Luye Pharma (Germany)

Bu çalışma, Cengiz Aytmatov’un Gün Olur Asra Bedel adlı romanını coğrafya-edebiyat ilişkisi ve edebî ekoloji yaklaşımı çerçevesinde incelemeyi amaçlamaktadır. Araştırma, edebî metinlerde coğrafi mekânın yalnızca olayların geçtiği edilgen bir zemin değil, kültürel bellek, ideolojik çatışma ve çevresel dönüşüm süreçlerini taşıyan kurucu bir unsur olduğu varsayımından hareket etmektedir. Bu doğrultuda roman, Sarı Özek bozkırı merkezinde karasal iklim koşulları, sınırlı biyoçeşitlilik, insan-doğa ilişkileri ve antropojenik müdahaleler bağlamında nitel ve yorumlayıcı bir yöntemle analiz edilmiştir. Çalışmada, öncelikle Sarı Özek coğrafyasının sert karasal iklim özelliklerinin, roman kişilerinin yaşam pratiklerini ve anlatının ritmini belirlediği ortaya konulmuştur. İklimsel koşullar, insanın doğayla uyum içinde var olma zorunluluğunu vurgulayan ekolojik bir çerçeve sunmaktadır. Ardından, romanda sınırlı sayıda yer alan hayvan figürlerinin (tilki ve deve) bozkır ekosisteminin kırılgan yapısını ve geleneksel yaşam biçimlerinin çevreyle kurduğu dengeli ilişkiyi simgesel düzeyde temsil ettiği gösterilmiştir. Bu figürler aracılığıyla doğa, etik ve kültürel anlamlar üreten canlı bir sistem olarak kurgulanmaktadır. Araştırmanın bulguları, demir yolu hattının Sarı Özek coğrafyasında yarattığı mekânsal ve ekolojik parçalanmanın, Sovyet modernleşme ve sanayileşme ideolojisinin doğaya müdahalesini simgelediğini ortaya koymaktadır. Tren yolu, bozkırın doğal ritmiyle uyumsuz, mekanik ve hız odaklı bir yaşam anlayışını temsil ederken, geleneksel mekânsal sürekliliği kesintiye uğratmaktadır. Bu antropojenik müdahalenin en çarpıcı sonucu ise Ana-Beyit Mezarlığı’nın uzay üssüne dönüştürülmesiyle görünür hâle gelmektedir. Kutsal ve kültürel bir hafıza mekânının askerî ve teknolojik bir alana dönüştürülmesi, ekolojik belleğin ve kültürel sürekliliğin sistematik biçimde silinmesini temsil etmektedir.

Otitis externa (OE) is a frequently reported disorder in dogs associated with secondary infections by Staphylococcus, Pseudomonas and yeast pathogens. The presence of biofilms may play an important role in the resistance of otic pathogens to antimicrobial agents. Biofilm production of twenty Staphylococcus pseudintermedius and twenty Pseudomonas aeruginosa canine otic isolates was determined quantitatively using a microtiter plate assay, and each isolate was classified as a strong, moderate, weak or nonbiofilm producer. Minimum biofilm eradication concentration (MBEC) of two ionophores (narasin and monensin) and three adjuvants (N-acetylcysteine (NAC), Tris-EDTA and disodium EDTA) were investigated spectrophotometrically (OD570nm ) and quantitatively (CFU/ml) against selected Staphylococcus and Pseudomonas biofilm cultures. Concurrently, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of planktonic cultures were assessed. 16/20 of the S.pseudintermedius clinical isolates were weak biofilm producers. 19/20 P.aeruginosa clinical isolates produced biofilms and were distributed almost equally as weak, moderate and strong biofilm producers. While significant antibiofilm activity was observed, no MBEC was achieved with narasin or monensin. The MBEC for NAC ranged from 5,000-10,000µg/ml and from 20,000-80,000µg/ml against S.pseudintermedius and P.aeruginosa, respectively. Tris-EDTA eradicated P.aeruginosa biofilms at concentrations ranging from 6,000/1,900 to 12,000/3,800µg/ml. The MBEC was up to 16-fold and eightfold higher than the MIC/MBC of NAC and Tris-EDTA, respectively. Disodium EDTA reduced biofilm growth of both strains at concentrations of 470µg/ml and higher. It can be concluded that biofilm production is common in pathogens associated with canine OE. NAC and Tris-EDTA are effective antibiofilm agents in vitro that could be considered for the treatment of biofilm-associated OE in dogs.

Abstract We report on the pharmacological profile of the novel pan-CDK inhibitor BAY 1000394. Loss of cell cycle control and increased resistance to apoptosis represent major hallmarks of cancer. Cyclin-dependent kinases (CDKs) belong to a family of serine/threonine kinases which associate with an activating cyclin regulatory subunit. Cell cycle CDKs 1, 2, 4 & 6 are required for the correct timing and order of the events of the cell division cycle, whereas non-cell cycle CDKs 7 and 9 have been shown to be involved in gene transcription via regulation of RNA polymerase II activity. Deregulated CDK activity results in loss of cell cycle checkpoint function and increased expression of anti-apoptotic proteins, which has been directly linked to the molecular pathology of cancer. BAY 1000394 is a nanomolar pan CDK inhibitor (IC50s: CDK1/CycB, 7 nM; CDK2/CycE, 9 nM; CDK4/CycD1, 11 nM; CDK9/CycT1, <10 nM). This inhibitor shows a broad spectrum profile of cell proliferation inhibition carried out in a panel of 26 human tumor cell lines with a mean IC50 of 16 nM (8-37 nM). The cellular activity of BAY 1000394 was independent of the presence of functional p53 or retinoblastoma (Rb) tumor suppressor proteins. BAY 1000394 induced disappearance of the hyperphosphorylated form of Rb protein in MCF7 and HCT116 tumor cells indicating intracellular inhibition of CDK2 and CDK4. Furthermore, the compound inhibited the phosphorylation of the mitotic CDK1 substrate protein nucleophosmin in HeLa cells. Cell cycle profiles of BAY 1000394 treated HeLa cells were consistent with inhibition of CDK 1, 2 and 4 as demonstrated in cell cycle block and release experiments. A robust decrease of viability of non-proliferating peripheral blood mononuclear cells isolated from a B-CLL patient (EC50: 15 nM) was observed and indicated inhibition of intracellular CDK9. Oral dosing of BAY 1000394 at various schedules (QD or BID x 2 and 5 days off) potently inhibited growth of human cervical HeLa-MaTu xenograft tumors in a dose-dependent manner. The MTD for BAY 1000394 was found to be 2.0 mg/kg on QD schedule and 2.5 mg/kg on a BID intermittent schedule. At these two doses and schedules tumor growth inhibition (TGI) of 104% and 106% was achieved in this model. A single oral dose of 2.0 mg/kg of BAY 1000394 resulted in complete suppression of the hyperphosphorylated form of Rb protein in HeLa-MaTu tumor tissue for at least 7 hrs. BAY 1000394 was also highly efficacious in a paclitaxel-refractory HeLa-MaTu-ADR Res xenograft model, and in a cisplatin-refractory A2780-Cis human ovarian xenograft model. Furthermore, the growth of human colorectal HCT116 tumors in nude rats treated on once daily (QD) or on intermittent (BID x 2 and 5 days off) schedules was strongly inhibited (TGI of 85 - 88%). In conclusion, BAY 1000394 is a highly potent oral pan-CDK inhibitor with a pharmacological profile suggesting activity in a broad range of histological tumor subtypes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3883.

Eine Zusammenfassung vorliegender Labor‐ und Freilandprüfungsergebnisse sowie des Verhaltens zugelassener Kartoffelsorten in der Pflanzgutkontrolle unterstrich die Notwendigkeit der Ergänzung der in den Sortenkatalogen der ehemaligen DDR veröffentlichten zusammengefaßten Resistenzgruppe durch spezifische Resistenzangaben hinsichtlich der einzelnen Viren. Aus der Analyse der Virusresistenzprüfungen von Kartoffeln in der ehemaligen DDR werden Schlußfolgerungen für ihre zukünftige Gestaltung gezogen und die dazu notwendigen wissenschaftlichen Vorleistungen abgeleitet.