Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Neptunium(V) transport in granitic rock : A laboratory scale study on the influence of bentonite colloids

In the present study neptunium(V) uptake by crystalline granitic rock (Kuru Grey granite) and the role of stable and mobile bentonite colloids (MX-80) on the migration of neptunium(V) was investigated. Two different experimental setups were utilized, batch-type experiments under stagnant conditions and column experiments under flowing water conditions. The uptake of 10(-6) M neptunium(V) by 40 g/L crushed granite in 10 mM NaClO4 was found to be pH-dependent, whereas neptunium(V) uptake by MX-80 bentonite colloids (0.08-0.8 g/L) was pH-independent up to a pH-value of approximately 11. Column experiments were conducted in the presence and absence of colloids at two pH values (pH = 8 and 10) and two flow rates (0.3 and 0.8 mL/h) in 10 mM NaClO4. The injected neptunium(V) concentration was 2x10(-4) M and the colloid concentration ranged from 0.08 to 0.32 g/L. The properties of the flow field in the columns were investigated with a conservative chloride tracer, at the same two flow rates of 0.8 and 0.3 mL/h. The resulting breakthrough curves were modeled using the analytical solution of advection-matrix diffusion equation. A tailing of neptunium(V) breakthrough curves in comparison to the conservative tracer was observed, which could be explained by a slightly higher retardation of neptunium(V) in the column caused by sorption on the granite. The sorption was in general lower at pH 8 than at pH 10. In addition, the tailing was almost identical in the absence and presence of MX-80 bentonite colloids, implying that the influence of colloids on the neptunium(V) mobility is almost negligible.Peer reviewe

Lateralization of face processing in the human brain

Are visual face processing mechanisms the same in the left and right cerebral hemispheres? The possibility of such ‘duplicated processing’ seems puzzling in terms of neural resource usage, and we currently lack a precise characterization of the lateral differences in face processing. To address this need, we have undertaken a three-pronged approach. Using functional magnetic resonance imaging, we assessed cortical sensitivity to facial semblance, the modulatory effects of context and temporal response dynamics. Results on all three fronts revealed systematic hemispheric differences. We found that: (i) activation patterns in the left fusiform gyrus correlate with image-level face-semblance, while those in the right correlate with categorical face/non-face judgements. (ii) Context exerts significant excitatory/inhibitory influence in the left, but has limited effect on the right. (iii) Face-selectivity persists in the right even after activity on the left has returned to baseline. These results provide important clues regarding the functional architecture of face processing, suggesting that the left hemisphere is involved in processing ‘low-level’ face semblance, and perhaps is a precursor to categorical ‘deep’ analyses on the right.John Merck FundSimons FoundationJames S. McDonnell FoundationNational Eye Institute (NIH, grant number R21-EY015521

A Match in Time Saves Nine: Deterministic Online Matching With Delays

We consider the problem of online Min-cost Perfect Matching with Delays (MPMD) introduced by Emek et al. (STOC 2016). In this problem, an even number of requests appear in a metric space at different times and the goal of an online algorithm is to match them in pairs. In contrast to traditional online matching problems, in MPMD all requests appear online and an algorithm can match any pair of requests, but such decision may be delayed (e.g., to find a better match). The cost is the sum of matching distances and the introduced delays. We present the first deterministic online algorithm for this problem. Its competitive ratio is $O(m^{\log_2 5.5})$ $= O(m^{2.46})$, where $2 m$ is the number of requests. This is polynomial in the number of metric space points if all requests are given at different points. In particular, the bound does not depend on other parameters of the metric, such as its aspect ratio. Unlike previous (randomized) solutions for the MPMD problem, our algorithm does not need to know the metric space in advance

Batch sorption and spectroscopic speciation studies of neptunium uptake by montmorillonite and corundum

Peer reviewe

Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate cancer patients exhibiting various clinical features. Fifteen polymorphic polymerase chain reaction (PCR) markers were used to identify the separately deleted areas and the findings were compared with clinicopathological variables and 5-year survival of the patients. The results indicated that there are at least three independently deleted regions at 16q. Allelic losses at the central and distal areas were associated significantly with aggressive behaviour of the disease (16q24.1–q24.2, P< 0.01, and 16q24.3–qter, P< 0.05), and the central area of deletion was further significantly associated with poorly differentiated tumour cells (P< 0.05) and with recurrent (P< 0.01) growth of the tumour. During the follow-up period, 28% of the patients initially with M0 disease developed distant metastases. Of the patients showing allelic loss at 16q24.1–q24.2, distant metastasis were found in 45% during the 5-year follow-up period, and 31% of the patients showing loss at 16q21.1 also developed distant metastases. After the 5-year follow-up period, 14 (32%) of the patients remained alive, whereas 19 (43%) had died because of their prostate cancer. The overall survival rate of the patients showing allelic loss at 16q21.1 or 16q24.1–q24.2 was significantly lower than that of the patients with retained heterozygosity. © 1999 Cancer Research Campaig

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial

Objective: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics.Design: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test.Results: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions.Conclusions: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.</p

Oro-facial pain experience among symphony orchestra musicians in Finland is associated with reported stress, sleep bruxism and disrupted sleep-Independent of the instrument group

Background To evaluate whether oro-facial pain experience was related to the type of musical instrument and to learn more about the roles of sleep and sleep-related issues in the pain among professional musicians. Objectives A standard questionnaire was sent to all Finnish symphony orchestras (n = 19), with altogether 1005 professional musicians and other personnel. Methods The questionnaire covered descriptive data, instrument group, items on perceived quality of sleep, possible sleep bruxism, stress experience and oro-facial pain experience during the past 30 days. Results In the present study, which included the musicians only, the response rate was 58.7% (n = 488). All orchestras participated in the study, and there was no significant difference in the response rate between the orchestras. The mean age of men (52.3%) was 47.7 (SD 10.3) and of women (47.7%) was 43.4 (SD 9.8) years (P <0.001). Overall, current pain in the oro-facial area was reported by 28.9%, frequent bruxism by 12.1% and frequent stress by 20.8%. According to Somers' d, there were statistically significant but moderate correlations between overall pain reports in the oro-facial area and disrupted sleep (d = 0.127, P = 0.001), sleep bruxism (d = 0.241, P <0.001) and stress experiences (d = 0.193, P <0.001). Logistic regression revealed, independent of the instrument group (string, woodwind, brass wind, percussion), that current oro-facial pain experience was significantly associated with disrupted sleep (P = 0.001), frequent sleep bruxism (P <0.001) and frequent stress (P = 0.002) experiences. Conclusions Among symphony orchestra musicians, oro-facial pain experience seems to be related to perceptions of stress, sleep bruxism and disrupted sleep rather than the instrument group.Peer reviewe