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•KYS202004A, a novel bispecific protein, antagonizes TNF-α and IL-17A simultaneously.•Superior to monotherapies in reducing disease markers in arthritis and psoriasis ...models.•Demonstrates robust inhibition of cytokine-induced CXCL1 expression in vitro.•Offers a dual-targeted therapeutic approach, enhancing efficacy over current treatments.
The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2 mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.
This article focuses on the contents of Encounter magazine in 1962–63, the final years that it received secret indirect funding from the CIA. It demonstrates that the editorial policy of the magazine ...was staunchly pro-European and was often highly critical of British isolationism. In particular, this chapter examines in detail two symposia stage-managed by editor Melvin Lasky: ‘Going into Europe’ and ‘Suicide of a Nation?’ The first symposium, spread over four issues, canvassed the opinions of prominent intellectuals regarding Britain’s application to join the Common Market (they were in favour by a ratio 5:1) and contained an editorial from Lasky reacting to devastating news of Charles de Gaulle’s veto. The second symposium took the form of a special issue guest-edited by the Hungarian refugee, Arthur Koestler, and was provocatively titled ‘Suicide of a Nation?’ In this special issue, Koestler criticized Britain’s apparent failure to adapt to the post-war world. Other contributors, notably Michael Shanks and Andrew Shonfield, elaborated on modern Britain’s economic and social ills, advising the UK to join forces with a resurgent western Europe. This article argues that supporters of US foreign policy were an important force on British public debate regarding Europe and pays close attention to the dynamics of the Cold War as a shaping context for these symposia. It shows that contributions by controversial public intellectual Koestler shed light on aspects of the anti-Communist editorial policy of Encounter. This article closes by gauging the impact of these symposia on attempts to reform the British Establishment.
Mast cells are immune cells which have a widespread distribution in nearly all tissues. These cells and their mediators are canonically viewed as primary effector cells in allergic disorders. ...However, in the last years, mast cells have gained recognition for their involvement in several physiological and pathological conditions. They are highly heterogeneous immune cells displaying a constellation of surface receptors and producing a wide spectrum of inflammatory and immunomodulatory mediators. These features enable the cells to act as sentinels in harmful situations as well as respond to metabolic and immune changes in their microenvironment. Moreover, they communicate with many immune and nonimmune cells implicated in several immunological responses. Although mast cells contribute to host responses in experimental infections, there is no satisfactory model to study how they contribute to infection outcome in humans. Mast cells modulate physiological and pathological angiogenesis and lymphangiogenesis, but their role in tumor initiation and development is still controversial. Cardiac mast cells store and release several mediators that can exert multiple effects in the homeostatic control of different cardiometabolic functions. Although mast cells and their mediators have been simplistically associated with detrimental roles in allergic disorders, there is increasing evidence that they can also have homeostatic or protective roles in several pathophysiological processes. These findings may reflect the functional heterogeneity of different subsets of mast cells.
The main objective of this study is to propose a novel verification secure framework for patient authentication between an access point (patient enrolment device) and a node database. For this ...purpose, two stages are used. Firstly, we propose a new hybrid biometric pattern model based on a merge algorithm to combine radio frequency identification and finger vein (FV) biometric features to increase the randomisation and security levels in pattern structure. Secondly, we developed a combination of encryption, blockchain and steganography techniques for the hybrid pattern model. When sending the pattern from an enrolment device (access point) to the node database, this process ensures that the FV biometric verification system remains secure during authentication by meeting the information security standard requirements of confidentiality, integrity and availability. Blockchain is used to achieve data integrity and availability. Particle swarm optimisation steganography and advanced encryption standard techniques are used for confidentiality in a transmission channel. Then, we discussed how the proposed framework can be implemented on a decentralised network architecture, including access point and various databases node without a central point. The proposed framework was evaluated by 106 samples chosen from a dataset that comprises 6000 samples of FV images. Results showed that (1) high-resistance verification framework is protected against spoofing and brute-force attacks; most biometric verification systems are vulnerable to such attacks. (2) The proposed framework had an advantage over the benchmark with a percentage of 55.56% in securing biometric templates during data transmission between the enrolment device and the node database.
The 9/11 and WMD controversies have encouraged new trends in CIA historiography. The writing of timely leadership memoirs means that in-house viewpoints now tend to precede outside assessment, ...eliminating one of intelligence historiography's distinctive quirks. At the same time, former CIA personnel are far more willing to go on the record with journalists and scholars thus ensuring that their version of events reaches the widest possible audience. Finally, an invasion of British scholars into the field comes with the promise of objectivity conferred by distance. It is argued that, because of that distance, there has been a disposition to rely on the kind of source material that lends itself to a cultural approach to CIA history.
Geochemical parameters obtained from the analysis of sediments and sedimentary rocks are widely used to infer weathering and paleo-weathering conditions in source areas. Chemical indices of ...weathering, however, may not reflect weathering only, or even principally. The concentration of chemical elements in terrigenous sediments is constrained by the original mineralogy of source rocks, and is thus provenance-dependent. Moreover, the mineralogy and consequently the geochemistry of sediments may undergo substantial modifications by diverse physical processes during transport and deposition, including recycling and hydraulic sorting by size, density or shape, and/or by chemical dissolution and precipitation during diagenesis.
Around the island of Taiwan, temperature and rainfall are consistently high and relatively homogeneous, and no significant correlation is observed between geochemical and climatic parameters. Physical erosion, fostered by landslides induced by frequent earthquakes and typhoons, prevails because of high relief and extreme rates of tectonic uplift. In such a dynamic orogenic setting, all chemical indices of weathering are controlled principally by the geology of source terranes. Sedimentaclastic and metasedimentaclastic sands carried by western Taiwan rivers draining the pro-wedge display the strongest depletion in Na, Ca, Mg and Sr relative to average upper continental crust, and no depletion or even enrichment in K, Rb and Ba. Low WIP indices reflect erosion of phyllosilicate-dominated rocks in the Slate Belt and extensive recycling of clastic rocks exposed in the Western Foothills. Instead, metamorphiclastic sands carried by eastern Taiwan rivers draining the retro-wedge show no depletion or even enrichment in Mg and Ca, and low CIA and PIA, reflecting contributions from the Tailuko Belt and Coastal Range. Volcaniclastic sands have the same CIA values of their andesitic source rocks (47±1 versus 47±7), indicating that weathering is subordinate both along the eastern side of the island and at its northern edge where annual rainfall is double.
Full caution is required when chemical weathering indices are used to extract climatic and paleoclimatic information from the sedimentary archive, especially in the case of diagenized sandstones where commonly massive precipitation of authigenic carbonate is very difficult to accurately correct for, especially in the absence of detailed petrographic and mineralogical data.
The CIA on Latin America Becker, Marc
The journal of intelligence history,
07/03/2021, Letnik:
20, Številka:
2
Journal Article
Recenzirano
A mythology has grown among scholars that during the early years of the Cold War the CIA was so preoccupied with a perceived Soviet threat that except for highly exceptional events such as the 1954 ...coup in Guatemala the agency largely ignored Latin America. In this narrative, it took the 1959 Cuban revolution to bring the region front and center in its imagination (but even then, still only as a pawn of the Soviet Union). A review of CIA documentation, however, indicates that from its beginnings the agency dedicated a significant amount of attention to the region. Not only does the material that the CIA's case officers and their agents generated challenge our assumptions about the agency's presumed priorities, it also highlights the value of a largely unexploited source to understand domestic developments in Latin America in the early post-World War Two period.
Information security is very significant needs to be secured due to people relying on networks and communication. Therefore, protecting information is a major challenge with the number of users ...increases rapidly in recent years. The aim of this article is to review Confidentiality, Integrity and Availability (CIA) in information security. This article focuses on the issues of information security and the requirements of information security. The articles, journals and conference papers are reviewed by researchers were published in 2016-2021. Security issues are analyzed in the recent methodologies. The result of the relationship between CIA in each information security requirement is at a moderate level. It is suggested cybersecurity risk awareness program for society is needed. Therefore, every user could get full advantages in networks and digital platforms.
Quantum mechanical lineshapes of collision-induced absorption (CIA), collision-induced light scattering (CILS) and collision-induced hyper-Rayleigh scattering (CIHR) at room temperature (295 K) are ...computed for gaseous mixtures of molecular hydrogen with neon, krypton and xenon. The induced spectra are detected using theoretical values for induced dipole moment, pair-polarizability trace and anisotropy, hyper-polarizability and updated intermolecular potentials. Good agreement is observed for all spectra when the literature and the present potentials which are constructed from the transport and thermo-physical properties are used.
Ta’ Andi’ Rokok (Cia-cia) is a Madurese dangdut song adaptated from Indian song entitledChaiyya-Chaiyya. The song lyrics are very infl uenced by the conception or perspective ofthe creator. This ...reasearch aims to understand paradigm of Madurese people representedthrough the song by using Foucault’s theory. The reasearch uses multidiscipline approachesby involving several different studies in order to reach comprehensive understanding.The research showsthat the Cia-cia song contains the discourse that consists of a groupof statements (speech) of debt and humour. Through the statements, the kinship andcharacteristic model of Madurese people may be taken as conclusion. Some discourse thenconstruct some dominant subjects which are,tarétan (cousins), kanca tatanggâ (neighbour),kanca main (friends), oréng teggâs (fi rm person), oréng sabbâr (patient person), humourist,and honest person. While some subordinate subjects are Bhâlâ Jâuh (extended family),moneylender, the other, oréng lécak (the indecisive), temperamental person, serious person,and deceitful.
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