Empirical Analysis of Mergers and Acquisitions: Evidence from International and Comparative Supply Chain Operations in Russian Market

Fifty mergers and acquisitions deals that occurred in the period 2014-2017 in the Russian market were analyzed. Deals were randomly selected. The largest number of selected transactions accounted for 2015. 32% of all transactions occurred in the oil and gas sector of the economy. Within the framework of the study, two hypotheses were put forward: 1) the effectiveness of a merger and acquisition transaction increases with an increase in the capitalization of the company-buyer, 2) the effectiveness of a merger and acquisition transaction increases with an increase in its amount. The effectiveness of the merger and acquisition deal was expressed through the growth of the economic profit of the purchasing companies based on the comparative supply chain. Fifteen variables were selected as independent ones (return on invested capital; weighted average cost of capital; return on equity; return on assets; return on sales; multiplier “share returnâ€; multiplier “price / earningsâ€; multiplier “price / book value of assetsâ€; multiplier “ business value / revenue â€; multiplier“ Business cost / profit before interest, taxes and amortization â€; profitability of the company before interest, taxes and the multiplier “earnings before interest, taxes and depreciation / book value of assetsâ€; the dollar exchange rate, etc.), however, only two of them were included in the final type of the regression model: the price / net profit multiplier and the amount of the merger / acquisition transaction

Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression

<p>Abstract</p> <p>Background</p> <p>Cisplatin based chemotherapy cures over 80% of metastatic testicular germ cell tumours (TGCT). In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from TGCTs are hypersensitive to cisplatin reflecting the clinical response. Earlier findings suggested that a reduced repair capacity might contribute to the cisplatin hypersensitivity of testis tumour cells (TTC), but the critical DNA damage has not been defined. This study was aimed at investigating the formation and repair of intrastrand and interstrand crosslinks (ICLs) induced by cisplatin in TTC and their contribution to TTC hypersensitivity.</p> <p>Results</p> <p>We observed that repair of intrastrand crosslinks is similar in cisplatin sensitive TTC and resistant bladder cancer cells, whereas repair of ICLs was significantly reduced in TTC. γH2AX formation, which serves as a marker of DNA breaks formed in response to ICLs, persisted in cisplatin-treated TTC and correlated with sustained phosphorylation of Chk2 and enhanced PARP-1 cleavage. Expression of the nucleotide excision repair factor ERCC1-XPF, which is implicated in the processing of ICLs, is reduced in TTC. To analyse the causal role of ERCC1-XPF for ICL repair and cisplatin sensitivity, we over-expressed ERCC1-XPF in TTC by transient transfection. Over-expression increased ICL repair and rendered TTC more resistant to cisplatin, which suggests that ERCC1-XPF is rate-limiting for repair of ICLs resulting in the observed cisplatin hypersensitivity of TTC.</p> <p>Conclusion</p> <p>Our data indicate for the first time that the exceptional sensitivity of TTC and, therefore, very likely the curability of TGCT rests on their limited ICL repair due to low level of expression of ERCC1-XPF.</p

Экономический потенциал Республики Беларусь после присоединения к ШОС: преимущества и возможности

In the era of globalization, integration groupings have become an important tool for the development of many countries in the world economy. They contribute to the formation of close economic ties and coordination of foreign trade between the participants, which in turn has a favorable effect on the development of the national economy of the country. Participation in integration associations is of great importance for the development of Belarus’ economy and increasing its role in the international arena. Membership in the SCO opens up new prospects for the country and provides an opportunity to expand cooperation with other countries of the Asian region. Once Belarus becomes a full-fledged member of the association, the country will have new ways to develop its potential in various areas, including the economy, logistics, transport, security, culture, education, healthcare, tourism, industrial and agricultural sector, science, as well as experience in international multilateral cooperation. The article is devoted to the topic of assessing the potential of joining the Shanghai Cooperation Organization integration association of the Republic of Belarus. In order to assess the prospects of economic cooperation more accurately, the authors conducted an econometric analysis using a modified version of the traditional gravity model of Belarus’ foreign trade with the member countries. As a result, the authors have identified the most significant factors influencing the volume of trade with the member countries. By analyzing the ratio of calculated indicators to the actual level of exports and imports, the authors made a conclusion about the level of realization of trade potential with the SCO countries. As a consequence, the authors proposed possible ways to implement trade by analyzing the commodity structure of foreign trade flows of the Republic of Belarus with the members of the integration association.В эпоху глобализации интеграционные группировки стали важным инструментом для развития множества стран в мировом хозяйстве. Они способствуют формированию тесных экономических связей и координации внешней торговли между участниками, что, в свою очередь, благоприятно сказывается на развитии национальной экономики страны. Участие в интеграционных объединениях имеет большое значение для развития экономики Беларуси и увеличения ее роли на международной арене. Вступление в ШОС открывает новые перспективы для страны и дает возможность расширять кооперацию с другими странами Азиатского региона. После становления Беларуси полноправным участником объединения перед страной откроются новые пути развития потенциала в различных сферах, включая экономику, логистику, транспорт, безопасность, культуру, образование, здравоохранение, туризм, промышленный и сельскохозяйственный сектор, науку, а также опыт международного многостороннего сотрудничества. Исследование посвящено оценке потенциала вступления Республики Беларусь в интеграционное объединение Шанхайской организации сотрудничества. Для более точной оценки перспектив экономического сотрудничества, авторами был проведен эконометрический анализ с использованием модифицированной версии традиционной гравитационной модели внешней торговли Беларуси со странами-участницами. В результате авторами были выявлены самые значимые факторы влияния на объем торговли со странами-участницами. В результате анализа отношения расчетных показателей к фактическому уровню экспорта и импорта авторы сделали вывод об уровне реализации торгового потенциала со странами ШОС, вследствие чего предложены возможные пути реализации торговли с помощью анализа товарной структуры потоков внешней торговли Республики Беларусь с участницами интеграционного объединения

Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State

Dendritic cells (DCs) are pivotal for the induction and maintenance of antigen-specific tolerance and immunity. miRNAs mediate post-transcriptional gene regulation and control in part the differentiation and stimulation-induced immunogenic function of DCs. However, the relevance of miRNAs for the induction and maintenance of a tolerogenic state of DCs has scarcely been highlighted yet. We differentiated mouse bone marrow cells to conventional/myeloid DCs or to tolerogenic antigen presenting cells (APCs) by using a glucocorticoid (dexamethasone) or interleukin-10, and assessed the miRNA expression patterns of unstimulated and LPS-stimulated cell populations by array analysis and QPCR. Differentially tolerized mouse APCs convergingly down-regulated a set of miRNA species at either state of activation as compared with the corresponding control DC population (mmu-miR-9-5p, mmu-miR-9-3p, mmu-miR-155-5p). These miRNAs were also upregulated in control DCs in response to stimulation. In contrast, miRNAs that were convergingly upregulated in both tolerized APC groups at stimulated state (mmu-miR-223-3p, mmu-miR-1224-5p) were downregulated in control DCs in response to stimulation. Overexpression of mmu-miR-223-3p in DCs was sufficient to prevent stimulation-associated acquisition of potent T cell stimulatory capacity. Overexpression of mmu-miR-223-3p in a DC line resulted in attenuated expression of known (Cflar, Rasa1, Ras) mRNA targets of this miRNA species shown to affect pathways that control DC activation. Taken together, we identified sets of miRNAs convergingly regulated in differentially tolerized APCs, which may contribute to imprint stimulation-resistant tolerogenic function as demonstrated for mmu-miR-223-3p. Knowledge of miRNAs with protolerogenic function enables immunotherapeutic approaches aimed to modulate immune responses by regulating miRNA expression

Untersuchungen zur Chemosensitivität von testikulären Tumorzellen gegenüber Cisplatin

Metastasierender Krebs ist bei Erwachsenen in der Regel nicht heilbar. Eine Ausnahme stellen testikuläre Keimzelltumoren (TKZT) dar, da über 75 % der Patienten mit fortgeschrittenen metastasierenden TKZT mit einer auf Cisplatin basierenden Kombinations-Chemotherapie geheilt werden können. Zelllinien, die aus TKZT isoliert wurden, behalten diese Cisplatin- Sensitivität in vitro bei. Somit spiegeln Testistumorzelllinien die klinische Situation wider und sind deswegen ein gutes Modellsystem um zu untersuchen, welche Faktoren der Cisplatin-Sensitivität zugrunde liegen. Die Ursachen der Cisplatin-Sensitivität in Testistumoren sind nicht bekannt. Es wurde bereits gezeigt, dass Testistumorzellen eine geringe Kapazität für die Entfernung von Cisplatin-induzierten DNA-Platinierungen aufweisen. Dieser Defekt in der DNA-Reparatur könnte ein Faktor für die beobachtete Cisplatin-Sensitivität sein. Cisplatin induziert sowohl Intrastrang-Vernetzungen als auch Interstrang-Vernetzungen (ICLs). Die Bildung und Reparatur der Cisplatin-induzierten Intrastrang-Vernetzungen wurde mittels DNA-Slot-Blot, die Bildung und Entfernung von Interstrang-Vernetzungen wurde mithilfe des Comet-Assays untersucht. In der vorliegenden Arbeit wurde gezeigt, dass die Reparatur von Intrastrang-Vernetzungen in Testis- und Blasentumorzelllinien vergleichbar ist. Somit sind Testistumorzellen in diesem Reparaturweg nicht beeinträchtigt. Im Unterschied dazu zeigte sich, dass Testistumorzellen die ICLs nicht oder nur mit einer reduzierten Kapazität entfernen können.Da die ICL-Reparatur über die Bildung von DNA-Doppelstrangbrüchen (DSB) mit anschließender DSB-Reparatur verläuft, wurde die Kinetik der DSB-Reparatur anhand der Immundetektion der Histon-Variante γH2AX, die zur Visualisierung von DSB verwendet wird, verfolgt. γH2AX Foci wurden nach Behandlung mit Cisplatin in Testistumorzellen und Blasentumorzellen gebildet. Anders als in Blasentumorzellen blieb der Prozentsatz an γH2AX-positiven Zellen in Testistumorzellen bestehen. Offensichtlich konnten die Testistumorzellen die Cisplatin-induzierten ICLs nicht korrekt prozessieren, was dazu führte, dass γH2AX Foci persistierten. Da unreparierte DNA-Läsionen eine DNA-schadensabhängige Antwort einleiten können, wurde die Aktivierung der Hauptfaktoren dieser Signalwege untersucht. In den Testistumorzellen zeigte sich eine Erhöhung der p53 Proteinmenge nach Cisplatin-Behandlung. Des Weiteren wurde die durch Cisplatin induzierte Aktivierung von ATM/ATR, Chk1/Chk2, Bax und Noxa in Testis- und Blasentumorzellen vergleichend untersucht. Es wurde bereits gezeigt, dass der Reparaturfaktor ERCC1-XPF in Testistumorzelllinien reduziert vorliegt. Um eine mögliche Rolle von ERCC1-XPF für die Reparatur-Defizienz der ICLs und Cisplatin-Sensitivität in Testistumorzellen zu analysieren, wurde ERCC1-XPF in der Testistumorenzelllinie 833K mithilfe eines Expressionsvektors überexprimiert, und der Einfluss von ERCC1-XPF auf ICL-Reparatur sowie Cisplatin-Sensitivität wurde ermittelt. Überexpression von ERCC1-XPF führte zur Reparatur der ICLs in 833K-Zellen und verminderte die Cisplatinsensitivität. Somit scheint die Cisplatinsensitivität der Testistumorzellen, zumindest zum Teil, auf einer verminderten ICL-Reparatur zu beruhen. Des Weiteren wurde in „proof of principle“ Experimenten ERCC1-XPF in der Cisplatin-resistenten Blasentumorzelllinie MGH-U1 mittels siRNA herunterreguliert, und die Auswirkung der Herunterregulation auf die ICL-Reparatur und die Cisplatinsensitivität wurde geprüft. RNA-Interferenz-vermittelte Herunterregulierung von ERCC1-XPF reduzierte die Prozessierung der Cisplatin-induzierten ICLs und verstärkte die Cisplatinsensitivität in MGH-U1 Zellen. Somit wurde in dieser Arbeit zum ersten Mal gezeigt, dass die Testistumorzellen in Vergleich zu Blasentumorzellen in der Reparatur von ICLs defizient sind, wobei die verminderte ICL-Reparatur auf die geringe Expression von ERCC1-XPF zurückgeführt werden konnte. Diese ICL-Reparatur-Defizienz könnte, zumindest zu einem Teil, für die Sensitivität der Testistumoren gegenüber Cisplatin verantwortlich sein.Metastatic testicular germ cell tumors are cured in over 75 % of patients using cisplatin-based combination therapy. In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from testicular germ cell tumors retain this cisplatin hypersensitivity in vitro, therefore providing a good model system for investigating the factors controlling cisplatin sensitivity. The reasons underlying the cisplatin sensitivity are not yet known. Earlier findings showed that testis tumor cells have a reduced capacity to repair cisplatin induced DNA damage suggesting that repair deficiency might be a factor for the observed cisplatin sensitivity. Cisplatin induces both intrastrand adducts (IAs) and interstrand crosslinks (ICLs). To investigate repair of IAs we used the method of DNA slot blotting, repair of ICLs was investigated using the Comet assay. We found that testis tumor cells have a similar repair rate of IAs compared to cisplatin resistant bladder cancer cells. In contrast, the repair of ICLs was significantly reduced in testis tumor cells compared to bladder cancer cells. It is proposed that ICL repair proceeds via the formation of a double strand break. To visualize DSBs we used immunodetection of histone variant γH2AX. We found that γH2AX foci formed in both bladder and testis tumor cells after cisplatin treatment. However the γH2AX foci persisted in the testis tumor cells indicating a reduction in removal of the DSBs in the testis tumor cells compared to bladder cancer cells. Persisting DNA damage might result in activation of downstream processing pathways of the lesions. We found that treatment of testis tumor cells with cisplatin lead to activation of p53 in a time dependent manner. Phosphorylation of ATM/ATR, Chk1/2 and induction of apoptotic factors controlled by p53 was investigated in testis versus bladder cancer cells. Earlier studies showed that the nucleotide excision repair factor ERCC1-XPF is reduced in testis tumor cell lines indicating a possible role of ERCC1- XPF for repair deficiency and cisplatin sensitivity of testis tumor cells. To investigate the role of ERCC1-XPF, we overexpressed ERCC1-XPF in testis tumor cells using a mammalian expression vector. Overexpression of ERCC1-XPF increased ICL repair and rendered the cells more resistant to cisplatin suggesting that ERCC1-XPF is rate-limiting for repair of ICLs and subsequent cisplatin sensitivity of testis tumor cells. In proof of principle experiments we down regulated ERCC1-XPF in the cisplatin resistant bladder cancer cell line MGH-U1. ERCC1 siRNA reduced the level of ERCC1 and led to a significant increase in cisplatin sensitivity in MGH-U1 cells.Our data indicate for the first time that the exceptional sensitivity of testis tumor cells and, therefore, very likely the curability of testicular germ cell tumors rests at least in part on their limited ICL repair due to low level of expression of ERCC1-XPF

Secondary ossification center induces and protects growth plate structure

Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment