The gravity of light

A solution of the old problem raised by Tolman, Ehrenfest, Podolsky and Wheeler, concerning the lack of attraction of two light pencils "moving parallel", is proposed, considering that the light can be source of nonlinear gravitational waves corresponding (in the would be quantum theory of gravity) to spin-1 massless particles.Comment: Style is changed in standard latex, abstract has been reduced and the order of sections has been change

Alternative Canonical Formalism for the Wess-Zumino-Witten Model

We study a canonical quantization of the Wess--Zumino--Witten (WZW) model which depends on two integer parameters rather than one. The usual theory can be obtained as a contraction, in which our two parameters go to infinity keeping the difference fixed. The quantum theory is equivalent to a generalized Thirring model, with left and right handed fermions transforming under different representations of the symmetry group. We also point out that the classical WZW model with a compact target space has a canonical formalism in which the current algebra is an affine Lie algebra of non--compact type. Also, there are some non--unitary quantizations of the WZW model in which there is invariance only under half the conformal algebra (one copy of the Virasoro algebra).Comment: 22 pages; UR-133

The AKT inhibitor triciribine in combination with paclitaxel has order-specific efficacy against Zfp217-induced breast cancer chemoresistance

We previously identified the transcription factor ZNF217 (human) / Zfp217 (mouse) as an oncogene and prognostic indicator of reduced survival, increased metastasis, and reduced response to therapy in breast cancer patients. Here we investigated the role of Zfp217 in chemotherapy resistance. Preclinical animal models of Zfp217 overexpression were treated with a combination therapy of the microtubule inhibitor epothilone B, doxorubicin (Adriamycin), and cyclophosphamide (EAC). Tumors overexpressing Zfp217 increased their tumor burden compared to control tumors after treatment and accumulated a mammary gland progenitor cell population (K8+K14+). To overcome this chemoresistance after ZNF217 overexpression, we treated tumors ± Zfp217 overexpression with paclitaxel and triciribine, a nucleoside analog and AKT inhibitor that kills cells that overexpress ZNF217. Treatment order critically impacted the efficacy of the therapy. Combination treatment of triciribine followed by paclitaxel (TCN→PAC) inhibited tumor burden and increased survival in tumors that overexpressed Zfp217, whereas single agent or combination treatment in the reverse order (PAC→TCN) did not improve response. Analysis of these tumors and patient-derived tumor xenograft tumors treated with the same therapies suggested that Zfp217 overexpression in tumors contributes both to decreased microvessel density and vessel maturity, while TCN→PAC tumors overexpressing Zfp217 showed improved vessel maturity

On the SO(2,1) symmetry in General Relativity

The role of the SO(2,1) symmetry in General Relativity is analyzed. Cosmological solutions of Einstein field equations invariant with respect to a space-like Lie algebra G_r, with r between 3 and 6 and containing so(2,1) as a subalgebra, are also classified.Comment: 10 pages, latex, no figure

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network

Dietary calcium intake and adiposity in children and adolescents: Cross-sectional and longitudinal results from IDEFICS/I.Family cohort

Background and aims: Studies in children and adolescents suggest that higher dairy consumption may exert a protective effect on adiposity. However, only few studies examined the association between dietary calcium intake and body mass measures with conflicting results. We evaluated the association between total dietary calcium, calcium from dairy and non-dairy sources and anthropometric indices in a large European cohort of children and adolescents. Methods and Results: As many as 6, 696 children belonging to the IDEFICS study were eligible for the cross-sectional analysis (Boys = 51%; age 6.0 ± 1.8 years; mean ± SD). Of these, 2, 744 were re-examined six years later (Boys = 49.6%; age = 11.7 ± 1.8 years) in the framework of the I.Family study. The exposures were the baseline energy-adjusted total, dairy and non-dairy calcium intakes measured by a validated 24-h dietary recall. Multivariable linear regression was used to determine the association between calcium intake and z-scores of anthropometric indices (body mass index, BMI; waist circumference, WC; sum of skinfolds, SS; fat mass index, FMI) at baseline, and their variation over the 6 years follow-up. The association of dietary calcium with the incidence of overweight/obesity was also assessed. At baseline, an inverse association between total calcium intake and all the adiposity indices was consistently observed in boys, while only SS and FMI were significant in girls. The prevalence of overweight/obesity decreased significantly (P < 0.0001) across tertiles of calcium intake, in both sexes. Over the follow-up, boys with higher baseline calcium intake value showed significantly lower increase in BMI, WC and FMI z-scores, while in girls only a lower increase in WC z-score was observed. Only in boys, the risk to become overweight/obese decreased significantly across tertiles of calcium intake. Similar results were observed by analyzing only dietary calcium from dairy, while no association was observed between non-dairy calcium and adiposity indices. Conclusions: We showed in a large cohort of European children and adolescents that dietary calcium intake may play a role in the modulation of body fat in developmental age. The association between dietary calcium and adiposity indices was driven by dairy calcium, while no effect was observed for non-dairy calcium intake. The existence of a sex-related difference in the association deserves further investigations

International Web-based consultation on priorities for translational breast cancer research

Background Large numbers of translational breast cancer research topics have been completed or are underway, but they differ widely in their immediate and/or future importance to clinical management. We therefore conducted an international Web-based consultation of breast cancer professionals to identify the topics most widely considered to be of highest priority. Methods Potential participants were contacted via two large e-mail databases and asked to register, at a Web site, the issues that they felt to be of highest priority. Four hundred nine questions were reduced by a steering committee to 70 unique issues, and registrants were asked to select the 6 questions they considered to be the most important. Results Votes were recorded from 420 voters ( 2,520 votes) from 48 countries, with 48% of voters coming from North America. Half of the voters identified themselves as clinicians, with the remainder being academics, research scientists, or pathologists. The highest priority was to identify molecular signatures to select patients who could be spared chemotherapy, which gained about 50% more votes than the second topic and was consistently voted top by voters in North America, Europe, and the rest of the world. Research scientists voted the determination of the role of stem cells in breast cancer development, progression, and treatment sensitivity as the most important issue, but this was considered the sixth priority for clinicians and fourth overall. Conclusion This exercise may bring a greater focus of research resources onto issues voted as top priorities

Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies

Purpose Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Methods Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. Results The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus > 1–2.5 cm (1.45, 1.47), age ≥ 50 versus 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. Conclusions The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects