Comparing charge transfer tuning effects by chemical substitution and uniaxial pressure in the organic charge transfer complex tetramethoxypyrene-tetracyanoquinodimethane

In the search for novel organic charge transfer salts with variable charge transfer degree we study the effects of two modifications to the recently synthesized donor-acceptor Tetramethoxypyrene (TMP)-Tetracyanoquinodimethane (TCNQ). One is of chemical nature by substituting the acceptor TCNQ molecules by F4TCNQ molecules. The second consists in simulating the application of uniaxial pressure along the stacking axis of the system. In order to test the chemical substitution, we have grown single crystals of TMP-F4TCNQ and analyzed its electronic structure via electronic transport measurements, ab initio density functional theory (DFT) calculations and UV/VIS/IR absorption spectroscopy. This system shows an almost ideal geometrical overlap of nearly planar molecules alternately stacked (mixed stack) and this arrangement is echoed by a semiconductor-like transport behavior with an increased conductivity along the stacking direction. This is in contrast to TMP-TCNQ which shows a less pronounced anisotropy and a smaller conductivity response. Our bandstructure calculations confirm the one-dimensional behavior of TMP-F4TCNQ with pro- nounced dispersion only along the stacking axis. Infrared measurements illustrating the CN vibration frequency shift in F4TCNQ suggest however no improvement on the degree of charge transfer in TMP-F4TCNQ with respect to TMP-TCNQ. In both complexes about 0.1 is transferred from TMP to the acceptor. Concerning the pressure effect, our DFT calculations on designed TMP-TCNQ and TMP-F4TCNQ structures under different pressure conditions show that application of uniaxial pressure along the stacking axis of TMP-TCNQ may be the route to follow in order to obtain a much more pronounced charge transfer

Inzidenz und Differentialdiagnose unterschiedlicher synchroner Leberraumforderungen bei Erstdiagnose einer malignen Grunderkrankung : Stellenwert von Klinik, Ultraschall, CT, MRT, PET-CT und Histologie

Hintergrund: Ziel der Studie ist es, die Inzidenz synchroner fokaler Leberläsionen bei Erstdiagnose einer malignen Grunderkrankung zu bestimmen. Außerdem soll der Stellenwert der Bildgebungen CEUS, CT, MRT und PET-CT in der Abklärung der Leberraumforderungen untersucht werden. Patienten und Methoden: N = 446 Patienten mit synchroner Leberraumforderung bei Erstdiagnose einer malignen Grunderkrankung, welche am Universitätsklinikum Marburg sonographisch abgeklärt wurden, wurden in die Studie aufgenommen. Es wurde die endgültige Diagnose der Leberraumforderung verwendet. Der Einsatz und die Ergebnisse von CEUS, CT, MRT und PET-CT wurden miteinander verglichen. Ergebnisse: Von den n = 446 Leberläsionen waren n = 182 (40,8%) benigne und n = 264 (59,2%) maligne. Bei den benignen Leberraumforderungen handelte es sich um n = 94 Zysten (21,1%), n = 55 Hämangiome (12,3%), n = 21 fokale Fettverteilungsstörungen (4,7%), n = 4 fokal noduläre Hyperplasien (0,9%), n = 3 nicht weiter spezifizierte gutartige Läsionen (0,7%), n = 2 Regeneratknoten (0,4%) und n = 1 Adenom (0,2%). Bei den malignen Läsionen handelte es sich um n = 250 Metastasen (56,1%) und n = 14 Primärtumoren der Leber (3,1%). Es zeigte sich kein signifikanter Unterschied in der Sensitivität auf Malignität einer Leberraumforderung zwischen den unterschiedlichen Bildgebenden Verfahren Sonographie mit CEUS, CT, MRT und PET-CT. In der Spezifität für Malignität liegt die CT signifikant niedriger als die CEUS, alle anderen Verfahren unterscheiden sich nicht signifikant in der Spezifität. Fazit: Synchrone Leberraumforderungen bei Erstdiagnose einer malignen Grunderkrankung sind in 59,2% der Fälle maligne und sollten aufgrund der hohen therapeutischen Relevanz bei Lebermetastasen immer abschließend geklärt werden. Sonographie mit CEUS, CT, MRT und PET-CT sind für die Differenzierung und Spezifizierung synchroner Leberraumforderungen bei Erstdiagnose eine malignen Grunderkrankung in der klinischen Praxis von annähernd gleichem Stellenwert. Da bei Erstdiagnose einer malignen Grunderkrankung die Feststellung von Lebermetastasen oft schon für ein palliatives Behandlungssetting ausreicht, wären in diesem Fall weitere Erkenntnisse aus CT, MRT und PET-CT für die Therapieentscheidung nicht mehr relevan

Real-Time MEG Source Localization Using Regional Clustering

With its millisecond temporal resolution, Magnetoencephalography (MEG) is well suited for real-time monitoring of brain activity. Real-time feedback allows the adaption of the experiment to the subject’s reaction and increases time efficiency by shortening acquisition and off-line analysis. Two formidable challenges exist in real-time analysis: the low signal-to-noise ratio (SNR) and the limited time available for computations. Since the low SNR reduces the number of distinguishable sources, we propose an approach which downsizes the source space based on a cortical atlas and allows to discern the sources in the presence of noise. Each cortical region is represented by a small set of dipoles, which is obtained by a clustering algorithm. Using this approach, we adapted dynamic statistical parametric mapping for real-time source localization. In terms of point spread and crosstalk between regions the proposed clustering technique performs better than selecting spatially evenly distributed dipoles. We conducted real-time source localization on MEG data from an auditory experiment. The results demonstrate that the proposed real-time method localizes sources reliably in the superior temporal gyrus. We conclude that real-time source estimation based on MEG is a feasible, useful addition to the standard on-line processing methods, and enables feedback based on neural activity during the measurements.Deutsche Forschungsgemeinschaft (grant Ba 4858/1-1)National Institutes of Health (U.S.) (grants 5R01EB009048 and 2P41EB015896)Universitätsschule Jena (J21)German Academic Exchange Servic

Cerebral haemodynamics and carbon dioxide reactivity during sepsis syndrome

peer reviewed[en] BACKGROUND: Most patients with sepsis develop potentially irreversible cerebral dysfunctions. It is yet not clear whether cerebral haemodynamics are altered in these sepsis patients at all, and to what extent. We hypothesized that cerebral haemodynamics and carbon dioxide reactivity would be impaired in patients with sepsis syndrome and pathological electroencephalogram patterns. METHODS: After approval of the institutional ethics committee, 10 mechanically ventilated patients with sepsis syndrome and pathological electroencephalogram patterns underwent measurements of cerebral blood flow and jugular venous oxygen saturation before and after reduction of the arterial carbon dioxide partial pressure by 0.93 +/- 0.7 kPa iu by hyperventilation. The cerebral capillary closing pressure was determined from transcranial Doppler measurements of the arterial blood flow of the middle cerebral artery and the arterial pressure curve. A t test for matched pairs was used for statistical analysis (P < 0.05). RESULTS: During stable mean arterial pressure and cardiac index, reduction of the arterial carbon dioxide partial pressure led to a significant increase of the capillary closing pressure from 25 +/- 11 mmHg to 39 +/- 15 mmHg (P < 0.001), with a consecutive decrease of blood flow velocity in the middle cerebral artery of 21.8 +/- 4.8%/kPa (P < 0.001), of cerebral blood flow from 64 +/- 29 ml/100 g/min to 39 +/- 15 ml/100 g/min (P < 0.001) and of jugular venous oxygen saturation from 75 +/- 8% to 67 +/- 14% (P < 0.01). CONCLUSION: In contrast to other experimental and clinical data, we observed no pathological findings in the investigated parameters of cerebral perfusion and oxygenation

A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes

Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems

CXCL13 and CXCL9 CSF Levels in Central Nervous System Lymphoma-Diagnostic, Therapeutic, and Prognostic Relevance

Background: Diagnostic delay and neurologic deterioration are still a problem for the treatment of rapidly progressing CNS lymphoma (CNSL); there is an unmet need for a diagnostic test with a high diagnostic yield and limited risk, minimizing the time to the initiation of effective treatment. Methods: In this prospective monocentric study, we analyzed the utility of CXCL13 and CXCL9 as diagnostic, therapeutic and prognostic biomarkers for CNSL. Cerebrospinal fluid (CSF) from 155 consecutive patients admitted with brain lesions of various origins was collected. Levels of CXCL13 and CXCL9 were analyzed by ELISA. Additionally, CSF was analyzed during CNSL disease course (relapse, remission, progress) in 17 patients. Results: CXCL13 and CXCL9 CSF levels were significantly increased in patients with CNSL compared to control patients with lesions of other origin. Using logistic regression and a minimal-p-value approach, a cut-off value of 80 pg/ml for CXCL13 shows high sensitivity (90.7%) and specificity (90.1%) for the diagnosis of active CNSL. CXCL9 at a cut-off value of 84 pg/ml is less sensitive (61.5%) and specific (87.1%). Both cytokines correlate with the clinical course and response to therapy. Conclusions: Our results confirm the excellent diagnostic potential of CXCL13 and introduce CXCL9 as a novel albeit less powerful marker for PCNSL