Miracle-dz/UniFAR-FTUs huggingface dataset:
TIM-3, LAG-3, or 2B4 gene disruptions increase the anti-tumor response of engineered T cells

Background In adoptive T cell therapy, the long term therapeutic benefits in patients treated with engineered tumor specific T cells are limited by the lack of long term persistence of the infused cellular products and by the immunosuppressive mechanisms active in the tumor microenvironment. Exhausted T cells infiltrating the tumor are characterized by loss of effector functions triggered by multiple inhibitory receptors (IRs). In patients, IR blockade reverts T cell exhaustion but has low selectivity, potentially unleashing autoreactive clones and resulting in clinical autoimmune side effects. Furthermore, loss of long term protective immunity in cell therapy has been ascribed to the effector memory phenotype of the infused cells. Methods We simultaneously redirected T cell specificity towards the NY-ESO-1 antigen via TCR gene editing (TCRED) and permanently disrupted LAG3, TIM-3 or 2B4 genes (IRKO) via CRISPR/Cas9 in a protocol to expand early differentiated long-living memory stem T cells. The effector functions of the TCRED-IRKO and IR competent (TCRED-IRCOMP) cells were tested in short-term co-culture assays and under a chronic stimulation setting in vitro. Finally, the therapeutic efficacy of the developed cellular products were evaluated in multiple myeloma xenograft models. Results We show that upon chronic stimulation, TCRED-IRKO cells are superior to TCRED-IRCOMP cells in resisting functional exhaustion through different mechanisms and efficiently eliminate cancer cells upon tumor re-challenge in vivo. Our data indicate that TIM-3 and 2B4-disruption preserve T-cell degranulation capacity, while LAG-3 disruption prevents the upregulation of additional inhibitory receptors in T cells. Conclusion These results highlight that TIM-3, LAG-3, and 2B4 disruptions increase the therapeutic benefit of tumor specific cellular products and suggest distinct, non-redundant roles for IRs in anti-tumor responses.
A Method for Collecting Atmospheric Microbial Samples From Set Altitudes for Use With Next-Generation Sequencing Techniques to Characterize Communities

Dispersal of airborne microorganisms is an important ecological process, resulting in the distribution of bacteria to all habitats on Earth. Investigation of this process is limited by the ability to collect uncontaminated high-altitude microbial samples for use with next-generation sequencing approaches. Here, we describe the design of a Remote Airborne Microbial Passive sampling system. Troubleshooting experiments demonstrate that the samplers collect adequate DNA for bacterial 16S rRNA (ribosomal RNA) amplicon–based Mi-Seq sequencing at 2 and 150 m from the ground. When samplers are closed, they retain only a low number of sequences, and may be used as a negative control. We also demonstrate that the optimal amount of collection dishes to include in the sampler is 8, and that freezing collection dishes at −80°C is an alternative to immediate DNA extraction. Samplers may be used to address a variety of ecological and human health–related questions.
Factor Analysis of the Influence of River Crossing Ferry Use – A Case in Banjarmasin and Kuala Kurun

The objective of this research is to obtain factors influencing the use of river crossing ferry in Banjarmasin (South Kalimantan) and Kuala Kurun (Central Kalimantan). The variables reviewed include socio- demographic characteristics, trip, and ferry service. Data analysis has been done by Partial Least Square approach. The analysis results obtained 13 factors that influence the use of river crossing ferry. Judging from the socio-demographic characteristics of trip makers, the influencing factors are the condition of private vehicles, the travel habits, and the residence of the perpetrators of the trip. Furthermore, from the characteristics of the trip, the factors that influence the connection are the location of the destination trip with the crossing, the travel time, the ease of getting to the crossing, and the traffic conditions on the road. The factors that influence the characteristics of transportation services are the crossing time, the operating time and the schedule, the ease of boarding and alighting, the cleanliness and the comfort, the safety and the security, and the ease of paying the ticket. Keywords: River Crossing Ferry; Influence Factor; Partial Least Square
Evaluation of the antimalarial activity of SAM13-2HCl with morpholine amide (SKM13 derivative) against antimalarial drug-resistant Plasmodium falciparum and Plasmodium berghei infected ICR mice

Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC50) >100 μM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC50/IC50) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.
Endothelial Migration and Regeneration after Penetrating Trauma Injury in a Deep Anterior Lamellar Keratoplasty Graft: Case Presentation and Literature Overview

Background: Traumatic injuries in eyes previously treated with Deep Anterior Lamellar Keratoplasty (DALK) can lead to ruptures in the Descemet Membrane (DM) and damage to the corneal endothelium, a crucial layer for maintaining corneal clarity. Due to cell cycle constraints, the human corneal endothelium cannot proliferate; instead, it compensates for injury through cell enlargement and migration from adjacent areas. Methods: This study examines a notable case of corneal endothelial cell migration following a penetrating eye injury in a patient previously treated with DALK for keratoconus, supplemented by a review of relevant literature to contextualize the regenerative response. Results: A 39-year-old male with a history of DALK suffered a traumatic eye injury, resulting in damage to the Descemet Membrane and loss of the crystalline lens. After primary repair and considerations for further surgery, the patient’s cornea cleared remarkably, with an improved visual acuity. This demonstrates the DM’s potential for self-repair through endothelial cell migration. Conclusions: The outcomes suggest that delaying corneal transplant surgery for up to 3 months following Descemet Membrane injury due to ocular trauma could be advantageous. Allowing time for natural healing processes might eliminate the need for further invasive surgeries, thereby improving patient recovery outcomes.
Efficient Gene Editing for Heart Disease via ELIP-Based CRISPR Delivery System

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in vitro and in vivo, but ultrasound combined with ELIP notably improved penetration into heart cells and tissues. When ELIP was used to deliver Cas9-sg-IL1RL1 RNA, gene editing was successful and enhanced by ultrasound. This innovative approach shows promise for heart disease gene therapy using CRISPR technology.
Quantitative analysis of riverbank groundwater flow for the Qinhuai River, China, and its influence factors

Interactions of surface water and groundwater (SW–GW) play an important role in the physical, chemical, and ecological processes of riparian zones. The main objective of this study was to describe the two‐dimensional characteristics of riverbank SW–GW interactions and to quantify their influence factors. The SW–GW exchange fluxes for six sections (S1 to S6) of the Qinhuai River, China, were estimated using a heat tracing method, and field hydrogeological and thermodynamic parameters were obtained via inverse modelling. Global sensitivity analysis was performed to compare the effects of layered heterogeneity of hydraulic conductivity and river stage variation on SW–GW exchange. Under the condition of varied river stage, only the lateral exchange fluxes at S1 apparently decreased during the monitoring period, probably resulting from its relatively higher hydraulic conductivity. Meanwhile, the SW–GW exchanges for the other five sections were quite stable over time. The lateral exchange fluxes were higher than the vertical ones. The riverbank groundwater flow showed different spatial variation characteristics for the six sections, but most of the higher exchange fluxes occurred in the lower area of a section. The section with larger hydraulic conductivity has an apparent dynamic response to surface water and groundwater level differences, whereas lower permeabilities severely reduced the response of groundwater flow. The influence of boundary conditions on SW–GW interactions was restricted to a limited extent, and the impact extent will expand with the increase of peak water level and hydraulic conductivity. The SW–GW head difference was the main influence factors in SW–GW interactions, and the influence of both SW–GW head difference and hydraulic conductivity decreased with an increase of the distance from the surface water boundary. For each layer of riverbank sediment, its hydraulic conductivity had greater influence on its groundwater flow than the other layers, whereas it had negligible effects on its overlying/underlying layers. Consequently, the variations in river stage and hydraulic conductivity were the main factors influencing the spatial and temporal characteristics of riverbank groundwater flow, respectively.
Parameter Reputation Model for Cloud Service Recommendation and Ranking Using Opinion Mining

Enabling effective cloud service recommendation and ranking model helps cloud users settle on brief choices when they are up against by an enormous number of choices. This helps to improve the cloud users’, as well as the service providers’, satisfaction levels. In this paper, parameter reputation-based algorithms are proposed to boost the service selection and ranking. The proposed work employs prominent the parameters of the Service Measurement Index (SMI) standardized by the Cloud Service Measurement Index Consortium (CSMIC). The parameters are systematically analyzed in order to obtain a user review opinion, such as a positive, negative and neutral view about the parameters. Here, both the positive and negative parameter reputations are addressed. The positive parameter reputation increased the cloud users’ choice of service selection and ranking. The negative parameter reputation helped the service providers to realize where they are stand and give them a chance to improve their service provisioning in future endeavors. The detailed experimental results confirm that the proposed models enhance the choice of service selection and ranking.
Historical and Future Stream Temperature Change Predicted by a Lidar‐Based Assessment of Riparian Condition and Channel Width

Riparian forests attenuate solar radiation, thereby mediating an important component of the thermal budget of streams. Here, we investigate the relationship between riparian degradation, stream temperature, and channel width in the Chehalis River Basin, Washington State. We used lidar data to measure canopy opening angle, the angle formed between the channel center and trees on both banks; we assumed historical tree heights and calculated the change in canopy angle relative to historical conditions. We then developed an empirical relationship between canopy angle and water temperature using existing data, and simulated temperatures between 2002 and 2080 by combining a tree growth model with climate change scenarios from the NorWeST regional prediction. The greatest change between historical and current conditions (~7°C) occurred in developed portions of the river network, with the highest values of change predicted at channel widths less than ~40 m. Tree growth lessened climate change increases in maximum temperature and the length of river exceeding biologically critical thresholds by ~50%–60%. Moreover, the maximum temperature of channels with bankfull widths less than ~50 m remained similar to current conditions, despite climate change increases. Our findings are consistent with a possible role for the riparian landscape in explaining the low sensitivity of stream temperatures to air temperatures observed in some small mountain streams.
An Ultra-high Quality Factor Terahertz Photonic Crystal Cavity

High quality factor Terahertz (THz) cavities are highly desired for many THz applications. This paper presents an ultra-high quality factor terahertz planar photonic crystal cavity at 300 GHz range. Two approaches are employed to reduce the losses in the cavity increasing the quality factor of the cavity. Firstly, short embedded photonic crystal waveguides are employed to reduce the in – plane loss. Secondly, a novel way of hole displacement is adopted for four edged holes of the L3 – type photonic crystal cavity to decrease the radiation loss. An ultra – high quality factor of 65000 at a resonant frequency of 315.3 GHz was achieved for the designed cavity. This result could enable promising applications such as THz sensing.
Validity and Reliability Study of the Turkish Version of the Orbach Mikulincer Mental Pain Scale-8 in a Clinical Population

Purpose Suicide is a growing public health issue for all societies; identifying suicide risk is crucial. This study aims to evaluate the psychometric properties of the Turkish version of the Orbach and Mikulincer Mental Pain Scale-8 (OMMP-8), which enables the assessment of suicidality in a short time. Patients and Methods We conducted this study with 148 individuals diagnosed with major depressive disorder and 130 healthy controls. We administered the Hamilton Depression Scale (HDRS), Beck Hopelessness Scale (BHS), Beck Scale for Suicidal Ideation (BSIS), and Mee Bunney Psychological Pain Assessment Scale (MBPPAS) to all participants. Results Cronbach’s alpha values were 0.96, 0.97, and 0.98 for Factors 1, 2, and 3, respectively, and 0.92 for the entire scale. Exploratory (EFA) and confirmatory factor analyses (CFA) proved the 3-factor structure of the scale. The OMMP-8 total score and HDRS (r = 0.851), BSIS (r = 0.836), BHS (r = 0.825), and MBPPAS (r = 0.881) total scores were statistically significantly correlated, indicating convergent and concurrent validity of the scale. The scale successfully discriminated between depression and control groups (89.6%) and participants with and without suicide attempts in the depression group (82.4%). Conclusion This study demonstrates that the Turkish version of the OMMP-8 scale is valid and reliable for both individuals with depression and healthy controls and can be used in studies investigating suicide risk.
The impact of ir 4.0 technology acceptance on small medium enterprises behavior intention in the halal food and beverage industry in malaysia: a pilot study

This pilot study implemented Venkatesh, Morris, Davis and Davis (2003)'s model of Unified Theory of Acceptance and Use of Technology (UTAUT) in the field of halal food and beverage enterprises in Malaysia. 30 sets of questionnaires have been sent to participants which are from the management level in food and beverage establishment. The questionnaire is organized in eight parts and used 5 point Likert scale. The research variables are effort expectancy, performance expectancy, facilitating condition, social influence, price value and muamalat e-commerce. The dependent variable is Small Medium Enterprise (SME) behavior intention in halal food and beverage establishment. The findings highlighted the question items that performed and thus should be kept, as well as the question items that performed badly and should be discarded or studied further. Statistical Program for Social Science (SPSS) version 26 was also used to do a reliability analysis and factor analysis. The findings revealed that the data is trustworthy and has a fair level of normality. In the future, this pilot study will be followed by a full study.This pilot study implemented Venkatesh, Morris, Davis and Davis (2003)'s model of Unified Theory of Acceptance and Use of Technology (UTAUT) in the field of halal food and beverage enterprises in Malaysia. 30 sets of questionnaires have been send to participant which are from the management level in food and beverage establishment. The questionnaire is organized in eight parts and used 5 point Likert scale. The research variables are effort expectancy, performance expectancy, facilitating condition, social influence, price value and muamalat e-commerce. The dependent variable is Small Medium Enterprise (SME) behavior intention in halal food and beverage establishment. The findings highlighted the question items that performed and thus should be kept, as well as the question items that performed badly and should be discarded or studied further. Statistical Program for Social Science (SPSS) version 26 was also used to do a reliability analysis and factor analysis. The findings revealed that the data is trustworthy and has a fair level of normality. In the future, this pilot study will be followed by a full study.
Wind erosion enhanced by land use changes significantly reduces ecosystem carbon storage and carbon sequestration potentials in semiarid grasslands

Wind erosion exerts a fundamental influence on the biotic and abiotic processes associated with ecosystem carbon (C) cycle. However, how wind erosion under different land use scenarios will affect ecosystem C balance and its capacity for future C sequestration is poorly quantified. Here, we simulated different intensities of land uses in Inner Mongolia: control, 50% of vegetation mowed (50 M), 100% vegetation mowed (100 M), and tillage (TI). We monitored abiotic C flux caused by wind erosion, net ecosystem exchange (NEE), and soil characteristics from 2013 to 2016. We found that the frequency of heavy wind exerts a fundamental control over the severity of soil erosion, and its interaction with precipitation and vegetation characteristics explained 69% of the variation in erosion intensity. With increases in land use intensity, the abiotic C flux induced by wind erosion increased rapidly, equivalent to 33%, 86%, 111%, and 183% of the NEE of natural steppe in the control, 50 M, 100 M, and TI sites, respectively. The erosion‐induced decrease in fine fraction soils led to 31%, 43%, and 85% permanent losses of C sequestration potential in the surface soil for 50 M, 100 M, and TI sites. Overall, our study demonstrates that the abiotic C flux associated with wind erosion is too large to be ignored. The loss of C‐enriched fine particles not only reduces the current ecosystem C content but also results in an irreversible loss of future soil C sequestration potential. These dynamic soil characteristics need to be considered when projecting future ecosystem C balance in aeolian landscapes.
Transcriptomic analysis of nitrogen metabolism pathways in Klebsiella aerogenes under nitrogen-rich conditions

The acceleration of the nitrogen cycle and the nitrogen excess observed in some coastal waters has increased interest into understanding the biochemical and molecular basis of nitrogen metabolism in various microorganisms. To investigate nitrogen metabolism of a novel heterotrophic nitrification and aerobic denitrification bacterium Klebsiella aerogenes strain (B23) under nitrogen-rich conditions, we conducted physiological and transcriptomic high-throughput sequencing analyses on strain B23 cultured on potassium nitrate–free or potassium nitrate–rich media. Overall, K. aerogenes B23 assimilated 82.47% of the nitrate present into cellular nitrogen. Further, 1,195 differentially expressed genes were observed between K. aerogenes B23 cultured on potassium nitrate–free media and those cultured on potassium nitrate-rich media. Gene annotation and metabolic pathway analysis of the transcriptome were performed using a series of bioinformatics tools, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Non-Redundant Protein Database annotation. Accordingly, the nitrogen metabolism pathway of K. aerogenes B23 was analyzed; overall, 39 genes were determined to be involved in this pathway. Differential expression analysis of the genes involved in the nitrogen metabolism pathway demonstrated that, compared to the control, FNR, NarK/14945, fdx, gshA, proB, proA, gapA, argH, artQ, artJ, artM, ArgR, GAT1, prmB, pyrG, glnS, and Ca1 were significantly upregulated in the nitrogen-treated K. aerogenes B23; these genes have been established to be involved in the regulation of nitrate, arginine, glutamate, and ammonia assimilation. Further, norV, norR, and narI were also upregulated in nitrogen-treated K. aerogenes B23; these genes are involved in the regulation of NO metabolism. These differential expression results are important for understanding the regulation process of key nitrogen metabolism enzyme genes in K. aerogenes B23. Therefore, this study establishes a solid foundation for further research into the expression regulation patterns of nitrogen metabolism–associated genes in K. aerogenes B23 under nitrogen-rich conditions; moreover, this research provides essential insight into how K. aerogenes B23 utilizes nutritional elements.
Analysis of ASAR and PALSAR data for optimizing forest cover mapping - A GSE Forest Monitoring study

For the Russian Service Case of GSE FM ENVISAT ASAR APP data (HH/HV, swath 7) were used during the first two years. For optimal SAR based forest cover mapping a well suited SAR data set is required. Thus emphasis is put on the analysis of ASAR time series throughout the seasons. The investigation comprises for each image of the time series the analysis of the signatures of the relevant land cover classes and their separability. For forthcoming GSE FM service production PALSAR L-band data will be introduced. L-band data can be assumed to complement the data input and afford an improved forest cover mapping whilst the costly manual classification refinement effort is minimised. Various PALSAR products will be analysed regarding their suitability for forest map production. Regarding the separability of forest and non-forest, different PALSAR acquisition modes as well as winter coherence images have been investigated.