The crystal structure of the transcription factor IIB (TFIIB)/TATA box-binding protein (TBP)/TATA-element ternary complex is described at 2.7 A resolution. Core TFIIB resembles cyclin A, and recognizes the preformed TBP-DNA complex through protein-protein and protein-DNA interactions. The amino-terminal domain of core TFIIB forms the downstream surface of the ternary complex, where it could fix the transcription start site. The remaining surfaces of TBP and the TFIIB can interact with TBP-associated factors, other class II initiation factors, and transcriptional activators and coactivators.

We investigated the charge dynamics of the conductivity enhancement from 2 to 1000 S/cm in poly(3, 4-ethylenedioxythiophene):poly(styrenesulfonate) as induced by structural changes through the addition of a polar solvent and the following solvent bath treatment. Our results indicate that the addition of a polar solvent selectively enhanced the π-π coupling of the polymer chains, resulting in the reduction of disorder and tremendously increasing the charge carrier mobility, which yielded an insulator-to-metal transition. In contrast, the following solvent bath treatment selectively enhanced the intergrain coupling, which did not affect the disorder or the mobility but increased the charge carrier density. Therefore, we demonstrate that the conduction-character defining disorder in this conducting polymer system is determined by the extent of interchain coupling.

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is being used more and more to differentiate benign from malignant focal lesions and it has been shown to be more efficacious than conventional chest computed tomography (CT). However, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. Infectious diseases (mycobacterial, fungal, bacterial infection), sarcoidosis, radiation pneumonitis and post-operative surgical conditions have shown intense uptake on PET scan. On the other hand, tumors with low glycolytic activity such as adenomas, bronchioloalveolar carcinomas, carcinoid tumors, low grade lymphomas and small sized tumors have revealed false negative findings on PET scan. Furthermore, in diseases located near the physiologic uptake sites (heart, bladder, kidney, and liver), FDG-PET should be complemented with other imaging modalities to confirm results and to minimize false negative findings. Familiarity with these false positive and negative findings will help radiologists interpret PET scans more accurately and also will help to determine the significance of the findings. In this review, we illustrate false positive and negative findings of PET scan in a variety of diseases.

SUMMARY Background We conducted a prospective, randomised, double-blind trial to evaluate the efficacy of imatinib rechallenge in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) following objective progression of prior approved tyrosine kinase inhibitor (TKI) therapy. Method Between July 2010 and January 2013, 81 patients with prior benefit from first-line imatinib (initial response or stable disease for ≥6 months) and subsequent progression on at least imatinib and sunitinib were randomly assigned in a 1:1 ratio (by computer-generated randomisation list and the central coordinating center using telephone in a double-blind manner; randomised block permutation methods with block size of 2, 4, and 6; stratified by treatment line and performance status) to receive best supportive care with either imatinib 400 mg/day (n=41) or a placebo (n=40). At the time of disease progression, determined by the investigators, crossover to open-label imatinib was allowed. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review. Secondary endpoints included the disease control rate at 12 weeks, overall survival, and safety. All analyses were based on the full analysis set. This study is registered with ClinicalTrials.gov, number NCT01151852. Findings The median PFS was 1·8 months (95% confidence interval [CI], 1·7–3·6) with imatinib as compared with 0·9 months (95% CI, 0·9–1·7) with placebo (hazard ratio for progression or death, 0·46; 95% confidence interval [CI], 0·27–0·76; p=0·005, two-sided). In the placebo arm, 37 patients (93%) crossed over to open-label imatinib after progression. The most common grade 3 or higher adverse events of imatinib resumption was anemia (12 of 41, 29%), fatigue (four of 41, 10%), and hyperbilirubinemia (three of 41, 7%). Interpretation Despite prior resistance to imatinib, resumption of imatinib significantly improves PFS in GIST patients after disease progression on at least imatinib and sunitinib, demonstrating that residual bulk disease contains clones with continued sensitivity.

The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs, such as prostate and epididymis, as well as nonreproductive organs, such as muscle, hair follicles, and brain. Abnormalities in the androgen-AR signaling pathway have been linked to diseases, such as male infertility, Kennedy's disease, and prostate cancer. Regulation of AR activity can be achieved in several different ways: modulation of AR gene expression, androgen binding to AR, AR nuclear translocation, AR protein stability, and AR trans-activation. This review covers mechanisms implicated in the control of AR protein expression and degradation, and their potential linkage to the androgen-related diseases. A better understanding of such mechanisms may help us to design more effective androgens and antiandrogens to battle androgen-related diseases.

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We report the origin of the strong UV-irradiation dependence, generally known as a “light-soaking” process, in inverted polymer solar cells (I-PSCs) using the interface of an sol-gel processed titanium sub-oxide (TiOx) and indium tin oxide (ITO) cathode. When I-PSCs incorporating TiOx as an electron-selecting layer were fabricated, the as-prepared devices exhibited an anomalous J-V curve with a kink shape, resulting in an extremely low efficiency. However, the kink shape disappeared after white light irradiation for considerable duration, after which the device parameters recovered the normal values expected for this class of devices. By using electrochemical impedance spectroscopy and by measuring the contact potential difference and transient photoconductivity of the TiOx layer, we found that the light-soaking process in I-PSCs originates from the photoinduced “rearrangement of the Fermi levels” at the sol-gel processed TiOx and ITO cathode interface together with trap sites existing in the TiOx layer. Based on our data, we optimized I-PSC devices with a high fill factor (FF) of ∼70%.