Controlling water giant low-inertia nonlinear refractive index in the THz frequency range via temperature variation.

To create self-controlled radiation photonics systems, it is necessary to have complete information about the nonlinear properties of the materials used. In this Letter, the vibrational mechanism of the giant low-inertia cubic nonlinearity of the refractive index of water in the terahertz (THz) frequency range is experimentally proven. Its dominance, which manifests itself when the temperature of the liquid changes, is demonstrated. The measured nonlinear refractive index in the THz frequency range for a water jet at temperatures from 14°C to 21°C demonstrates a correlation with the theoretical approach, varies in the range 4-10 × 10-10 cm2/W, and is characterized by an inertial time constant of less than 1 ps.

Air-Oxygen Blenders for Mechanical Ventilators: A Literature Review.

Respiratory diseases are one of the most common causes of death in the world and this recent COVID-19 pandemic is a key example. Problems such as infections, in general, affect many people and depending on the form of transmission they can spread throughout the world and weaken thousands of people. Two examples are severe acute respiratory syndrome and the recent coronavirus disease. These diseases have mild and severe forms, in which patients gravely affected need ventilatory support. The equipment that serves as a basis for operation of the mechanical ventilator is the air-oxygen blender, responsible for carrying out the air-oxygen mixture in the proper proportions ensuring constant supply. New blender models are described in the literature together with applications of control techniques, such as Proportional, Integrative and Derivative (PID); Fuzzy; and Adaptive. The results obtained from the literature show a significant improvement in patient care when using automatic controls instead of manual adjustment, increasing the safety and accuracy of the treatment. This study presents a deep review of the state of the art in air-oxygen benders, identifies the most relevant characteristics, performs a comparison study considering the most relevant available solutions, and identifies open research directions in the topic.

Compression-Aware Aggregation and Energy-Aware Routing in IoT-Fog-Enabled Forest Environment.

Forest fire monitoring is very much needed for protecting the forest from any kind of disaster or anomaly leading to the destruction of the forest. Now, with the advent of Internet of Things (IoT), a good amount of research has been done on energy consumption, coverage, and other issues. These works did not focus on forest fire management. The IoT-enabled environment is made up of low power lossy networks (LLNs). For improving the performance of routing protocol in forest fire management, energy-efficient routing protocol for low power lossy networks (E-RPL) was developed where residual power was used as an objective function towards calculating the rank of the parent node to form the destination-oriented directed acyclic graph (DODAG). The challenge in E-RPL is the scalability of the network resulting in a long end-to-end delay and less packet delivery. Additionally, the energy of sensor nodes increased with different transmission range. So, for obviating the above-mentioned drawbacks in E-RPL, compressed data aggregation and energy-based RPL routing (CAA-ERPL) is proposed. The CAA-ERPL is compared with E-RPL, and the performance is analyzed resulting in reduced packet transfer delay, less energy consumption, and increased packet delivery ratio for 10, 20, 30, 40, and 50 nodes. This has been evaluated using a Contiki Cooja simulator.

Lightweight and Efficient Dynamic Cluster Head Election Routing Protocol for Wireless Sensor Networks.

Wireless Sensor Networks (WSNs) have gained great significance from researchers and industry due to their wide applications. Energy and resource conservation challenges are facing the WSNs. Nevertheless, clustering techniques offer many solutions to address the WSN issues, such as energy efficiency, service redundancy, routing delay, scalability, and making WSNs more efficient. Unfortunately, the WSNs are still immature, and suffering in several aspects. This paper aims to solve some of the downsides in existing routing protocols for WSNs; a Lightweight and Efficient Dynamic Cluster Head Election routing protocol (LEDCHE-WSN) is proposed. The proposed routing algorithm comprises two integrated methods, electing the optimum cluster head, and organizing the re-clustering process dynamically. Furthermore, the proposed protocol improves on others present in the literature by combining the random and periodic electing method in the same round, and the random method starts first at the beginning of each round/cycle. Moreover, both random and periodic electing methods are preceded by checking the remaining power to skip the dead nodes and continue in the same way periodically with the rest of the nodes in the round. Additionally, the proposed protocol is distinguished by deleting dead nodes from the network topology list during the re-clustering process to address the black holes and routing delay problems. Finally, the proposed algorithm's mathematical modeling and analysis are introduced. The experimental results reveal the proposed protocol outperforms the LEACH protocol by approximately 32% and the FBCFP protocol by 8%, in terms of power consumption and network lifetime. In terms of Mean Package Delay, LEDCHE-WSN improves the LEACH protocol by 42% and the FBCFP protocol by 15%, and regarding Loss Ratio, it improves the LEACH protocol by approximately 46% and FBCFP protocol by 25%.

Retrograde Regulation by the Viral Protein Kinase Epigenetically Sustains the Epstein-Barr Virus Latency-to-Lytic Switch To Augment Virus Production.

Herpesviruses are ubiquitous, and infection by some, like Epstein-Barr virus (EBV), is nearly universal. To persist, EBV must periodically switch from a latent to a replicative/lytic phase. This productive phase is responsible for most herpesvirus-associated diseases. EBV encodes a latency-to-lytic switch protein which, upon activation, sets off a vectorially constrained cascade of gene expression that results in production of infectious virus. While triggering expression of the switch protein ZEBRA is essential to lytic cycle entry, sustaining its expression is equally important to avoid premature termination of the lytic cascade. We report that the viral protein kinase (vPK), encoded by a gene that is kinetically downstream of the lytic switch, sustains expression of ZEBRA, amplifies the lytic cascade, increasing virus production, and, importantly, prevents the abortive lytic cycle. We find that vPK, through a noncanonical site phosphorylation, activates the cellular phosphatidylinositol 3-kinase-related kinase ATM to cause phosphorylation of the heterochromatin enforcer KAP1/TRIM28 even in the absence of EBV genomes or other EBV proteins. Phosphorylation of KAP1 renders it unable to restrain ZEBRA, thereby further derepressing and sustaining its expression to culminate in virus production. This partnership with a host kinase and a transcriptional corepressor enables retrograde regulation by vPK of ZEBRA, an observation that is counter to the unidirectional regulation of gene expression reminiscent of most DNA viruses.IMPORTANCE Herpesviruses infect nearly all humans and persist quiescently for the life of the host. These viruses intermittently activate into the lytic phase to produce infectious virus, thereby causing disease. To ensure that lytic activation is not prematurely terminated, expression of the virally encoded lytic switch protein needs to be sustained. In studying Epstein-Barr virus, one of the most prevalent human herpesviruses that also causes cancer, we have discovered that a viral kinase activated by the viral lytic switch protein partners with a cellular kinase to deactivate a silencer of the lytic switch protein, thereby providing a positive feedback loop to ensure successful completion of the viral productive phase. Our findings highlight key nodes of interaction between the host and virus that could be exploited to treat lytic phase-associated diseases by terminating the lytic phase or kill cancer cells harboring herpesviruses by accelerating the completion of the lytic cascade.

A Smart Waste Management Solution Geared towards Citizens.

Global industry is undergoing major transformations with the genesis of a new paradigm known as the Internet of Things (IoT) with its underlying technologies. Many company leaders are investing more effort and money in transforming their services to capitalize on the benefits provided by the IoT. Thereby, the decision makers in public waste management do not want to be outdone, and it is challenging to provide an efficient and real-time waste management system. This paper proposes a solution (hardware, software, and communications) that aims to optimize waste management and include a citizen in the process. The system follows an IoT-based approach where the discarded waste from the smart bin is continuously monitored by sensors that inform the filling level of each compartment, in real-time. These data are stored and processed in an IoT middleware providing information for collection with optimized routes and generating important statistical data for monitoring the waste collection accurately in terms of resource management and the provided services for the community. Citizens can easily access information about the public waste bins through the Web or a mobile application. The creation of the real prototype of the smart container, the development of the waste management application and a real-scale experiment use case for evaluation, demonstration, and validation show that the proposed system can efficiently change the way people deal with their garbage and optimize economic and material resources.

Looking at Fog Computing for E-Health through the Lens of Deployment Challenges and Applications.

Fog computing is a distributed infrastructure where specific resources are managed at the network border using cloud computing principles and technologies. In contrast to traditional cloud computing, fog computing supports latency-sensitive applications with less energy consumption and a reduced amount of data traffic. A fog device is placed at the network border, allowing data collection and processing to be physically close to their end-users. This characteristic is essential for applications that can benefit from improved latency and response time. In particular, in the e-Health field, many solutions rely on real-time data to monitor environments, patients, and/or medical staff, aiming at improving processes and safety. Therefore, fog computing can play an important role in such environments, providing a low latency infrastructure. The main goal of the current research is to present fog computing strategies focused on electronic-Health (e-Health) applications. To the best of our knowledge, this article is the first to propose a review in the scope of applications and challenges of e-Health fog computing. We introduce some of the available e-Health solutions in the literature that focus on latency, security, privacy, energy efficiency, and resource management techniques. Additionally, we discuss communication protocols and technologies, detailing both in an architectural overview from the edge devices up to the cloud. Differently from traditional cloud computing, the fog concept demonstrates better performance in terms of time-sensitive requirements and network data traffic. Finally, based on the evaluation of the current technologies for e-Health, open research issues and challenges are identified, and further research directions are proposed.

A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype.

Ataxia-telangiectasia (A-T), an autosomal recessive disease caused by mutations in the ATM gene is characterised by cerebellar atrophy and progressive neurodegeneration which has been poorly recapitulated in Atm mutant mice. Consequently, pathways leading to neurodegeneration in A-T are poorly understood. We describe here the generation of an Atm knockout rat model that does not display cerebellar atrophy but instead paralysis and spinal cord atrophy, reminiscent of that seen in older patients and milder forms of the disorder. Loss of Atm in neurons and glia leads to accumulation of cytosolic DNA, increased cytokine production and constitutive activation of microglia consistent with a neuroinflammatory phenotype. Rats lacking ATM had significant loss of motor neurons and microgliosis in the spinal cord, consistent with onset of paralysis. Since short term treatment with steroids has been shown to improve the neurological signs in A-T patients we determined if that was also the case for Atm-deficient rats. Betamethasone treatment extended the lifespan of Atm knockout rats, prevented microglial activation and significantly decreased neuroinflammatory changes and motor neuron loss. These results point to unrepaired damage to DNA leading to significant levels of cytosolic DNA in Atm-deficient neurons and microglia and as a consequence activation of the cGAS-STING pathway and cytokine production. This in turn would increase the inflammatory microenvironment leading to dysfunction and death of neurons. Thus the rat model represents a suitable one for studying neurodegeneration in A-T and adds support for the use of anti-inflammatory drugs for the treatment of neurodegeneration in A-T patients.

High Kerr nonlinearity of water in THz spectral range.

The values of the nonlinear refractive index coefficient for various materials in the terahertz frequency range exceed the ones in both visible and NIR ranges by several orders of magnitude. This allows to create nonlinear switches, modulators, systems requiring lower control energies in the terahertz frequency range. We report the direct measurement of the nonlinear refractive index coefficient of liquid water by using the Z-scan method with broadband pulsed THz beam. Our experimental result shows that nonlinear refractive index coefficient in water is positive and can be as large as 7×10-10 cm2/W in the THz frequency range, which exceeds the values for the visible and NIR ranges by 6 orders of magnitude. To estimate n2, we use the theoretical model that takes into account ionic vibrational contribution to the third-order susceptibility. We show that the origins of the nonlinearity observed are the anharmonicity of molecular vibrations.

Double-pump technique - one step closer towards efficient liquid-based THz sources.

By irradiating a water jet with double pulses, we demonstrate 4-fold higher THz wave generation than for a single pump pulse. The dependence of the enhanced THz signal on the temporal delay between two collinear pulses reveals the optimal time for launching signal pulse is near 2-4 ps, which corresponds to the time needed to create the complete pre-ionization state when sufficient electron density is already induced, and there is no plasma reflection of the pump pulse radiation. The increase in THz waves generation efficiency corresponds to the case of water jet excitation by the pulses with an optimal duration for a certain jet thickness, which is determined by the spatial pulse size. Using a theoretical model of the interaction of a high-intensity sub-picosecond pulse with an isotropic medium, we held a numerical simulation, which well describes the experimental results when using 3 ps value of population relaxation time. Thus, in this work, double pump method allows not only to increase the energy of the generated THz waves, but also to determine the characteristic excited state lifetime of liquid water. The optical-to-terahertz conversion efficiency in case of double pulse excitation of water column is of the order of 0.5⋅10 -3, which exceeds the typical values for THz waves generation during two-color filamentation in air and comparable with the achievable values due to the optical rectification in some crystals.

Flat liquid jet as a highly efficient source of terahertz radiation.

Polar liquids are strong absorbers of electromagnetic waves in the terahertz range, therefore, historically such liquids have not been considered as good candidates for terahertz sources. However, flowing liquid medium has explicit advantages, such as a higher damage threshold compared to solid-state sources and more efficient ionization process compared to gases. Here we report systematic study of efficient generation of terahertz radiation in flat liquid jets under sub-picosecond single-color optical excitation. We demonstrate how medium parameters such as molecular density, ionization energy and linear absorption contribute to the terahertz emission from the flat liquid jets. Our simulation and experimental measurements reveal that the terahertz energy has quasi-quadratic dependence on the optical excitation pulse energy. Moreover, the optimal pump pulse duration, which depends on the thickness of the jet is theoretically predicted and experimentally confirmed. The obtained optical-to-terahertz energy conversion efficiency is more than 0.05%. It is comparable to the commonly used optical rectification in most of electro-optical crystals and two-color air filamentation. These results, significantly advancing prior research, can be successfully applied to create a new alternative source of terahertz radiation.

Impact of laser-ionized liquid nonlinear characteristics on the efficiency of terahertz wave generation.

The generation of terahertz (THz) radiation during the propagation of subpicosecond pulses in liquid media is investigated using a theoretical model considering the relative contribution of Kerr and plasma nonlinearity. The dependences of the THz emission generation efficiency on the contribution of plasma nonlinearity with a fixed third-order nonlinearity value revealed the existence of weak and strong ionization modes. It is shown that the transition between these modes is determined by the ratio of plasma to Kerr nonlinearity coefficients and the pump energy. In the strong ionization mode and with the fixed contribution of plasma nonlinearity, the optical-to-THz conversion efficiency decreases with increasing Kerr nonlinearity due to the redistribution of the pump energy for the third-order effects. These results contribute to estimating the potential of liquid media as highly efficient THz sources.

Blockchain in Smart Grids: A Review on Different Use Cases.

With the integration of Wireless Sensor Networks and the Internet of Things, the smart grid is being projected as a solution for the challenges regarding electricity supply in the future. However, security and privacy issues in the consumption and trading of electricity data pose serious challenges in the adoption of the smart grid. To address these challenges, blockchain technology is being researched for applicability in the smart grid. In this paper, important application areas of blockchain in the smart grid are discussed. One use case of each area is discussed in detail, suggesting a suitable blockchain architecture, a sample block structure and the potential blockchain technicalities employed in it. The blockchain can be used for peer-to-peer energy trading, where a credit-based payment scheme can enhance the energy trading process. Efficient data aggregation schemes based on the blockchain technology can be used to overcome the challenges related to privacy and security in the grid. Energy distribution systems can also use blockchain to remotely control energy flow to a particular area by monitoring the usage statistics of that area. Further, blockchain-based frameworks can also help in the diagnosis and maintenance of smart grid equipment. We also discuss several commercial implementations of blockchain in the smart grid. Finally, various challenges to be addressed for integrating these two technologies are discussed.

Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM-dependence for translocation from the cytoplasm to the nucleus. These data provide new insights into the activation of ATM by oxidative stress through identification of novel substrates for ATM in the cytoplasm.

Control of Mycobacterial Infections in Mice Expressing Human Tumor Necrosis Factor (TNF) but Not Mouse TNF.

Tumor necrosis factor (TNF) is an important cytokine for host defense against pathogens but is also associated with the development of human immunopathologies. TNF blockade effectively ameliorates many chronic inflammatory conditions but compromises host immunity to tuberculosis. The search for novel, more specific human TNF blockers requires the development of a reliable animal model. We used a novel mouse model with complete replacement of the mouse TNF gene by its human ortholog (human TNF [huTNF] knock-in [KI] mice) to determine resistance to Mycobacterium bovis BCG and M. tuberculosis infections and to investigate whether TNF inhibitors in clinical use reduce host immunity. Our results show that macrophages from huTNF KI mice responded to BCG and lipopolysaccharide similarly to wild-type macrophages by NF-κB activation and cytokine production. While TNF-deficient mice rapidly succumbed to mycobacterial infection, huTNF KI mice survived, controlling the bacterial burden and activating bactericidal mechanisms. Administration of TNF-neutralizing biologics disrupted the control of mycobacterial infection in huTNF KI mice, leading to an increased bacterial burden and hyperinflammation. Thus, our findings demonstrate that human TNF can functionally replace murine TNF in vivo, providing mycobacterial resistance that could be compromised by TNF neutralization. This new animal model will be helpful for the testing of specific biologics neutralizing human TNF.

A patient-derived olfactory stem cell disease model for ataxia-telangiectasia.

The autosomal recessive disorder ataxia-telangiectasia (A-T) is characterized by genome instability, cancer predisposition and neurodegeneration. Although the role of ataxia-telangiectasia mutated (ATM) protein, the protein defective in this syndrome, is well described in the response to DNA damage, its role in protecting the nervous system is less clear. We describe the establishment and characterization of patient-specific stem cells that have the potential to address this shortcoming. Olfactory neurosphere (ONS)-derived cells were generated from A-T patients, which expressed stem cell markers and exhibited A-T molecular and cellular characteristics that included hypersensitivity to radiation, defective radiation-induced signaling and cell cycle checkpoint defects. Introduction of full-length ATM cDNA into these cells corrected defects in the A-T cellular phenotype. Gene expression profiling and pathway analysis revealed defects in multiple cell signaling pathways associated with ATM function, with cell cycle, cell death and DNA damage response pathways being the most significantly dysregulated. A-T ONS cells were also capable of differentiating into neural progenitors, but they were defective in neurite formation, number of neurites and length of these neurites. Thus, ONS cells are a patient-derived neural stem cell model that recapitulate the phenotype of A-T, do not require genetic reprogramming, have the capacity to differentiate into neurons and have potential to delineate the neurological defect in these patients.

Dual functions of ASCIZ in the DNA base damage response and pulmonary organogenesis.

Zn²(+)-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn²(+)-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential cofactor of the ATM kinase. Here we show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion knock-down does not affect ATM levels and activation in mouse, chicken, or human cells. Unexpectedly, Asciz-deficient embryos also exhibit severe respiratory tract defects with complete pulmonary agenesis and severe tracheal atresia. Nkx2.1-expressing respiratory precursors are still specified in the absence of ASCIZ, but fail to segregate properly within the ventral foregut, and as a consequence lung buds never form and separation of the trachea from the oesophagus stalls early. Comparison of phenotypes suggests that ASCIZ functions between Wnt2-2b/ß-catenin and FGF10/FGF-receptor 2b signaling pathways in the mesodermal/endodermal crosstalk regulating early respiratory development. We also find that ASCIZ can activate expression of reporter genes via its SQ/TQ-cluster domain in vitro, suggesting that it may exert its developmental functions as a transcription factor. Altogether, the data indicate that, in addition to its role in the DNA base damage response, ASCIZ has separate developmental functions as an essential regulator of respiratory organogenesis.

Autophosphorylation and ATM activation: additional sites add to the complexity.

The recognition and signaling of DNA double strand breaks involves the participation of multiple proteins, including the protein kinase ATM (mutated in ataxia-telangiectasia). ATM kinase is activated in the vicinity of the break and is recruited to the break site by the Mre11-Rad50-Nbs1 complex, where it is fully activated. In human cells, the activation process involves autophosphorylation on three sites (Ser(367), Ser(1893), and Ser(1981)) and acetylation on Lys(3016). We now describe the identification of a new ATM phosphorylation site, Thr(P)(1885) and an additional autophosphorylation site, Ser(P)(2996), that is highly DNA damage-inducible. We also confirm that human and murine ATM share five identical phosphorylation sites. We targeted the ATM phosphorylation sites, Ser(367) and Ser(2996), for further study by generating phosphospecific antibodies against these sites and demonstrated that phosphorylation of both was rapidly induced by radiation. These phosphorylations were abolished by a specific inhibitor of ATM and were dependent on ATM and the Mre11-Rad50-Nbs1 complex. As found for Ser(P)(1981), ATM phosphorylated at Ser(367) and Ser(2996) localized to sites of DNA damage induced by radiation, but ATM recruitment was not dependent on phosphorylation at these sites. Phosphorylation at Ser(367) and Ser(2996) was functionally important because mutant forms of ATM were defective in correcting the S phase checkpoint defect and restoring radioresistance in ataxia-telangiectasia cells. These data provide further support for the importance of autophosphorylation in the activation and function of ATM in vivo.

ATM protein kinase: the linchpin of cellular defenses to stress.

ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.

Radiation shift from triple to quadruple frequency caused by the interaction of terahertz pulses with a nonlinear Kerr medium.

High-intensity optical radiation propagation in a transparent dielectric medium causes the phenomena of pulse self-action and radiation generation at triple frequencies due to the cubic nonlinearity of the medium. However, quadratic nonlinear effects usually outshine the cubic ones in anisotropic nonlinear crystals. In this work, we demonstrate that for certain experimental parameters the nonlinear effect of the third order can be stronger than the second order one in the MgO:[Formula: see text] crystal for terahertz frequency range. We experimentally and theoretically show that this effect can lead to the significant modification of the classical phenomenon of radiation generation at triple frequencies in the case when the pulse represents only one complete oscillation of the optical field. The experiment demonstrated that the phenomenon of generation of radiation at triple frequencies with respect to the frequency of the maximum spectral density in a nonlinear medium of the pulse disappears, and it is replaced by the generation of radiation at quadruple frequencies. The analysis confirms that this effect is based on the asymmetry and large width of the initial spectrum of such extremely short pulses in terms of the number of oscillations.