal health and normal visual function. Disruption of the RPE barrier and its dysfunction can lead to retinal disorders such as age-related macular degeneration (AMD). In the present study, we investigated the essential role of choroid endothelial cells (ECs) in the RPE barrier formation process and its dysfunction. We discovered that ECs promoted RPE barrier formation through angiocrine signaling. Through blocking or activating endothelial Notch signaling and conducting experiments in vitro and in vivo, we confirmed that endothelial Notch signaling regulated the expression of heparin-binding epidermal growth factor (HBEGF) and consequently impacted the expression and activity of matrix metalloproteinases (MMP)-9 in RPE cells. This modulation influenced the RPE extracellular matrix deposition, tight junctions and RPE barrier function. In in vivo experiments, the intravitreal administration of recombinant HBEGF (r-HBEGF) alleviated the RPE barrier disruption induced by subretinal injection (SI) or laser treatment and also rescued RPE barrier disruption in endothelial Notch-deficient mice. Our results showed that the endothelial Notch signaling drove HBEGF expression through angiocrine signaling and effectively improved RPE barrier function by regulating the MMP-9 expression in RPE cells. It suggests that the modulation of Notch signaling in the choroidal endothelium may offer a novel therapeutic strategy for retinal degenerative diseases.
PRELIMINARY MISSION ANALYSIS FOR A JUPITER ENTRY PROBE MISSION

Mission analysis results for an ESA study into a Jupiter entry probe mission are presented: transfer of one or two entry probe(s) to Jupiter, sequential targeting and deployment, entry conditions and atmospheric descent profiles, data relay, and a possible post-entry mission of the carrier, comprising Jupiter orbit insertion and a tour of the Galilean moons. The parametric results provided are useful as reference for future Jupiter mission design tasks. 1. Mission Framework A carrier spacecraft shall transport one or two Jupiter entry probes to Jupiter, target and deploy them from hyperbolic approach, perform data relay during the at least one-hour entry phase(s) (which will take the probes to the 100 bar level, i.e., approximately 240 km depth) and then may continue on an add-on mission.
A Decade of Experience With Alemtuzumab Therapy for Severe or Glucocorticoid-Resistant Kidney Transplant Rejection

Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated. Graft survival, graft function, lymphocyte depletion, serious infections, malignancies, and patient survival were analyzed and compared with a reference cohort of transplanted patients who did not require alemtuzumab anti-rejection therapy. A total of 225 patients treated with alemtuzumab were identified and compared with a reference cohort of 1,668 patients. Over 60% of grafts was salvaged with alemtuzumab therapy, but graft survival was significantly poorer compared to the reference cohort. The median time of profound T- and B lymphocyte depletion was 272 and 344 days, respectively. Serious infection rate after alemtuzumab therapy was 54.1/100 person-years. The risk of death (hazard ratio 1.75, 95%-CI 1.28–2.39) and infection-related death (hazard ratio 2.36, 95%-CI 1.35–4.11) were higher in the alemtuzumab-treated cohort. In conclusion, alemtuzumab is an effective treatment for severe kidney transplant rejection, but causes long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.
The Effectiveness of a Mechanical Ventilation System for Indoor PM2.5 in Residential Houses

The mechanical ventilation systems used in houses are designed to reduce carbon dioxide emissions while minimizing the energy loss resulting from ventilation. However, the increase in indoor fine particulate (PM2.5) concentration because of external PM2.5 influx through the ventilation system poses a problem. Here, we analyzed the changes in indoor PM2.5 concentration, distinguishing between cases of high and low outdoor PM2.5 concentrations and considering the efficiency of the filters used in residential mechanical ventilation systems. When using filters with the minimum efficiency reporting value (MERV) of 10 in the ventilation system, the outdoor PM2.5 concentration was 5 μg/m³; compared to the initial concentration, the indoor PM2.5 concentration after 60 min decreased to 73%. When the outdoor PM2.5 concentration was 30–40 μg/m³, the indoor PM2.5 concentration reached 91%. However, when MERV 13 filters were used, the indoor PM2.5 concentration consistently dropped to 73–76%, regardless of the outdoor PM2.5 concentration. Furthermore, by comparing the established equation with the mass balance model, the error was confirmed to be within 5%, indicating a good fit. This allows for the prediction of indoor PM2.5 under various conditions when using mechanical ventilation systems, enabling the formulation of strategies for maintaining indoor PM2.5, as recommended by the World Health Organization.
Examining the Influence of CEO Characteristics and Brand Image on Performance of Food and Beverages MSMEs in Indonesia: The Mediating Role of Competitive Advantage

Delve into the dynamic world of micro, small, and medium-sized enterprises (MSMEs) within Indonesia's vibrant food and beverages industry. This captivating study goes beyond the surface, exploring the intricate relationships that shape these businesses. We zero in on the captivating influence of CEO characteristics and the magnetic power of brand image. Unravel the mystery of how competitive advantage, like a skilled mediator, intertwines these factors, driving performance to new heights. Armed with data from a comprehensive survey of 210 respondents, our quantitative analysis paints a vivid picture. Brace yourself for the revelation: CEO Characteristics and Brand Image are not just players; they are the star performers, significantly impacting the dazzling world of Food and Beverages MSMEs. And there's more—Competitive Advantage takes center stage, weaving the threads of CEO Characteristics and Brand Image into a tapestry of success. As with any compelling narrative, this research isn't without its limitations. However, it sparks the flames of curiosity, paving the way for future explorations to unravel the deeper layers of this captivating story.
An Ethnobotanical Study of Medicinal Plants in Murari Devi and Surrounding Areas (Mandi District, Himachal Pradesh), India

Survey was conducted to study the diversity, utilization pattern and indigenous uses of floristic diversity in Murari Devi and surrounding areas of Mandi disrtict in Himachal Pradesh. Ethnobotanical uses of 220 plant species belonging to 184 genera and 88 families were recorded. These medicinal plants comprise of 31 trees, 134 herbs, 50 shrubs and 05 ferns. From the total, 35 were near endemic to Indian Himalayan Region (IHR). The present study represents an area specific approach.
Validation of Machine Learning Prediction Models

We address the estimation of the Integrated Squared Error (ISE) of a predictor $\eta (x)$ of an unknown function f learned using data acquired on a given design ${\mathbf{X}_{n}}$. We consider ISE estimators that are weighted averages of the residuals of the predictor $\eta (x)$ on a set of selected points ${\mathbf{Z}_{m}}$. We show that, under a stochastic model for f, minimisation of the mean squared error of these ISE estimators is equivalent to minimisation of a Maximum Mean Discrepancy (MMD) for a non-stationary kernel that is adapted to the geometry of ${\mathbf{X}_{n}}$. Sequential Bayesian quadrature then yields sequences of nested validation designs that minimise, at each step of the construction, the relevant MMD. The optimal ISE estimate can be written in terms of the integral of a linear reconstruction, for the assumed model, of the square of the interpolator residuals over the domain of f. We present an extensive set of numerical experiments which demonstrate the good performance and robustness of the proposed solution. Moreover, we show that the validation designs obtained are space-filling continuations of ${\mathbf{X}_{n}}$, and that correct weighting of the observed interpolator residuals is more important than the precise configuration ${\mathbf{Z}_{m}}$ of the points at which they are observed.
Long-Term Assessment of Treatment Timing for Rapid Maxillary Expansion and Facemask Therapy Followed by Fixed Appliances: A Multicenter Retro-Prospective Study

Background: to determine the role of treatment timing in the long-term effects produced by rapid maxillary expansion and facemask therapy (RME/FM) in Class III patients. Methods: This study compared two sample groups treated with RME/FM followed by fixed appliances: the early prepubertal group (EPG) (17 patients; mean age before treatment (T0), 5.8 ± 0.7 years; range, 4.3–6.9 years) and the late prepubertal group (LPG) (17 patients; mean age at T0, 10.1 ± 0.8 years; range, 9.0–11.1 years). Lateral cephalograms for the two groups were examined before treatment (T0) and at a long-term observation (T1) (EPG, 19.8 ± 1.0 years; LPG, 21.0 ± 2.1 years). Independent sample t-tests were performed to compare the two groups at T0 and T1. Results: No statistically significant differences were found for any of the cephalometric variables at T0, except for the total mandibular length, overjet, and inclination of the maxillary incisors to the palatal plane, which were greater in the LPG. At T1, no statistically significant differences were detected for any of the cephalometric variables. Conclusions: There were no significant long-term differences when treating Class III patients with RME/FM, either during an early prepubertal phase (≤7 years of age) or during a late prepubertal phase (≥9 years of age).
Reconstruction of the Steroid 1(2)-Dehydrogenation System from Nocardioides simplex VKM Ac-2033D in Mycolicibacterium Hosts

Microbial 1(2)-dehydrogenation of 3-ketosteroids is an important basis for the production of many steroid pharmaceuticals and synthons. When using the wild-type strains for whole cell catalysis, the undesirable reduction of the 20-carbonyl group, or 1(2)-hydrogenation, was observed. In this work, the recombinant strains of Mycolicibacterium neoaurum and Mycolicibacterium smegmatis were constructed with blocked endogenous activity of 3-ketosteroid-9α-hydroxylase, 3-ketosteroid-1(2)-dehydrogenase (3-KSD), and expressing 3-KSD encoded by the gene KR76_27125 (kstD2NS) from Nocardioides simplex VKM Ac-2033D. The in vivo activity of the obtained recombinant strains against phytosterol, 6α-methyl-hydrocortisone, and hydrocortisone was studied. When using M. smegmatis as the host strain, the 1(2)-dehydrogenation activity of the constructed recombinant cells towards hydrocortisone was noticeably higher compared to those on the platform of M. neoaurum. A comparison of the strengths of inducible acetamidase and constitutive hsp60 promoters in M. smegmatis provided comparable results. Hydrocortisone biotransformation by M. smegmatis BD/pMhsp_k expressing kstD2NS resulted in 95.4% prednisolone yield, and the selectivity preferred that for N. simplex. Mycolicibacteria showed increased hydrocortisone degradation at 35 °C compared to 30 °C. The presence of endogenous steroid catabolism in Mycolicibacterium hosts does not seem to confer an advantage for the functioning of KstD2NS. The results allow for the evaluation of the prospects for the development of simple technological methods for the selective 1(2)-dehydrogenation of 3-ketosteroids by growing bacterial cells.
Endothelin Modulates Rhythm Disturbances and Autonomic Responses to Acute Emotional Stress in Rats

Simple Summary Our body’s reaction to acute emotional stress differs, depending on several factors, which include a small molecule called endothelin. Excessive responses are important, as they can trigger (sometimes serious) heartbeat disturbances. To further investigate the role of endothelin in this process, we compared the reactions to laboratory-induced stress in two groups of rats, known to have diverse baseline levels of endothelin in the blood. We found distinct responses leading to slow heartbeat disturbances in the latter group. This feature resembles that observed in people with a tendency to faint after strong emotions, a common problem with many unknown aspects. Our study calls for further research on the effects of endothelin on fainting and irregular heartbeat after acute emotional stress. Abstract The ubiquitous peptide endothelin is currently under investigation as a modulatory factor of autonomic responses to acute emotional stress. Baseline plasma levels of endothelin alter blood pressure responses, but it remains unclear whether autonomic activity and arrhythmogenesis (i.e., brady- or tachyarrhythmias) are affected. We recorded sympathetic and vagal indices (derived from heart rate variability analysis), rhythm disturbances, voluntary motion, and systolic blood pressure after acute emotional stress in conscious rats with implanted telemetry devices. Two strains were compared, namely wild-type and ETB-deficient rats, the latter displaying elevated plasma endothelin. No differences in heart rate or blood pressure were evident, but sympathetic responses were blunted in ETB-deficient rats, contrasting prompt activation in wild-type rats. Vagal withdrawal was observed in both strains at the onset of stress, but vagal activity was subsequently restored in ETB-deficient rats, accompanied by low voluntary motion during recovery. Reflecting such distinct autonomic patterns, frequent premature ventricular contractions were recorded in wild-type rats, as opposed to sinus pauses in ETB-deficient rats. Thus, chronically elevated plasma endothelin levels blunt autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. Our study provides further insights into the pathophysiology of stress-induced tachyarrhythmias and syncope.
Relationships between lightning and properties of convective cloud clusters

Satellite observations of convective system properties and lightning flash rate are used to investigate the ability of potential lightning parameterizations to capture both the dominant land‐ocean contrast in lightning occurrence and regional differences between Africa, the Amazon and the islands of the maritime continent. As found in previous studies, the radar storm height is tightly correlated with the lightning flash rate. A roughly second order power‐law fit to the mean radar echo top height above the 0°C isotherm is shown to capture both regional and land‐ocean contrasts in lightning occurrence and flash rate using a single set of parameters. Recent developments should soon make it possible to implement a parameterization of this kind in global models. Parameterizations based on cloud top height, convective rain rate and convective rain fraction all require the use of separate fits over land and ocean and fail to capture observed differences between continental regions.
Evaluation of Intangible Losses due to Coastal Floods: Applicability of Available Economic Valuation Methods

Storm surges in the North Sea have caused massive floods in Germany and are expected to occur more frequently due to climate change. The German XtremRisK project was started with the main objective to determine flood risks in estuarine areas and at open coasts in Hamburg and Sylt Island, due to extreme storm events in the North Sea. The risk is estimated using the definition ‘product of probability and the expected damages’ (Oumeraci, 2004). The expected damages are either tangible, generally evaluated in monetary terms (Smith and Ward, 1998; Jonkman and Vrijling, 2008) or intangible. Evaluation of intangible damages such as health impacts, cultural and environmental damages in monetary terms is extremely difficult (e.g. Tapsell et al., 2002; Messner et al., 2006), but cannot be omitted when calculating the overall risk. Therefore, the main focus of this research is to determine the applicability of available valuation methodologies to evaluate intangible damages induced by floods in an estuary and at open coast, represented by Hamburg and Sylt Island, respectively.
Sofisticación y cultura política en estudiantes universitarios, un análisis desde sus hábitos comunicativos

En este artículo distinguimos cómo los hábitos comunicativos y de consumo de medios de estudiantes universitarios se relacionan con su participación política. Para el estudio se diseñaron grupos de enfoque con estudiantes de la Universidad Autónoma de Nuevo León, antes y después de la elección de 2018. En los resultados observamos que la conversación familiar deja una huella importante en la construcción de la cultura política de los universitarios. Se concluye que el involucramiento de los estudiantes con la vida política del país está orientado principalmente al voto.
Effect of Light Intensity on Photosynthesis in Aquatic Plants in Australia

Purpose: The aim of the study was to investigate the Effect of Light Intensity on Photosynthesis in Aquatic Plants in Australia. Methodology: The study adopted a desktop methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library Findings: In the study examining the impact of light intensity on photosynthesis in Australian aquatic plants, key findings emerged. It was evident that light intensity played a crucial role, with higher light levels in shallower waters leading to increased photosynthesis rates. This underscored the significance of light as a primary determinant of photosynthesis in these ecosystems. Additionally, the study highlighted the impressive adaptability of Australian aquatic plants, some of which employed unique photo protective mechanisms to prevent photo inhibition under varying light conditions. Unique Contribution to Theory, Practice and Policy: Theory of Liebig's Law of the Minimum, Theory of The Beer-Lambert Law and Optimal Foraging Theory may be used to anchor future studies on the Effect of Light Intensity on Photosynthesis in Aquatic Plants in Australia. Develop practical guidelines for growers to optimize light conditions for maximum photosynthetic efficiency. Advocate for policies that recognize the significance of aquatic plants in maintaining healthy aquatic ecosystems. Promote the conservation and restoration of natural habitats for aquatic plants, especially in areas threatened by pollution or habitat destruction.
Tectonics and Structure of the Western Canada Foreland Basin: Chapter 3

In Western Canada, a series of deformational events, probably the result of the accretion of a series of allochthonous terranes and accompanying subduction, have deformed the miogeoclinal sediment prism that previously formed the western margin of North America. The miogeoclinal prism was composed of a series of Proterozoic, Paleozoic, and early Mesozoic sedimentary successions, apparently deposited in response to an extended series of episodes of rifting and subsidence. Tectonism leading to the development of the Western Canada foreland basin commenced in the Middle Jurassic, apparently the result of the initial collision between North America and the allochthonous terranes to the west. Various clastic wedge successions were shed eastward into the foreland basin through ate Jurassic to Paleocene, but at present they can only be loosely linked to identified tectonic episodes in the interior of the Canadian Cordillera. Transpressional tectonics, and deposition of foreland basin sediments, terminated at about the Paleocene-Eocene boundary as a change in tectonic regime produced large-scale extension in the interior of the Cordillera that lasted through the mid-Tertiary. The foreland fold and thrust belt, developed along the eastern margin of the cordillera, overlaps and deforms sediments of the foreland basin. For much of its length through Canada, the foreland belt exhibits a thin-skinned structural style. The North American craton, essentially undeformed, extends westward beneath detached, horizontally compressed, and tectonically thickened strata of the miogeocline, the cratonic platform cover, and the foreland basin. Thrust faulting, with associated folding, was the dominant deformation mechanism in the foreland belt. The style of thrusting, and its relationship to folding, were influenced by several factors such as the geometry and End_Page 81------------------------- composition of the deformed sedimentary sequence, the magnitude of shortening, the lateral extent of the basal detachment, and possibly pore-fluid overpressures. The Foothills belt is a significant source of hydrocarbons. The major reservoir units are Devonian, Mississippian, and Triassic dolostones, all rocks belonging originally to the miogeoclinal succession. Hydrocarbon gases and oils filling the reservoirs were probably produced around the time of greatest burial, which broadly coincided with the time of maximum thrusting (Late Cretaceous-Paleocene).
Z-QuadTree : une nouvelle structure de quadtree pour cartes de profondeur

Cet article presente une structure de donnees "Z-quadtree" permettant de reduire le nombre de quads dans un quadtree representant une carte de profondeur. La methode se focalise en particulier sur les zones de discontinuites de profondeur. Dans un quadtree classique, la decomposition est tres fine autour des discontinuites, meme si les surfaces en avant plan et arriere plan sont planes. La methode proposee consiste a fusionner les quads d'arriere plan ensemble, tout en conservant les quads d'avant plan formant le contour d'un objet. Les premiers resultats ont montre que le nombre de quads a pu etre reduit de 20 a 25% sans degradation de la qualite visuelle.
Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation.