Probing Charge Transfer in Benzodifuran-C-60 Dumbbell-Type Electron Donor-Acceptor Conjugates: Ground- and Excited-State Assays

Rigid electron donor-acceptor conjugates (1-3) that combine -extended benzodifurans as electron donors and C-60 molecules as electron acceptors with different linkers have been synthesized and investigated with respect to intramolecular charge-transfer events. Electrochemistry, fluorescence, and transient absorption measurements revealed tunable and structure-dependent charge-transfer processes in the ground and excited states. Our experimental findings are underpinned by density-functional theory calculations.

Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-gamma enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity.

A study of reduced penetrance retinoblastoma

Retinoblastoma is a pediatric tumor which is associated with somatic and inherited mutations at the retinoblastoma susceptibility locus, RB1. Although most cases of retinoblastoma fit the previously described 'two hit' model of oncogenesis, the molecular mechanisms underlying rare instances of familial retinoblastoma with reduced penetrance are not well understood. To better understand this phenomenon, a study was undertaken to uncover the molecular cause of low penetrance retinoblastoma in a limited number of families. In one case, a unique cryptic splicing alteration was discovered in the RB1 gene and demonstrated to reduce the level of normal RB1 mRNA produced. Penetrance in the large family known to carry this mutation is less than 50%. Data about the mutation supports a theory that reduced penetrance retinoblastoma is caused by partially functional mutations in RB1. In another family, three independent causes of retinoblastoma or the related phenotype of retinoma were indicated by linkage analysis, a finding unique in retinoblastoma research. A novel polymorphism restricted to Asian populations was also described during the course of this study. ^

Geschichte, Religionsgrundsätze und staatsbürgerliche Verhältnisse der Juden : ein Noth- u. Hülfsbüchlein f. d. gegenwärtige Zeit

von Ferdinand Schubert

Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3

A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high-risk prostate cancer, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway. miR-221 expression sensitized prostate cancer cells for IFN-γ-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer.

Grand duo pour piano e viola

arr. par F. Hermann d'après Le Grand Septuor Oeuvre 20 composé par L. van Beethoven