Miracle-dz/UniFAR-FTUs huggingface dataset:
A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), encoding a transcriptional regulator of many genes, including brain-derived neurotrophic factor (Bdnf). BDNF mRNA and protein levels are lower in RTT autopsy brains and in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of a brain penetrant, small molecule ligand of its TrkB receptors. Applied in vitro, LM22A-4 increased dendritic spine density in pyramidal neurons in cultured hippocampal slices from postnatal day (P) 7 male Mecp2 knockout (KO) mice as much as recombinant BDNF, and both effects were prevented by the TrkB receptor inhibitors K-252a and ANA-12. Consistent with its partial agonist activity, LM22A-4 did not affect spine density in CA1 pyramidal neurons in slice cultures from male wildtype (WT) mice, where typical BDNF levels outcompete its binding to TrkB. To identify neurons of known genotypes in the ‘mosaic’ brain of female Mecp2 heterozygous (HET) mice, we treated 4–6-month-old female MeCP2-GFP WT and HET mice with peripheral injections of LM22A-4 for 4 weeks. Surprisingly, mutant neurons lacking MeCP2-GFP showed dendritic spine volumes comparable to that in WT controls, while MeCP2-GFP-expressing neurons showed larger spines, similar to the phenotype we described in symptomatic male Mecp2 KO mice where all neurons lack MeCP2. Consistent with this non-cell-autonomous mechanism, a 4-week systemic treatment with LM22A-4 had an effect only in MeCP2-GFP-expressing neurons in female Mecp2 HET mice, bringing dendritic spine volumes down to WT control levels, and without affecting spines of MeCP2-GFP-lacking neurons. At the behavioral level, we found that female Mecp2 HET mice engaged in aggressive behaviors significantly more than WT controls, which were reduced to WT levels by a 4-week systemic treatment with LM22A-4. Altogether, these data revealed differences in dendritic spine size and altered behaviors in Mecp2 HET mice, in addition to provide support to the potential usefulness of BDNF-related therapeutic approaches such as the partial TrkB agonist LM22A-4.
A high-density diffuse optical tomography dataset of naturalistic viewing

Traditional laboratory tasks offer tight experimental control but lack the richness of our everyday human experience. As a result many cognitive neuroscientists have been motivated to adopt experimental paradigms that are more natural, such as stories and movies. Here we describe data collected from 58 healthy adult participants (aged 18–76 years) who viewed 10 minutes of a movie (The Good, the Bad, and the Ugly, 1966). Most (36) participants viewed the clip more than once, resulting in 106 sessions of data. Cortical responses were mapped using high-density diffuse optical tomography (first-through fourth nearest neighbor separations of 1.3, 3.0, 3.9, and 4.7 cm), covering large portions of superficial occipital, temporal, parietal, and frontal lobes. Consistency of measured activity across subjects was quantified using intersubject correlation analysis. Data are provided in both channel format (SNIRF) and projected to standard space (NIfTI), using an atlas-based light model. These data are suitable for methods exploration as well as investigating a wide variety of cognitive phenomena.
Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.
Tetrameric UvrD helicase is located at the E. coli replisome

frequent replication blocks 2 Adam J. M Wollman1,2,3,, Aisha H. Syeda, Jamieson A. L. Howard1,2, Alex Payne-Dwyer1,2, Andrew 3 Leech4 , Colin Guy5, 6, Peter McGlynn2,6, Michelle Hawkins2 and Mark C. Leake1,2 4 The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint 5 First Authors 6 1 School of Physics, Engineering and Technology, University of York, York YO10 5DD, United 7 Kingdom. 8 2 Department of Biology, University of York, York YO10 5DD, United Kingdom. 9 3 Current address: Biosciences Institute, Newcastle University, NE1 7RU, United Kingdom. 10 4 Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, United 11 Kingdom 12 5 Current address: Covance Laboratories Ltd., Otley Road, Harrogate, HG3 1PY, United Kingdom 13 6 Previous address: School of Medical Sciences, Institute of Medical Sciences, University of 14 Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom 15 16 17
The pAblo·pCasso self-curing vector toolset for unconstrained cytidine and adenine base-editing in Gram-negative bacteria

A synthetic biology toolkit, exploiting clustered regularly interspaced short palindromic repeats (CRISPR) and modified CRISPR-associated protein (Cas) base-editors, was developed for genome engineering in Gram-negative bacteria. Both a cytidine base-editor (CBE) and an adenine base-editor (ABE) have been optimized for precise single-nucleotide modification of plasmid and genome targets. CBE comprises a cytidine deaminase conjugated to a Cas9 nickase from Streptococcus pyogenes (SpnCas9), resulting in C→T (or G→A) substitutions. Conversely, ABE consists of an adenine deaminase fused to SpnCas9 for A→G (or T→C) editing. Several nucleotide substitutions were achieved using these plasmid-borne base-editing systems and a novel protospacer adjacent motif (PAM)-relaxed SpnCas9 (SpRY) variant. Base-editing was validated in Pseudomonas putida and other Gram-negative bacteria by inserting premature STOP codons into target genes, thereby inactivating both fluorescent proteins and metabolic (antibiotic-resistance) functions. The functional knockouts obtained by engineering STOP codons via CBE were reverted to the wild-type genotype using ABE. Additionally, a series of induction-responsive vectors was developed to facilitate the curing of the base-editing platform in a single cultivation step, simplifying complex strain engineering programs without relying on homologous recombination and yielding plasmid-free, modified bacterial cells.
Quantitative study of effects of the sea chlorophyll-a concentration by typhoon based on remote-sensing

The study of effect to the ocean color environment caused by typhoon is another application of satellite ocean remote sensing.There are less remote sensing data in the period of hurricanes,so many scholars in the world mainly study some special typhoons' effects on the sea surface temperature(SST),chlorophyll-a(chl-a) and the primary product and there are fewer people to carry through quantitative analysis and modeling to the effects by remote sensing data.From 2000 to 2007,there were nearly 100 times typhoons passing through China sea area and the northwest Pacific Ocean.By analysing the level "3A" data of chlorophyll-a of the MODIS and SeaWiFS,the authos get some conclusions as follows.first,the chlorophyll-a concentration in the correlative area has increased,it averagely rises to about 1.426 times than the usual,even over 5 times in several areas.This growing up lagged about 3～6 d and it came back to the normal value after 7～10 d.Second,by using statistic linear regression to the rate of chl-a concentration increment(R chl-a) and typhoon-effect-factor(T w),the authors get an equation as follows: R chl-a =0.001 2 T w +1.017 and the correlation coefficient is 0.8. Thirdly,the concentration(C chl-a) of chl-a with typhoon and without typhoon has a strong linear relation,which meets such equation as C chl-a = 1.236 7 C 0chl-a +0.063 6,and the correlation coefficient is up to 0.98. It is helpful to deeply understand the effects of the ocean color environment by the typhoon using remote sensing.
An Historical Overview of the Middle School Movement, 1963–2015

Abstract Over 50 years of articles related to the middle school movement in the United States were examined and analyzed in order to uncover the movement’s primary themes associated with practice, research, and policy. Using a qualitative content approach, researchers created themes to represent the movement decade by decade. The years 1963–1979 were identified as the beginning of the Middle School Movement and its search for an identity. The next decade, 1980–1989, was a time of advancement and progress, and the movement became identified with practices, such as team teaching, interdisciplinary curriculum, and advisory. The years 1990–1999 saw pressure on the movement advancing from national policies, but the movement persisted with a sense of hope. To combat challenges to the middle school movement’s core beliefs and practices, an era of research on middle school practices emerged, and this research focus characterized 2000–2009. The current decade continued the research focus with an international perspective and efforts to identify and describe a “signature” middle school pedagogy. From this historical perspective, it was determined that core middle school practices must continue to grow and thrive in order to meet the social and academic needs of future generations of young adolescents.
Boosting Application Performance using Heterogeneous Virtual Channels: Challenges and Opportunities

Interactive networked applications require high throughput, low latency, and high reliability from the network to provide a seamless user experience. While meeting these three requirements simultaneously is difficult, there has been an emergence of heterogeneous virtual channels (HVCs) which support some subset of them at the expense of the others. For instance, URLLC sacrifices throughput to achieve low latency and reliability in 5G NR, and Wi-Fi 7 and other novel Internet architectures provide similar disparate types of service. Prior work either focuses on aggregating the bandwidth of these channels whilst neglecting their unique properties or fails to generalize in the sense of achieving high performance across different applications and channels. To utilize HVCs to their fullest, we argue that there are challenges and opportunities across the network, transport and application layers, and the application-transport interface of the network stack. In this work, we explore the trade-offs of these architectural choices in the context of web browsing and real-time video, and identify the constituting principles of a design that is general, performant, and deployable.
On-demand Geographic Forwarding for producer mobility support in Named Data Networking

With the rapid advancement of mobile devices and the continuously increasing generated traffic have made mobility support in networks a critical requirement. Recently, named data networking (NDN) has emerged as potential alternative architecture to address the challenges of the current IP-based Internet architecture, such as scalability, privacy, and security. However, despite the implicit handling of consumer mobility in the NDN architecture, producer mobility remains a major challenge and is especially important for emerging applications such as virtual and augmented reality, IoT devices, and 5G networks. This paper introduces a new approach to handle producer mobility in NDN, called on-demand geographic forwarding (OGF). The OGF mechanism redirects Interest packets to the mobile producer's next access point location via a fixed Rendezvous server, using the location information of the access points. Our proposed solution anticipates the mobile producer's handoff and chooses the next access point before the handoff occurs. We have evaluated our proposed solution using ndnSIM simulation and compared its performance with a popular tracing-based solution called Kite, proposed by the NDN research group. The simulation results clearly illustrate that the OGF solution outperforms Kite by reducing signaling overhead by 90%, decreasing packet loss by 25%, and saving 13% of handoff delay time.
Hydraulic and Thermal Conductivities of Kaolin–Silica Mixtures under Different Consolidation Stresses

Stable backfill materials for the heat sensitive structures of buried power cables, hot water pipes, and gas pipelines are suggested to have low permeability and high heat transfer characteristics. The hydraulic and thermal conductivities of backfill materials or clay liners are important parameters in proper design and construction of geotechnical structures involved with heat transfers. In this study, to investigate the optimal natural backfill or liner materials, thermal and hydraulic conductivities of kaolin–silica mixtures examined based on the results from laboratory tests under different consolidation conditions. From the experiment results, the thermal conductivity increases while hydraulic conductivity decreases with increasing density during consolidation process. As a result, back-fill materials with high kaolin content under low consolidation stress were desirable materials for burial of heat sensitive structures.
Bio-magnetochronology for the upper Campanian – Maastrichtian from the Gubbio area, Italy: new results from the Contessa Highway and Bottaccione sections

A new bio-chronostratigraphic framework is presented for the upper Campanian – Maastrichtian pelagic sediments of the Gubbio area (Bottaccione and Contessa Highway sections, Italy). New planktonic foraminiferal (FO of P. hantkeninoides), calcareous nannofossil (FO of M. prinsii, base acme of M. murus) and magnetostratigraphic data are provided and integrated to construct an age-depth curve based on the recent astronomical calibration of the late Campanian – Maastrichtian magnetic polarity time scale (Husson, D., Galbrun, B., Laskar, J., Hinnov, L. A., Thibault, N., Gardin, S., Locklair, R. E., 2011. Astronomical calibration of the Maastrichtian, Late Cretaceous. Earth and Planetary Science Letters 305, 328–340). All bio-horizons recorded in both sections fall on or are very close to the Line of Correlation (LOC), which testifies to the reliability of biochronologic studies in the Umbria-Marche basin. The proposed age model allows to estimate the sedimentation rates and the ages of calcareous nannofossil and planktonic foraminiferal bio-horizons in both sections. Also, it provides an excellent late Campanian – Maastrichtian reference for sections in the Umbria-Marche area and the entire Tethys. Due to the presence of a ~ 425 kyr-long hiatus in Chron C31n of the Bottaccione section, the Contessa Highway section constitutes a more complete late Campanian – Maastrichtian reference for bio-magnetochronology in the Tethyan realm.
Garnet-biotite relationships in high grade metamorphic rocks at Broken Hill, Australia

Summary Garnets and biotites from pelitic, psammitic and quartzofeldspathic rock enclosing the Broken Hill orebodies are sensitive to syn and post high grade metamorphic metasomatism associated with orebody-wall rock reactions but the overall garnet—biotite partitioning relationships remain unchanged. KMg-FeDgarnet-biotite and metamorphic grade calculations increase from NW to SE over the 1000 m section examined which is in accord with the regional grade variation.
A Hyperparameter Optimization Strategy to Boost Fake News Detection

Currently, Fake News easily go viral on social networks, this is a cause for concern worldwide. An alternative to detect this type of information is the use of Machine Learning and Natural Language Processing. Nevertheless, due to the high volume of information it is crucial to define mechanism easy to implement and to deploy. The aim of this research is to demonstrate that the use of basic Neural Networks together with a modified hyperparameter optimization algorithm, allows obtaining similar results to those obtained when using SVM and NLP. The source of information covers verified trending news in the country as well as false headers from mid-2021 to February 2023. The output of the experiments determines that 86% of true news can be accurately identified with the proposed approach. While, the 78% of fake news can be accurately identified too with a mean error around 0.049.
Development of glacial Llyn Teifi, west Wales: evidence for lake-level fluctuations at the margins of the Irish Sea ice sheet

A thick sequence of Quaternary laminated silt and clay, sand, gravel, and diamict has recently been proven at Llandudoch (St Dogmaels), west Wales. Most of these deposits accumulated in a tributary valley of Afon (River) Teifi, that formed prior to the last glaciation. The laminated silt and clay occur up to 103 m above present sea level, and are considered to have been deposited in Llyn (Lake) Teifi—a large ice-dammed lake that developed in the Teifi valley as the Irish Sea ice sheet impinged onto the Welsh mainland during the late Devensian. Rhythmic units are interpreted as annual varves, whose composition was determined by the distance from the sediment discharge point. Short-term climate fluctuations during the summer months are evident in some of the varve units. Stratigraphic variations within the laminated deposits are considered to reflect different levels of Llyn Teifi, which varied according to the position of the Irish Sea ice sheet in the Teifi valley and the elevations of three overspill channels. The overlying diamict, sand and gravel deposits are thought to have accumulated close to the ice front as it encroached into Llyn Teifi. During the final retreat of the Irish Sea ice sheet a series of kamiform sand and gravel deposits formed along the margins of the glacier.
POAGuard: A Defense Mechanism Against Preemptive Table Overflow Attack in Software-Defined Networks

In Software-Defined Networks (SDN), the limited flow table capacity of switches makes them susceptible to flow table overflow attacks, which can lead to performance degradation or network corruption. Prior research has mainly focused on rate-based overflow attacks (ROA), which exhibit varying attack effects depending on the overflow rate. This study introduces a novel attack called the preemptive overflow attack (POA), which exploits flow entry eviction mechanism to preempt the flow entries of normal applications, resulting in amplified performance degradation. Notably, when using the widely deployed Least Frequently Used (LFU) eviction algorithm, POA achieves a significant impact while consuming fewer flow entries than existing ROA methods. Furthermore, the detection of POA remains challenging owing to the lack of distinctive flow features. To mitigate POA, we propose POAGuard as a defense mechanism. POAGuard incorporates a table segmentation method for table management, a score-based eviction algorithm that evicts suspicious flow entries, and a concept drift-based detection method that identifies and defends against POA. Extensive experiments are conducted to verify the effectiveness of POAGuard, and the results demonstrate that POAGuard can effectively defend against POA.
Identification and Severity Assessment of COVID-19 Using Lung CT Scans

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, continues to have a significant impact on the global population. To effectively triage patients and understand the progression of the disease, a metric-based analysis of diagnostic techniques is necessary. The objective of the present study is to identify COVID-19 from chest CT scans and determine the extent of severity, defined by a severity score that indicates the volume of infection. An unsupervised preprocessing pipeline is proposed to extract relevant clinical features and utilize this information to employ a pretrained ImageNet EfficientNetB5 model to extract discriminative features. Subsequently, a shallow feed-forward neural network is trained to classify the CT scans into three classes, namely COVID-19, Community-Acquired Pneumonia, and Normal. Through various ablation studies, we find that a domain-specific preprocessing pipeline has a significant positive impact on classification accuracy. The infection segmentation mask generated from the preprocessed pipeline performs better than state-of-the-art supervised semantic segmentation models. Further, the estimated infection severity score is observed to be well correlated with radiologists’ assessments. The results confirm the importance of domain-specific preprocessing for training machine learning algorithms.
Methodology of Combining Empirical Stress Testing and Formal-Methods Based Schedulability Analysis for Real-Time Multicore Software

Current certification guidance documents for aircraft provide plans, processes, and objectives. This has been successful in terms of achieving safety but it comes at the expense of leading to a less agile software development; this makes software development slow for greenfield development, prevents rapid updates of software, and prevents rapid upgrades of hardware. The use of formal methods (FM) has the potential to avoid some of these drawbacks. A critical issue today is the use of multicore and their potential to introduce inter-core interference which can violate real-time requirements. Therefore, in this paper, we present a two-step reasoning framework that can be used to bring some FM to the analysis of real-time requirements of software executing on multicore.