ADVISE: Symbolism and External Knowledge for Decoding Advertisements

In order to convey the most content in their limited space, advertisements embed references to outside knowledge via symbolism. For example, a motorcycle stands for adventure (a positive property the ad wants associated with the product being sold), and a gun stands for danger (a negative property to dissuade viewers from undesirable behaviors). We show how to use symbolic references to better understand the meaning of an ad. We further show how anchoring ad understanding in general-purpose object recognition and image captioning improves results. We formulate the ad understanding task as matching the ad image to human-generated statements that describe the action that the ad prompts, and the rationale it provides for taking this action. Our proposed method outperforms the state of the art on this task, and on an alternative formulation of question-answering on ads. We show additional applications of our learned representations for matching ads to slogans, and clustering ads according to their topic, without extra training.Comment: To appear, Proceedings of the European Conference on Computer Vision (ECCV

The Complexity of Drawing Graphs on Few Lines and Few Planes

It is well known that any graph admits a crossing-free straight-line drawing in $\mathbb{R}^3$ and that any planar graph admits the same even in $\mathbb{R}^2$. For a graph $G$ and $d \in \{2,3\}$, let $\rho^1_d(G)$ denote the minimum number of lines in $\mathbb{R}^d$ that together can cover all edges of a drawing of $G$. For $d=2$, $G$ must be planar. We investigate the complexity of computing these parameters and obtain the following hardness and algorithmic results. - For $d\in\{2,3\}$, we prove that deciding whether $\rho^1_d(G)\le k$ for a given graph $G$ and integer $k$ is ${\exists\mathbb{R}}$-complete. - Since $\mathrm{NP}\subseteq{\exists\mathbb{R}}$, deciding $\rho^1_d(G)\le k$ is NP-hard for $d\in\{2,3\}$. On the positive side, we show that the problem is fixed-parameter tractable with respect to $k$. - Since ${\exists\mathbb{R}}\subseteq\mathrm{PSPACE}$, both $\rho^1_2(G)$ and $\rho^1_3(G)$ are computable in polynomial space. On the negative side, we show that drawings that are optimal with respect to $\rho^1_2$ or $\rho^1_3$ sometimes require irrational coordinates. - Let $\rho^2_3(G)$ be the minimum number of planes in $\mathbb{R}^3$ needed to cover a straight-line drawing of a graph $G$. We prove that deciding whether $\rho^2_3(G)\le k$ is NP-hard for any fixed $k \ge 2$. Hence, the problem is not fixed-parameter tractable with respect to $k$ unless $\mathrm{P}=\mathrm{NP}$

Theory of STM Spectroscopy of Kondo Ions on Metal Surfaces

The conduction electron density of states nearby a single magnetic impurity, as measured recently by scanning tunneling microscopy (STM), is calculated. It is shown that the Kondo effect induces a narrow Fano resonance as an intrinsic feature in the conduction electron density of states. The line shape varies with the distance between STM tip and impurity, in qualitative agreement with experiments, and is sensitive to details of the band structure. For a Co impurity the experimentally observed width and shift of the Kondo resonance are in accordance with those obtained from a combination of band structure and strongly correlated calculations.Comment: 5 pages, 4 figures, presented at the NATO Advanced Research Workshop on "Size Dependent Magnetic Scattering", Pecs, Hungary, May 28 - June 1, 200

What should the detection rates of cancers be in breast screening programmes?

Minimum detection rates at screening are sometimes laid down as standards for breast cancer screening programmes, based on underlying incidence of the disease in the age group screened. Detection rates should also depend on desired sensitivity, mean sojourn time, interscreening interval and the screening round – that is, prevalent (first) or incident (second or subsequent). In this paper, we use these quantities to derive expected, minimum and maximum detection rates proportional to the underlying incidence as well as estimated underlying incidence rates from extrapolation of prescreening trends in England and Wales to derive alternative standard minimum, expected and maximum detection rates per 1000 women screened for the UK Breast Screening Programme, as follows: minimum detection rates should be 4.1 and 4.3 at prevalence screen and incidence screens, respectively; expected rates should be 6.9 and 4.8 and maximum rates of 9.6 and 5.5. These are consistent with observed detection rates in the UK programme

Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

The association between HIV tri-therapy with the development of Type-2 Diabetes Mellitus in a rural South African District: A case-control study

Background Combination antiretroviral drugs (cARVs) prolong patients’ lives but are unfortunately thought to increase complications related to metabolic disorders including type-2 Diabetes Mellitus (DM). We sought to confirm the association of cARVs with type-2 DM and ascertain the extent of this association in a rural South African setting. Methods A case-control study of 177 (33.33%) cases with HIV/AIDS and type-2 DM were selected and compared with 354 (66.67%) non-DM HIV/AIDS unmatched controls from a rural district of South Africa’s third most populous province (Eastern Cape). Cases were identified from community health centres using the district health information system, and controls were identified using simple random sampling from the same health facilities. Odds Ratios (OR), together with 95% confidence intervals, were calculated for all the univariable and multivariable logistic analyses. Results This study found that cARVs significantly increased the occurrence of type-2 DM among HIV patients. Patients on protease inhibitors (PIs) were at least 21 times significantly (p<0.0001) more likely to be diabetic than those on the fixed dose combination (FDC); those on stavudine (D4T) and zidovudine (AZT) were 2.45 times and 9.44 times respectively more likely to be diabetic than those on FDC (p<0.05). The odds of diabetes increased by more than three-folds for those who had been on antiretroviral drugs for more than 6 years (p<0.005). Conclusion This study has been able to establish the association between cARVs and type-2 DM. It therefore proposes consideration of the usage of AZT, D4T, lopivavir and ritonavir for the treatment of HIV. The study further proposes more prospective research to test these findings further

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Optimization of Monoclonal Antibodies Purification Expressed in H-192 cells using Preparative Native-Polyacrylamide Gel Electrophoresis

Monoclonal antibodies (mAbs) are unique and specific drug molecules targeting the treatment of various diseases such as arthritis, immune disorders, infectious diseases, and cancer etc. Different methods such as antibody coupled affinity chromatography, hydrophobic interaction chromatography, etc., can be applied to purify mAbs from various sources. This article provides a simple, cost effective, preparative native-polyacrylamide gel electrophoresis (n-PAGE) technique to purify mAbs expressed in H-192 cells (Hybridoma murine cell lines) against an antigen i.e. 17-alpha-hydroxyprogesterone (17-OHP), which further can have diagnostic application to detect Congenital Adrenal Hyperplasia (CAH). Furthermore, different parameters such as concentration and volume of the feedstock (medium containing antibodies), pore size of gel, height of resolving gel etc. were optimized to obtain the maximum purity and yield of mAbs

Spectroscopic and in vitro Investigations of Fe2+/alpha-Ketoglutarate-Dependent Enzymes Involved in Nucleic Acid Repair and Modification

The activation of molecular oxygen for the highly selective functionalization and repair of DNA and RNA nucleobases is achieved by alpha-ketoglutarate (alpha-KG)/iron-dependent dioxygenases. Of special interest are the human homologues AlkBH of Escherichia coli EcAlkB and ten-eleven translocation (TET) enzymes. These enzymes are involved in demethylation or dealkylation of DNA and RNA, although additional physiological functions are continuously being found. Given their importance, studying enzyme-substrate interactions, turnover and kinetic parameters is pivotal for the understanding of the mode of action of these enzymes. Diverse analytical methods, including X-ray crystallography, UV/Vis absorption, electron paramagnetic resonance (EPR), circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy have been employed to study the changes in the active site and the overall enzyme structure upon substrate, cofactor, and inhibitor addition. Several methods are now available to assess the activity of these enzymes. By discussing limitations and possibilities of these techniques for EcAlkB, AlkBH and TET we aim to give a comprehensive synopsis from a bioinorganic point-of-view, addressing researchers from different disciplines working in the highly interdisciplinary and rapidly evolving field of epigenetic processes and DNA/RNA repair and modification