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Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.

In the context of global navigation satellite systems (GNSS), synchronization is crucial for successfully decoding the navigation message and accurately estimating pseudoranges. Synchronization of each received GNSS signal typically involves at least two tracking loops: a delay lock loop (DLL) and a phase lock loop (PLL). The reception of a spoofed signal disrupts the synchronization process, potentially leading to erroneous pseudorange estimation or loss of service. This paper investigates the impact of spoofing on code, carrier phase, and frequency tracking estimates and proposes a transformation-based strategy to characterize the joint DLL and PLL under spoofing, focusing on the system's stable equilibria (SE), linearity and interdependence, transient response, and noise impact. The study reveals the nonlinearity and interdependence of the tracking loops (i.e., PLL and DLL cannot be considered separately) and shows the emergence of multiple SE, leading to potential chaotic behavior and bifurcation.

High-frequency (HF) communication is critical for applications such as over-the-horizon positioning and ionospheric detection. However, precise time-delay estimation in complex HF channels faces significant challenges from multipath fading, Doppler shifts, and noise. This paper proposes a Modulation Signal-based Adaptive Time-Delay Estimation (MATE) algorithm, which effectively decouples carrier and modulation signals and integrates phase-locked loop (PLL) and delay-locked loop (DLL) techniques. By leveraging the autocorrelation properties of 8PSK (Eight-Phase Shift Keying) signals, MATE compensates for carrier frequency deviations and mitigates multipath interference. Simulation results based on the Watterson channel model demonstrate that MATE achieves an average time-delay estimation error of approximately 0.01 ms with a standard deviation of approximately 0.01 ms, representing a 94.12% reduction in mean error and a 96.43% reduction in standard deviation compared to the traditional Generalized Cross-Correlation (GCC) method. Validation with actual measurement data further confirms the robustness of MATE against channel variations. MATE offers a high-precision, low-complexity solution for HF time-delay estimation, significantly benefiting applications in HF communication systems. This advancement is particularly valuable for enhancing the accuracy and reliability of time-of-arrival (TOA) detection in HF-based sensor networks and remote sensing systems.

SALT, a new dedicated readout Application Specific Integrated Circuit (ASIC) for the Upstream Tracker, a new silicon detector in the Large Hadron Collider beauty (LHCb) experiment, has been designed and developed. It is a 128-channel chip using an innovative architecture comprising a low-power analogue front-end with fast pulse shaping and a 40 MSps 6-bit Analog-to-Digital Converter (ADC) in each channel, followed by a Digital Signal Processing (DSP) block performing pedestal and Mean Common Mode (MCM) subtraction and zero suppression. The prototypes of SALT were fabricated and tested, confirming the full chip functionality and fulfilling the specifications. A signal-to-noise ratio of about 20 is achieved for a silicon sensor with a 12 pF input capacitance. In this paper, the SALT architecture and measurements of the chip performance are presented.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that plays significant regulatory roles in the differentiation of the central nervous system and peripheral organs. A lack of the neuropeptide can lead to abnormalities in long bone development. In callus formation, a possible signaling balance shift in PACAP KO mice has been demonstrated, but Notch signalization, with its potential connection with PACAP 1-38, has not been investigated in ossification. Our main goal was to show connections between PACAP and Notch signaling in osteogenesis. Notch signalization showed an elevation in the long bones of PACAP-gene-deficient mice, and it was also elevated during the PACAP 1-38 treatment of UMR-106 and MC3T3-E1 osteogenic cells. Moreover, the inhibition of Notch signaling was compensated by the addition of PACAP 1-38 in vitro. The inorganic and organic matrix production of UMR-106 cells was increased during PACAP 1-38 treatment under the inhibition of Notch signaling. As a possible common target, the expression and nuclear translocation of NFATc1 transcription factor was increased during the disturbance of PACAP and Notch signaling. Our results indicate a possible synergistic regulation during bone formation by PACAP and Notch signalization. The crosstalk between Notch and PACAP signaling pathways highlights the complexity of bone development and homeostasis.

India's power demand is increasing at a compound annual growth rate (CAGR) of 7.18% due to rapid urbanization. The paper examines the planning for the extension of transmission to suit the increased load development. Before deregulation due to the power monopoly, optimization techniques were undeveloped, contingency analyses were not conducted, resulting in inefficient transmission investments, increased transmission charges, and diminished reliability, which resulted in inferior quality and increased electricity prices for consumers. The Cost/Benefit index is formulated based on the revenue generated by the line and employed for the optimization of transmission lines. Urbanization will result in Right of Way (RoW) issues for new line installation, necessitating the usage of high-power conductors (HPCs) in these regions. Dynamic line loading (DLL) may or may not yield a \"return on investment\" in countries facing extreme heat conditions. Consequently, the partial DLL using ambient temperature was employed as a test model in this paper instead of explicitly implementing the complete DLL. This technique is applied to the IEEE 14 test bus system, based on the assumption of a 60% uniform load growth and non-uniform load growth rates of 18%, 21%, and 24% at various buses.

Extreme value analysis (EVA) is well-established to derive hydrometeorological design values for infrastructures that have to withstand extreme events. Since there is concern about increased extremes with higher hazard potential under climate change, alterations of EVA are introduced for which statistical properties are no longer assumed to be constant but vary over time. In this study, both stationary and non-stationary EVA models are used to derive design life levels (DLLs) of daily precipitation in the pre-alpine Oberland region of Southern Germany, an orographically complex region characterized by heavy precipitation events and climate change. As EVA is fraught with uncertainties, it is crucial to quantify its methodological impacts: two theoretical distributions (i.e., Generalized Extreme Value (GEV) and Generalized Pareto (GP) distribution), four different parameter estimation techniques (i.e., Maximum Likelihood Estimation (MLE), L-moments, Generalized Maximum Likelihood Estimation (GMLE), and Bayesian estimation method) are evaluated and compared. The study reveals large methodological uncertainties. Discrepancies due to the parameter estimation methods may reach up to 45% of the mean absolute value, while differences between stationary and non-stationary models are of the same magnitude (differences in DLLs up to 40%). For the end of this century in the Oberland region, there is no robust tendency towards increased extremes found.

Stingers, evolved from ovipositors, are an important defense organ for the Apidae, Vespidae, and Formicidae species. However, the molecular mechanism of stinger development remains unclear. Here, we show that the earliest time point for the appearance of stingers in Apis mellifera is at the 1-day-old worker pupal stage based on morphological observations and anatomy from the pre-pupal to adult stages. To discover the genes related to stinger development, we first comprehensively compared the stinger transcriptome at different stages and screened 1282, 186, and 166 highly expressed genes in the stingers of 1- and 5-day-old worker pupae and newly emerged worker bees (NEBs), respectively, then identified 25 DEGs involved in the early stage of stinger development. We found that Dll was a key candidate gene in the early development of A. mellifera stingers by combining analyses of the protein–protein interaction network and spatiotemporal expression patterns. An RNAi experiment showed that about 20% of individuals exhibited tip bending in the piercing parts of their stingers in the Dll-dsRNA-treated group, with the morphology presenting as side–side or front–back tip bending. This indicates that Dll plays a vital role in the early development of A. mellifera stingers. Together, our study provides insight into the molecular mechanism of Hymenoptera stinger development and an inspiration for the molecular breeding of gentle honeybee species with stinger abnormalities.

Expansion of the neocortex is thought to pave the way towards acquisition of higher cognitive functions in mammals. The highly conserved Notch signaling pathway plays a crucial role in this process by regulating the size of the cortical progenitor pool, in part by controlling the balance between self-renewal and differentiation. In this review, we introduce the components of Notch signaling pathway as well as the different mode of molecular mechanisms, including trans- and cis-regulatory processes. We focused on the recent findings with regard to the expression pattern and levels in regulating neocortical formation in mammals and its interactions with other known signaling pathways, including Slit-Robo signaling and Shh signaling. Finally, we review the functions of Notch signaling pathway in different species as well as other developmental process, mainly somitogenesis, to discuss how modifications to the Notch signaling pathway can drive the evolution of the neocortex.

The global navigation satellite system (GNSS) spoofing technology is an important method to control the targets that pose threats and protect sensitive areas. Traction spoofing can gradually take over the tracking loop by spoofing signals. To achieve more covert spoofing of a receiver configured with phase lock loop (PLL) assisted delay lock loop (DLL) loop, the following research work has been carried out: First, the response of the combined loop to GNSS spoofing is analyzed; Second, a new asynchronous traction signal spoofing algorithm is proposed; in the design of the code rate and carrier frequency of spoofing signal, the dynamic performance of the loop is fully considered, while maintaining a good consistency with the carrier frequency. In the design of the power of the spoofing signal, the success rate of spoofing is improved as much as possible while avoiding absolute power monitoring. Finally, the calculation method of the parameters of the spoofing signal is given. Third, by building the GNSS signal generation software and software receiver platform to carry out experimental verification and through experimental comparison and analysis with many existing representative spoofing schemes, it is proved that the new algorithm can successfully achieve spoofing. The spoofing takes 107.8 s, which makes the local code rate increase 0.03 Hz, the carrier frequency increase 50 Hz, the average value of consistency spoofing detection is 9.40 × 10−3, and finally stabilized at the convergence value  − 2.95 × 10−8, that is, during the spoofing process, spoofing signal maintains the consistency of the authentic signal, which can well avoid the consistency spoofing detection of the receiver, the effectiveness and superiority of the proposed algorithm compared with other spoofing methods are fully verified.