Штучний інтелект в діяльності органів правопорядку та юстиції: вітчизняний та європейський досвід

The primary concerns of this research paper are to reveal current issues of the application of artificial intelligence technologies in law enforcement and justice bodies in the conditions of martial law and global threats; to identify the main trends, issues and forensic research prospects using artificial intelligence through the prism of European integration processes; to highlight gaps in the normative and legal regulation of the use of digital technologies; outline directions for its improvement. In order to reach objectives, general scientific and special methods (in particular, dialectical, analytical, induction and deduction, and others) were applied. The domestic and European experience in the application of artificial intelligence technologies in law enforcement and justice bodies was analyzed, and their promising directions were determined. We consider that legal regulation of the application of artificial intelligence in Ukraine should be carried out according to European standards, rules and recommendations in accordance with the European integration course chosen by our state. Note that introduction of the artificial intelligence into legal proceedings should be based preliminary on the principles of the rule of law, observance of basic human rights, respect for honor and dignity, equality before the law and the court, proportionality, competition between the parties, transparency, impartiality and justice. Artificial intelligence is not capable of completely replacing judges, however, its implementation will contribute to the optimization of the work of the judge and court. It is substantiated that in today’s military realities, the issue on increasing the effectiveness of the investigation of modern war crimes and cybercrimes with the help of digital technologies has become acute.Мета статті — дослідити актуальні проблеми застосування технологій штучного інтелекту в діяльності органів правопорядку та юстиції в умовах воєнного стану і глобальних загроз; визначити основні тенденції, проблеми й перспективи криміналістичних досліджень із використанням штучного інтелекту крізь призму євроінтеграційних процесів; висвітлити прогалини в нормативно-правовому регулюванні використання цифрових технологій, окреслити напрями його вдосконалення. Для досягнення поставленої мети застосовано загальнонаукові та спеціальні методи наукового дослідження (зокрема, діалектичний, аналітичний, індукції й дедукції та ін.). Проаналізовано вітчизняний і європейський досвід застосування технологій штучного інтелекту в діяльності органів правопорядку та юстиції, визначено їхні перспективні напрями. Убачаємо, що правове регулювання використання штучного інтелекту в Україні доцільно здійснювати за європейськими стандартами, правилами й рекомендаціями — згідно з обраним нашою державою євроінтеграційним курсом. Зауважено, що запровадження штучного інтелекту в судочинство має передусім ґрунтуватися на принципах верховенства права, дотримання основних прав людини, поваги до честі й гідності, рівності перед законом і судом, пропорційності, змагальності сторін, прозорості, неупередженості та справедливості. Штучний інтелект не здатний цілком замінити суддів, однак його застосування сприятиме оптимізації роботи судді й суду. Обґрунтовано, що у воєнних реаліях сьогодення гостро постало питання про підвищення ефективності розслідування сучасних воєнних злочинів і кіберзлочинів за допомогою цифрових технологій

Titration Calorimetry Standards and the Precision of Isothermal Titration Calorimetry Data

Current Isothermal Titration Calorimetry (ITC) data in the literature have relatively high errors in the measured enthalpies of protein-ligand binding reactions. There is a need for universal validation standards for titration calorimeters. Several inorganic salt co-precipitation and buffer protonation reactions have been suggested as possible enthalpy standards. The performances of several commercial calorimeters, including the VP-ITC, ITC200, and Nano ITC-III, were validated using these suggested standard reactions

Measurement of Nanomolar Dissociation Constants by Titration Calorimetry and Thermal Shift Assay – Radicicol Binding to Hsp90 and Ethoxzolamide Binding to CAII

The analysis of tight protein-ligand binding reactions by isothermal titration calorimetry (ITC) and thermal shift assay (TSA) is presented. The binding of radicicol to the N-terminal domain of human heat shock protein 90 (Hsp90αN) and the binding of ethoxzolamide to human carbonic anhydrase (hCAII) were too strong to be measured accurately by direct ITC titration and therefore were measured by displacement ITC and by observing the temperature-denaturation transitions of ligand-free and ligand-bound protein. Stabilization of both proteins by their ligands was profound, increasing the melting temperature by more than 10 ºC, depending on ligand concentration. Analysis of the melting temperature dependence on the protein and ligand concentrations yielded dissociation constants equal to 1 nM and 2 nM for Hsp90αN-radicicol and hCAII-ethoxzolamide, respectively. The ligand-free and ligand-bound protein fractions melt separately, and two melting transitions are observed. This phenomenon is especially pronounced when the ligand concentration is equal to about half the protein concentration. The analysis compares ITC and TSA data, accounts for two transitions and yields the ligand binding constant and the parameters of protein stability, including the Gibbs free energy and the enthalpy of unfolding

Thermodynamics of Aryl-Dihydroxyphenyl-Thiadiazole Binding to Human Hsp90

The design of specific inhibitors against the Hsp90 chaperone and other enzyme relies on the detailed and correct understanding of both the thermodynamics of inhibitor binding and the structural features of the protein-inhibitor complex. Here we present a detailed thermodynamic study of binding of aryl-dihydroxyphenyl-thiadiazole inhibitor series to recombinant human Hsp90 alpha isozyme. The inhibitors are highly potent, with the intrinsic Kd approximately equal to 1 nM as determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Dissection of protonation contributions yielded the intrinsic thermodynamic parameters of binding, such as enthalpy, entropy, Gibbs free energy, and the heat capacity. The differences in binding thermodynamic parameters between the series of inhibitors revealed contributions of the functional groups, thus providing insight into molecular reasons for improved or diminished binding efficiency. The inhibitor binding to Hsp90 alpha primarily depended on a large favorable enthalpic contribution combined with the smaller favorable entropic contribution, thus suggesting that their binding was both enthalpically and entropically optimized. The enthalpy-entropy compensation phenomenon was highly evident when comparing the inhibitor binding enthalpies and entropies. This study illustrates how detailed thermodynamic analysis helps to understand energetic reasons for the binding efficiency and develop more potent inhibitors that could be applied for therapeutic use as Hsp90 inhibitors

New Monoclonal Antibodies for a Selective Detection of Membrane-Associated and Soluble Forms of Carbonic Anhydrase IX in Human Cell Lines and Biological Samples

Monoclonal antibodies (MAbs) selectively targeting tumor-associated antigens such as carbonic anhydrase IX (CA IX) can significantly contribute to research, diagnostics, and treatment of CA IX-related cancers. CA IX is overexpressed in numerous hypoxic cancers where it promotes tumor progression. Therefore, it is considered as a promising tumor biomarker. A novel collection of MAbs against recombinant CA IX was developed and evaluated in different immunoassays for studying CA IX expression. The reactivity of MAbs with native cell surface protein was confirmed by flow cytometry and the presence of hypoxia-inducible CA IX was investigated in several human cancer cell lines. In addition, the applicability of MAbs for visualization of CA IX-positive tumor cells by immunofluorescence microscopy was demonstrated. MAb H7 was identified as the most promising MAb for different immunoassays. It recognized a linear epitope covering CA IX sequence of 12 amino acid residues 55-GEDDPLGEEDLP-66 within the proteoglycan domain. The MAb H7 was the only one of the collection to immunoprecipitate CA IX protein from cell lysates and detect the denatured CA IX with near-infrared fluorescence Western blot. It was also employed in sandwich enzyme-linked immunosorbent assay to detect a soluble form of CA IX in growth medium of tumor cells and blood plasma samples. The diagnostic potential of the MAb H7 was confirmed on formalin-fixed and paraffin-embedded tissue specimen of cervical carcinoma in situ by immunohistochemistry. The generated MAbs, in particularly clone H7, have great potential in diagnostics and research of CA IX-related cancers

The intrinsic thermodynamic parameters of ICPD compound binding to Hsp90 at 37°C.

<p>The intrinsic thermodynamic parameters of ICPD compound binding to Hsp90 at 37°C.</p

The intrinsic binding thermodynamic parameters (

<p>○ <b>– enthalpies, ▪ – entropies, and ▴ – Gibbs free energies) of ICPD47 (Panel A), ICPD62 (Panel B), ICPD34 (Panel C), and ICPD26 (Panel D) to Hsp90 plotted as a function of temperature.</b> The intrinsic binding parameters are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036899#pone-0036899-t002" target="_blank">Table 2</a>.</p

Bar chart comparing relative contributions of intrinsic enthalpies and intrinsic entropies to the Gibbs free energies of binding of ICPD compound to Hsp90 at 37°C.

<p>Note, that with the partial exception of ICPD62, the compounds bound with major exothermic enthalpy contribution and minor favorable entropy contribution. Favorable contributions of both components make the compounds such potent binders.</p

Chemical structures of selected natural and synthetic Hsp90 inhibitors.

<p>ICPD series of compounds are the subject of this study.</p