Ordered Level Planarity, Geodesic Planarity and Bi-Monotonicity

We introduce and study the problem Ordered Level Planarity which asks for a planar drawing of a graph such that vertices are placed at prescribed positions in the plane and such that every edge is realized as a y-monotone curve. This can be interpreted as a variant of Level Planarity in which the vertices on each level appear in a prescribed total order. We establish a complexity dichotomy with respect to both the maximum degree and the level-width, that is, the maximum number of vertices that share a level. Our study of Ordered Level Planarity is motivated by connections to several other graph drawing problems. Geodesic Planarity asks for a planar drawing of a graph such that vertices are placed at prescribed positions in the plane and such that every edge is realized as a polygonal path composed of line segments with two adjacent directions from a given set $S$ of directions symmetric with respect to the origin. Our results on Ordered Level Planarity imply $NP$-hardness for any $S$ with $|S|\ge 4$ even if the given graph is a matching. Katz, Krug, Rutter and Wolff claimed that for matchings Manhattan Geodesic Planarity, the case where $S$ contains precisely the horizontal and vertical directions, can be solved in polynomial time [GD'09]. Our results imply that this is incorrect unless $P=NP$. Our reduction extends to settle the complexity of the Bi-Monotonicity problem, which was proposed by Fulek, Pelsmajer, Schaefer and \v{S}tefankovi\v{c}. Ordered Level Planarity turns out to be a special case of T-Level Planarity, Clustered Level Planarity and Constrained Level Planarity. Thus, our results strengthen previous hardness results. In particular, our reduction to Clustered Level Planarity generates instances with only two non-trivial clusters. This answers a question posed by Angelini, Da Lozzo, Di Battista, Frati and Roselli.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

The Function of Hypoxia-Inducible Factor (HIF) Is Independent of the Endoplasmic Reticulum Protein OS-9

The protein “amplified in osteosarcoma-9” (OS-9) has been shown previously to interact with the prolyl hydroxylases PHD2 and PHD3. These enzymes initiate oxygen-dependent degradation of the α-subunit of hypoxia-inducible factor (HIF), a transcription factor that adapts cells to insufficient oxygen supply (hypoxia). A new model has been proposed where OS-9 triggers PHD dependent degradation of HIF-α. It was the aim of our study to define the molecular mode of action of OS-9 in the regulation of PHD and HIF activity. Although initial co-immunoprecipitation experiments confirmed physical interaction between OS-9 and PHD2, neither overexpression nor lentiviral inhibition of OS-9 expression affected HIF regulation. Subcellular localization experiments revealed a distinct reticular staining pattern for OS-9 while PHD2 was mainly localized in the cytoplasm. Further cell fractionation experiments and glycosylation tests indicated that OS-9 is a luminal ER protein. In vivo protein interaction analysis by fluorescence resonance energy transfer (FRET) showed no significant physical interaction of overexpressed PHD2-CFP and OS-9-YFP. We conclude that OS-9 plays no direct functional role in HIF degradation since physical interaction of OS-9 with oxygen sensing HIF prolyl hydroxylases cannot occur in vivo due to their different subcellular localization

Oxygen-Independent Stabilization of Hypoxia Inducible Factor (HIF)-1 during RSV Infection

BACKGROUND: Hypoxia-inducible factor 1 (HIF)-1alpha is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1alpha as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1alpha as transcriptional regulator during infections with RSV. METHODOLOGY, PRINCIPAL FINDINGS: We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1alpha. These studies revealed that RSV-positive cells also stained for HIF-1alpha, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1alpha protein 24 h after RSV infection. In contrast, HIF-1alpha activation was abolished utilizing UV-treated RSV. Moreover, HIF-alpha-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1alpha dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1alpha. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1alpha activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-alpha-activation in a murine in vivo model. CONCLUSIONS/SIGNIFICANCE: Taking together, these studies suggest hypoxia-independent activation of HIF-1alpha during infection with RSV in vitro and in vivo

Generation of first-order expressions from a broad coverage HPSG grammar

This paper describes an application for computing first-order semantic representations of English texts. It is based on a combination of hybrid shallow-deep components arranged within the middleware framework Heart of Gold. The shallowdeep semantic analysis employs Robust Minimal Recursion Semantics (RMRS) as a common semantic underspecification formalism for natural language processing components. In order to compute efficiently first-order representations of the input text, the intermediate RMRS results of the shallow-deep analysis are transformed into the dominance constraints formalism and resolved by the underspecification resolver UTool. First-order expressions can serve as a formal knowledge representation of natural text and thus can be utilized in knowledge engineering or textual reasoning. At the end of this paper, we describe their application for recognizing textual entailment

Linking the thermal evolution and emplacement history of an upper-crustal pluton to its lower-crustal roots using zircon geochronology and geochemistry (southern Adamello batholith, N. Italy)

The Val Fredda igneous complex in the southern Adamello batholith (N. Italy) consists of dioritic to gabbroic sills and dykes that were injected at 6-10km depth into partly crystallized tonalites and granodiorites. High-precision U-Pb age determinations by chemical abrasion-isotope dilution-thermal ionization mass spectrometry (CA-ID-TIMS) show very similar dispersion of zircon U-Pb dates over 90-200ka and identical age distributions with a dominant mode at 42.5Ma for six samples ranging in composition from gabbro to granodiorite. The co-variation of the probability density curves of zircon dates from mafic and felsic units suggests that they shared a common thermal history with periods of enhanced and reduced zircon growth, reflecting lowered and increased magma temperatures, respectively. However, trace element compositions, Ti-in-zircon temperatures and Hf isotopic compositions of zircon from mafic lithologies are distinctly different from those in felsic zircon and suggest their crystallization occurred in isotopically and chemically diverse magma batches. These magma batches formed in the lower crust from mingling and mixing of residual melts (derived from fractional crystallization of mainly amphibole from basaltic melt) with crustal partial melts at high temperatures above zircon saturation. Zircons crystallized during incipient cooling of these magmas and were entrained into the ascending melts, which were emplaced and rapidly solidified in the upper crust. The reported age dispersions imply that fractional crystallization and hybridization in the lower-to-middle crust, ascent into the upper crust and solidification did not last for more than 200ka. The small magma volumes and flux also preclude significant zircon crystallization at the upper crustal emplacement level

Development of an open prospective observational multicentre cohort study to determine the impact of standardization of laparoscopic intraperitoneal onlay mesh repair (IPOM) for incisional hernia on clinical outcome and quality of life (LIPOM-Trial)

Background: Incisional hernias are one of the most frequent complications in abdominal surgery. Laparoscopic repair has been widely used since its first description but has not been standardized. A panel of hernia experts with expertise on the subject “incisional hernia” was established to review existing literature and define a standard approach to laparoscopic IPOM-repair for incisional hernia. All involved surgeons agreed to perform further IPOM-repairs of incisional hernia according to the protocol. Methods/design: This article summarizes the development of an open prospective observational multicentre cohort study to analyse the impact of a standardization of laparoscopic IPOM-repair for incisional hernia on clinical outcome and quality of life (health care research study). Discussion: Our literature search found that there is a lack of standardization in the surgical approach to incisional hernia and the use of medical devices. The possibility of different surgical techniques, various meshes and a variety of mesh fixation techniques means that the results on outcome after incisional hernia repair are often not comparable between different studies. We believe there is a need for standardization of the surgical procedure and the use of medical devices in order to make the results more comparable and eliminate confounding factors in interpreting the results of surgical hernia repair. This approach, in our view, will also illustrate the influence of the operative technique on the general quality of surgical treatment of incisional hernias better than a “highly selective” study and will indicate the “reality” of surgical treatment not only in specialist centres. Trial registration: The LIPOM-trial is registered at www.clinicaltrials.gov, with identifier: NCT02089958