Transatlantic intelligence and security cooperation

Despite recent advances in transatlantic intelligence and security cooperation, significant problems remain. The bombings in Madrid in March 2004 have demonstrated how terrorists and criminals can continue to exploit the limits of hesitant or partial exchange to dangerous effect. Intelligence and security cooperation remain problematic because of the fundamental tension between an increasingly networked world, which is ideal terrain for the new religious terrorism, and highly compartmentalized national intelligence gathering. If cooperation is to improve, we require a better mutual understanding about the relationship between privacy and security to help us decide what sort of intelligence should be shared. This is a higher priority than building elaborate new structures. While most practical problems of intelligence exchange are ultimately resolvable, the challenge of agreeing what the intelligence means in broad terms is even more problematic. The last section of this article argues that shared NATO intelligence estimates would be difficult to achieve and of doubtful value

Modelling of Fed-batch Fermentation Process with Droppings for L-lysine Production

The aim of the article is the development of dynamic unstructured model of L-lysine fed-batch fermentation process with droppings. This approach includes the following procedures: description of the process by generalized stoichiometric equations; preliminary data processing; identification of the specific rates (growth rate (mu) , substrate utilization rate (nu), production rate (rho); establishment and optimization of the dynamic model of the process; simulation researches

Regulation of cell death in cancer diseases - importance and therapeutic effect

Комплексната роля на различните видове кле- тъчна смърт при раковите заболявания е сложна и продължава да се разкрива. Наблюденията показват, че и трите процеса: апоптоза, автофа- гия и некроза, могат да съществуват в един ту- мор и тяхното относително участие диктува траекторията на туморния растеж, регресия и отговор към антитуморна терапия. Анализът на клетъчната сигнализация може да разкрие и да осигури нови биомаркери, отразяващи функ- ционалната активност на тези процеси, кои- то ще подпомогнат индивидуализираната терапия при карциномно болните. В този преглед сме се спрели на някои основни пътища и регула- тори, свързани с клетъчната смърт и оцеляване, които осигуряват метаболитна устойчивост в туморите, водещи до резистентност към хими- отерапия и неуспешно лечение на рака.The complex role of different types of cell death in cancer is very complicated and continues to be re- vealed. Тhe observations show that all three processes- apoptosis, autophagy and necrosis may exist in a tu- mor, and their relative involvement dictates the trajec- tory of tumor growth, regression and response to an- ti-tumor therapy. Cellular signaling analysis may re- veal and provide new biomarkers reflecting the func- tional activity of these processes that will support in- dividualized therapy in cancer patients. In this review we have accentuated of some major roads and regu- lators associated with cell death and survival, which provide the metabolic stability in tumors, leading to resistance to chemotherapy and unsuccessful cancer treatment

BECLIN 1 - Регулаторен протеин на автофагията

Изучаването на пропатогенните ефекти на автофагията е сравнително нова област на из- следване, показваща, че тя може да упражни многофункционални патогенетични роли, свър- зани с клетъчното оцеляване или смърт. Нару- шенията в процесите на автофагия предизвик- ват чувствителност към метаболитен стрес, геномно увреждане, неконтролирана клетъчна пролиферация, резистентност към химиоте- рапия и оцеляване на ракови клетки. Beclin 1 бе първият открит иницииращ протеин с доказа- на роля в регулиране на процесите на автофа- гия, която обаче проявява функционална двой- ственост при селективното взаимодействие на Beclin 1 с регулатори на клетъчната хомеостаза, смърт, растеж, имунен отговор, вкл. вируси и др. Това прави проучванията на Beclin 1 значими не само като специфичен маркер в идентифицира- нето на регулаторните механизми, участващи в тези процеси, но и като прицелна молекула за фармакологично модулиране на клиничното про- тичане при различни заболявани

RIPK3 expression as a potential predictive and prognostic marker in metastatic colon cancer

Background: Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of patient outcomes. Recently a new type of programmed cell death was discovered—necroptosis, which depends on receptor interacting protein 3 (RIPK3). Preclinical data showed that necroptotic cell death is an important effector mechanism of 5-FU-mediated anticancer activity. Purpose: To investigate the predictive and prognostic performance of RIPK3 expression in primary tumors. Methods: Colon cancer patients (n=74) with metastatic stage were included in this retrospective study and all were treated with first-line 5-FU based chemotherapy. Immunohistochemical staining was performed. Results: The progression free survival for the low expression group of RIPK3 was 5.6 months (95% CI, 4.4-6.8) vs 8.4 months (95% CI, 6.4-10.3) of the group with high expression (p=0.02). Moreover, patients with high expression of RIPK3 were associated with lower risk of disease progression HR 0.61 (95% CI, 0.38-0.97; p=0.044). Patients with high expression levels of RIPK3 also had significantly longer mean overall survival (OS) of 29.3 months (95% CI, 20.8-37.8) as compared with those with low expression: 18.5 months (95% CI, 15.06-21.9) (p= 0.036). In addition, univariate analysis showed that high level of RIPK3 expression was associated with a longer OS HR 0.59 (95% CI, 0.35-0.98; p=0.044). Conclusions: This study suggests that expression of RIPK3 in primary tumors of metastatic colon cancer patients should be further investigated for its potential as a promising predictive and prognostic marker