How to project a bipartite network?

The one-mode projecting is extensively used to compress the bipartite networks. Since the one-mode projection is always less informative than the bipartite representation, a proper weighting method is required to better retain the original information. In this article, inspired by the network-based resource-allocation dynamics, we raise a weighting method, which can be directly applied in extracting the hidden information of networks, with remarkably better performance than the widely used global ranking method as well as collaborative filtering. This work not only provides a creditable method in compressing bipartite networks, but also highlights a possible way for the better solution of a long-standing challenge in modern information science: How to do personal recommendation?Comment: 7 pages, 4 figure

Cooling of Dense Gas by H2O Line Emission and an Assessment of its Effects in Chondrule-Forming Shocks

We consider gas at densities appropriate to protoplanetary disks and calculate its ability to cool due to line radiation emitted by H2O molecules within the gas. Our work follows that of Neufeld & Kaufman (1993; ApJ, 418, 263), expanding on their work in several key aspects, including use of a much expanded line database, an improved escape probability formulism, and the inclusion of dust grains, which can absorb line photons. Although the escape probabilities formally depend on a complicated combination of optical depth in the lines and in the dust grains, we show that the cooling rate including dust is well approximated by the dust-free cooling rate multiplied by a simple function of the dust optical depth. We apply the resultant cooling rate of a dust-gas mixture to the case of a solar nebula shock pertinent to the formation of chondrules, millimeter-sized melt droplets found in meteorites. Our aim is to assess whether line cooling can be neglected in chondrule-forming shocks or if it must be included. We find that for typical parameters, H2O line cooling shuts off a few minutes past the shock front; line photons that might otherwise escape the shocked region and cool the gas will be absorbed by dust grains. During the first minute or so past the shock, however, line photons will cool the gas at rates ~ 10,000 K/hr, dropping the temperature of the gas (and most likely the chondrules within the gas) by several hundred K. Inclusion of H2O line cooling therefore must be included in models of chondrule formation by nebular shocks.Comment: Accepted for publication in The Astrophysical Journa

Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR

© 2020 The Authors Rising numbers of cases of multidrug- and extensively drug-resistant Pseudomonas aeruginosa over recent years have created an urgent need for novel therapeutic approaches to cure potentially fatal infections. One such approach is virulence attenuation where anti-virulence compounds, designed to reduce pathogenicity without affording bactericidal effects, are employed to treat infections. P. aeruginosa uses the pqs quorum sensing (QS) system, to coordinate the expression of a large number of virulence determinants as well as bacterial-host interactions and hence represents an excellent anti-virulence target. We report the synthesis and identification of a new series of thiazole-containing quinazolinones capable of inhibiting PqsR, the transcriptional regulator of the pqs QS system. The compounds demonstrated high potency (IC50 < 300 nM) in a whole-cell assay, using a mCTX:PpqsA-lux-based bioreporter for the P. aeruginosa PAO1-L and PA14 strains. Structural evaluation defined the binding modes of four analogues in the ligand-binding domain of PqsR through X-ray crystallography. Further work showed the ability of 6-chloro-3((2-pentylthiazol-4-yl)methyl)quinazolin-4(3H)-one (18) and 6-chloro-3((2-hexylthiazol-4-yl)methyl)quinazolin-4(3H)-one (19) to attenuate production of the PqsR-regulated virulence factor pyocyanin. Compounds 18 and 19 showed a low cytotoxic profile in the A549 human epithelial lung cell line making them suitable candidates for further pre-clinical evaluation

North Korean Decisionmaking

Discerning the decisionmaking of Kim Jong-Un and the North Korean regime on issues of peaceful engagement and warlike actions endures as a mighty challenge for U.S. intelligence analysts and policymakers. In this report, we seek to inform analysis of Democratic People’s Republic of Korea (DPRK) leadership decisionmaking. To do so, we use three discussion papers that were written to facilitate discussion of an interagency working group. The three papers are assembled here in a single report. The first discussion paper describes decisionmaking among different authoritarian regimes, including North Korea, and the opening up of those economies to outside engagement. The second paper outlines two different scenarios that might occur when conventional deterrence on the Korean Peninsula breaks down and the resulting decisions that North Korea’s leadership could face. The third paper assesses DPRK decisionmaking about nuclear weapon use. The report concludes with some observations, drawn from the issues covered in these three discussion papers, about DPRK decisionmaking and stability on the Korean Peninsula

A nonlinear hydrodynamical approach to granular materials

We propose a nonlinear hydrodynamical model of granular materials. We show how this model describes the formation of a sand pile from a homogeneous distribution of material under gravity, and then discuss a simulation of a rotating sandpile which shows, in qualitative agreement with experiment, a static and dynamic angle of repose.Comment: 17 pages, 14 figures, RevTeX4; minor changes to wording and some additional discussion. Accepted by Phys. Rev.

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.National Institutes of Health (U.S.) (Grant R01 EB006365-06)Brain Science Foundation (Private Grant 106708

Changing times in England: the influence on geography teachers’ professional practice

School geography in England has been characterised as a pendulum swinging between policies that emphasise curriculum and pedagogy alternately. In this paper, I illustrate the influence of these shifts on geography teacher's professional practice, by drawing on three “moments” from my experience as a student, teacher and teacher educator. Barnett's description of teacher professionalism as a continuous project of “being” illuminates how geography teachers can adapt to competing influences. It reflects teacher professionalism as an unfinished project, which is responsive, but not beholden, to shifting trends, and is informed by how teachers frame and enact policies. I argue that recognising these contextual factors is key to supporting geography teachers in “being” geography education professionals. As education becomes increasingly competitive on a global scale, individual governments are looking internationally for “solutions” to improve educational rankings. In this climate, the future of geography education will rest on how teachers react locally to international trends. Geography teacher educators can support this process by continuing to inform the field through meaningful geography education research, in particular in making the contextual factors of their research explicit. This can be supported through continued successful international collaboration in geography education research

Tissue distribution and elimination of C-14 apixaban in rats

Abbreviations used: AUC, area under the plasma concentration-time curve; BCRP, breast cancer resistance protein; BLQ, below limit of quantitation; LSC, liquid scintillation counting; LC/MS, liquid chromatography/mass spectrometry; MS/MS, tandem mass spectrometry; Mrp, multidrug resistance protein; LLOQ, low limit of quantitation; P-gp, Pglycoprotein; PK, pharmacokinetics; QWBA, Whole-body autoradiography; SD, SpragueDawley rats. ABSTRACT Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial and venous thrombotic diseases. The distribution, metabolism, and elimination of C-14 apixaban were investigated in male, female, pregnant and lactating rats following single oral doses. Tissue distribution of radioactivity in rats was measured using quantitative whole-body autoradiography. Following single oral administration, radioactivity distributed quickly in rats with C max at 1 h for most tissues. The elimination t 1/2 of radioactivity in blood was 1.7 to 4.2 h. The blood AUC of radioactivity was similar between male and female rats and was slightly higher in pregnant and lower in lactating rats. The radioactivity concentration in tissues involved in elimination was greater than blood with the highest concentration in gastrointestinal tracts, liver, urinary bladder/contents, and lowest level in brains. In pregnant rats, the whole-body autoradiogram showed that low levels of radioactivity were present in fetal blood, liver, and kidney, and were much lower than the radioactivity in respective maternal organs. Fecal route was the major (74% of dose) and urinary was minor pathway (14%) for apixaban elimination. Following single oral doses of C-14 apixaban to lactating rats, apixaban exhibited extensive lacteal excretion with apixaban as the major component. In summary, tissue distribution of apixaban in rats was extensive, but with limited transfer to fetal and brain tissues and extensive secretion into rat milk with parent drug as the major component. Milk excretion could account for 10% of apixaban dose, which was comparable to urinary elimination in rats. Tissue distribution and drug excretion of apixaban are consistent with a moderately permeable drug that is a substrate for P-gp and BCRP efflux transporters

Continent-Wide Survey Reveals Massive Decline in African Savannah Elephants

African elephants (Loxodonta africana) are imperiled by poaching and habitat loss. Despite global attention to the plight of elephants, their population sizes and trends are uncertain or unknown over much of Africa. To conserve this iconic species, conservationists need timely, accurate data on elephant populations. Here, we report the results of the Great Elephant Census (GEC), the first continent-wide, standardized survey of African savannah elephants. We also provide the first quantitative model of elephant population trends across Africa. We estimated a population of 352,271 savannah elephants on study sites in 18 countries, representing approximately 93% of all savannah elephants in those countries. Elephant populations in survey areas with historical data decreased by an estimated 144,000 from 2007 to 2014, and populations are currently shrinking by 8% per year continent-wide, primarily due to poaching. Though 84% of elephants occurred in protected areas, many protected areas had carcass ratios that indicated high levels of elephant mortality. Results of the GEC show the necessity of action to end the African elephants’ downward trajectory by preventing poaching and protecting habitat

THE ROLE OF INTERDEPENDENCE IN THE MICRO-FOUNDATIONS OF ORGANIZATION DESIGN: TASK, GOAL, AND KNOWLEDGE INTERDEPENDENCE

Interdependence is a core concept in organization design, yet one that has remained consistently understudied. Current notions of interdependence remain rooted in seminal works, produced at a time when managers’ near-perfect understanding of the task at hand drove the organization design process. In this context, task interdependence was rightly assumed to be exogenously determined by characteristics of the work and the technology. We no longer live in that world, yet our view of interdependence has remained exceedingly task-centric and our treatment of interdependence overly deterministic. As organizations face increasingly unpredictable workstreams and workers co-design the organization alongside managers, our field requires a more comprehensive toolbox that incorporates aspects of agent-based interdependence. In this paper, we synthesize research in organization design, organizational behavior, and other related literatures to examine three types of interdependence that characterize organizations’ workflows: task, goal, and knowledge interdependence. We offer clear definitions for each construct, analyze how each arises endogenously in the design process, explore their interrelations, and pose questions to guide future research