The Minimum Wiener Connector

The Wiener index of a graph is the sum of all pairwise shortest-path distances between its vertices. In this paper we study the novel problem of finding a minimum Wiener connector: given a connected graph $G=(V,E)$ and a set $Q\subseteq V$ of query vertices, find a subgraph of $G$ that connects all query vertices and has minimum Wiener index. We show that The Minimum Wiener Connector admits a polynomial-time (albeit impractical) exact algorithm for the special case where the number of query vertices is bounded. We show that in general the problem is NP-hard, and has no PTAS unless $\mathbf{P} = \mathbf{NP}$. Our main contribution is a constant-factor approximation algorithm running in time $\widetilde{O}(|Q||E|)$. A thorough experimentation on a large variety of real-world graphs confirms that our method returns smaller and denser solutions than other methods, and does so by adding to the query set $Q$ a small number of important vertices (i.e., vertices with high centrality).Comment: Published in Proceedings of the 2015 ACM SIGMOD International Conference on Management of Dat

Отношения правителя и знати в Северо­Восточной Руси

RésuméLes relations entre le prince et la noblesse en Russie du Nord-Est (xive-début du xvie s.) : le baiser sur la croix comme serment de fidélité ?Au Moyen žge, les nobles russes qui entraient au service d’un prince lui juraient-ils fidélité ? Répondre à cette question est essentiel pour comprendre l’idéologie et le rituel des relations entre le prince et la noblesse. Malgré quelques voix discordantes, la majorité des historiens considèrent qu'en Russie du Nord-Est le serment de fidélité prenait la forme d’un baiser sur la croix. L’article examine les sources attestant que les nobles baisaient la croix en signe de fidélité au grand-prince de Moscou. Il s’agit des chartes dites krestoceloval´nye, conservées depuis la seconde moitié du xve siècle. Or, ces documents n’avaient pas pour but de s’assurer de la fidélité de tous les nobles mais seulement de ceux qui étaient soupçonnés de vouloir fuir à l’étranger. Il faut remarquer également qu’à ces actes étaient jointes des chartes de caution, par lesquelles des nobles et des prélats se portaient garants de leurs pairs suspectés, s’engageant à verser des sommes importantes si ceux-ci manquaient à leur parole. L’auteur conclut que le baiser sur la croix comme serment de fidélité d’un noble à son prince n’est apparu qu’à la fin du xive siècle, en raison de la rivalité entre Moscou et la grande-principauté de Lituanie, qui toutes deux cherchaient à réunir les territoires russes à leur profit. Une autre pratique fut introduite parallèlement : lorsqu’un nouveau prince accédait au trône, la noblesse dans son ensemble devait lui prêter serment. Il s’agissait d’un serment obligatoire, public et collectif qui revêtait notamment la forme d’un baiser sur la croix. Ces deux pratiques de baiser sur la croix n’ont rien de commun avec les rituels de vassalité en Europe occidentale. Elles sont liées à la formation de la monarchie moscovite centralisée.AbstractRelations between the prince and the gentry in northeastern Russia between the fourteenth and early sixteenth centuries : was kissing the cross used as an oath of allegiance ?In the Middle Ages, did members of the gentry who entered the service of a prince pledge loyalty to him ? The answer to this question is crucial for understanding the ideology and ritual involved in the relationship between the prince and the gentry. With few exceptions, most historians agree that the oath of allegiance in northeastern Russia consisted in kissing the cross. This article examines sources attesting that the gentry kissed the cross as a sign of loyalty to the grand prince of Moscow. These are the krestotseloval´nye charters, which date back to the second half of the fifteenth century. They were not meant to ascertain the loyalty of all the members of the gentry, but only of those who were suspected of possible defection abroad. Mention must also be made that these charters were accompanied by documents in which noblemen and prelates stood security for their suspected peers and committed themselves to paying large sums of money if they failed to keep their word. The author concludes that kissing the cross as an oath of allegiance appeared as late as the end of the fourteenth century because of the rivalry opposing Moscow and the grand princedom of Lithuania in the gathering of Russian lands. A new practice was also introduced then : when a new prince acceded to the throne, the whole gentry had to pledge allegiance. This was obligatory, public, and collective, and involved kissing the cross. These two practices have nothing in common with the vassalage rituals of Western Europe. They are related to the formation of the centralized Muscovite monarchy

Birth and death: Infant burials from Vlasac and Lepenski Vir

Why were infants buried beneath house-floors at the Mesolithic and early Neolithic site of Lepenski Vir? Undertaking a new analysis of the neonate remains at Vlasac and Lepenski Vir the authors reject the idea of sacrificial infanticide, and demonstrate a consistency of respect in these burials. They suggest that the deaths were mourned and the dead, like the living, were given protection by the houses they were buried in. The treatment of mothers and children suggests increasing social cohesion from the Mesolithic at Vlasac to the early Neolithic at Lepenski Vir

Functional expression of PHO1 to the Golgi and trans-Golgi network and its role in export of inorganic phosphate.

Arabidopsis thaliana PHO1 is primarily expressed in the root vascular cylinder and is involved in the transfer of inorganic phosphate (Pi) from roots to shoots. To analyze the role of PHO1 in transport of Pi, we have generated transgenic plants expressing PHO1 in ectopic A. thaliana tissues using an estradiol-inducible promoter. Leaves treated with estradiol showed strong PHO1 expression, leading to detectable accumulation of PHO1 protein. Estradiol-mediated induction of PHO1 in leaves from soil-grown plants, in leaves and roots of plants grown in liquid culture, or in leaf mesophyll protoplasts, was all accompanied by the specific release of Pi to the extracellular medium as early as 2-3 h after addition of estradiol. Net Pi export triggered by PHO1 induction was enhanced by high extracellular Pi and weakly inhibited by the proton-ionophore carbonyl cyanide m-chlorophenylhydrazone. Expression of a PHO1-GFP construct complementing the pho1 mutant revealed GFP expression in punctate structures in the pericycle cells but no fluorescence at the plasma membrane. When expressed in onion epidermal cells or in tobacco mesophyll cells, PHO1-GFP was associated with similar punctate structures that co-localized with the Golgi/trans-Golgi network and uncharacterized vesicles. However, PHO1-GFP could be partially relocated to the plasma membrane in leaves infiltrated with a high-phosphate solution. Together, these results show that PHO1 can trigger Pi export in ectopic plant cells, strongly indicating that PHO1 is itself a Pi exporter. Interestingly, PHO1-mediated Pi export was associated with its localization to the Golgi and trans-Golgi networks, revealing a role for these organelles in Pi transport

Topical Corticosteroids Normalize both Skin and Systemic Inflammatory Markers in Infant Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood. Aims: We used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy. Methods: Seventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls. Results: TCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF. Conclusions: The profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy

Systematics and plastid genome evolution of the cryptically photosynthetic parasitic plant genus Cuscuta (Convolvulaceae)

<p>Abstract</p> <p>Background</p> <p>The genus <it>Cuscuta </it>L. (Convolvulaceae), commonly known as dodders, are epiphytic vines that invade the stems of their host with haustorial feeding structures at the points of contact. Although they lack expanded leaves, some species are noticeably chlorophyllous, especially as seedlings and in maturing fruits. Some species are reported as crop pests of worldwide distribution, whereas others are extremely rare and have local distributions and apparent niche specificity. A strong phylogenetic framework for this large genus is essential to understand the interesting ecological, morphological and molecular phenomena that occur within these parasites in an evolutionary context.</p> <p>Results</p> <p>Here we present a well-supported phylogeny of <it>Cuscuta </it>using sequences of the nuclear ribosomal internal transcribed spacer and plastid <it>rps2</it>, <it>rbcL </it>and <it>matK </it>from representatives across most of the taxonomic diversity of the genus. We use the phylogeny to interpret morphological and plastid genome evolution within the genus. At least three currently recognized taxonomic sections are not monophyletic and subgenus <it>Cuscuta </it>is unequivocally paraphyletic. Plastid genes are extremely variable with regards to evolutionary constraint, with <it>rbcL </it>exhibiting even higher levels of purifying selection in <it>Cuscuta </it>than photosynthetic relatives. Nuclear genome size is highly variable within <it>Cuscuta</it>, particularly within subgenus <it>Grammica</it>, and in some cases may indicate the existence of cryptic species in this large clade of morphologically similar species.</p> <p>Conclusion</p> <p>Some morphological characters traditionally used to define major taxonomic splits within <it>Cuscuta </it>are homoplastic and are of limited use in defining true evolutionary groups. Chloroplast genome evolution seems to have evolved in a punctuated fashion, with episodes of loss involving suites of genes or tRNAs followed by stabilization of gene content in major clades. Nearly all species of <it>Cuscuta </it>retain some photosynthetic ability, most likely for nutrient apportionment to their seeds, while complete loss of photosynthesis and possible loss of the entire chloroplast genome is limited to a single small clade of outcrossing species found primarily in western South America.</p

Designing data warehouses for geographic OLAP querying by using MDA

Data aggregation in Geographic Information Systems (GIS) is a desirable feature, spatial data are integrated in OLAP engines for this purpose. However, the development and operation of those systems is still a complex task due to methodologies followed. There are some ad hoc solutions that deal only with isolated aspects and do not provide developer and analyst with an intuitive, integrated and standard framework for designing all relevant parts. To overcome these problems, we have defined a model driven approach to accomplish Geographic Data Warehouse (GDW) development. Then, we have defined a data model required to implement and query spatial data. Its modeling is defined and implemented by using an extension of UML metamodel and it is also formalized by using OCL language. In addition, the proposal has been verified against a example scenario with sample data sets. For this purpose, we have accomplished a developing tool based on Eclipse platform and MDA standard. The great advantage of this solution is that developers can directly include spatial data at conceptual level, while decision makers can also conceptually make geographic queries without being aware of logical details.This work has been partially supported by the ESPIA project (TIN2007-67078) from the Spanish Ministry of Education and Science and by the QUASIMODO project (PAC08-0157-0668) from the Castilla-La Mancha Ministry of Education and Science (Spain). Octavio Glorio is funded by the University of Alicante under the 11th Latin American grant program

Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort

Background: Lower urinary tract symptoms are highly prevalent and a large proportion of these symptoms are known to be associated with a dysfunction of the afferent pathways. Diagnostic tools for an objective and reproducible assessment of afferent nerve function of the lower urinary tract are missing. Previous studies showed first feasibility results of sensory evoked potential recordings following electrical stimulation of the lower urinary tract in healthy subjects and patients. Nevertheless, a refinement of the methodology is necessary. Methods: This study is a prospective, randomized trial conducted at Balgrist University Hospital, Zürich, Switzerland. Ninety healthy subjects (forty females and fifty males) without lower urinary tract symptoms are planned to be included in the study. All subjects will undergo a screening visit (including standardized questionnaires, 3-day bladder diary, urinalysis, medical history taking, vital signs, physical examination, neuro-urological examination) followed by two measurement visits separated by an interval of 3 to 4 weeks. Electrical stimulations (0.5Hz-5Hz, bipolar, square wave, pulse width 1 ms) will be applied using a custom-made transurethral catheter at different locations of the lower urinary tract including bladder dome, trigone, proximal urethra, membranous urethra and distal urethra. Every subject will be randomly stimulated at one specific site of the lower urinary tract. Sensory evoked potentials (SEP) will be recorded using a 64-channel EEG cap. For an SEP segmental work-up we will place additional electrodes on the scalp (Cpz) and above the spine (C2 and L1). Visit two and three will be conducted identically for reliability assessment. Discussion: The measurement of lower urinary tract SEPs elicited by electrical stimulation at different locations of the lower urinary tract has the potential to serve as a neurophysiological biomarker for lower urinary tract afferent nerve function in patients with lower urinary tract symptoms or disorders. For implementation of such a diagnostic tool into clinical practice, an optimized setup with efficient and reliable measurements and data acquisition is crucial. In addition, normative data from a larger cohort of healthy subjects would provide information on variability, potential confounding factors and cut-off values for investigations in patients with lower urinary tract dysfunction/symptoms. Trial registration: Clinicaltrials.gov; Identifier: NCT02272309

MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.

Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein heme oxygenase-1 (HO-1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO-1 following intramembrane proteolysis. Our results highlight how ER-resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail-anchored proteins

A comprehensive survey on antennas on-chip based on metamaterial, metasurface, and substrate integrated waveguide principles for millimeter-waves and terahertz integrated circuits and systems

Antennas on-chip are a particular type of radiating elements valued for their small footprint. They are most commonly integrated in circuit boards to electromagnetically interface free space, which is necessary for wireless communications. Antennas on-chip radiate and receive electromagnetic (EM) energy as any conventional antennas, but what distinguishes them is their miniaturized size. This means they can be integrated inside electronic devices. Although on-chip antennas have a limited range, they are suitable for cell phones, tablet computers, headsets, global positioning system (GPS) devices, and WiFi and WLAN routers. Typically, on-chip antennas are handicapped by narrow bandwidth (less than 10%) and low radiation efficiency. This survey provides an overview of recent techniques and technologies investigated in the literature, to implement high performance on-chip antennas for millimeter-waves (mmWave) and terahertz (THz) integrated-circuit (IC) applications. The technologies discussed here include metamaterial (MTM), metasurface (MTS), and substrate integrated waveguides (SIW). The antenna designs described here are implemented on various substrate layers such as Silicon, Graphene, Polyimide, and GaAs to facilitate integration on ICs. Some of the antennas described here employ innovative excitation mechanisms, for example comprising open-circuited microstrip-line that is electromagnetically coupled to radiating elements through narrow dielectric slots. This excitation mechanism is shown to suppress surface wave propagation and reduce substrate loss. Other techniques described like SIW are shown to significantly attenuate surface waves and minimise loss. Radiation elements based on the MTM and MTS inspired technologies are shown to extend the effective aperture of the antenna without compromising the antenna’s form factor. Moreover, the on-chip antennas designed using the above technologies exhibit significantly improved impedance match, bandwidth, gain and radiation efficiency compared to previously used technologies. These features make such antennas a prime candidate for mmWave and THz on-chip integration. This review provides a thorough reference source for specialist antenna designers.This work was supported in part by the Universidad Carlos III de Madrid and the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant 801538, in part by the Icelandic Centre for Research (RANNIS) under Grant 206606, and in part by the National Science Centre of Poland under Grant 2018/31/B/ST7/02369