Glioblastoma multiforme (GBM) is a devastating brain tumor with poor prognosis and low median survival time. Standard treatment includes radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). However, a large percentage of tumors are resistant to the cytotoxic effects of the TMZ-induced DNA lesion O 6 -methylguanine due to elevated expression of the repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) or a defect in the mismatch repair (MMR) pathway. Although a majority of the TMZ-induced lesions (N7-methylguanine and N3-methyladenine) are base excision repair (BER) substrates, these DNA lesions are also readily repaired. However, blocking BER can enhance response to TMZ and therefore the BER pathway has emerged as an attractive target for reversing TMZ resistance. Our lab has recently reported that inhibition of BER leads to the accumulation of repair intermediates that induce energy depletion-mediated cell death via hyperactivation of poly(ADP-ribose) polymerase. On the basis of our observation that TMZ-induced cell death via BER inhibition is dependent on the availability of nicotinamide adenine dinucleotide (NAD þ ), we have hypothesized that combined BER and NAD þ biosynthesis inhibition will increase TMZ efficacy in glioblastoma cell lines greater than BER inhibition alone. Importantly, we find that the combination of BER and NAD þ biosynthesis inhibition significantly sensitizes glioma cells with elevated expression of MGMT and those deficient in MMR, two genotypes normally associated with TMZ resistance. Dual targeting of these two interacting pathways (DNA repair and NAD þ biosynthesis) may prove to be an effective treatment combination for patients with resistant and recurrent GBM. Cancer Res; 71(6); 2308-17. Ó2011 AACR.

Nanodiamonds have attracted remarkable scientific attention for bioimaging and therapeutic applications owing to their low toxicity with many cell lines, convenient surface properties and stable fluorescence without photobleaching. Newer techniques are being applied to enhance fluorescence. Interest is also growing in exploring the possibilities for modifying the nanodiamond surface and functionalities by attaching various biomolecules of interest for interaction with the targets. The potential of Raman spectroscopy and fluorescence properties of nanodiamonds has been explored for bioimaging and drug delivery tracing. The interest in nanodiamonds' biological/medical application appears to be continuing with enhanced focus. In this review an attempt is made to capture the scope, spirit and recent developments in the field of nanodiamonds for biomedical applications.

Detailed insight into the excitation behavior for charge versus proton transfer in p-N,N-ditolylaminosalicylaldehyde (Ia) has been gained via luminescence spectroscopy and femtosecond dynamics. In cyclohexane, following an ultrafast rate (∼2.0 × 10 12 s -1 ) of excited-state intramolecular proton transfer (ESIPT), fast equilibrium takes place between normal (N*) and tautomer excited states (T*), resulting in dual fluorescence maximized at 450 and 540 nm, respectively, with a common population decay rate of 360 ps -1 . The normal emission exhibits drastic solvent-polarity dependence and has been concluded to originate from a chargetransfer species incorporating excited-state intramolecular charge transfer from ditolylamine to carbonyl oxygen. In dipolar solvents, competitive rates between ESIPT and solvent relaxation were observed, and the solvated charge-transfer state is thermodynamically more favorable, so that the T* f N* reverse proton transfer takes places. Supplementary support was provided by the corresponding experiments for the methoxy derivative of Ia as well as other relevant analogues. The results shed light on detailed proton/charge transfer coupled dynamics as well as the associated solvent-relaxation dynamics at an early time domain.

Nanodiamonds (ND) have emerged to be a widely-discussed nanomaterial for their applications in biological studies and for medical diagnostics and treatment. The potentials have been successfully demonstrated in cellular and tissue models in vitro. For medical applications, further in vivo studies on various applications become important. One of the most challenging possibilities of ND biomedical application is controllable drug delivery and tracing. That usually assumes ND interaction with the blood system. In this work, we study ND interaction with rat blood and analyze how the ND surface modification and coating can optimize the ND interaction with the blood. It was found that adsorption of a low concentration of ND does not affect the oxygenation state of red blood cells (RBC). The obtained in vivo results are compared to the results of in vitro studies of nanodiamond interaction with rat and human blood and blood components, such as red blood cells and blood plasma. An in vivo animal model shows ND injected in blood attach to the RBC membrane and circulate with blood for more than 30 min; and ND do not stimulate an immune response by measurement of proinflammatory cytokine TNF-α with ND injected into mice via the caudal vein. The results further confirm nanodiamonds’ safety in organisms, as well as the possibility of their application without complicating the blood’s physiological conditions.

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________________________________________________________________________This study presents a novel approach to automatic emotion recognition from text. First, emotion generation rules (EGRs) are manually deduced from psychology to represent the conditions for generating emotion. Based on the EGRs, the emotional state of each sentence can be represented as a sequence of semantic labels (SLs) and attributes (ATTs); SLs are defined as the domain-independent features, while ATTs are domain-dependent. The emotion association rules (EARs) represented by SLs and ATTs for each emotion are automatically derived from the sentences in an emotional text corpus using the a priori algorithm. Finally, a separable mixture model (SMM) is adopted to estimate the similarity between an input sentence and the EARs of each emotional state. Since some features defined in this approach are domain-dependent, a dialog system focusing on the students' daily expressions is constructed, and only three emotional states, happy, unhappy, and neutral, are considered for performance evaluation. According to the results of the experiments, given the domain corpus, the proposed approach is promising, and easily ported into other domains.

BackgroundSolar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health.ResultsThe efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm2 of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models.ConclusionsNDs are feasible and safe materials for preventing UVB-induced skin damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0094-4) contains supplementary material, which is available to authorized users.

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