Miracle-dz/UniFAR-FTUs huggingface dataset:
A new family of CRISPR‐type V nucleases with C‐rich PAM recognition

Most CRISPR‐type V nucleases are stimulated to cleave double‐stranded (ds) DNA targets by a T‐rich PAM, which restricts their targeting range. Here, we identify and characterize a new family of type V RNA‐guided nuclease, Cas12l, that exclusively recognizes a C‐rich (5'‐CCY‐3′) PAM. The organization of genes within its CRISPR locus is similar to type II‐B CRISPR‐Cas9 systems, but both sequence analysis and functional studies establish it as a new family of type V effector. Biochemical experiments show that Cas12l nucleases function optimally between 37 and 52°C, depending on the ortholog, and preferentially cut supercoiled DNA. Like other type V nucleases, it exhibits collateral nonspecific ssDNA and ssRNA cleavage activity that is triggered by ssDNA or dsDNA target recognition. Finally, we show that one family member, Asp2Cas12l, functions in a heterologous cellular environment, altogether, suggesting that this new group of CRISPR‐associated nucleases may be harnessed as genome editing reagents.
Between ‘shopper’ and ‘owner’: emerging agency of lifelong learner in South Korea’s marketing-driven expansion of lifelong education

ABSTRACT This study explores the expansion of Korean lifelong education over the last two decades in terms of conceptualising the lifelong learner as identity and agency. Based on qualitative interviews with lifelong educators and learners at lifelong education institutions, the authors describe the lifelong educators’ use of marketing strategies to turn learners into core members who continuously consume their programmes, which greatly resembles loyal customers. However, these loyal customers did not remain ‘shoppers. ’ They came to exercise owner-agency since they felt like they were a part of the institution, which led them into conflict with the lifelong educators over the institutions’ management. This study reveals that in Korea, marketing contributed to the expansion of lifelong education and cultivated the identity and agency of lifelong learners as both shoppers and owners.
School-level implementation of a state-wide professional development model for developing globally competent teachers

ABSTRACT In-service K–12 teachers require preparation and support to conceptualize and incorporate global competence into their classroom teaching practices. The state of North Carolina created a state-wide framework for such professional development: the Global Educator Digital Badge (GEDB). The GEDB focuses on developing knowledge and practices of globally competent teaching. To explore state policy to school practice, this intrinsic case study reports findings from teachers, administrators, and professional development providers from a K–5 school with 90% teacher participation in the GEDB. Tenets of effective PD and the Global Competence Teaching Continuum served as frameworks to analyze surveys, focus group, interviews, classroom observations, and documents to discern teachers’ abilities to conceptualize and enact globally competent teaching (via curriculum and instruction). Findings describe teachers’ abilities to define global education, embed global competencies within their curriculum, and implement recommended pedagogical strategies. Shifts in teachers’ practices toward globally competent curriculum and instruction are discussed.
MVP: measuring internet routing from the most valuable points

Scrutinizing BGP routes is part of the everyday tasks that network operators and researchers conduct to monitor their networks and measure Internet routing. This task is facilitated by the expansion of routing information services such as RIPE RIS [2] and Route-Views [3] that collect BGP routes from an increasing number of Vantage Points (VPs). Unfortunately, while more data is often beneficial, in the case of BGP, it involves downloading and processing large volumes of route updates that exhibit a high level of redundancy. Today with more than one billion route updates collected every day, users often have no other option than to focus on a subset of the VP. Because of the highly skewed location of the VP, randomly selecting them may result in a lot of missing information.
A comparative analysis of certificate pinning in Android & iOS

TLS certificate pinning is a security mechanism used by applications (apps) to protect their network traffic against malicious certificate authorities (CAs), in-path monitoring, and other methods of TLS tampering. Pinning can provide enhanced security to defend against malicious third-party access to sensitive data in transit (e.g., to protect sensitive banking and health care information), but can also hide an app's personal data collection from users and auditors. Prior studies found pinning was rarely used in the Android ecosystem, except in high-profile, security-sensitive apps; and, little is known about its usage on iOS and across mobile platforms. In this paper, we thoroughly investigate the use of certificate pinning on Android and iOS. We collect 5,079 unique apps from the two official app stores: 575 common apps, 1,000 popular apps each, and 1,000 randomly selected apps each. We develop novel, cross-platform, static and dynamic analysis techniques to detect the usage of certificate pinning. Thus, our study offers a more comprehensive understanding of certificate pinning than previous studies. We find certificate pinning as much as 4 times more widely adopted than reported in recent studies. More specifically, we find that 0.9% to 8% of Android apps and 2.5% to 11% of iOS apps use certificate pinning at run time (depending on the aforementioned sets of apps). We then investigate which categories of apps most frequently use pinning (e.g., apps in the "finance" category), which destinations are typically pinned (e.g., first-party destinations vs those used by third-party libraries), which certificates are pinned and how these are pinned (e.g., CA vs leaf certificates), and the connection security for pinned connections vs unpinned ones (e.g., the use of weak ciphers or improper certificate validation). Lastly, we investigate how many pinned connections are amenable to binary instrumentation to reveal the contents of their connections; for those that are, we analyze the data sent over pinned connections to understand what is protected by pinning.
TSPU: Russia's decentralized censorship system

Russia's Sovereign RuNet was designed to build a Russian national firewall. Previous anecdotes and isolated events in the past two years reflected centrally coordinated censorship behaviors across multiple ISPs, suggesting the deployment of "special equipment" in networks, colloquially known as "TSPU". Despite the TSPU comprising a critical part of the technical stack of RuNet, very little is known about its design, its capabilities, or the extent of its deployment. In this paper, we develop novel techniques and run in-country and remote measurements to discover the how, what, and where of TSPU's interference with users' Internet traffic. We identify different types of blocking mechanisms triggered by SNI, IP, and QUIC, and we find the TSPU to be in-path and stateful, and possesses unique state-management characteristics. Using fragmentation behaviors as fingerprints, we identify over one million endpoints in Russia from 650 ASes that are behind TSPU devices and find that 70% of them are at most two hops away from the end IP. Considering that TSPU devices progressed from ideation to deployment in three years, we fear that the emerging TSPU architecture may become a blueprint for other countries with similar network topology.
A microscopic view of bursts, buffer contention, and loss in data centers

Managing data center networks with low loss requires understanding traffic dynamics at short (millisecond) time-scales, especially the burstiness of traffic, and to what extent bursts contend for switch buffer resources. Yet, monitoring traffic over such intervals is a challenge at scale. We make two contributions. First, we present Millisampler, a lightweight traffic characterization tool deployed across all Meta hosts. Millisampler takes a host-centric perspective to data collection, which is scalable and allows for correlating traffic patterns with transport layer statistics. Further, simultaneous collection of Millisampler data across servers in a rack enables analysis of how synchronized traffic interacts in rack buffers. In particular, we study contention, which occurs when multiple bursts arrive simultaneously at the dynamically shared rack buffer. Second, we present a data-center-scale analysis of contention, including a unique joint analysis of burstiness, contention, and loss. Our results show (i) contention characteristics vary widely across and within a region and is influenced by service placement; (ii) contention varies significantly over short time-scales; (iii) bursts are likely to encounter some contention; and (iv) higher contention need not lead to more loss, and the interplay with workload and burst properties matters. We discuss implications for data center design including service placement, buffer sharing algorithms and congestion control.
A first look at the name resolution latency on handshake

The domain name system (DNS) has been an important base of the Internet; however, it faces various issues, including DNS server attacks. Blockchain-based DNS services have recently emerged to solve these DNS issues. Among them, Handshake provides a decentralized root zone and supports state-of-the-art features. However, few studies have investigated the performance evaluations of Handshake. We measure the name resolution latency on Handshake to assess its suitability as an alternative to the current DNS root servers and reveal that it has a practical drawback compared to current root servers at the current early stage.
iGDB: connecting the physical and logical layers of the internet

Maps of physical and logical Internet connectivity that are informed by and consistent with each other can expand scope and improve accuracy in analysis of performance, robustness and security. In this paper, we describe a methodology for linking physical and logical Internet maps that aims toward a consistent, cross-layer representation. Our approach is constructive and uses geographic location as the key feature for linking physical and logical layers. We begin by building a representation of physical connectivity using online sources to identify locations that house transport hardware (i.e., PoPs, colocation centers, IXPs, etc.), and approximate locations of links between these based on shortest-path rights-of-way. We then utilize standard data sources for generating maps of IP-level and AS-level logical connectivity, and graft these onto physical maps using geographic anchors. We implement our methodology in an open-source framework called the Internet Geographic Database (iGDB), which includes tools for updating measurement data and assuring internal consistency. iGDB is built to be used with ArcGIS, a geographic information system that provides broad capability for spatial analysis and visualization. We describe the details of the iGDB implementation and demonstrate how it can be used in a variety of settings.
Major River Floodplain Forest Restoration: A Case Study in Western Massachusetts

ABSTRACT Although efforts to restore floodplain forests are becoming more popular in the northeastern United States, best management practices are not well defined. In this study, we demonstrate the success of a planting effort in western Massachusetts to increase the extent of a floodplain forest along the Housatonic River. Over 1700 floodplain-adapted tree saplings were planted in an old field and in two hayfields at Bartholomew's Cobble, a property located in Sheffield, Massachusetts, and individually tagged to follow their growth and survival. Planted trees had relatively high rates of survival over a 6 y period, especially the two most commonly planted tree species: silver maple (Acer saccharinum, 42.5% survival) and boxelder (Acer negundo, 71.7%), although plantings were more successful in the old field compared to the two hayfields. Tree dbh after 6 y differed across fields for silver maples and boxelders with those planted within the old meadow significantly larger than those planted into hayfields (silver maple dbh 9.8 cm old field vs. 6.5–6.6 cm hayfields; boxelder dbh 10.4 cm old field vs. 4.4–6.6 cm hayfields). By documenting which floodplain-adapted tree species were successful in establishing under which conditions, our observational study provides valuable insights for future restoration efforts.
The Best of Both Worlds High Availability CDN Routing Without Compromising Control

Content delivery networks (CDNs) provide fast service to clients by replicating content at geographically distributed sites. Most CDNs route clients to a particular site using anycast or unicast with DNS-based redirection. We analyze anycast and unicast and explain why neither of them provides both precise control of user-to-site mapping and high availability in the face of failures, two fundamental goals of CDNs. Anycast compromises control (and hence performance), and unicast compromises availability. We then present new hybrid techniques and demonstrate via experiments on the real Internet that these techniques provide both a high level of traffic control and fast failover following site failures.
Design and development of innovative vanadium oxide, CNT, and graphene based high-performance microbolometer

Present microbolometer technology for infrared (IR) sensing and imaging has featured microbridges comprising Si3N4 as well as VOx materials and shown decent performance for IR band detection applications. Nevertheless, further integration of carbon nanotubes (CNTs) and graphene can improve the temperature coefficient of resistance (TCR) to provide even higher dynamic range. For the development of high performance and low noise IR microbolometer detectors with improved TCR, vanadium oxide (VOx) layers were grown on 4-inch SiO2/Si wafers as well as on Si substrates using a DC sputtering process with flow of oxygen and argon gases. From energy-dispersive X-ray spectroscopy (EDS) measurements of the sputter-assisted VOx layer growth it was determined that reduced Ar:O flow resulted in lower measured O/V ratios, and therefore more optimal stochiometric properties in the VOx layers. Likewise, analysis of scanning electron microscopy (SEM) images demonstrated that DC sputtering power had a substantial impact on the deposition rates and corresponding VOx layer thickness. Using a gas flow ratio of 18.7:1.3, with DC sputtering powers of approximately 300 W, V/O ratios in the 1.8-1.9 target range and 200 nm target thicknesses, respectively, were achievable in VOx layer growth on SiO2/Si substrates. The electrical and performance properties of these optimized VOx layer test structures were then measured and characterized in view of integration with graphene and single wall and multiwall carbon nanotubes (CNTs) for advanced long-wave infrared (LWIR) detection. These demonstrated significant noise reductions and as well as enhancements in the TCR, indicating the potential for improved noise equivalent temperature difference (NETD) for high imaging cameras and microbolometer focal plane array (FPA) performance for defense and commercial LWIR sensing applications.
Solarization effects in optical glass from UV to blue

The decrease of transmittance due to electromagnetic radiation is called solarization. UV radiation generates color-centers in the glass that act as absorption sites. The spectral characteristic and level of solarization depends mainly on the composition. In microlithography applications optical glasses are used that are optimized for UV irradiations at 365 nm with minimized solarization effects. The solarization behavior of optical glass at SCHOTT is usually characterized using a Philips mercury high-pressure gas-discharge lamp type HOK-4/120 or a 365 nm LED. A method for solarization classification is described in the Japanese JOGIS standard 04-2019. Results are shown and discussed in comparison for several UV transmitting optical glasses and glasses used in i-line lithography applications. In recent years blue laser applications became more and more present in industrial and commercial applications. It was surprisingly found that high power blue laser irradiation also leads to solarization of optical glass. Therefore SCHOTT established a blue laser irradiation setup and spectral photometer measurement facility to characterize blue laser solarization effects on optical glass. Additionally stabilization strategies have been applied to stabilize optical glass against blue laser solarization. This paper discusses the actual status of the developments.
Nanostructured antireflection coating technology for enhanced MWIR and LWIR band sensing performance

Nanostructured antireflection (AR) coatings reducing optical reflections and maximizing radiation transmitted onto the surfaces of substrates, optics and optical devices such as detectors have many potential optical applications over ultraviolet (UV) to infrared (IR) wavebands including for NASA sensor applications. Through nanoengineering optical layers and tuning their refractive indexes, broadband and omnidirectional suppression of light reflection and scattering is achievable with increased optical transmission for enhanced IR detector and system performance over a wide range of light incidence angles. AR nanostructures have been developed that enable the realization of optimal AR coatings with high laser damage thresholds and high reliability in extreme low temperature environments and under launch conditions. These advanced nanostructured AR coatings we have developed and tested on GaSb and IR detector arrays devices primarily for 3-5 and 8-14 µm MWIR/LWIR applications provide substantial improvements over more conventional thin film AR coating technologies such as quarter-wavelength coatings. The growth of step-graded nanostructured layers using a process involving deposition at different tilt angles has produced single-layer AR coatings utilizing ZnS demonstrating below 4% reflectance, compared to ~34% reflectance for uncoated GaSb, across LWIR bands of interest with substantial improvement in quantum efficiency. In this paper we review and present latest developments and testing results for these high-performance nanostructure-based AR coatings for advanced LWIR band NASA Earth Science sensing and imaging applications.
Proteomic and phosphorylated proteomic landscape of injured lung in juvenile septic rats with therapeutic application of umbilical cord mesenchymal stem cells

Acute lung injury (ALI) is the most common complication of sepsis. Intravenous injection of HUMSCs can regulate the level of circulating endothelial cytokines and alleviate lung injury in juvenile septic rats. In this study, we performed proteomic and phosphorylated proteomic analysis of lung tissue of juvenile septic rats after Human Umbilical Cord Mesenchymal Stem Cells (HUMSCs) intervention for the first time, and screened the potential proteins and pathways of HUMSCs for therapeutic effect. The 4D proteome quantitative technique was used to quantitatively analyze the lung tissues of septic rats 24 hours (3 biological samples) and 24 hours after HUMSCs intervention (3 biological samples). A total of 213 proteins were identified as differentially expressed proteins, and 971 phosphorylation sites changed significantly. Based on the public database, we analyzed the functional enrichment of these proteins and phosphorylated proteins. In addition, Tenascin-C may be the key differential protein and ECM receptor interaction pathway may be the main signal pathway by using various algorithms to analyze the protein-protein interaction network. Phosphorylation analysis showed that tight junction pathway was closely related to immune inflammatory reaction, and EGFR interacted most, which may be the key differential phosphorylated protein. Finally, 123 conserved motifs of serine phosphorylation site (pS) and 17 conserved motifs of threonine (pT) phosphorylation sites were identified by motif analysis of phosphorylation sites. Results from proteomics and phosphorylated proteomics, the potential new therapeutic targets of HUMSCs in alleviating lung injury in juvenile septic rats were revealed.
Centriolar subdistal appendages promote double strand break repair through homologous recombination

The centrosome is a cytoplasmic organelle with roles in microtubule organization which has also been proposed to act as a hub for cellular signaling. Some centrosomal components are required for full activation of the DNA Damage Response. However, if the centrosome regulates specific DNA repair pathways is not known. Here, we show that centrosomes presence is required to fully activate recombination, specifically to completely license its initial step, the so-called DNA end resection. Furthermore, we identify a centriolar structure, the subdistal appendages, and a specific factor, CEP170, as the critical centrosomal component involved in the regulation of recombination and resection, albeit it does not control end-joining repair. Cells lacking centrosomes or depleted for CEP170 are, consequently, hyper-sensitive to DNA damaging agents. Moreover, low levels of CEP170 in multiple cancer types correlate with an increase of the mutation burden associated with specific mutational signatures and a better prognosis, suggesting that changes in CEP170 can act as a mutation driver but also could be targeted to improve current oncological treatments.
ResFinderFG v2.0: a database of antibiotic resistance genes obtained by functional metagenomics

Metagenomics can be used to monitor the spread of antibiotic resistance genes (ARGs). ARGs found in databases such as ResFinder and CARD primarily originate from culturable and pathogenic bacteria, while ARGs from non-culturable and non-pathogenic bacteria remain understudied. Functional metagenomics is based on phenotypic gene selection and can identify ARGs from non-culturable bacteria with a potentially low identity shared with known ARGs. In 2016, the ResFinderFG v1.0 database was created to collect ARGs from functional metagenomics studies. Here, we present the second version of the database, ResFinderFG v2.0, which is available on the Center of Genomic Epidemiology web server (https://cge.food.dtu.dk/services/ResFinderFG/). It comprises 3,913 ARGs identified by functional metagenomics from 50 carefully curated datasets. We assessed its potential to detect ARGs in comparison to other popular databases in gut, soil and water (marine + freshwater) Global Microbial Gene Catalogues (https://gmgc.embl.de). ResFinderFG v2.0 allowed for the detection of ARGs that were not detected using other databases. These included ARGs conferring resistance to beta-lactams, cycline, phenicol, glycopeptide/cycloserine and trimethoprim/sulfonamide. Thus, ResFinderFG v2.0 can be used to identify ARGs differing from those found in conventional databases and therefore improve the description of resistomes. GRAPHICAL ABSTRACT Caption: Additional use of ResFinderFG v2.0 database (composed of antibiotic resistance genes obtained with functional metagenomics) on the Center of Genomic Epidemiology webserver (https://cge.food.dtu.dk/services/ResFinderFG/), allows for more exhaustive resistome descriptions.