Finance and growth in the EU: new evidence from the liberalisation and harmonisation of the banking industry

JEL Classification: G21, G28, O5Banking Deregulation, Economic Growth, European Union, Financial Development

Characterization of 2S albumin allergenic proteins for anaphylaxis in common buckwheat

2S albumin (2SA) is responsible for anaphylaxis following consumption of buckwheat in allergic individuals. To reduce allergen incidents, characterization of 2SA polypeptides is prerequisite, thus was analyzed in this study. Of the five 2S albumin genes (g03, g11, g13, g14, and g28), g03 was seemingly non-functional. The g14 content was 3- and 40-fold higher than that of g11/g28 and g13, respectively. The g11/g28 were more processed to a ∼8 kDa band from a 16 kDa band than g14 in seeds, agreeing with that g11/g28 have high similarity with Fag e 8kD. Meanwhile, anti-g13 produced only a single ∼10 kDa band. Modification of g13 and domain exchange between g13 and g14 suggested that the hydrophobicity of the first domain and the nature of some amino acids in g13 contributed, at least in part, to the lower apparent molecular weight of g13 than expected. Thus, g13 might be an unexplored and noteworthy allergen

On epsilon_K beyond lowest order in the Operator Product Expansion

We analyse the structure of long distance (LD) contributions to the CP-violating parameter epsilon_K, that generally affect both the absorptive (Gamma_12) and the dispersive (M_12) parts of the K0 -- K0bar mixing amplitude. We point out that, in a consistent framework, in addition to LD contributions to Im(Gamma_12), estimated recently by two of us, also LD contributions to Im(M_12) have to be taken into account. Estimating the latter contributions the impact of LD effects on epsilon_K is significantly reduced (from -6.0 % to -3.6 %). The overall effect of LD corrections and of the superweak phase being different from 45 degrees is summarised by the multiplicative factor kappa_epsilon = 0.94 +/- 0.02.Comment: 10 pages, 2 figures. v3: minor typos fixed. Matches journal versio

(-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.

()-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo

A new non-arithmetic lattice in PU(3,1)

We study the arithmeticity of the Couwenberg-Heckman-Looijenga lattices in PU(n,1), and show that they contain a non-arithmetic lattice in PU(3,1) which is not commensurable to the non-arithmetic Deligne-Mostow lattice in PU(3,1)

Effects of novelly synthesized nucleolipides on different tumor cell lines (HT29, HepG2, Panc-1, RenCa) with special respect to glioma cell lines (BT4Ca, GOS3, G28, G112, U251, U87) of human or other species

Today cancer is the second leading cause of death around the world. The World Health Organization predicts an increase from 9.6 million in 2018 up to 16.4 million cancer deaths in 2040. Although tumors of the brain and the nervous system are rather unusual among adults (2 %), they are the second most common diagnosed types of cancer in childhood. Gliomas and meningiomas are the most frequent types of brain tumors and account for 30 % of all tumors in the brain and central nervous system as well as for 80 % of all malignant intra-cranial tumors. Usually surgical excision is the first step in the treatment of cancer followed by radio- and chemotherapy. Due to the mainly intracranial location of gliomas, surgical interventions are extremely risky. Therefore, the use of radiation and chemotherapeutic agents become more important. 5-Fluorouracil (5-FU) is a well-known drug, usually used as chemotherapeutic agent in the standard treatment of fast proliferating cancer cells. Unfortunately, it carries along a wide range of unpleasant side effects in multiple organ systems. To improve the passage through the blood-brain-barrier and the cell membrane penetration thereby gaining a higher efficiency, our cooperation partners Prof. Dr. Rosemeyer and his colleagues from the Institute of Chemistry and Materials of the University of Osnabrück synthesized more than 120 novel nucleolipids. These molecules have been designed based on the 5-FU derivative 5-Fluorouridine (5-FUrd) or the nucleosides adenosine, cladribin, formycin, guanosine, inosine and others. The derivatives are modified at several positions and have different additional chemical side groups to mainly influence the hydrophilicity and lipophilicity and thus, to consequently improve the permeability across the blood-brain-barrier as well as the uptake into the cells. At first we screened the impact of 5-FUrd and the 120 novelly synthesized derivatives on the viability of rat BT4Ca and human GOS3 glioma cells as well as differentiated human macro-phages (THP1). Five derivatives (S.18, 19, 38, 98 and 101), which show low cytotoxic effects on the macrophages and are effective against both, the rat BT4Ca and the human GOS3 glioma cells, were selected to be further analyzed. Although we screened 120 derivatives consisting of purines and pyrimidines, it is remarkable that all five selected, most effective derivatives (S.18, 19, 38, 98 and 101) belong to the group of pyrimidines. Comparing the chemical structure of the selected derivatives, the position of the attached farnesyl chain seems to be of high importance for the effectiveness of the most efficient derivative (S.98) against rat as well as human glioma cell lines. We were able to show that the selected derivatives, derived out of the nucleosides adenosine (S.38), formycin (S.98) and inosine (S.18, 19 and 101) are able to keep up with or even overcome the cytostatic/cytotoxic effects of the well-known chemotherapeutic agent 5-FU on further human glioma cell lines (G28, G112, U251 and U87) and several other tumor entities (HT29, HepG2, Panc-1 and RenCa). Certainly, these effects depend on the applied derivative as well as its concentration and vary among the specific cell type analyzed. Furthermore, using the rat BT4Ca glioma cells as a model of fast proliferating glioblastomas, we studied several intracellular mechanisms, possibly responsible for the examined cytotoxic effects of the selected derivatives (S.18, 19, 38, 98 and 101). Our results indicate that the treatment of the rat BT4Ca glioma cells with each derivative lead to a concentration-dependent increase of the apoptotic cell rate. At concentrations 25 and 50 µM each of the selected derivatives led to a distinct activation of the caspase 3, confirming the induction of apoptosis. We also observed an increase of the necrotic cell rate with ascending concentration (12.5, 25 and 50 µM) of each derivative presumably due to secondary necrosis. Beside the loss of cell mass due to apoptosis, we detected lower levels of PCNA after the treatment with any selected derivative (12.5 and 25 µM) indicating a reduced cell proliferation of the rat BT4Ca glioma cells. In contrast, the treatment of the rat BT4Ca glioma cells with 5-FUrd did not affect the amount of PCNA. Thus, at our experimental conditions 5-FUrd showed no impact on the proliferation rate consistent with its cytostatic effects. Moreover, we determined a tremendous accumulation of ROS per cell after the treatment with each derivative (50 µM). Especially the treatment with the derivatives S.18, 38 and 98 caused high oxidative stress in the rat BT4Ca glioma cells. But regarding the ratio of rGSH/GSSG only the derivative S.98 showed an explicit effect on the glutathione antioxidant system by lowering the rGSH/GSSG ratio. Nevertheless, the activation of NFκB, through the translocation of the subunit p65 from the cytoplasm to the nucleus, was not triggered by the treatment with any selected derivative or 5-FUrd. For a validation of the effects of the derivatives on the migratory capacity of the rat BT4Ca glioma cells during the treatment, further experiments need to be done with a more accurate method. The results indicate that our five selected derivatives S.18, 19, 38, 98 and 101 bear fundamen-tal attributes, which are beneficial for the treatment of malignant cancer cells. These proper-ties and the broad range of cytotoxicity as well as the inhibition of the cell proliferation make the five derivatives, especially S.19 and S.98, highly interesting as prospects against several tumor entities for the use as possible novel drugs with a high potential as chemotherapeutic agent.Aktuell gehört Krebs zu den häufigsten Todesursachen weltweit. Die Welt-Gesundheits-Organisation prognostiziert einen Anstieg von 9,5 Millionen Krebs assoziierten Todesfällen im Jahre 2018 auf 16,4 Millionen im Jahre 2040. Obwohl Tumore des Gehirns und des zentralen Nervensys-tems bei Erwachsenen eher selten vorkommen (2 %), sind sie bei Kindern die am zweithäufigsten diagnostizierte Krebsart. Gliome und Meningiome stellen 30 % aller Tumore des Gehirns und Zent-ralen Nervensystems sowie 80 % aller bösartigen intrakranialen Tumore. Die Standardtherapie beginnt im Regelfall mit der operativen Entfernung, gefolgt von Radio- und Chemotherapie. Auf Grund der intrakranialen Lokalisation von Gliomen sind chirurgische Maßnahmen jedoch sehr ris-kant, wodurch Bestrahlungen und chemotherapeutische Behandlungen an Bedeutung gewinnen. 5-Fluorouracil (5-FU) ist ein seit vielen Jahren genutzter Wirkstoff, das als Chemotherapeutikum gegen schnell wachsende Krebszellen eingesetzt wird. Bedauerlicherweise bringt er auch ein breites Spektrum an unerwünschten Nebeneffekten für einige Organsysteme mit sich. Um die Passage durch die Blut-Hirn-Schranke und die Aufnahme in die Zelle und damit die Effektivität solcher Sub-stanzen zu verbessern, entwickelten und synthetisierten unsere Kooperationspartner Prof. Dr. Ro-semeyer und seine Kollegen am Institut für Chemie und Materialien der Universität Osnabrück über 120 neue Nukleolipidderivate. Die Struktur dieser Nukleolipide beruht auf dem 5-FU Derivat 5-Fluorouridine (5-FUrd) oder den Nukleosiden Adenosin, Cladribin, Formycin, Guanosin, Inosin und weiteren. Die Derivate dieser Grundsubstanzen sind an mehreren Positionen verändert und tragen zusätzlich verschiedene chemische Seitenketten um ihre Wasser- und Fettlöslichkeit zu beeinflus-sen. Durch diese Modifikationen soll der Übergang durch die Blut-Hirn-Schranke sowie die Aufnahme in die Zelle erleichtert werden. Zu Beginn der Studie untersuchten wir den Einfluss von 5-FUrd und den 120 neu synthetisierten Derivaten auf die Viabilität der aus Ratten stammenden BT4Ca und humanen GOS3 Gliom Zellen sowie differenzierten humanen Makrophagen (THP1). Fünf Derivate (S.18, 19, 38, 98 und 101), die keine oder nur eine geringe schädliche Wirkung für die Makrophagen zeigten, gleichzeitig jedoch effektiv gegen beide Gliom Zelllinien (BT4Ca und GOS3) wirkten, wurden ausgewählt und weiter analysiert. Bemerkenswert ist, dass trotz der Anzahl von 120 getesteten Substanzen, die sowohl Purine als auch Pyrimidine einschlossen, alle fünf ausgewählten Derivate zur Gruppe der Pyrimidine gehören. Vergleicht man die chemische Struktur der ausgewählten Derivate, spielt die Position der angehängten Farnesylkette offenbar eine wichtige Rolle für die Effektivität (S.98 versus S.18, 38 und 101). Wir zeigen, dass die ausgewählten Derivate, deren Grundlage Adenosin (S.38), Formycin (S.98) und Inosin (S.18, 19, 101) bilden, einen vergleichbaren oder sogar stärkeren zytostati-schen/zytotoxischen Effekt wie das bekannte chemotherapeutische Mittel 5-FU haben. Auch bei weiteren untersuchten humanen Gliom Zellen (G28, G112, U251 und U87) und anderen Tumorenti-täten (HT29, HepG2, Panc-1 und RenCa) können wir diese Effekte beobachten. Diese sind abhängig vom eingesetzten Derivat sowie dessen Konzentration und des verwendeten, spezifischen Zelltyps. Für weiterführende Versuche wurden die Ratten BT4Ca Gliom Zellen exemplarisch als Model für schnellwachsende Glioblastomzellen verwendet. Wir analysierten unterschiedliche intrazelluläre Mechanismen, die möglicherweise an den bereits beobachteten zytotoxischen Wirkungen der fünf ausgewählten Derivate (S.18, 19, 38, 98 und 101) beteiligt sind. Unsere Versuchsergebnisse dokumentieren, dass die Behandlung der Ratten BT4Ca Gliom Zellen mit einem dieser fünf Derivate zu einem konzentrationsabhängigen Anstieg der apoptotischen Zellzahl führt. In den Konzentrationen 25 und 50 µM löst jedes der ausgewählten Derivate eine deutliche Steigerung der Capspase 3 Aktivität aus, wodurch die beobachtete Induktion der Apoptose bestätigt wird. Mit steigenden Konzentrationen (12.5, 25 und 50 µM) sehen wir allerdings auch einen erhöhten Anteil an nekrotischen Zellen. Dieser Anstieg ist vermutlich auf den Prozess der sekundär-Nekrose zurückzuführen. Neben dem Zelltod durch Apoptose, detektieren wir nach der Behandlung mit den jeweiligen Derivaten auch ein verringertes Level des Proteins PCNA, wodurch die Zellteilung der Ratten BT4Ca Zellen zusätzlich vermindert wird. Im Gegensatz zu den Derivaten hat die Behandlung mit 5-FUrd keinen Einfluss auf die gemessene Menge von PCNA. Demnach hat 5-FUrd unter unseren experimentellen Bedingungen keinen Einfluss auf die Zellteilungsrate der Ratten BT4Ca Zellen, was den beobachteten zytostatischen Effekt von 5-FUrd erklärt. Darüber hinaus beobachten wir nach der Behandlung der Ratten BT4Ca Zellen mit den Derivaten (50 µM) eine enorme Anhäufung von Sauerstoff Radikalen (ROS) pro Zelle. Besonders der Einsatz der Derivate S.18, 38 und 98 verursacht hohen oxidativen Stress für die Ratten BT4Ca Zellen. Allerdings führt nur die Behandlung mit Derivat S.98 zu einer eindeutigen Verringerung des rGSH/GSSG Verhältnisses und beeinflusst damit die physiologisch zur Verfügung stehende Menge des Antioxidans Glutathion. Keines der fünf ausgewählten Derivate führt zur Translokation der NFκB-Untereinheit p65 vom Zytoplasma in den Zellkern und damit zur Aktivierung von NFκB in den Ratten BT4Ca Zellen. Der Einfluss der Derivate auf die Migration der Ratten BT4Ca Zellen muss durch weitere Untersu-chungen validiert werden. Die bisherigen Analysen zeigen, dass die Derivate S.18, 19, 38, 98 und 101 grundlegende Eigenschaften aufweisen, wodurch sie für die Behandlung von diversen bösarti-gen Krebszellen geeignet sind. Die fünf ausgewählten Derivate, besonders, S.19 und S.98, tragen durch ihr breites zytotoxisches Wirkungsspektrum und die Hemmung der Zellteilungsrate ein hohes Potential gegen mehrere, unterschiedliche Tumorentitäten als neue Wirkstoffe im Bereich der Chemotherapie Verwendung zu finden

EEG–fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG

We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG–fMRI. We therefore modeled asymmetrical EEG delta activity at 1–3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1–3 Hz but not at 4–7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG–fMRI even in the absence of clear interictal discharges