The structured backbone of temporal social ties

In many data sets, crucial information on the structure and temporality of a system coexists with noise and non-essential elements. In networked systems, for instance, some edges might be non-essential or exist only by chance. Filtering them out and extracting a set of relevant connections, the "network backbone", is a non-trivial task, and methods put forward until now do not address time-resolved networks, whose availability has strongly increased in recent years. We develop here such a method, by defining an adequate temporal network null model, which calculates the random chance of nodes to be connected at any time after controlling for their activity. This allows us to identify, at any level of statistical significance, pairs of nodes that have more interactions than expected given their activities: These form a backbone of significant ties. We apply our method to empirical temporal networks of socio-economic interest and find that (i) at given level of statistical significance, our method identifies more significant ties than methods considering temporally aggregated networks, and (ii) when a community structure is present, most significant ties are intra-community edges, suggesting that the weights of inter-community edges can be explained by the null model of random interactions. Most importantly, our filtering method can assign a significance to more complex structures such as triads of simultaneous interactions, while methods based on static representations are by construction unable to do so. Strikingly, we uncover that significant triads are not equivalent to triangles composed by three significant edges. Our results hint at new ways to represent temporal networks for use in data-driven models and in anonymity-preserving ways.Comment: Main text: 18 pages, 6 figures. SI: 22 pages, 17 figure

Cyclooxygenase 2 Modulates Killing of Cytotoxic T Lymphocytes by Colon Cancer Cells

Although anti-cancer effects of cyclooxygenase 2 (COX2) inhibitors have been reported, most studies focused on the direct effects of COX2 inhibiters on colon cancer cells. On the other hand, several types of cancers express Fas ligand (FasL) and/or TRAIL and mediate apoptosis of T cells in vitro. The “counter-attack” machinery may account for the mechanisms by which tumors evade host immune surveillance. In this study we determined if COX2 inhibitor could modulate effector molecules of cell death on colon cancer cells changing their effects on cytotoxic T lymphocytes. Colon adenocarcinoma cells, HCA7 and HCT116, the former COX2-positive and the latter COX2-negative, were pre-incubated with/without a COX2 inhibitor, NS398. Subsequently, the cells were co-cultured with Jurkat T cell leukemia cells and damage to Jurkat cells was determined. Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells. The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells. Preincubation of HCA7 cells with NS398 before co-culture blunted the HCA7 cell-induced cell toxicity on Jurkat cells. In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing. Our results suggest that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against cytotoxic T cells, which may lead to compromised host immune responses

Iridium-catalyzed α-selective deuteration of alcohols

新規重水素化触媒反応を開発 --医薬品への直接重水素導入を達成--. 京都大学プレスリリース. 2022-07-21.The development of chemoselective C(sp³)-H deuteration is of particular interest in synthetic chemistry. We herein report the α-selective, iridium(III)-bipyridonate-catalyzed hydrogen(H)/deuterium(D) isotope exchange of alcohols using deuterium oxide (D₂O) as the primary deuterium source. This method enables the direct, chemoselective deuteration of primary and secondary alcohols under basic or neutral conditions without being affected by coordinative functional groups such as imidazole and tetrazole. Successful substrates for deuterium labelling include the pharmaceuticals losartan potassium, rapidosept, guaifenesin, and diprophylline. The deuterated losartan potassium shows higher stability towards the metabolism by CYP2C9 than the protiated analogue. Kinetic and DFT studies indicate that the direct deuteration proceeds through dehydrogenation of alcohol to the carbonyl intermediate, conversion of [Ir[III]–H] to [Ir[III]−D] with D₂O, and deuteration of the carbonyl intermediate to give the α-deuterated product

Artificial neural network approach for selection of susceptible single nucleotide polymorphisms and construction of prediction model on childhood allergic asthma

BACKGROUND: Screening of various gene markers such as single nucleotide polymorphism (SNP) and correlation between these markers and development of multifactorial disease have previously been studied. Here, we propose a susceptible marker-selectable artificial neural network (ANN) for predicting development of allergic disease. RESULTS: To predict development of childhood allergic asthma (CAA) and select susceptible SNPs, we used an ANN with a parameter decreasing method (PDM) to analyze 25 SNPs of 17 genes in 344 Japanese people, and select 10 susceptible SNPs of CAA. The accuracy of the ANN model with 10 SNPs was 97.7% for learning data and 74.4% for evaluation data. Important combinations were determined by effective combination value (ECV) defined in the present paper. Effective 2-SNP or 3-SNP combinations were found to be concentrated among the 10 selected SNPs. CONCLUSION: ANN can reliably select SNP combinations that are associated with CAA. Thus, the ANN can be used to characterize development of complex diseases caused by multiple factors. This is the first report of automatic selection of SNPs related to development of multifactorial disease from SNP data of more than 300 patients

Long-term effectiveness of right septal pacing vs. right apical pacing in patients with atrioventricular block

AbstractBackgroundLong-term right ventricular apical (RVA) pacing increases the risk of heart failure (HF) by inducing ventricular dyssynchronization. Although recent studies suggest that right ventricular septal (RVS) pacing results in improved short-term outcomes, its long-term effectiveness remains unclear.Methods and resultsThis study investigated 149 consecutive patients who underwent implantation of a dual chamber pacemaker for atrioventricular block with either RVS-pacing between July 2007 and June 2010 or RVA-pacing between January 2003 and June 2007. The endpoint was defined as death and hospitalization due to heart failure (HF). The rates of mortality and hospitalization due to HF were significantly lower in the RVS-pacing group than that in the RVA-pacing group (event free RVS: 1 year, 98% and 2 years, 98%; RVA: 1 year, 85% and 2 years, 81%; p<0.05). None of the patients died from HF in the RVS-pacing group, while 4 patients died from HF in the RVA-pacing group within 2 years after pacemaker implantation. The paced QRS interval was significantly shorter with RVS pacing than with RVA pacing at different times after pacemaker implantation (RVS: immediately 157.8±24.0ms, after 3 months 157.3±17.5ms, after 6 months 153.6±21.7ms, after 12 months 153.6±19.4ms, after 24 months 149.3±24.0ms vs. RVA: immediately 168.3±23.7ms, after 3 months 168.7±26.0ms, after 6 months 168.0±22.8ms, after 12 months 171.2±22.3ms, after 24 months 176.1±25.5ms; p<0.05).ConclusionsRVS pacing is feasible and safe with more favorable clinical benefits than RVA pacing