Учёт и анализ движения основных средств

Объектом исследования является ООО «ТДК-СИБИРЬ». Цель работы – разработка рекомендаций по улучшению технического состояния и обеспеченности основными средствами ООО «ТДК-СИБИРЬ». В дипломной работе рассматривались теоретические аспекты бухгалтерского учет аосновных средств, и практические – анализа наличия и движения основных средств. В ходе выполнения дипломной работы рассмотрены теоретические аспекты бухгалтерского учета основных средств в РФ, рассмотрен бухгалтерский учет наличия и движения основных средств ООО «ТДК-СИБИРЬ», проведен анализ наличия и движения основных средств, а также даны рекомендации по улучшению технического состояния и обеспеченности основных средств.The object of this study is LLC "TDK-Siberia". Purpose - to develop recommendations to improve the technical condition and security of the main means of "TDK-Siberia". The research paper examines the theoretical aspects of accounting aosnovnyh tools and practical - the analysis of the presence and movement of fixed assets. In the course of the thesis deals with the theoretical aspects of accounting of fixed assets in the Russian Federation, considered the accounting the presence and movement of fixed assets of "TDK-Siberia", analyzes the presence and movement of fixed assets, as well as recommendations for improvement of the technical condition and security of fixed assets

Preparation of a First 18F-Labeled Agonist for M1 Muscarinic Acetylcholine Receptors

M1 muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several 11C-labeled probes. However, protocols for the preparation of 18F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an 18F-labeled M1 mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (n = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an 18F-labeled M1 mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a 18F-labeled M1 selective PET tracer for experimental and diagnostic applications

Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems

Delivery of most drugs into the central nervous system (CNS) is restricted by the blood–brain barrier (BBB), which remains a significant bottleneck for development of novel CNS-targeted therapeutics or molecular tracers for neuroimaging. Consistent failure to reliably predict drug efficiency based on single measures for the rate or extent of brain penetration has led to the emergence of a more holistic framework that integrates data from various in vivo, in situ and in vitro assays to obtain a comprehensive description of drug delivery to and distribution within the brain. Coupled with ongoing development of suitable in vitro BBB models, this integrated approach promises to reduce the incidence of costly late-stage failures in CNS drug development, and could help to overcome some of the technical, economic and ethical issues associated with in vivo studies in animal models. Here, we provide an overview of BBB structure and function in vivo, and a summary of the pharmacokinetic parameters that can be used to determine and predict the rate and extent of drug penetration into the brain. We also review different in vitro models with regard to their inherent shortcomings and potential usefulness for development of fast-acting drugs or neurotracers labeled with short-lived radionuclides. In this regard, a special focus has been set on those systems that are sufficiently well established to be used in laboratories without significant bioengineering expertise

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

Gliomas are the most common primary brain tumors in adults. A diffuse infiltrative growth pattern and high resistance to therapy make them largely incurable, but there are significant differences in the prognosis of patients with different subtypes of glioma. Mutations in isocitrate dehydrogenase (IDH) have been recognized as an important biomarker for glioma classification and a potential therapeutic target. However, current clinical methods for detecting mutated IDH (mIDH) require invasive tissue sampling and cannot be used for follow-up examinations or longitudinal studies. PET imaging could be a promising approach for non-invasive assessment of the IDH status in gliomas, owing to the availability of various mIDH-selective inhibitors as potential leads for the development of PET tracers. In the present review, we summarize the rationale for the development of mIDH-selective PET probes, describe their potential applications beyond the assessment of the IDH status and highlight potential challenges that may complicate tracer development. In addition, we compile the major chemical classes of mIDH-selective inhibitors that have been described to date and briefly consider possible strategies for radiolabeling of the most promising candidates. Where available, we also summarize previous studies with radiolabeled analogs of mIDH inhibitors and assess their suitability for PET imaging in gliomas

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment

C-(4-[(18)F]fluorophenyl)-N-phenyl nitrone: A novel (18)F-labeled building block for metal free [3+2]cycloaddition

© 2011 Elsevier Ltd. All rights reserved

A Practical Method for the Preparation of 18F-Labeled Aromatic Amino Acids from Nucleophilic [18F]Fluoride and Stannyl Precursors for Electrophilic Radiohalogenation

In a recent contribution of Scott et al., the substrate scope of Cu-mediated nucleophilic radiofluorination with [18F]KF for the preparation of 18F-labeled arenes was extended to aryl- and vinylstannanes. Based on these findings, the potential of this reaction for the production of clinically relevant positron emission tomography (PET) tracers was investigated. To this end, Cu-mediated radiofluorodestannylation using trimethyl(phenyl)tin as a model substrate was re-evaluated with respect to different reaction parameters. The resulting labeling protocol was applied for 18F-fluorination of different electron-rich, -neutral and -poor arylstannyl substrates in RCCs of 16-88%. Furthermore, this method was utilized for the synthesis of 18F-labeled aromatic amino acids from additionally N-Boc protected commercially available stannyl precursors routinely applied for electrophilic radiohalogenation. Finally, an automated synthesis of 6-[18F]fluoro-l-m-tyrosine (6-[18F]FMT), 2-[18F]fluoro-l-tyrosine (2-[18F]F-Tyr), 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine (6-[18F]FDOPA) and 3-O-methyl-6-[18F]FDOPA ([18F]OMFD) was established furnishing these PET probes in isolated radiochemical yields (RCYs) of 32-54% on a preparative scale. Remarkably, the automated radiosynthesis of 6-[18F]FDOPA afforded an exceptionally high RCY of 54 +/- 5% (n = 5)

Automated synthesis of 4-[18^{18}F]fluoroanisole, [18^{18}F]DAA1106 and 4-[18^{18}F]FPhe using Cu-mediated radiofluorination under “minimalist” conditions

The application of the “minimalist” approach to Cu-mediated radiofluorination allows the efficient preparation of 18F-labeled arenes regardless of their electronic properties. The implementation of this methodology on a commercially available synthesis module (hotboxthree, Scintomics, Germany) enabled the automated production of 4-[18F]fluoroanisole as well as the clinically relevant PET-tracers, 4-[18F]FPhe and [18F]DAA1106, in radiochemical yields of 41–61% and radiochemical purities of >95% within 30–60 min. These results demonstrated the high efficacy and versatility of the developed method that will open up opportunities for a broad application of Cu-mediated radiofluorination in PET-chemistry

Desmethyl SuFEx-IT: SO₂F₂‑Free Synthesis and Evaluation as a Fluorosulfurylating Agent

Access to SuFExable compounds was remarkably simplified by introduction of the solid FO2S-donor SuFEx-IT. However, the published process for preparation of this reagent relies on the use of sulfuryl fluoride (SO2F2), which is difficult to obtain and highly toxic. Herein, we disclose a simple protocol for SO2F2-free, hectogram-scale preparation of the analogous desmethyl SuFEx-IT from inexpensive starting materials. The reagent was prepared in a high (85%) total yield and without chromatographic purification steps. In addition, we demonstrate the utility of desmethyl SuFEx-IT by successful preparation of a series of fluorosulfates and sulfamoyl fluorides in high to excellent yields. As such, our work recognizes desmethyl SuFEx-IT as a valuable alternative to common FO2S-donors and enables cost-efficient access to substrates for SuFEx click chemistry