A new approach to materials discovery for electronic and thermoelectric properties of single-molecule junctions

We have investigated a large set of symmetric and asymmetric molecules to demonstrate a general rule for molecular-scale quantum transport, which provides a new route to materials design and discovery. The rule states “the conductance GXBY of an asymmetric molecule is the geometric mean of the conductance of the two symmetric molecules derived from it and the thermopower SXBY of the asymmetric molecule is the algebraic mean of their thermopowers”. The studied molecules have a structure X-B-Y, where B is the backbone of the molecule, while X and Y are anchor groups, which bind the molecule to metallic electrodes. When applied to experimentally-measured histograms of conductance and thermopower, the rules apply to the statistically-most-probable values. We investigated molecules with anchors chosen from the following family: cyano, pyridl, dihydrobenzothiol, amine and thiol. For the backbones B, we tested fourteen different structures. We found that the formulae (GXBY)2 = GXBX*GYBY and SXBY=(SXBX+SYBY)/2 were satisfied in the large majority of the cases, provided the Fermi energy is located within the HOMO-LUMO gap of the molecules. The circuit rules imply that if measurements are performed on molecules with nA different anchors and nB different backbones, then properties of nA(nA+1)nB/2 molecules can be predicted. So for example, in the case of 20 backbones and 10 anchors, 30 measurements (or reliable calculations) can provide a near quantitative estimate for 1070 measurements of other molecules, no extra cost

Rab7 GTPase controls lipid metabolic signaling in myeloid-derived suppressor cells

Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines. The GST pull down assay using the recombinant GST-Rab7 GTPase fusion protein showed that Rab7 GTPase interacts with the mTOR N-terminal heat repeat domain. Rab7 GTPase siRNA knocking down reversed the altered lysosome/mTOR distribution and expression levels in HD1B cells. Rab7 GTPase siRNA knocking down in isolated bone marrow lal-/- MDSCs or HD1B cells not only reduced over-activation of mTOR and its downstream effector S6, but also decreased glucose consumption, decreased ROS over-production, and increased healthy mitochondria by membrane potential measurement. Inhibition of Rab7 GTPase led to reduced lal-/- MDSCs differentiation from bone marrow Lin- progenitor cells, reduced lal-/- MDSCs trans-endothelial migration, and reversed lal-/- MDSCs suppression of T cell proliferation. Furthermore, inhibition of Rab7 GTPase reduced lal-/- MDSCs ability to stimulate tumor cell proliferation in vitro, tumor growth in vivo, and tumor invasion. Together, these results showed that Rab7 GTPase is critically involved in MDSCs homeostasis and pathogenic functions

Magic ratios for connectivity-driven electrical conductance of graphene-like molecules

Experiments using a mechanically-controlled break junction and calculations based on density functional theory demonstrate a new magic ratio rule (MRR),which captures the contribution of connectivity to the electrical conductance of graphene-like aromatic molecules. When one electrode is connected to a site i and the other is connected to a site i' of a particular molecule, we assign the molecule a magic integer Mii'. Two molecules with the same aromatic core, but different pairs of electrode connection sites (i,i' and j,j' respectively) possess different magic integers Mii' and Mjj'. Based on connectivity alone, we predict that when the coupling to electrodes is weak and the Fermi energy of the electrodes lies close to the centre of the HOMO-LUMO gap, the ratio of their conductances is equal to (Mii' /Mjj')2. The MRR is exact for a tight binding representation of a molecule and a qualitative guide for real molecules

Cross-Domain Recommendation for Cold-Start Users via Neighborhood Based Feature Mapping

Collaborative Filtering (CF) is a widely adopted technique in recommender systems. Traditional CF models mainly focus on predicting a user's preference to the items in a single domain such as the movie domain or the music domain. A major challenge for such models is the data sparsity problem, and especially, CF cannot make accurate predictions for the cold-start users who have no ratings at all. Although Cross-Domain Collaborative Filtering (CDCF) is proposed for effectively transferring users' rating preference across different domains, it is still difficult for existing CDCF models to tackle the cold-start users in the target domain due to the extreme data sparsity. In this paper, we propose a Cross-Domain Latent Feature Mapping (CDLFM) model for cold-start users in the target domain. Firstly, in order to better characterize users in sparse domains, we take the users' similarity relationship on rating behaviors into consideration and propose the Matrix Factorization by incorporating User Similarities (MFUS) in which three similarity measures are proposed. Next, to perform knowledge transfer across domains, we propose a neighborhood based gradient boosting trees method to learn the cross-domain user latent feature mapping function. For each cold-start user, we learn his/her feature mapping function based on the latent feature pairs of those linked users who have similar rating behaviors with the cold-start user in the auxiliary domain. And the preference of the cold-start user in the target domain can be predicted based on the mapping function and his/her latent features in the auxiliary domain. Experimental results on two real data sets extracted from Amazon transaction data demonstrate the superiority of our proposed model against other state-of-the-art methods.Comment: 16 pages, 8 figure

Identification of the chemical components of ethanol extract of Chenopodium ambrosioides and evaluation of their in vitro antioxidant and anti tumor activities

Purpose: To determine the characteristic chemical components of the ethanol extract of Chenopodium ambrosioides and evaluate their antioxidant and anti-tumor effects in vitro. Methods: The plant powder (5 g) was extracted with 1 L of 80 % ethanol at room temperature for 45 min, and then placed at 60 oC at varying microwave power and duration to obtain optimal extraction conditions. Characteristic chemical components were detected using ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). Kaempferitrin was isolated from the 80 % ethanol extract using a D101 macroporous resin column, and its content was assessed by high performance liquid chromatography (HPLC). The antioxidant effect of kaempferitrin was evaluated by its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radicals, while its anti-proliferation activity in human liver cancer cells SMMC-7721 was determined using cell counting kit-8 (CCK-8) reagent. Results: Three characteristic components of ethanol extract of C. ambrosioides were obtained, namely, kaempferitrin, kaempferol-3-O-apigenin-7-O-rhamnoside and kaempferol-3-O-acetylapigenin-7-O-rhamnoside. Kaempferitrin was shown to possess strong DPPH radical and moderate ABTS radical scavenging activities. Kaempferitrin significantly inhibited the proliferation of SMMC-7721 cells at doses of 4 and 8 μg/mL, with half-maximal concentration (IC50) of 0.38 μM (p < 0.05). Conclusion: Kaempferitrin extracted from C. ambrosioides has antioxidant and anti-tumor activities. The results reported here indicate that C. ambrosioides may have potential use in herbal medicine practice

Development of a Nicotinic Acetylcholine Receptor nAChR α7 Binding Activity Prediction Model

Despite the well-known adverse health effects associated with tobacco use, addiction to nicotine found in tobacco products causes difficulty in quitting among users. Nicotinic acetylcholine receptors (nAChRs) are the physiological targets of nicotine and facilitate addiction to tobacco products. The nAChR-α7 subtype plays an important role in addiction; therefore, predicting the binding activity of tobacco constituents to nAChR-α7 is an important component for assessing addictive potential of tobacco constituents. We developed an α7 binding activity prediction model based on a large training data set of 843 chemicals with human α7 binding activity data extracted from PubChem and ChEMBL. The model was tested using 1215 chemicals with rat α7 binding activity data from the same databases. Based on the competitive docking results, the docking scores were partitioned to the key residues that play important roles in the receptor−ligand binding. A decision forest was used to train the human α7 binding activity prediction model based on the partition of docking scores. Five-fold cross validations were conducted to estimate the performance of the decision forest models. The developed model was used to predict the potential human α7 binding activity for 5275 tobacco constituents. The human α7 binding activity data for 84 of the 5275 tobacco constituents were experimentally measured to confirm and empirically validate the prediction results. The prediction accuracy, sensitivity, and specificity were 64.3, 40.0, and 81.6%, respectively. The developed prediction model of human α7 may be a useful tool for high-throughput screening of potential addictive tobacco constituents

Poly(ADP-ribose) polymerases regulate cell division and development in Arabidopsis roots

Root organogenesis involves cell division, differentiation and expansion. The molecular mechanisms regulating root development are not fully understood. In this study, we identified poly (ADP-ribose) polymerases (PARPs) as new players in root development. PARP catalyzes poly (ADP-ribosyl)ation of proteins by repeatedly adding ADP-ribose units onto proteins using nicotinamide adenine dinucleotide (NAD+) as the donor. We found that inhibition of PARP activities by 3-aminobenzomide (3-AB) increased the growth rates of both primary and lateral roots, leading to a more developed root system. The double mutant of Arabidopsis PARPs, parp1parp2, showed more rapid primary and lateral root growth. Cyclin genes regulating G1-to-S and G2-to-M transition were up-regulated upon treatment by 3-AB. The proportion of 2C cells increased while cells with higher DNA ploidy cells declined in the roots of treated plants, resulting in an enlarged rootmeristematic zone. The expression level of PARP2 was very low in the meristematic zone but high in the maturation zones, consistent with a role of PARP in inhibiting mitosis and promoting cell differentiation. Our results suggest that PARPs play an important rolein root development by negatively regulating root cell division