Miracle-dz/UniFAR-FTUs huggingface dataset:
Insufficiency of compound immune checkpoint blockade to overcome engineered T cell exhaustion in pancreatic cancer

Background Achieving robust responses with adoptive cell therapy for the treatment of the highly lethal pancreatic ductal adenocarcinoma (PDA) has been elusive. We previously showed that T cells engineered to express a mesothelin-specific T cell receptor (TCRMsln) accumulate in autochthonous PDA, mediate therapeutic antitumor activity, but fail to eradicate tumors in part due to acquisition of a dysfunctional exhausted T cell state. Methods Here, we investigated the role of immune checkpoints in mediating TCR engineered T cell dysfunction in a genetically engineered PDA mouse model. The fate of engineered T cells that were either deficient in PD-1, or transferred concurrent with antibodies blocking PD-L1 and/or additional immune checkpoints, were tracked to evaluate persistence, functionality, and antitumor activity at day 8 and day 28 post infusion. We performed RNAseq on engineered T cells isolated from tumors and compared differentially expressed genes to prototypical endogenous exhausted T cells. Results PD-L1 pathway blockade and/or simultaneous blockade of multiple coinhibitory receptors during adoptive cell therapy was insufficient to prevent engineered T cell dysfunction in autochthonous PDA yet resulted in subclinical activity in the lung, without enhancing anti-tumor immunity. Gene expression analysis revealed that ex vivo TCR engineered T cells markedly differed from in vivo primed endogenous effector T cells which can respond to immune checkpoint inhibitors. Early after transfer, intratumoral TCR engineered T cells acquired a similar molecular program to prototypical exhausted T cells that arise during chronic viral infection, but the molecular programs later diverged. Intratumoral engineered T cells exhibited decreased effector and cell cycle genes and were refractory to TCR signaling. Conclusions Abrogation of PD-1 signaling is not sufficient to overcome TCR engineered T cell dysfunction in PDA. Our study suggests that contributions by both the differentiation pathways induced during the ex vivo T cell engineering process and intratumoral suppressive mechanisms render engineered T cells dysfunctional and resistant to rescue by blockade of immune checkpoints.
Multi‐decadal environmental change in the Barents Sea recorded by seal teeth

Multiple environmental forcings, such as warming and changes in ocean circulation and nutrient supply, are affecting the base of Arctic marine ecosystems, with cascading effects on the entire food web through bottom‐up control. Stable nitrogen isotopes (δ15N) can be used to detect and unravel the impact of these forcings on this unique ecosystem, if the many processes that affect the δ15N values are constrained. Combining unique 60‐year records from compound specific δ15N biomarkers on harp seal teeth alongside state‐of‐the‐art ocean modelling, we observed a significant decline in the δ15N values at the base of the Barents Sea food web from 1951 to 2012. This strong and persistent decadal trend emerges due to the combination of anthropogenic atmospheric nitrogen deposition in the Atlantic, increased northward transport of Atlantic water through Arctic gateways and local feedbacks from increasing Arctic primary production. Our results suggest that the Arctic ecosystem has been responding to anthropogenically induced local and remote drivers, linked to changing ocean biology, chemistry and physics, for at least 60 years. Accounting for these trends in δ15N values at the base of the food web is essential to accurately detect ecosystem restructuring in this rapidly changing environment.
An emerging coastal wetland management dilemma between mangrove expansion and shorebird conservation

Coastal wetlands around the world have been degraded by human activities. Global declines in the extent of important coastal wetlands, including mangroves, salt marshes, and tidal flats, necessitate mitigation and restoration efforts. However, some well‐meaning management actions, particularly mangrove afforestation, can inadvertently cause further loss and degradation of other habitats if these actions are not planned carefully. In particular, there is a potential conflict between mangrove and shorebird conservation because mangrove afforestation and restoration may occur at the expense of bare tidal flats, which form the main foraging habitats for threatened shorebirds and support other coastal organisms. We examined several case studies that illustrate the trade‐off between mangrove restoration and bare tidal flat maintenance. To investigate whether these examples reflect an emerging broad‐scale problem, we used satellite imagery to quantify the change in mangrove habitat extent in 22 important shorebird areas in mainland China from 2000 to 2015.The extent of tidal flat across all sites declined significantly (p < 0.01, n = 22) while among sites with mangroves present, the extent of mangroves expanded significantly (p < 0.01, n = 14). Our results suggest mangrove expansion and tidal flat loss have considerably reduced shorebird habitat in 8 of these sites. To improve the overall conservation outcome, we devised a decision tree for addressing the dilemma. Important factors to consider include whether the area of interest is of importance to shorebirds and what the potential impacts of mangrove expansion are; what the value of the proposed mangrove ecosystem is compared with the existing ecosystem; and that a conflict‐resolution process will be needed if the choices are very similar. With careful consideration of alternative management strategies, decision makers can ensure that the conservation of mangroves does not imperil migratory shorebirds.
Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome

The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.
Atypical functional connectivity of the left fusiform gyrus in infants at familial risk for developmental dyslexia

Importance: Developmental dyslexia (dyslexia) is a genetic-based learning disorder affecting 7-10% of the general population and has detrimental impacts on mental health and vocational potential. Individuals with dyslexia show altered functional organization of the language and reading neural networks; however, it remains unknown how early these neural network alterations emerge in association with familial(genetic) vulnerability to dyslexia. Objective: To determine whether the early development of large-scale functional neural connectivity is altered as a function of familial risk for dyslexia. Design: This cohort study included 98 infants with (FHD+) and without (FHD-) a familial history of dyslexia recruited at Boston Children's Hospital (BCH) between May 2011 and February 2019. Setting: Participants underwent structural and resting-state functional magnetic resonance imaging in the Department of Pediatric Radiology at BCH. Participants: FHD+ infants were defined as having at least one first-degree relative with dyslexia or reading difficulties and infants without familial risk for dyslexia (i.e., FHD-) were controls. Main outcomes and measures: Whole-brain functional connectivity patterns associated with 20 pre-defined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific functional connectivity patterns that differentiated between FHD+ and FHD- infants. Results: The final sample consisted of 35 FHD+ (mean = 8.9 months, SD = 2.4 months, 15 females) and 63 FHD- (mean = 8.3, SD = 2.3 months, 36 females) infants. Multivariate pattern analyses identified distinctive functional connectivity patterns between the FHD+ and FHD- infants in the left fusiform gyrus (LFFG: accuracy = 0.55, p < 0.001, corrected, effect size: Cohen's d = 0.76, 99% CI of the classification performance (classification accuracy-chance level) = [0.046, 0.062]). Moreover, the top five connections with the greatest contribution to the classification performance connected LFFG with the frontal and temporoparietal regions of the language network. Conclusion and relevance: The current study demonstrates that familial vulnerability to dyslexia is associated with an early onset of atypical functional connectivity of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading (dis)abilities will be essential for further elucidating the ontogenetic mechanisms underlying the development of dyslexia.
A dual circular and linear polarized rectenna for RF energy harvesting at 0.9 and 1.8 GHz GSM bands

ABSTRACT In this paper, a dual wideband rectenna using a monopole spiral antenna with an improved impedance matching is proposed to provide dual circularly and linearly polarized wave reception capability at the 0.9 and 1.8 GHz GSM bands. To improve the rectenna’s output power, coupled-line and open stub matching networks are applied to achieve the match between the rectifying diodes and antenna. The rectenna has been optimized at −15 dBm per arbitrary polarized incident waves and dedicated to contactless and remote supply low feasting sensors. It has been verified with low power levels from −30 to +20 dBm, the proposed configuration shows a maximum output DC voltage and an overall efficiency of 2.7 V and 70%, respectively, when the azimuthal angle of the incident field varies between −90° and +90°. This kind of rectenna can be practically be used in a wide range of wireless low-power devices.
Low Cost Printed Dipole Array Antenna for 5G Sub-6GHz Base Stations Implementing Beam-tilting, Ground-backing, and Series-Feeding

ABSTRACT An antenna array dedicated to wideband 5 G sub-6 GHz base station applications is presented. It combines several features to arrive at a very effective and low-cost topology. Printed dipole elements printed on both sides of a single substrate are used to reach a sufficient −10 dB bandwidth of 25.3%. The eight dipole elements are series-fed, which is ideal to realize down-tilt beam shaping in the E-plane. Ground-backing makes the antenna unidirectional with a peak realized gain of more than 9 dBi over the entire band, with a maximum of 12 dBi at 3.5 GHz. The array has a half-power beamwidth (HPBW) varying between 35° and 47° in E plane and between 82° and 86° in H-plane, respectively. The antenna is compared to similar designs in literature and reaches a superior performance.
Associations of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Cognitive Impairment Among the Oldest-Old in China

Recent literature suggested that ALDH2 mutation is associated with alcohol metabolism, and ethanol intake might jointly increase the risk of Alzheimer’s disease (AD) in mice. However, it is unclear whether this synergistic effect exists among humans. We examined the associations of four single nucleotide polymorphisms (SNPs) on aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) genes (i.e., ALDH2 rs671, ADH1B rs1229984, ADH1B rs1042026, and ADH1C rs1693482) and cognitive impairment among the oldest-old. We also investigated whether this association was modified by ethanol intake from alcohol consumption. Data were from the Chinese Longitudinal Healthy Longevity Survey genetic sub-study, including 1,949 participants aged over 90 years. Participants with a Mini-Mental State Examination (MMSE) score of < 18 were considered cognitively impaired. Alcohol consumption was categorized as heavy, moderate, or never drinkers. With the dominant model, carrying A allele on rs671, C allele on rs1229984, and T allele on rs1042026 was associated with 33% (95% confidence interval [CI]: 5%, 69%), 33% (95% CI: 2%, 75%), and 29% (95% CI: 3%, 62%) higher odds of cognitive impairment in the multivariable-adjusted logistic model, respectively. We did not observe a significant interaction between those SNPs and alcohol consumption. Among the oldest-old, carrying ALDH2 rs671 mutation was associated with higher odds of cognitive impairment independent of alcohol consumption.
Petrological and geochronological investigations on the individual nappes of the Meran-Mauls nappe stack (Austroalpine unit/South Tyrol, Italy)

Abstract The Meran-Mauls nappe stack is part of the Austroalpine unit in South Tyrol (Italy). There it holds a special position directly in front of the Southalpine Dolomites indenter and west of the Tauern Window. It is situated in the hanging wall of the Southalpine unit, above a NW dipping segment of the Periadriatic fault system, namely the Meran-Mauls fault. Also all other sides are defined by Oligocene-Miocene strike-slip and normal faults. Based on recent mapping the Meran-Mauls nappe stack consists of three nappes separated by NW to NNW dipping shear zones. The lowermost nappe in the southwest is represented by the Schenna (Scena) unit. It is overlain along the Masul shear zone by a nappe consisting of the Hirzer (Punta Cervina) unit and the Pens (Pennes) unit including Triassic (meta)sediments. Separated by the Fartleis fault the St. Leonhard (San Leonardo) unit forms the uppermost nappe. The aim of this study is to describe the individual units and the separating structural elements more properly, based on new structural, petrological, geothermobarometric and geochronological data and to compare these units to other Austroalpine elements in the vicinity. Sillimanite-bearing paragneiss, minor amphibolite and quartzite as well as a distinct marble layer close to its base characterise the Schenna unit. Further, it contains pegmatite dikes, presumably Permian in age. Amphibolite-facies P-T conditions of c. 0.55 ± 0.15 GPa and 600 ± 100°C are thus correlated with a Permian metamorphic imprint. The Masul shear zone mostly consists of mylonitic paragneiss of the Hirzer unit. It is pre-Alpine in age and probably formed during the Jurassic. For the paragneiss of the Hirzer unit upper greenschist- to amphibolite-facies metamorphic conditions of 0.4-0.50 ± 0.15 GPa and 550 ± 70°C are attributed to the Variscan tectonometamorphic imprint. The whole Pens unit represents a shear zone. Due to the occurrence of Permotriassic (meta)-sediments within this shear zone, it is an Alpine structure, as well as the bordering Fartleis fault. Rb/Sr biotite ages yield sometimes partly reset pre-Alpine age values in the whole Meran-Mauls nappe stack, indicating a pervasive anchizonal to lowermost greenschist-facies metamorphic overprint during the Eoalpine tectonometamorphic event. Tectonostratigraphically the Meran-Mauls nappe stack can be attributed to the Drauzug-Gurktal nappe system. The latter forms the uppermost structural element of the Austroalpine nappe stack and thus only shows a weak Eoalpine metamorphic overprint. With respect to its special lithologic composition the Schenna unit can be correlated with the Tonale unit in the southwest and the Strieden-Komplex in the east.
An Autoencoder-Enhanced Stacking Neural Network Model for Increasing the Performance of Intrusion Detection

Abstract Security threats, among other intrusions affecting the availability, confidentiality and integrity of IT resources and services, are spreading fast and can cause serious harm to organizations. Intrusion detection has a key role in capturing intrusions. In particular, the application of machine learning methods in this area can enrich the intrusion detection efficiency. Various methods, such as pattern recognition from event logs, can be applied in intrusion detection. The main goal of our research is to present a possible intrusion detection approach using recent machine learning techniques. In this paper, we suggest and evaluate the usage of stacked ensembles consisting of neural network (SNN) and autoen-coder (AE) models augmented with a tree-structured Parzen estimator hyperparameter optimization approach for intrusion detection. The main contribution of our work is the application of advanced hyperparameter optimization and stacked ensembles together. We conducted several experiments to check the effectiveness of our approach. We used the NSL-KDD dataset, a common benchmark dataset in intrusion detection, to train our models. The comparative results demonstrate that our proposed models can compete with and, in some cases, outperform existing models.
Asymmetrical organization of oral structures in the primary and secondary somatosensory cortices in rats: An optical imaging study

In rodents, the representation of the body surface in the primary somatosensory cortex (S1) forms a mirror image along the ventral border of the S1 in the secondary somatosensory cortex (S2). Sensory information from the oral region is processed in the S1 and the border region between the S2 and insular oral region (IOR). We examined the relationship between somatosensory representations in the S1 and S2/IOR using optical imaging with a voltage‐sensitive dye in urethane‐anesthetized rats. In reference to the rhinal fissure and middle cerebral artery, we made a somatosensory map by applying electrical or air puff stimulation. The initial neural excitation in the S1 to facial structures, including the eyebrow, cornea, pinna, whisker pad, nasal tip, and nasal mucosa, spread toward the ventral area, putatively the S2. The initial cortical responses in the S1 to oral structures, including the lower lip, tongue, and teeth, were spatially separated from those in the S2/IOR. The representation of the tongue center, tongue tip, mandibular molar pulp, mandibular incisor pulp, and mandibular incisor periodontal ligament were almost linearly arranged from caudal to rostral in both S1 and S2/IOR. The lower lip was represented in the dorsal area from the representation of teeth and tongue in both S1 and S2/IOR. The representations of maxillary teeth were caudal and dorsal to the representations of mandibular teeth in the S1 and S2/IOR, respectively. These results suggest that the representation of oral structures in the S1 formed a non‐mirror image, not a mirror image, in the S2/IOR.
Resiliency-Aware Power Management of Microgrids using Agent-based Dynamic Programming and Q-learning

Appropriate planning and optimization strategies for day-ahead power management play important roles in efficient operation of Microgrids (MGs). Due to the uncertainties in electricity demand and renewable generations, and the multi-objective (MO) nature of MG power management, conventional optimization techniques have not been as effective in giving satisfactory results. This paper aims at solving the day-ahead power management problem as a MO optimization problem, with a focus on increasing the system's resiliency using an agent-based Dynamic Programming (DP) approach named Value Iteration (VI) and a model-free Q-learning (QL) algorithm. The two objectives of the MO problem are: maximizing load serviceability and minimizing operational cost. Both the approaches are data-driven, and the behavior of the agent of each component of a MG is formulated as a finite-horizon Markov Decision Process (MDP). VI guarantees an optimal solution to the MO problem given the MDP model, and QL has the ability to work under uncertainty and incomplete information. The effectiveness of the two algorithms have been evaluated using a benchmark MG test system.
Mechanism for Predicting Forest Land Cover from Remote Sensing

As humans intrude on forest areas, deforestation occurs. The main effect of this must be resolved by detecting and evaluating certain methods to protect the area of the forest. For example, deforestation has become a significant contributor to biodi versity loss and environmental problems. A model which may provide interpretable forecasts of deforestation is a significant tool for preventing the loss of forest area such as unlawful logging and grazing or planting. Advances in the study of satellite data and artificial neural networks have resulted in several ways to develop such a model. This article discusses the most commonly used machine learning methods. The primeval aim of this research is to develop a framework for comparing several evaluation metrics in order to enhance the existing solution and provide interpretable temporal predictions. This means that the image processing technique have tremendous promise for predicting deforestation in forests. The findings of this research will help to improve forest observation and policy initiatives for rehabilitation. This research deals with the vandalur forest area and detects the prediction of how much deforestation has been happened from 2008 to 2021 using satellite images. By comparing various models, the efficacy amongst the most frequently used assessment measures is investigated. The research finding suggests that different model for forecasting degradation may be used, as well as the areas lost throughout the research period. According to the data, 50% of the land cover area was deteriorated between 2008 and 2021. By 2030, it is predicted that 75% of the land cover area would have been damaged by constructions, condominiums, and parks.