627 research outputs found
Computational Investigations into Nucleic Acid-Related Chemistry
Nucleic acids are biopolymers of nucleotides, which are composed of a phosphate, nucleobase and ribose sugar. In addition to acting as the genetic carrier, nucleic acids play a variety of other important roles in biological systems. In this thesis, nucleic acid-related chemistry is investigated using computational methods.
Chapter 1 presents an overview of the problems addressed in this thesis, whereas Chapter 2 discusses various theoretical methods. Then, Chapter 3 investigates the feasibility of using the phosphate oxygens as the general base to catalyze the aminoacyl transfer reaction in histidyl-tRNA synthetase. Three possible mechanisms with different phosphate oxygens acting as the base to abstract the 3\u27-OH group of A76 were examined and compared. Chapter 4 elucidates the catalytic mechanism of the repair of an alkylated nucleobase by the enzyme AlkB. It was found that this mechanism consists of four stages and that our calculated barrier for the rate-controlling step is in good agreement with experimental studies. Chapter 5 addresses the catalytic mechanism of the HDV ribozyme. Both cytosine and hydrated Mg2+ ion were found to be involved in the reaction with the former acting as the acid and the latter as the base. Chapter 6 studies the protonation of guanine quartets and quartet stacks. Each quartet plane was found to be able to accept maximally two protons. Chapter 7 deals with the interactions of metal ions with ribose and locked ribose. Four metal ions, Na+, K+, Mg2+ and Cd2+ were chosen and their properties upon interacting with ribose and locked ribose were compared. Chapter 8 presents the influences of the selection of computational methods and chemical models on the amide bond formation as catalyzed by the ribosome. Two proton transfer processes involving four- and six-membered transition structures were systematically examined using a variety of methods. Finally, Chapter 9 summarizes the main conclusions and possible extensions of the current work
Enterpriseās Strategies to Deal with Epidemic Crisis Based on Super-Dynamic Capability Theory
In this paper, the supply chain management risks arising from 2019-novel coronavirus (hereinafter referred to as āCOVID-19ā) outbreak was proposed, and they were further analyzed from three main aspects such as change in demand conditions of domestic customers, change in domestic supply market, impact on domestic logistics industry. Besides, multiple feasible strategies for coping with such epidemic situation were proposed for enterprises based on the super-dynamic capability theory. The research in this paper has powerful theoretical value and practical significance for the current development of enterprises, especially the reorganization of enterprises under the current epidemic crisis in China
All Your DNS Records Point to Us Understanding the Security Threats of Dangling DNS Records
In a dangling DNS record (Dare), the resources pointed to by the DNS record are invalid, but the record itself has not yet been purged from DNS. In this paper, we shed light on a largely overlooked threat in DNS posed by dangling DNS records. Our work reveals that Dare can be easily manipulated by adversaries for domain hijacking. In particular, we identify three attack vectors that an adversary can harness to exploit Dares. In a large-scale measurement study, we uncover 467 exploitable Dares in 277 Alexa top 10,000 domains and 52 edu zones, showing that Dare is a real, prevalent threat. By exploiting these Dares, an adversary can take full control of the (sub) domains and can even have them signed with a Certificate Authority (CA). It is evident that the underlying cause of exploitable Dares is the lack of authenticity checking for the resources to which that DNS record points. We then propose three defense mechanisms to effectively mitigate Dares with little human effort
Ready Raider One: Exploring the Misuse of Cloud Gaming Services
Cloud gaming has become an emerging computing paradigm in recent years, allowing computer games to offload complex graphics and logic computation to the cloud. To deliver a smooth and high-quality gaming experience, cloud gaming services have invested abundant computing resources in the cloud, including adequate CPUs, top-tier GPUs, and high-bandwidth Internet connections. Unfortunately, the abundant computing resources offered by cloud gaming are vulnerable to misuse and exploitation for malicious purposes. In this paper, we present an in-depth study on security vulnerabilities in cloud gaming services. Specifically, we reveal that adversaries can purposely inject malicious programs/URLs into the cloud gaming services via game mods. Using the provided features such as in-game subroutines, game launch options, and built-in browsers, adversaries are able to execute the injected malicious programs/URLs in cloud gaming services. To demonstrate that such vulnerabilities pose a serious threat, we conduct four proof-of-concept attacks on cloud gaming services. Two of them are to abuse the CPUs and GPUs in cloud gaming services to mine cryptocurrencies with attractive profits and train machine learning models at a trivial cost. The other two are to exploit the high-bandwidth connections provided by cloud gaming for malicious Command & Control and censorship circumvention. Finally, we present several countermeasures for cloud gaming services to protect their valuable assets from malicious exploitation
Quantized and unquantized zero-bias tunneling conductance peaks in Majorana nanowires: Conductance below and above
Majorana zero modes can appear at the wire ends of a 1D topological
superconductor and manifest themselves as a quantized zero-bias conductance
peak in the tunneling spectroscopy of normal-superconductor junctions. However,
in superconductor-semiconductor hybrid nanowires, zero-bias conductance peaks
may arise owing to topologically trivial mechanisms as well, mimicking the
Majorana-induced topological peak in many aspects. In this work, we
systematically investigate the characteristics of zero-bias conductance peaks
for topological Majorana bound states, trivial quasi-Majorana bound states and
low-energy Andreev bound states arising from smooth potential variations, and
disorder-induced subgap bound states. Our focus is on the conductance peak
value (i.e., equal to, greater than, or less than ), as well as the
robustness (plateau- or spike-like) against the tuning parameters (e.g., the
magnetic field and tunneling gate voltage) for zero-bias peaks arising from the
different mechanisms. We find that for Majoranas and quasi-Majoranas, the
zero-bias peak values are no more than , and a quantized conductance
plateau forms generically as a function of parameters. By contrast, for
conductance peaks due to low-energy Andreev bound states or disorder-induced
bound states, the peak values may exceed , and a conductance plateau is
rarely observed unless through careful postselection and fine-tuning. Our
findings should shed light on the interpretation of experimental measurements
on the tunneling spectroscopy of normal-superconductor junctions of hybrid
Majorana nanowires.Comment: 16 pages, 10 figure
Arbitrating Traffic Contention for Power Saving with Multiple PSM Clients
Data transmission over WiFi quickly drains the batteries of mobile devices. Although the IEEE 802.11 standards provide power save mode (PSM) to help mobile devices conserve energy, PSM fails to bring expected benefits in many real scenarios. In particular, when multiple PSM mobile devices associate to a single access point (AP), PSM does not work well under transmission contention. Optimizing power saving of multiple PSM clients is a challenging task, because each PSM client expects to complete data transmission early so that it can turn to low power mode. In this paper, we define an energy conserving model to describe the general PSM traffic contention problem. We prove that the optimization of energy saving for multiple PSM clients under constraint is an NPcomplete problem. Following this direction, we propose a solution called harmonious power saving mechanism (HPSM) to address one specific case, in which multiple PSM clients associate to a single AP. In HPSM, we first use a basic sociological concept to define the richness of a PSM client based on the link resource it consumes. Then, we separate these poor PSM clients from rich PSM clients in terms of link resource consumption and favor the former to save power when they face PSM transmission contention. We implement prototypes of HPSM based on the open source projects Mad-wifi and NS-2. Our evaluations show that HPSM can help the poor PSM clients effectively save power while only slightly degrading the rich PSM clients\u27 performance in comparison with the existing PSM solutions
Dial N for NXDomain: The Scale, Origin, and Security Implications of DNS Queries to Non-Existent Domains
Non-Existent Domain (NXDomain) is one type of the Domain Name System (DNS) error responses, indicating that the queried domain name does not exist and cannot be resolved. Unfortunately, little research has focused on understanding why and how NXDomain responses are generated, utilized, and exploited. In this paper, we conduct the first comprehensive and systematic study on NXDomain by investigating its scale, origin, and security implications. Utilizing a large-scale passive DNS database, we identify 146,363,745,785 NXDomains queried by DNS users between 2014 and 2022. Within these 146 billion NXDomains, 91 million of them hold historic WHOIS records, of which 5.3 million are identified as malicious domains including about 2.4 million blocklisted domains, 2.8 million DGA (Domain Generation Algorithms) based domains, and 90 thousand squatting domains targeting popular domains. To gain more insights into the usage patterns and security risks of NXDomains, we register 19 carefully selected NXDomains in the DNS database, each of which received more than ten thousand DNS queries per month. We then deploy a honeypot for our registered domains and collect 5,925,311 incoming queries for 6 months, from which we discover that 5,186,858 and 505,238 queries are generated from automated processes and web crawlers, respectively. Finally, we perform extensive traffic analysis on our collected data and reveal that NXDomains can be misused for various purposes, including botnet takeover, malicious file injection, and residue trust exploitation
Multiple bombesin-like peptides with opposite functions from skin of Odorrana grahami
AbstractBombesin-like peptides (BLPs) are a family of neuroendocrinic peptides that mediate a variety of biological activities. Three mature BLPs from the skin secretions of the frog Odorrana grahami were purified. Several bombesin-like peptide cDNA sequences encoding precursors of BLPs were identified from the skin cDNA library of O. grahami. This is the maximal diversity of BLPs ever found in animals. Five mature BLPs (B1āB5) based on the amino acid sequences derived from the cDNA cloning were synthesized. In the in vitro myotropic contraction experiment, all synthesized BLPs displayed a stimulating effect toward rat stomach strips, except B4 and B5 which showed the opposite effect, suggesting that certain BLPs may act as antagonists of bombesin receptors while most other BLPs act as agonists. This finding will facilitate the finding of novel bombesin receptors and novel ligands of bombesin receptors. The diversity of amphibian BLPs and their precursors were also analyzed and results suggest that amphibian BLPs and corresponding precursors of various sizes and processing patterns can be used as markers of taxonomic and molecular phylogenetics. The remarkable similarity of preproregions gives rise to very different BLPs and 3ā²-terminal regions in distantly related frog species, suggesting that the corresponding genes form a multigene family originating from a common ancestor. The diversification of BLP loci could thus be part of an evolutionary strategy developed by amphibian species as a result of shifts to novel ecological niches when environmental factors change rapidly
Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS
<p>Abstract</p> <p>Backgound</p> <p>Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a <it>Drosophila </it>model to examine the toxicity of Fus, its <it>Drosophila </it>orthologue Cabeza (Caz), and the ALS-related Fus mutants.</p> <p>Results</p> <p>Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of <it>caz </it>in <it>Drosophila </it>led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death.</p> <p>Conclusions</p> <p>These data demonstrate that the overexpression of Fus/Caz causes <it>in vivo </it>toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different.</p
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