ROM THE HISTORY OF TRADE AND BANKING IN SVISHTOV. TRADING-AND-BANKING (MONEY-CHANGING) COMPANIES AND BANKING HOUSES AND THEIR IMPORTANCE FOR THE TOWN ECONOMY (1878-1912)

Based on archival sources not used so far, periodicals and other sources of information, the study reviews the economic life of Svishtov in the period 1878-1912, with an emphasis on the development of trade. Against this background, it examines the issue of re-directing trading capital to banking. The focus of the study is the trading-and-banking (money-changing) companies and banking houses (8 partnerships and 9 sole proprietorships). The study answers a wide range of questions concerning their emergence, institutional characteristics, the nature of the capital mobilized in them; the banking operations and services they offered, with a focus on credit and the circumstances that allowed banking houses at certain periods to make a greater contribution to lending money to local trade and production; the psychological profile of the Svishtov merchant; the reasons why the joint-stock principle did not establish itself firmly and permanently in the economic life of the town. It also reveals the leading role of the Bulgarian National Bank in lending money to local trade and to the two savings joint-stock companies that existed in the 1890s and shows the importance of the banking houses for the development of the town’s economy in three directions – they were subjects in the process of initial capital accumulation; they provided short-term credit and increased the common funds for performing payment operations; they brought stability to the functioning of the banking and lending system especially in times of changes in the central bank’s policy. They also played the role of a ‘financial buffer’ that ensured the survival of companies in times of temporary hardships. The conclusion reached is that being away from joint-stock entrepreneurship, especially in banking, and the inability of local economic forces to create a jointstock bank, was one of the main reasons for the economic backwardness of the town, beginning at the end of the nineteenth century

Preparation of Antioxidant Enzymatic Hydrolysates from Honeybee-Collected Pollen Using Plant Enzymes

Enzymatic hydrolysates of honeybee-collected pollen were prepared using food-grade proteinase and aminopeptidases entirely of plant origin. Bromelain from pineapple stem was applied (8 mAU/g substrate) in the first hydrolysis stage. Aminopeptidase (0.05 U/g substrate) and proline iminopeptidase (0.03 U/g substrate) from cabbage leaves (Brassica oleracea var. capitata), and aminopeptidase (0.2 U/g substrate) from chick-pea cotyledons (Cicer arietinum L.) were involved in the additional hydrolysis of the peptide mixtures. The degree of hydrolysis (DH), total phenolic contents, and protein contents of these hydrolysates were as follows: DH (about 20–28%), total phenolics (15.3–27.2 μg/mg sample powder), and proteins (162.7–242.8 μg/mg sample powder), respectively. The hydrolysates possessed high antiradical scavenging activity determined with DPPH (42–46% inhibition). The prepared hydrolysates of bee-collected flower pollen may be regarded as effective natural and functional dietary food supplements due to their remarkable content of polyphenol substances and significant radical-scavenging capacity with special regard to their nutritional-physiological implications

Snow and ice melt flow features on Devon Island, Nunavut, Arctic Canada as possible analogs for recent slope flow features on Mars

Based on morphologic and contextual analogs from Devon Island, Arctic Canada, the recent martian slope flow features reported by Malin and Edgett are reinterpreted as being due not necessarily to groundwater seepage but possibly to snow or ice melt

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Yoghurt strain Lactobacillus LBL-4 cultivated for 8-10 h at pH ∼6.0 was investigated as a considerable food-grade source of intracellular aminopeptidase. Cell-free extract manifesting >200 AP U/l was obtained from cells harvested from 1 L culture media. Subtilisin-induced hydrolysates of casein, soybean isolate, and Scenedesmus cell protein with degree of hydrolysis 20-22% incubated at 45 • C for 10 h by 10 AP U/g peptides caused an enlarging of DH up to 40-42%, 46-48%, and 38-40% respectively. The DH increased rapidly during the first 4 h, but gel chromatography studies on BioGel P-2 showed significant changes occurred during 4-10 h of enzyme action when the DH increased gradually. After the digestion, the remained AP activity can be recovered by ultrafiltration (yield 40-50%). Scenedesmus protein hydrolysate with DH 20% was inoculated by Lactobacillus LBL-4 cells, and after 72 h cultivation the DH reached 32%. The protein hydrolysates (DH above 40%) obtained from casein and soybean isolate (high Q value) demonstrated a negligible bitterness while Scenedesmus protein hydrolysates (low Q value) after both treatments were free of bitterness

The HSP90 Inhibitor, AUY-922, Ameliorates the Development of Nitrogen Mustard-Induced Pulmonary Fibrosis and Lung Dysfunction in Mice

Increased levels of heat shock protein 90 (HSP90) have been recently implicated in the pathogenesis of pulmonary fibrosis and the use of HSP90 inhibitors constitutes a potential therapeutic approach. Similarly, acute exposure to nitrogen mustard (NM) is related to the development of chronic lung injury driven by TNF-α, TGF-β, ERK and HSP90. Thus, we developed a murine model of NM-induced pulmonary fibrosis by instilling C57BI/6J mice with 0.625 mg/kg mechlorethamine hydrochloride. After 24 h, mice began receiving AUY-922, a second generation HSP90 inhibitor, at 1 mg/kg 2 times per week or 2 mg/kg 3 times per week, for either 10 or 30 days. AUY-922 suppressed the NM-induced sustained inflammation, as reflected in the reduction of leukocyte and protein concentrations in bronchoalveolar lavage fluid (BALF), and inhibited the activation of pro-fibrotic biomarkers, ERK and HSP90. Furthermore, AUY-922 maintained normal lung function, decreased the overexpression and accumulation of extracellular matrix proteins, and dramatically reduced histologic evidence of fibrosis in the lungs of mice exposed to NM. The HSP90 inhibitor, AUY-922, successfully blocked the adverse effects associated with acute exposures to NM, representing a promising approach against NM-induced pulmonary fibrosis

Mars: Periglacial Morphology and Implications for Future Landing Sites

At the Mars Phoenix landing site and in much of the Martian northern plains, there is ice-cemented ground beneath a layer of dry permafrost. Unlike most permafrost on Earth, though, this ice is not liquid at any time of year. However, in past epochs at higher obliquity the surface conditions during summer may have resulted in warmer conditions and possible melting. This situation indicates that the ice-cemented ground in the north polar plains is likely to be a candidate for the most recently habitable place on Mars as near-surface ice likely provided adequate water activity approximately 5 Myr ago. The high elevation Dry Valleys of Antarctica provide the best analog on Earth of Martian ground ice. These locations are the only places on Earth where ice-cemented ground is found beneath dry permafrost. The Dry Valleys are a hyper-arid polar desert environment and in locations above 1500 m elevation, such as University Valley, air temperatures do not exceed 0 C. Thus, similarly to Mars, liquid water is largely absent here and instead the hydrologic cycle is dominated by frozen ice and vapor phase processes such as sublimation. These conditions make the high elevation Dry Valleys a key Mars analog location where periglacial processes and geomorphic features can be studied in situ. This talk will focus on studies of University Valley as a Mars analog for periglacial morphology and ice stability. We will review a landing site selection study encompassing this information gleaned from the Antarctic terrestrial analog studies plus Mars spacecraft data analysis to identify candidate landing sites for a future mission to search for life on Mars

Real-Time Science Operations to Support a Lunar Polar Volatiles Rover Mission

Future human exploration of the Moon will likely rely on in situ resource utilization (ISRU) to enable long duration lunar missions. Prior to utilizing ISRU on the Moon, the natural resources (in this case lunar volatiles) must be identified and characterized, and ISRU demonstrated on the lunar surface. To enable future uses of ISRU, NASA and the CSA are developing a lunar rover payload that can (1) locate near subsurface volatiles, (2) excavate and analyze samples of the volatile-bearing regolith, and (3) demonstrate the form, extractability and usefulness of the materials. Such investigations are important both for ISRU purposes and for understanding the scientific nature of these intriguing lunar volatile deposits. Temperature models and orbital data suggest near surface volatile concentrations may exist at briefly lit lunar polar locations outside persistently shadowed regions. A lunar rover could be remotely operated at some of these locations for the approx. 2-14 days of expected sunlight at relatively low cost. Due to the limited operational time available, both science and rover operations decisions must be made in real time, requiring immediate situational awareness, data analysis, and decision support tools. Given these constraints, such a mission requires a new concept of operations. In this paper we outline the results and lessons learned from an analog field campaign in July 2012 which tested operations for a lunar polar rover concept. A rover was operated in the analog environment of Hawaii by an off-site Flight Control Center, a rover navigation center in Canada, a Science Backroom at NASA Ames Research Center in California, and support teams at NASA Johnson Space Center in Texas and NASA Kennedy Space Center in Florida. We find that this type of mission requires highly efficient, real time, remotely operated rover operations to enable low cost, scientifically relevant exploration of the distribution and nature of lunar polar volatiles. The field demonstration illustrated the need for science operations personnel in constant communications with the flight mission operators and the Science Backroom to provide immediate and continual science support and validation throughout the mission. Specific data analysis tools are also required to enable immediate data monitoring, visualization, and decision making. The field campaign demonstrated that this novel methodology of real-time science operations is possible and applicable to providing important new insights regarding lunar polar volatiles for both science and exploration

Analysis of the pharmacoeconomic effectiveness of the tyrosine kinase inhibitors therapy in patients with chronic myeloid leukemia in a Single Hematology Center in Plovdiv, Bulgaria

Summary: Chronic myelogenous leukemia (CML) is a pluripotent hemopoietic stem cell malignancy characterized by the presence of a BCR-ABL1 fusion gene derived from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22) (q34; q11)] known as the Philadelphia (Ph) chromosome. CML is an acquired hematopoietic stem cell disease common to myelo- and lymphopoiesis, characterized by uncontrolled proliferation of granulopoiesis (Shuvaev et al. 2015; Yordanov and Varbanova 2019). Relevance and goals: Second-generation tyrosine kinase inhibitors (TKIs) (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in the frequency and speed of achieving cytogenetic and molecular responses in the treatment of chronic myelogenous leukemia (CML), but they cause severe adverse effects and are much more expensive than imatinib, especially if we compare them to the prices of the registered generic products of Imatinib and Dasatinib. “Novartis Tasigna® trial shows superior results to Glivec® in patients with early-stage chronic myeloid leukemia”, reported on 10/20/2021 by Pierre Perrin-Montlouis. In the first direct comparison of these two oral therapies back in 2009 (Тasigna (nilotinib) 2009), as first-line treatment for CML, the results of Tasigna showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blast phase, with responses achieved faster in the Tasigna group than in the Glivec group. Furthermore, in the last ten years, CML patients who have achieved a stable deep molecular response for at least 2 years have been included in clinical trials for the management of treatment-free remission (TFR) (Kim et al. 2013; Saußele et al. 2016). On the other hand, the ever-increasing costs of diagnosis, treatment and monitoring of the response of CML to the various therapeutic strategies require conducting pharmacoeconomic analyses of the cost-effectiveness and cost-utility types in order to evaluate which are the cost-effective strategies with a view to introducing them into therapeutic practice. The present study aims to analyze the pharmacoeconomic efficiency of the TKI inhibitors used by the patients with CML-CP in the first and second lines, treated in the hematology clinic at UMHAT “St. George”, MU- Plovdiv during the period 2018–2022. Methods: An economic analysis of the medicinal use of TKIs for a 5-year period (2018–2022) was performed at the national level according to data from the National Health Insurance Fund and the availability, accessibility, and usability of original and generic TKIs in Bulgaria were evaluated. The direct medical costs for the therapy of all patients were calculated, including the costs of the TKI therapy, laboratory tests, and monitoring of the molecular response for the entire treatment period from the appointment of the TKI therapy until the end of 2022. A comparative analysis was conducted to assess the cost-effectiveness of the different therapeutic strategies with TKIs on the first and second lines of treatment of patients with CML-CP in the hematology clinic at UMHAT “St. George” Medical University, Plovdiv, using the decision analysis method and conducting one-way and probalistic sensitivity analyses. Results: The sensitivity analyzes of all pharmacoeconomic models showed the robustness and reliability of the obtained results. The threshold limits of medical costs and the frequency of achieving a deep molecular response determining the choice of first- and second-generation tyrosine kinase inhibitors as first- and second-line therapy for patients with chronic myeloid leukemia in the chronic phase have been determined. Prescribing doctors prefer the original MPs to generic analogues, which is also assumed by the current regulations, according to which even for expensive MPs dispensing by protocols, the prescription is by trade and not by international non-proprietary names (INN), which is why the use of the much cheaper generic MPs is negligibly low compared to original MPs. A personalized approach to the patient’s therapy and monitoring the patient’s molecular response to it, as well as stopping therapy in 25–30% of patients suitable to stop it safely when in TFR phase with a probability of more than 50% of not having a relapse will save additional costs that, by improving the cost-effectiveness of therapy for patients with CML, will be directed towards the treatment of new patients with this or other diseases. Conclusion: These pharmacoeconomic models can be applied to improve diagnostic and therapeutic standards in clinical practice and for the efficient use of the very limited resources for health care in countries like Bulgaria. The conducted cost-effectiveness analyses confirmed that the hematologists at the University Center in Plovdiv adhere to the recommendations of Leukemia Net and the Bulgarian Medical Society of Hematology and achieve not only good therapeutic but also pharmacoeconomic efficiency in the treatment of CML-СР patients in first- and second- line therapy

Near Real Time Prospecting for Lunar Volatiles: Demonstrating RESOLVE Science in the Field

The Regolith and Environment Science and Oxygen & Lunar Volatile Extraction (RESOLVE) project aims to demonstrate the utility of "in situ resource utilization". In situ resource utilization (ISRU) is a way to rebalance the economics of spaceflight by reducing or eliminating materials that must be brought up from Earth and placed on the surface of the Moon for human use. RESOLVE is developing a rover-borne payload that (1) can locate near subsurface volatiles, (2) excavate and analyze samples of the volatile-bearing regolith, and (3) demonstrate the form, extractability and usefulness of the materials. Such investigations are important not only for ISRU but are also critically important for understanding the scientific nature of these intriguing lunar polar volatile deposits. Temperature models and orbital data suggest near surface volatile concentrations may exist at briefly lit lunar polar locations outside persistently shadowed regions. A lunar rover could be remotely operated at some of these locations for the 4-7 days of expected sunlight at relatively low cost. In July 2012 the RESOLVE project conducted a full-scale field demonstration. In particular, the ability to perform the real-time measurement analysis necessary to search for volatiles and the ability to combine the various measurement techniques to meet the mission measurement and science goals. With help from the Pacific International Space Center for Exploration Systems (PISCES), a lunar rover prototype (provided by the Canadian Space Agency) was equipped with prospecting instruments (neutron spectrometer and near-infrared spectrometer), subsurface access and sampling tools, including both an auger and coring drill (provided by CSA) and subsurface sample analysis instrumentation, including a sample oven system, the Oxygen and Volatile Extraction Node (OVEN), and Gas Chromatograph / Mass Spectrometer system, the Lunar Advanced Volatile Analysis (LAVA) system. Given the relatively short time period this lunar mission is being designed to, prospecting needs to occur in near real-time. The two prospecting instruments are the neutron and NIR spectrometers. In the field demo a small radioactive source was provided the neutron flux. The NIR spectrometer, which includes its own light source, looks at surface reflectance for signatures of bound H20/0H and general mineralogy. Once a "hot spot" was found by the prospecting instruments, the drill could either auger or core. The auger drill worked to a depth of 50 cm and is monitored with a drill camera and the NIR spectrometer. As cuttings are brought up the NIR spectra is monitored. If a particular location is considered of high -interest then the decision to core could be made. The coring drill (a push-tube) allowed a meter sample to be acquired processed by the OVEN/LAVA sys-tem. This presentation will provide details as how these instruments worked together and how and if the planned measurements and science was obtained