Inapproximability of maximal strip recovery

In comparative genomic, the first step of sequence analysis is usually to decompose two or more genomes into syntenic blocks that are segments of homologous chromosomes. For the reliable recovery of syntenic blocks, noise and ambiguities in the genomic maps need to be removed first. Maximal Strip Recovery (MSR) is an optimization problem proposed by Zheng, Zhu, and Sankoff for reliably recovering syntenic blocks from genomic maps in the midst of noise and ambiguities. Given $d$ genomic maps as sequences of gene markers, the objective of \msr{d} is to find $d$ subsequences, one subsequence of each genomic map, such that the total length of syntenic blocks in these subsequences is maximized. For any constant $d \ge 2$, a polynomial-time 2d-approximation for \msr{d} was previously known. In this paper, we show that for any $d \ge 2$, \msr{d} is APX-hard, even for the most basic version of the problem in which all gene markers are distinct and appear in positive orientation in each genomic map. Moreover, we provide the first explicit lower bounds on approximating \msr{d} for all $d \ge 2$. In particular, we show that \msr{d} is NP-hard to approximate within $\Omega(d/\log d)$. From the other direction, we show that the previous 2d-approximation for \msr{d} can be optimized into a polynomial-time algorithm even if $d$ is not a constant but is part of the input. We then extend our inapproximability results to several related problems including \cmsr{d}, \gapmsr{\delta}{d}, and \gapcmsr{\delta}{d}.Comment: A preliminary version of this paper appeared in two parts in the Proceedings of the 20th International Symposium on Algorithms and Computation (ISAAC 2009) and the Proceedings of the 4th International Frontiers of Algorithmics Workshop (FAW 2010

Social welfare and profit maximization from revealed preferences

Consider the seller's problem of finding optimal prices for her $n$ (divisible) goods when faced with a set of $m$ consumers, given that she can only observe their purchased bundles at posted prices, i.e., revealed preferences. We study both social welfare and profit maximization with revealed preferences. Although social welfare maximization is a seemingly non-convex optimization problem in prices, we show that (i) it can be reduced to a dual convex optimization problem in prices, and (ii) the revealed preferences can be interpreted as supergradients of the concave conjugate of valuation, with which subgradients of the dual function can be computed. We thereby obtain a simple subgradient-based algorithm for strongly concave valuations and convex cost, with query complexity $O(m^2/\epsilon^2)$, where $\epsilon$ is the additive difference between the social welfare induced by our algorithm and the optimum social welfare. We also study social welfare maximization under the online setting, specifically the random permutation model, where consumers arrive one-by-one in a random order. For the case where consumer valuations can be arbitrary continuous functions, we propose a price posting mechanism that achieves an expected social welfare up to an additive factor of $O(\sqrt{mn})$ from the maximum social welfare. Finally, for profit maximization (which may be non-convex in simple cases), we give nearly matching upper and lower bounds on the query complexity for separable valuations and cost (i.e., each good can be treated independently)

On-chip beam rotators, polarizers and adiabatic mode converters through low-loss waveguides with variable cross-sections

Photonics integrated circuitry would benefit considerably from the ability to arbitrarily control waveguide cross-sections with high precision and low loss, in order to provide more degrees of freedom in manipulating propagating light. Here, we report on a new optical-fibres-compatible glass waveguide by femtosecond laser writing, namely spherical phase induced multi-core waveguide (SPIM-WG), which addresses this challenging task with three dimensional on-chip light control. Precise deformation of cross-sections is achievable along the waveguide, with shapes and sizes finely controllable of high resolution in both horizontal and vertical transversal directions. We observed that these waveguides have high refractive index contrast of 0.017, low propagation loss of 0.14 dB/cm, and very low coupling loss of 0.19 dB coupled from a single mode fibre. SPIM-WG devices were easily fabricated that were able to perform on-chip beam rotation through varying angles, or manipulate polarization state of propagating light for target wavelengths. We also demonstrated SPIM-WG mode converters that provide arbitrary adiabatic mode conversion with high efficiency between symmetric and asymmetric non-uniform modes; examples include circular, elliptical modes and asymmetric modes from ppKTP waveguides which are generally applied in frequency conversion and quantum light sources. Created inside optical glass, these waveguides and devices have the capability to operate across ultra-broad bands from visible to infrared wavelengths. The compatibility with optical fibre also paves the way toward packaged photonic integrated circuitry, which usually needs input and output fibre connections

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Transcription profiles of non-immortalized breast cancer cell lines

BACKGROUND: Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. METHODS: Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs) were used in addition to commercially-available normal breast epithelial cells (HMECs), established breast cancer cell lines (T-est) and established normal breast cells (N-est). The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. RESULTS: According to Significance Analysis of Microarray (SAM) and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. CONCLUSION: The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research

Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells

BACKGROUND: In-vitro expansion of functional beta cells from adult human islets is an attractive approach for generating an abundant source of cells for beta-cell replacement therapy of diabetes. Using genetic cell-lineage tracing we have recently shown that beta cells cultured from adult human islets undergo rapid dedifferentiation and proliferate for up to 16 population doublings. These cells have raised interest as potential candidates for redifferentiation into functional insulin-producing cells. Previous work has associated dedifferentiation of cultured epithelial cells with epithelial-mesenchymal transition (EMT), and suggested that EMT generates cells with stem cell properties. Here we investigated the occurrence of EMT in these cultures and assessed their stem cell potential. METHODOLOGY/PRINCIPAL FINDINGS: Using cell-lineage tracing we provide direct evidence for occurrence of EMT in cells originating from beta cells in cultures of adult human islet cells. These cells express multiple mesenchymal markers, as well as markers associated with mesenchymal stem cells (MSC). However, we do not find evidence for the ability of such cells, nor of cells in these cultures derived from a non-beta-cell origin, to significantly differentiate into mesodermal cell types. CONCLUSIONS/SIGNIFICANCE: These findings constitute the first demonstration based on genetic lineage-tracing of EMT in cultured adult primary human cells, and show that EMT does not induce multipotency in cells derived from human beta cells

Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 Activation

The main purpose of the present study is to envisage the molecular mechanism of inhibitory action ofdehydrocostuslactone (DCE) andcostunolide (CS), two naturally occurring sesquiterpene lactones, towards the activation of signal transducer and activator of transcription 3 (STAT3). We report that, in human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of 10 µM with concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an α-β-unsatured carbonyl moiety and function as potent Michael reaction acceptor, induce a rapid drop in intracellular glutathione (GSH) concentration by direct interaction with it, thereby triggering S-glutathionylation of STAT3. Dehydrocostunolide (HCS), the reduced form of CS lacking only the α-β-unsaturated carbonyl group, fails to exert any inhibitory action. Finally, the glutathione ethylene ester (GEE), the cell permeable GSH form, reverts the inhibitory action of DCE and CS on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene lactones are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function

Estimation of the number of synapses in the hippocampus and brain-wide by volume electron microscopy and genetic labeling

Determining the number of synapses that are present in different brain regions is crucial to understand brain connectivity as a whole. Membrane-associated guanylate kinases (MAGUKs) are a family of scaffolding proteins that are expressed in excitatory glutamatergic synapses. We used genetic labeling of two of these proteins (PSD95 and SAP102), and Spinning Disc confocal Microscopy (SDM), to estimate the number of fluorescent puncta in the CA1 area of the hippocampus. We also used FIB-SEM, a three-dimensional electron microscopy technique, to calculate the actual numbers of synapses in the same area. We then estimated the ratio between the three-dimensional densities obtained with FIB-SEM (synapses/µm) and the bi-dimensional densities obtained with SDM (puncta/100 µm). Given that it is impractical to use FIB-SEM brain-wide, we used previously available SDM data from other brain regions and we applied this ratio as a conversion factor to estimate the minimum density of synapses in those regions. We found the highest densities of synapses in the isocortex, olfactory areas, hippocampal formation and cortical subplate. Low densities were found in the pallidum, hypothalamus, brainstem and cerebellum. Finally, the striatum and thalamus showed a wide range of synapse densities.This work was supported by grants from the following entities: the Spanish “Ministerio de Ciencia, Innovación y Universidades” (Grant PGC2018-094307-B-I00 and the Cajal Blue Brain Project [C080020-09; the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland]; the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 785907 (Human Brain Project, SGA2); the Wellcome Trust (Technology Development Grant 202932); and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (695568 SYNNOVATE). L.T.-R. is a recipient of grants from the EMBO Long-term fellowship 2016–2018 and the IBRO-PERC InEurope grants programme