bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Readiness of the Equipment of the Launch Space Complex at the Early Stages of its Creation
Authors: Эртман Л.В. , Рудаков В.Б. 
Published: March 2022

Оценивание готовности оборудования стартового космического комплекса (СКК) на этапе его создания вызывает существенные затруднения вследствие отсутствия или недостаточного объема экспериментальных данных о характеристиках его надежности. В настоящей статье предлагается осуществлять оценивание готовности СКК на основе таких характеристик как: характеристики надежности его элементов, структурная схема надежности на уровне элементов, алгоритм его функционирования в период дежурства, проектные значения показателей восстановления работоспособного состояния при возникновении отказа, проектные характеристики системы диагностики. Предлагаются математические зависимости и способы имитационного моделирования, которые используют данные характеристики СКК для расчета коэффициента готовности СКК.
Assessing the readiness of the equipment of the launch space complex (LSC) at the stage of its creation causes significant difficulties due to the lack or insufficient amount of experimental data on the characteristics of its reliability. In the article, we propose to evaluate the readiness of the LSC based on such characteristics as: reliability characteristics of its elements, a structural diagram of reliability at the level of elements, an algorithm for its operating during duty, project values of indicators for restoring the operational state in the event of a failure, project characteristics of the diagnostic system. In addition, we propose mathematical dependencies and simulation methods used these LSC characteristics for calculating of the LSC readiness coefficient.
Near real-time detection of blockages in the proximity of combined sewer overflows using evolutionary ANNs and statistical process control
Authors: Rosin T. R. , Kapelan Z. , Keedwell E. , Romano M. 
Published: March 2022

Abstract
Blockages are a major issue for wastewater utilities around the world, causing loss of service, environmental pollution, and significant clean-up costs. Increasing telemetry in combined sewer overflows (CSOs) provides the opportunity for near real-time data-driven modelling of wastewater networks. This paper presents a novel methodology, designed to detect blockages and other unusual events in the proximity of CSO chambers in near real-time. The methodology utilises an evolutionary artificial neural network (EANN) model for short-term CSO level predictions and statistical process control (SPC) techniques to analyse unusual level behaviour. The methodology was evaluated on historic blockage events from several CSOs in the UK and was demonstrated to detect blockage events quickly and reliably, with a low number of false alarms.
Particle size characteristics of sediment by sheet erosion and their responses to related parameters on a Loess hillslope: a plot-scale study
Authors: Zhang Qingwei , Ma Sanbao , Liu Sijun , Lei Xin , Liu Shanshan , Du Xue 
Published: March 2022

Abstract
Particle size distribution (PSD) of sediment by sheet erosion not only indicates erosion behaviors, but also provides a basis for potential nutrient losses. PSDs are significantly influenced by topographic, rainfall, and associate runoff characteristics, such as rainfall intensity (I), rainfall kinetic energy (KE), slope gradient (S), runoff velocity (v), and stream power (Ω), while their effects have not been fully understood so far. To fill this research gap, in this study, simulated rainfall experiments were conducted to investigate the characteristics of effective and ultimate PSDs of sediments, as well as their responses to related parameters, under five levels of I and S. The results showed that (1) for effective PSDs, there was a significant enrichment of clay-sized and silt-sized fractions (P&lt;2μm and P2–50μm) in sediment (percentage range: 12.11–20.64% and 57.09–65.94%), whereas there was a depletion of sand-sized fractions (P50–250μm and P250–2000μm). The ultimate PSDs of sediment were, however, similar to the soil matrix under experimental conditions. (2) With an increase in I and S, P&lt;2μm and P2–50μm decreased exponentially or logarithmically, and P50–250μm and P&gt;250μm increased correspondingly. The contribution rates (PCs) of the effect of I on clay-, silt-, fine-sand-, and coarse-sand-sized fractions in sediment were 23.44, 35.45, 29.09, and 56.82%, respectively, whereas the PCs of that of S were 56.54, 24.42, 59.89, and 31.47%, respectively, indicating that S plays a more pivotal role in influencing P&lt;2μm and P50–250μm, whereas P2–50μm and P&gt;250μm were more sensitive to I than to S. (3) The aggregation ratio (AR) for the fractions of different sizes indicated that clay-sized particles tend to be transported as aggregates, while silt-sized particles tend to be transported as primary particles. A higher I or steeper S leads to a larger proportion of particles being transported as aggregates. (4) KE, Ω, and unit stream power (U) were the most correlated parameters influencing effective PSDs. Equations were finally established using KE, Ω, and U to predict the effective PSDs of sediment by sheet erosion. This study can further the understanding of the sheet erosion process and provide a scientific basis for the establishment of a sheet erosion model.
Free Radical Generating and Scavenging Compounds as a New Type of Drug
Authors: Matsugo Seiichi , Mizuno Masashi , Konishi Tetsuya 
Published: March 2022

Abstract:
Recently, the free radical investigations cover a broad field of research related to chemistry, biology, medicine and biochemistry. One of the reasons for this is that the free radicals play crutial roles in many pathogenic disorders, typically carcinogenesis. So, in this sense it is very important to elucidate the precise mechanism of action of free radicals in vivo from the aspect of tumor necrosis. Indeed, many drugs have been extensively studied in relation to free radicals in recent years. These studies can be divided into two categories one of which emphasizes the advantageous side of free radicals, while the other emphasizes the toxic aspects of free radicals. In tis review article, we will discuss four major studies related free radical studies based on the chemical standpoint of view. Frist we will introduce the recent advances of radical generating drugs such as bleomycin and some ene-diyne natural products in the medicinal field. Second, we will introduce the possible use of free radical generating compounds as a condidate of the new-type of drug. Third, we will show the protective effects and importance of some recent advances in antioxidants research, which show the potentiality of natural antioxidants as the protective or therapeutic medicine for free radical deseases. Finally, we will introduce some recent progress in the gene-regulation studies by the antioxidants and show our ideas for the future application for this concept in the medicinal fields.
Steroidal and Non-Steroidal Inhibitors of Steroid Sα-Reductase
Authors: Abell A.D. , Henderson B.R. 
Published: March 2022

Abstract:
A good deal of interest exists in developing inhibitors of steroid Sa-reductase (SR) as a therapy for pharmacological disorders associated with elevated levels of dihydrotestosterone (DHT), the product of SR action on testosterone (T). The recent identification of two isoforms of SR (Types 1 and 2) has intensified this effort to include the design of isoform selective and dual isoform SR inhibitors. It is anticipated that such inhibitors will provide a more efficient and specific therapy for disorders including benign prostatic hyperplasia, some prostatic cancers, certain skin disorders and male pattern baldness.	The structural features which are responsible for the potency,
isoform selectivity and SR species selectivity of the traditional classes of steroid-based inhibitors, typified by epristeride 7 and finasteride 15, have been identified. This information is being applied to the design of new classes of SR inhibitors. A new and rapidly expanding area of this work is the identification of non-steroidal inhibitors of SR. A survey of the main classes of SR inhibitor is followed by a review of the key structural features that are known to influence inhibitor potency and selectivity.
Strategies for the Development of Photodynamic Sensitizers
Authors: Morgan Alan R. 
Published: March 2022

Abstract:
The use of light activated dyes in photomedicine offers the potential to administer to patients an inert compound which can be selectively activated by photoirradiation. Such a process allows for unique control of the photochemotherapeutic process, using techniques to enhance drug targeting and/or selective irradiation of target tissues. Substantial progress has been made iri recent years in developing biologically compatible photosensitizers and in understanding their mechanisms of action. In one field of photcimedicine called Photodynamic Therapy, excitation of the sensitizer leads to the generation of activated oxygen species which then oxidize biological .substrates such as protein and
lipids. Since different sensitizers localize in different cell types and in differe-nt subcellular organelles, the mechanisms of cell necrosis may differ. Current research is aimed at better understanding the parameters responsible for these properties of photosensitizers and in expanding the disease indications to which phototherapy can be applied.
Strategies to Enhance the Localization of Anticancer lmmunoconjugates
Authors: Schreiber George J. , Kerr David E. 
Published: March 2022

Abstract:
Monoclonal antibodies (mAb) that bind to tumor-associated antigens have been used to selectively deliver toxic agents such as drugs, radionuclides, or protein toxins to tumors. A number of mAb conjugates have been effective in killing tumor cells in vitro and in causing tumor regressions in mice; but as yet have not been curative against solid tumors in humans. One of the problems that has been identified for mAb tumor targeting is that systemic clearance tends to be slow, resulting in low tumor-to-blood ratios even many days after administration. Many strategies have been explored to accelerate mAb conjugate clearance without affecting intratumoral uptake.
This can be accomplished by extracorporeal adsorption or plasmapheresis to remove the conjugate from the blood, or by complexing the conjugate with an agent that is cleared very quickly from the blood. Such agents include carbohydrates, avidin, and mAbs directed against the immunoconjugate. Each of these strategies have been employed to enhance the tumor-to- blood ratio of immunoconjugates.
New Analogs of Methotrexate in Cancer and Arthritis
Authors: DeGraw Joseph I. , Colwell William T. , Pipert James R. , Sirotnak Francis M. , Smith R. Lane 
Published: March 2022

Abstract:
Aminopterin and its N10-methyl analog; methotrexate, were synthesized in the late
1940s and methotrexate was subsequently incorporated into clinical use as an antitumor agent in the mid-1950s. In more recent years methotrexate has also become accepted as an effective agent for treatment of rheumatoid arthritis. Structure-activity studies have been ongoing over the past 40 years in an effort to develop a safer and more effective version of this powerful antifolate. Early work featured replacement of nitrogen atoms at various positions in the pterin ring, substitution about the phenyl ring in the side chain and alteration in the glutamic acid subunit. These studies shed considerable light on structural requirements for antitumor activity. However, new agents with serious potential for clinical introduction were not encountered until structural modification of the region bridging the pterin and benzoyl glutamate side chain took place. A series of 10-substituted-10-deazaaminopterin analogs was investigated and found to have activity superior to methotrexate in several tumor models in vivo. There was in vitro evidence for facilitated transport into tumor cells versus sensitive host tissue cells and increased polyglutamylation within the tumor cells such that a selective accumulation was achieved in tumor tissue. 10-Ethyl-10-deazaaminopterin (Edatrexate) was found to be clinically effective against lung and breast solid tumors.
Our laboratories have continued to pursue structural modifications of 10-deaza, 5,10-dideaza and 8,10-dideazaaminopterins in an effort to improve upon the efficacy of edatrexate. Additional variation has been made in the "bridge region" and various heterocyclic rings have been introduced in place of the side chain phenyl ring. These modifications have resulted in additional new antitumor agents and compounds with activity exceeding that of methotrexate in rheumatoid arthritis.
Macrocyclic Peptidomimetics Forcing Peptides into Bioactive Conformations
Authors: Fairlie David P. , Abbenante Giovanni , March Darren R. 
Published: March 2022

Abstract:
Cyclic peptides that are potent regulators of biological processes are rapidly emerging as important mechanistic probes and drug leads. Nature clearly uses macrocycles to. constrain peptides into conformations that can selectively bind proteins or. small molecules. Therapeutic effects of such macrocycles, often containing additional conformational constraints that fine­ tune structure (e.g. D-amino acids, N-methyl substituents, aromatic rings, to name a few), have so far been mainly discovered by accident. However it is now becoming possible to rationally design synthetic macrocycles to selectively recognize and inhibit a specific protein. A receptor-binding struc­
ture is more easily adopted by macrocyclic peptidomimetics than more flexible acyclic peptides because the former have less conformational entropy. Macrocycles are often stable to hydrolysis by peptidases that degrade acyclic peptides and hydrophobic side chains can protect peptide bonds in macrocycles from hydrolysis, as well as enhance lipophilicity, cell permeability and bioavailability. Synthetic efforts to obtain bioactive conformations of short peptides have so far been substrate-based, guided by molecular modelling predictions and structure-activity data for modified amino acid sequences of substrates. However, dramatic advances in molecular biology, X-ray crystallography, NMR spectroscopy and computing are rapidly producing three dimensional structures of proteins, promising direct observation of protein-bound conformations of small molecules and receptor-based design of peptidomimetics with surface complementarity for proteins. This perspective review highlights examples of both natural and synthetic bioactive macrocyclic peptides containing constraints that fix conformation, and briefly illustrates the promise that receptor-based design holds for structural and functional mimicry of peptides by macrocycles.
Pyrrolic Photosensitizers
Authors: Sternberg E. , Dolphin D. 
Published: March 2022

Abstract:
There are three major classes of photosensitizers which can initiate a phototoxic effect to tissues upon irradiation. These are the cationic dyes (Type I Photosensitizer), the psoralens (Type I and II Photosensitizer),
and cyclic polypyrrolic compounds (Type II Photosensitizer). The polypyrrolic compounds such
as porphyrins have been investigated since the late 1800's for their ability to destroy tissue. In the last ten years, compounds such as chlorins and expanded porphyrins have begun to dominate the preclinical field because they can be activated with light at wavelengths tissue does not effectively absorb. The results of these investigation have been reported in more than
10,000 papers in the field covering aspects from mechanisms of action, photophysics, structure activity relationships, new compound development and clinical investigations. With the approval of PHOTOFRJN®, (porfimer sodium), the first of the pyrrolic compounds to win acceptance by international regulatory bodies and with nearly 10 other second generation compounds undergoing early clinical trials for diseases ranging from esophageal and skin cancers to age related macular degeneration, the field of photodynamic therapy would seem to have a bright future.
Novel Effects of Heme Biological Systemst and Heme-related Compounds in Biological Systems
Authors: Sassa Shigeru 
Published: March 2022

Abstract:
Heme and heme-related compounds such as porphyrins have a variety of biological and clinical activities. This review highlights some of the novel effects of these compounds in medicinal chemistry. Heme which has no photoreactive properties, can serve as the prosthetic group for various hemoproteins, or as a substrate for microsomal heme oxygenase (HO). In contrast, porphyrins have photodynamic activities but usually do not serve as substrates in biological systems. Thus, heme and heme analogues are often
used to influence enzyme activities in tissues, while porphyrins by taking advantage of their
photoreactive properties are used as drugs in medicine. There are four major applications of these compounds, namely the use of (i) heme in the treatment of porphyrias and hematological disorders, (ii) synthetic metalloporphyrins in the treatment of hyperbilirubinemia, (iii) metal-free porphyrins in photodynamic therapy of malignant tumors, and (iv) porphyrin derivatives as contrast reagents in radiography. Solubility, stability, pharmacokinetics, pharmacodynamics and analytical techniques are all important considerations in the medicinal chemistry of these compounds. In man and animals in vivo, the rate of synthesis and catabolism of heme, as well as disorders of heme synthesis are important in understanding pathophysiological effects of these compounds.
Reduction of Biliverdins to Bilirubins: Its Metabolic Regulation Under Various Physiological Conditions
Authors: Valasinas Aldonia , Frydman Benjamin 
Published: March 2022

Abstract:
Heme and hemoproteins are degraded in mammals by oxidation
to biliverdins. These linear tetrapyrroles are reduced to bilirubins by a
cytosolic biliverdin reductase (BvR) at the rate of 250-400 mg per day. While the bulk of biliary biliverdin is biliverdin IX α , other isomers such as biliverdins IXβ and IXγ are formed under conditions of oxidative stress by the chemical degradation of hemoproteins, or from the degradation of abnormal hemoglobins. Rat liver BvR was found to. be a NADPH-dependent reductase with a broad substrate specificity, which efficiently reduces a large number of biliverdins as long as they carry two propionate side-chains. The enzyme was found to exist in three molecular forms, two of which (molecular forms 1 and 3) interconvert under conditions of oxidative stress or in the presence of oxidant species. The different molecular forms have different reduction rates for the biliverdin isomers, thus securing the efficient reduction of biliverdins to bilirubins under different physiological conditions. The molecular mechanism of the enzymatic reduction entails the protonation of the basic pyrrolenine nitrogen (N23) which results in a mesomeric positive charge on the neighboring meso C-10 carbon. The C-10 then undergoes a nucleophilic addition of the hydride released by the NADPH cofactor of BvR. Our studies have established the structural requirements for a biliverdin to be efficiently reduced to a bilirubin. This metabolic step gains relevance as synthetic hemes and metalloporphyrins are increasingly used in therapeutics.
Recent Advances in the Development of Retinoids
Authors: Curley R.W. , Robarge M.J. 
Published: March 2022

Abstract:
Retinoic acid (RA) is a metabolite of retinol (vitamin A) which is necessary for a number of biological functions including the maintenance of growth and epithelial cell differentiation. It appears that most of these functions are mediated through formation of a complex with nuclear retinoid receptors which act in a steroid hormone-like mechanism. RA and its analogs (retinoids) have found use in treating dermatological diseases and show pro-
mise as cancer chemopreventive/chemotherapeutic agents because of this impact on epithelial tissue differentiation. RA is extensively metabolized and this has a profound impact on its actions and activity. Thus, a reasonably detailed discussion of the quantitatively and/or biologically important metabolites of RA is provided as well as molecular design efforts to inhibit metabolic inactivation processes and stabilize metabolic activation products. The review is concluded with a description of current efforts in the development of more heavily structurally modified analogs, particularly those with nuclear retinoid receptor or receptor subtype specificity.
COVID-19 Effects on Geriatric Population and Failures of Aminoquinoline
Therapy: Compilation of Studies from EU, USA, and China;
Safety and Efficacy of Vaccines in the Prevention and Treatment of
COVID-19
Authors: Beeraka Narasimha M. , Tulimilli SubbaRao V. , Greeshma Mandya V. , Dallavalasa Siva , Zhang Yaowen , Xiao Wenjing , Fan Ruitai , Zhao Di , Bettadapura Anjali D.S. , Nataraj Suma M. , Madhunapantula SubbaRao V. , Liu Junqi 
Published: March 2022

Background:
Mortality of the older adult population suffering from COVID-19 has
been increasing at an alarming rate, and people older than 76 years of age reported 18% mortality.
Mainly, the EU and USA exhibited a greater fatality rate due to lack of selective immunization and
anti-SARS Co-V-2 therapeutics. Very limited reports are available to delineate the impact of
COVID-19 on the geriatric population and the failures of aminoquinoline therapy.

Methods:
We performed a substantial literature review in the PubMed/Medline databases to extract
the information pertaining to the COVID-19 impact on the geriatric population and recent failures
of aminoquinoline therapy in COVID-19 patients of EU, China, USA and the requirement of vaccination.

Results and Discussions:
Both parental strains and mutant variants of SARS Co-V-2 can induce severe
respiratory complications, multiorgan failure, and clotting abnormalities in older adults due to
low immunocompetence. Aminoquinoline derivatives, such as chloroquine (CQ) and hydroxychloroquine
(HCQ), are preferred primarily for COVID-19 treatment, but several controversies
are being reported for its usage worldwide. In this review, we have provided the effects of
COVID-19 on the geriatric population of EU and an overview of the mechanism of action of aminoquinolines.
Furthermore, CQ and HCQ are not the preferred choice of drugs if the COVID-19 patients
already have existing co-morbid conditions viz., diabetes mellitus and hypertension.

Conclusion:
A new advent of COVID-19 vaccines, such as nucleic acid-based (DNA/mRNA)
vaccines, protein subunit vaccines, viral vector vaccines, and inactivated vaccines, have been developed
for treating SARS-CoV-2 infection after the failure of aminoquinoline therapy in EU, China,
and USA patients. However, some of the vaccines are yet to be examined against mutant strains of
SARS CoV-2 that originated in the UK, Nigeria, South Africa, Brazil, and India.