Miracle-dz/UniFAR-FTUs huggingface dataset:
Aspergillus fumigatus Supernatants Disrupt Bronchial Epithelial Monolayers: Potential Role for Enhanced Invasion in Cystic Fibrosis

Aspergillus fumigatus is the most commonly isolated fungus in chronic lung diseases, with a prevalence of up to 60% in cystic fibrosis patients. Despite this, the impact of A. fumigatus colonisation on lung epithelia has not been thoroughly explored. We investigated the influence of A. fumigatus supernatants and the secondary metabolite, gliotoxin, on human bronchial epithelial cells (HBE) and CF bronchial epithelial (CFBE) cells. CFBE (F508del CFBE41o−) and HBE (16HBE14o−) trans-epithelial electrical resistance (TEER) was measured following exposure to A. fumigatus reference and clinical isolates, a gliotoxin-deficient mutant (ΔgliG) and pure gliotoxin. The impact on tight junction (TJ) proteins, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were determined by western blot analysis and confocal microscopy. A. fumigatus conidia and supernatants caused significant disruption to CFBE and HBE TJs within 24 h. Supernatants from later cultures (72 h) caused the greatest disruption while ΔgliG mutant supernatants caused no disruption to TJ integrity. The ZO-1 and JAM-A distribution in epithelial monolayers were altered by A. fumigatus supernatants but not by ΔgliG supernatants, suggesting that gliotoxin is involved in this process. The fact that ΔgliG conidia were still capable of disrupting epithelial monolayers indicates that direct cell–cell contact also plays a role, independently of gliotoxin production. Gliotoxin is capable of disrupting TJ integrity which has the potential to contribute to airway damage, and enhance microbial invasion and sensitisation in CF.
‘Targeting’ Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer—An Updated Review

Antibody-Drug conjugates (ADCs) are a relatively new class of drugs with a promise to improve the outcomes in specific cancers. By delivering the cytotoxic agent to tumor cells expressing specific antigens, ADCs achieve a better therapeutic index and more potency. ADCs have been approved for several hematological and solid malignancies, including breast, urothelial and gastric carcinoma. Recently, trastuzumab deruxtecan (TDXd) was the first ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer (NSCLC). Many promising ADCs are in the pipeline for clinical development in non-small cell lung cancer, including sacituzumab govitecan, patritumab deruxtecan, datopotamab deruxtecan and tusamitamab ravtansine. There is a hope that these drugs would cater to the unmet need of specific patient populations, including patients with currently untargetable mutations. We hope these drugs, e.g., TROP2 targeted ADCs, will also give more options for therapy in NSCLC to improve outcomes for patients. In this comprehensive review, we will be discussing the recent evidence including targets, efficacy and the safety of newer ADC candidates in NSCLC. We will also briefly discuss the specific toxicities, novel biomarkers, overcoming resistance mechanisms, challenges and the way forward, as these new ADCs and combinations find a way into the clinical practice.
A parahippocampal-sensory Bayesian vicious circle generates pain or tinnitus: a source-localized EEG study

Abstract Pain and tinnitus share common pathophysiological mechanisms, clinical features, and treatment approaches. A source-localized resting-state EEG study was conducted in 150 participants: 50 healthy controls, 50 pain, and 50 tinnitus patients. Resting-state activity as well as functional and effective connectivity was computed in source space. Pain and tinnitus were characterized by increased theta activity in the pregenual anterior cingulate cortex, extending to the lateral prefrontal cortex and medial anterior temporal lobe. Gamma-band activity was increased in both auditory and somatosensory cortex, irrespective of the pathology, and extended to the dorsal anterior cingulate cortex and parahippocampus. Functional and effective connectivity were largely similar in pain and tinnitus, except for a parahippocampal-sensory loop that distinguished pain from tinnitus. In tinnitus, the effective connectivity between parahippocampus and auditory cortex is bidirectional, whereas the effective connectivity between parahippocampus and somatosensory cortex is unidirectional. In pain, the parahippocampal-somatosensory cortex is bidirectional, but parahippocampal auditory cortex unidirectional. These modality-specific loops exhibited theta–gamma nesting. Applying a Bayesian brain model of brain functioning, these findings suggest that the phenomenological difference between auditory and somatosensory phantom percepts result from a vicious circle of belief updating in the context of missing sensory information. This finding may further our understanding of multisensory integration and speaks to a universal treatment for pain and tinnitus—by selectively disrupting parahippocampal-somatosensory and parahippocampal-auditory theta–gamma activity and connectivity.
The Problem of Reading Motivation Multidimensionality: Theoretical and Statistical Evaluation of a Reading Motivation Scale

Abstract Reading motivation is multidimensional and a critical contributor to students’ reading comprehension skill. Its multidimensionality is problematic, as there is currently no consensus on the dimensions underlying reading motivation, which are being tested through a variety of instruments that lack statistical validation. Our goal was to discuss the structure, reliability, and validity of a reading motivation scale in relation to prior theoretical proposals. The scale considered four affirming and four undermining reading motivations and was tested with 172 students from 2nd to 6th grade. Its structure was assessed using CFA and EFA. A four-factor structure had the best fit for the data: (1) Reading value and intrinsic motivation; (2) reading devalue and avoidance; (3) perceived self-efficacy; and (4) perceived difficulty. The results supported some prior theoretical distinctions, but question the appropriateness of widely used scales and suggest the need for more research on the multidimensionality of reading motivation.
Analisis Kesuksesan Implementasi E-Kinerja di Kota Salatiga Menggunakan Model DeLone-McLean

The Agency for Personnel and Human Resources Development (BKPSDM), Salatiga City, implements e-Kinerja to analyze job requirements, job workloads and units or work units, as a basis for calculating work performance and awarding awards. BKPSDM has never measured the success of using e-Kinerja. The purpose of this research is to evaluate the implementation of e-Kinerja in BKPSDM, Salatiga City using the DeLone-McLean model. E-Kinerja users in BKPSDM, Salatiga City are a sample of this research. The total sample was 66 respondents. The questionnaires were measured using Likert Scale and testing was conducted using the Pearson Product Moment Correlation method. Research obtained empirical evidence that successful implementation of e-Kinerja plays a role in improving performance in BKPSDM. The research findings are also robust in additional testing. The average weight of the measurement item, which is 4.04 and the success rate of e-Kinerja implementation is 80.8 percent. E-kinerja successful in improving job performance in BKPSDM, Salatiga City.
Benthic macroinvertebrate assemblages in large river secondary channels: Contemporaneous and legacy effects of flow connectivity

In large rivers, secondary channels occur where the main channel is divided by an instream island, forming one or multiple smaller channels outside the main channel. Secondary channels are highly variable in morphometry, flow characteristics, and degree of connectivity to the main channel. Engineered closing structures at the upstream end of most secondary channels restrict inflow from the main channel, resulting in gradients of flow connectivity among secondary channels that vary with river stage. We investigated the relationship of flow connectivity to benthic macroinvertebrate assemblage richness and structure among a series of secondary channels of the Lower Mississippi River. Samples were collected over 2 years at times of high and low river stages. We discovered (1) macroinvertebrate assemblage structure and taxonomic richness varied along the flow connectivity gradient, and (2) there was a legacy effect of prior connection on assemblage structure that lasted up to a year. We contend that for management and restoration planning aimed at conservation of large river biological diversity, an important consideration are the life history requirements of animals utilizing secondary channel habitats.
El Niño and La Niña

Abstract El Nino and La Nina are the two complementary phase of the Southern Oscillation. During E1 Nina, the area of high sea surface temperatures increases, while the atmospheric convection zones of the tropical Pacific expand and merge so that there is a tendency toward spatially homogeneous conditions. La Nina is associated with low sea surface temperatures near the equator, with atmospheric convergence zones that are isolated from each other, and with spatial wales smaller than those of El Nina. It is proposed that both phases of the Southern Oscillation can be attributed to unstable interactions between the tropical ocean and atmosphere. During El Nina, the increase release of latent heat to the atmosphere drives the instability. During La Nina, when the heating of the atmosphere decreases, the compression of the convection into smaller and smaller areas permits an instability that intensifies the trade winds and the oceanic currents. The unstable air-sea interactions are modulated by the seasonal m.
Circulating microRNA Biomarker for Detecting Breast Cancer in High-Risk Benign Breast Tumors

High-risk benign breast tumors are known to develop breast cancer at high rates. However, it is still controversial whether they should be removed during diagnosis or followed up until cancer development becomes evident. Therefore, this study sought to identify circulating microRNAs (miRNAs) that could serve as detection markers of cancers arising from high-risk benign tumors. Small RNA-seq was performed using plasma samples collected from patients with early-stage breast cancer (CA) and high-risk (HB), moderate-risk (MB), and no-risk (Be) benign breast tumors. Proteomic profiling of CA and HB plasma was performed to investigate the underlying functions of the identified miRNAs. Our findings revealed that four miRNAs, hsa-mir-128-3p, hsa-mir-421, hsa-mir-130b-5p, and hsa-mir-28-5p, were differentially expressed in CA vs. HB and had diagnostic power to discriminate CA from HB with AUC scores greater than 0.7. Enriched pathways based on the target genes of these miRNAs indicated their association with IGF-1. Furthermore, the Ingenuity Pathway Analysis performed on the proteomic data revealed that the IGF-1 signaling pathway was significantly enriched in CA vs. HB. In conclusion, these findings suggest that these miRNAs could potentially serve as biomarkers for detecting early-stage breast cancer from high-risk benign tumors by monitoring IGF signaling-induced malignant transformation.
Causal Transfer in Machine Learning

Methods of domain adaptation try to combine knowledge from several related domains (or tasks) to improve performance on a test domain. Inspired by causal methodology, we assume that the covariate shift assumption holds true for a subset of predictor variables: the conditional of the target variable given this subset of predictors is invariant over all tasks. We prove that in an adversarial setting using this subset for prediction is optimal if no examples from the test task are observed. For a specific scenario, in which tasks are drawn from a meta distribution, further optimality results are available. We introduce a practical method which allows for automatic inference of the above subset and provide corresponding code. We present results on synthetic data sets and a gene deletion data set.
Unsheltered Homelessness in Public Natural Areas Across an Urban-to-Wildland System: Institutional Perspectives

Abstract This article conceptualizes homelessness on public lands within a social-ecological systems framework, exploring dynamics in public natural areas in the Seattle metropolitan area (USA), a system with a compact urban-to-wildland gradient. While prior research has studied the dynamics of unsheltered homelessness within particular parks or cities—often in areas where camping is prohibited—our interview-based study makes integrated considerations of these dynamics across a range of jurisdictions. We present a thematic analysis that examines professionally diverse perspectives on the dynamics, stressors, and outcomes of public natural area usage by unsheltered individuals. We found a generally uncoordinated system in continual motion, in which considerable resources were expended for short-term, site-specific solutions that yielded system-wide detrimental outcomes perceived for unsheltered individuals, social service and environmental institutions, and ecosystem health. We discuss how improved institutional coordination and mutual understanding about intersecting governance systems could sustain better public land, public health, and social outcomes.
The dynamics of an SVIR epidemiological model with infection age

権利 Rights ©The Author 2015. This is a pre-copyedited, author-produced version of an art icle accepted for publicat ion in [IMA Journal of Applied Mathematics] following peer review. The version of record [IMA Journal of Applied Mathematics. 81(2): 321-343, Apr 2016] is available online at : ht tp://dx.doi. org/10.1093/imamat/hxv039. DOI 10.1093/imamat/hxv039 JaLCDOI URL http://www.lib. kobe-u.ac. jp/handle_kernel/90003818
Comparison of Automated and Traditional Western Blotting Methods

Traditional Western blotting is one of the most used analytical techniques in biological research. However, it can be time-consuming and suffer from a lack of reproducibility. Consequently, devices with different degrees of automation have been developed. These include semi-automated techniques and fully automated devices that replicate all stages downstream of the sample preparation, including sample size separation, immunoblotting, imaging, and analysis. We directly compared traditional Western blotting with two different automated systems, iBind™ Flex, which is a semi-automated system designed to perform the immunoblotting, and JESS Simple Western™, a fully automated and capillary-based system performing all steps downstream of sample preparation and loading, including imaging and image analysis. We found that a fully automated system can save time and importantly offer valuable sensitivity. This is particularly beneficial for limited sample amounts. The downside of automation is the cost of devices and reagents. Nevertheless, automation can be a good option to increase output and facilitate sensitive protein analyses.
Optimization of 2.5 μm VECSEL: influence of the QW active region

Using the (AlGaIn)(AsSb) material system, VECSELs covering the 2 – 3 μm wavelength range can be realized. The best laser performance of GaSb-based VECSELs was achieved so far at emission wavelengths around 2.0 μm with a slope efficiency of more than 30 %, a low threshold pump power density of 1.1 kW/cm2 at 20°C heatsink temperature and concomitant a high output power exceeding 7 W in CW operation (depending on the mounting technology). These parameters were degrading significantly for longer wavelength devices emitting around 2.5 μm and 2.8 μm. But for applications like the generation of MWIR light (3-8 μm) by pumping ZGP-OPOs, high-power VECSELs around 2.5 μm are required to suppress absorption losses, while for medical laser treatment, high-power operation near the water absorption peak at around 2.9 μm is desirable. We will present results of our ongoing research strand for further optimization of the semiconductor heterostructure design of ≥ 2.5 μm emitting GaSb-based VECSELs. By using a low quantum deficit design (i.e. optical pumping at around 1.5 μm) in combination with highly strained QWs (compressive strain 2.1 %) we were able to realize a 2.5 μm emitting VECSEL with a slope efficiency above 30 %, corresponding to an external quantum efficiency exceeding 50 %, and a low threshold pump power density of 0.8 kW/cm2. These values are as good as those for the best performing 2.0 μm VECSELs. With a frontside SiC heatspreader and operated in a standard linear cavity, over 7 W of CW output power were achieved for this 2.5 μm emitting VECSEL structure when operated at 20°C. Furthermore, we will compare laser structures with different emission wavelengths and discuss the role of the QW strain, band-offset and active region composition on laser performance.
Superdirective Unidirectional Mixed-Multipole Antennas: Designs, Analysis, and Simulations

Highly directive antenna systems that will address the needs of space-limited Internet-of-Things (IoT) devices and their NextG applications are in demand. Compact high-frequency high-directivity alternatives to complex, power-hungry phased arrays are desired. Several compact, unidirectional mixed-multipole antennas (UMMAs) based upon mixtures of primarily dipoles and quadrupoles are reported. The simulated performance characteristics of these 28-GHz near-field resonant parasitic (NFRP) antennas, notably their large peak directivities and front-to-back ratios (FTBRs), are presented; they are all demonstrated to be superdirective while having attractive radiation efficiencies. Uniform endfire arrays of active closely spaced equal-length idealized wire dipoles are exemplified as reference cases. The Rayleigh quotient (RQ) method typically used to determine their amplitude coefficients is extended for the first time to achieve unidirectional versions. Comparisons between these unconstrained and constrained RQ-designed arrays are made. While the performance characteristics of the single-source broadside-radiating UMMAs approach those of the reference arrays, a direct comparison of a realizable UMMA with the analogous unequal-length, nonuniformly spaced idealized dipole array demonstrates its superiority. A two-element UMMA array that is scalable to a larger number of elements is also presented and shown to be superdirective, illustrating that the attractive properties of its individual elements are maintained even when mutual coupling occurs.
Ultrahigh Raman Enhancement on Monolayer MoS2

Surface-enhanced Raman scattering (SERS) is commonly associated with noble metal substrates. However, over the years modest Raman enhancements ( 3 × 105 enhancement in SERS signal from an organic molecule (4-mercaptopyridine) placed in the near field of a two-dimensional semiconductor molybdenum disulfide (MoS2) monolayer. This large enhancement in the SERS signal is attributed to the charge transfer (CT) state formed at the interface of the 2D semiconductor and organic molecule and is found to occur when the excitation source is chosen to be in resonance with the CT state. This approach provides a new strategy for carrying out SERS experiments on molecules with very weak Raman sig.
Up-Regulation of miR-9-5p Inhibits Hypoxia-Ischemia Brain Damage Through the DDIT4-Mediated Autophagy Pathways in Neonatal Mice

Introduction Hypoxia-ischemia (HI) remains the leading cause of cerebral palsy and long-term neurological sequelae in infants. Despite intensive research and many therapeutic approaches, there are limited neuroprotective strategies against HI insults. Herein, we reported that HI insult significantly down-regulated microRNA-9-5p (miR-9-5p) level in the ipsilateral cortex of neonatal mice. Methods The biological function and expression patterns of protein in the ischemic hemispheres were evaluated by qRT-PCR, Western Blotting analysis, Immunofluorescence and Immunohistochemistry. Open field test and Y-maze test were applied to detect locomotor activity and exploratory behavior and working memory. Results Overexpression of miR-9-5p effectively alleviated brain injury and improved neurological behaviors following HI insult, accompanying with suppressed neuroinflammation and apoptosis. MiR-9-5p directly bound to the 3’ untranslated region of DNA damage-inducible transcript 4 (DDIT4) and negatively regulated its expression. Furthermore, miR-9-5p mimics treatment down-regulated light chain 3 II/light chain 3 I (LC3 II/LC3 I) ratio and Beclin-1 expression and decreased LC3B accumulation in the ipsilateral cortex. Further analysis showed that DDIT4 knockdown conspicuously inhibited the HI-up-regulated LC3 II/ LC3 I ratio and Beclin-1 expression, associating with attenuated brain damage. Conclusion The study indicates that miR-9-5p-mediated HI injury is regulated by DDIT4-mediated autophagy pathway and up-regulation of miR-9-5p level may provide a potential therapeutic effect on HI brain damage.
Quantifying reef-derived sediment generation: introducing the SedBudget methodology to support tropical coastline and island vulnerability studies

Standardised methodologies for assessing reef-derived sediment generation rates do not presently exist. This represents a major knowledge gap relevant to better predicting reef-derived shoreline sediment supply. The census-based SedBudget method introduced here generates estimates ofsediment composition and grain-size production as a function of the abundance and productivity of the major sediment-generating taxa at a reef site. Initial application of the method to several reefs in the northern Chagos Archipelago, Indian Ocean, generated total sediment generation estimates ranging from (mean (cid:1) SE) 0.7 (cid:1) 0.1 to 4.3 (cid:1) 1.3 kg CaCO 3 m (cid:3) 2 yr (cid:3) 1 . Sediment production was dominated by parrotfishes (>90% at most sites), with site-variable secondary contributions from sea urchins (up to 20%), endolithic sponges (~1 – 7%) and benthic foraminifera (~0.5 – 3.5%). These taxa-level contributions are predicted to generate sediments thatatallsitesarecoral-(83 – 94%)andcrustosecorallinealgae-dominated (range~5 – 12%). Comparisons between these estimates and sedimentary data from proximal reef and island beach samples generally show a high degree of consistency, suggesting promise in the SedBudget approach. We conclude by outlining areas where additional datasets and revised methodologies are most needed to improve rate estimates and hope that the methodology will stimulate research on questions around sediment production, transport and shoreline maintenance.
Economic Emission Load Dispatch with Multiple Fuel Options Using Cuckoo Search Algorithm with Gaussian and Cauchy distributions

Cuckoo Search Algorithm (CSA), a new meta-heuristic algorithm based on natural phenomenon of Cuckoo species and Levy flights random walk, has been successfully applied to several optimization problems so far. In the paper two modified versions of CSA, where new solutions are generated using two distributions including Gaussian and Cauchy distributions are proposed for economic emission load dispatch (EELD) problem with multiple fuel options. The advantages of CSA with Gaussian distribution (CSA-Gauss) and CSA with Cauchy distribution (CSA-Cauchy) over CSA with Levy distribution are fewer parameters and fewer equations and shorter computational process. The proposed method is tested on one test system consisting of ten generating units with various load demands and compared to other methods. In addition, the best compromise from the set of obtained solutions is found and compared to this from lamda-iteration (LI) method and Hopfield Lagrange Network (HLN). The result comparisons have indicated that the proposed method is a highly effective method.