318 research outputs found
Two algorithms for the student-project allocation problem
We study the Student-Project Allocation problem (SPA), a generalisation of the classical Hospitals / Residents problem (HR). An instance of SPA involves a set of students, projects and lecturers. Each project is offered by a unique lecturer, and both projects and lecturers have capacity constraints. Students have preferences over projects, whilst lecturers have preferences over students. We present two optimal linear-time algorithms for allocating students to projects, subject to the preference and capacity constraints. In particular, each algorithm finds a stable matching of students to projects. Here, the concept of stability generalises the stability definition in the HR context. The stable matching produced by the first algorithm is simultaneously best-possible for all students, whilst the one produced by the second algorithm is simultaneously best-possible for all lecturers. We also prove some structural results concerning the set of stable matchings in a given instance of SPA. The SPA problem model that we consider is very general and has applications to a range of different contexts besides student-project allocation
The exchange-stable marriage problem
In this paper we consider instances of stable matching problems, namely the classical stable marriage (SM) and stable roommates (SR) problems and their variants. In such instances we consider a stability criterion that has recently been proposed, that of <i>exchange-stability</i>. In particular, we prove that ESM — the problem of deciding, given an SM instance, whether an exchange-stable matching exists — is NP-complete. This result is in marked contrast with Gale and Shapley's classical linear-time algorithm for finding a stable matching in an instance of SM. We also extend the result for ESM to the SR case. Finally, we study some variants of ESM under weaker forms of exchange-stability, presenting both polynomial-time solvability and NP-completeness results for the corresponding existence questions
The Hospitals/Residents Problem with Couples: complexity and integer programming models
The Hospitals / Residents problem with Couples (hrc) is a generalisation of the classical Hospitals / Residents problem (hr) that is important in practical applications because it models the case where couples submit joint preference lists over pairs of (typically geographically close) hospitals. In this paper we give a new NP-completeness result for the problem of deciding whether a stable matching exists, in highly restricted instances of hrc, and also an inapproximability bound for finding a matching with the minimum number of blocking pairs in equally restricted instances of hrc. Further, we present a full description of the first Integer Programming model for finding a maximum cardinality stable matching in an instance of hrc and we describe empirical results when this model applied to randomly generated instances of hrc
Immunomodulation of inflammatory leukocyte markers during intravenous immunoglobulin treatment associated with clinical efficacy in chronic inflammatory demyelinating polyradiculoneuropathy
© 2016 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. Objective: The objective of the study was to profile leukocyte markers modulated during intravenous immunoglobulin (IVIg) treatment, and to identify markers and immune pathways associated with clinical efficacy of IVIg for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with potential for monitoring treatment efficacy. Methods: Response to IVIg treatment in newly diagnosed IVIg-naïve and established IVIg-experienced patients was assessed by changes in expression of inflammatory leukocyte markers by flow cytometry. The adjusted INCAT disability and Medical Research Council sum scores defined clinical response. Results: Intravenous immunoglobulin modulated immunopathogenic pathways associated with inflammatory disease in CIDP. Leukocyte markers of clinical efficacy included reduced CD185 + follicular helper T cells, increased regulatory markers (CD23 and CD72) on B cells, and reduction in the circulating inflammatory CD16 + myeloid dendritic cell (mDC) population and concomitant increase in CD62L and CD195 defining a less inflammatory lymphoid homing mDC phenotype. A decline in inflammatory CD16 + dendritic cells was associated with clinical improvement or stability, and correlated with magnitude of improvement in neurological assessment scores, but did not predict relapse. IVIg also induced a nonspecific improvement in regulatory and reduced inflammatory markers not associated with clinical response. Conclusions: Clinically effective IVIg modulated inflammatory and regulatory pathways associated with ongoing control or resolution of CIDP disease. Some of these markers have potential for monitoring outcome
Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages
Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats
MTRX1011A, a humanized anti-CD4 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a Phase I randomized, double-blind, placebo-controlled study incorporating pharmacodynamic biomarker assessments
The Drosophila G9a gene encodes a multi-catalytic histone methyltransferase required for normal development
Mammalian G9a is a histone H3 Lys-9 (H3–K9) methyltransferase localized in euchromatin and acts as a co-regulator for specific transcription factors. G9a is required for proper development in mammals as g9a(−)/g9a(−) mice show growth retardation and early lethality. Here we describe the cloning, the biochemical and genetical analyses of the Drosophila homolog dG9a. We show that dG9a shares the structural organization of mammalian G9a, and that it is a multi-catalytic histone methyltransferase with specificity not only for lysines 9 and 27 on H3 but also for H4. Surprisingly, it is not the H4–K20 residue that is the target for this methylation. Spatiotemporal expression analyses reveal that dG9a is abundantly expressed in the gonads of both sexes, with no detectable expression in gonadectomized adults. In addition we find a low but clearly observable level of dG9a transcript in developing embryos, larvae and pupae. Genetic and RNAi experiments reveal that dG9a is involved in ecdysone regulatory pathways
An analysis of national target groups for monovalent 2009 pandemic influenza vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11
<p>Abstract</p> <p>Background</p> <p>Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods.</p> <p>Methods</p> <p>Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted.</p> <p>Results</p> <p>We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines), 72 (monovalent pandemic 2009-10 vaccine) and 34 (seasonal 2010 and 2010-11 vaccines) countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to specific target groups and over one-third of the countries offered universal subsidy regarding the pandemic vaccine. There was also some inconsistency between countries in target groups.</p> <p>Conclusions</p> <p>Differences in target groups between countries may reflect variable objectives as well as uncertainties regarding the transmission dynamics, severity and age-specific immunity against influenza viruses before and after vaccination. Clarification on these points is essential to elucidate optimal and object-oriented vaccination strategies.</p
Supramolecular layers and versatile packing modes: the solid state behavior of ortho, ortho-linked bisphenols
A series of ortho-ortho-linked bisphenols featuring electron-withdrawing groups (EWGs) attached to the phenolic rings is reported. Their respective molecular structures and packing behaviors have been studied by X-ray diffraction, comparatively discussed and put into relation with the unsubstituted mother compound. Except for the mother compound, the molecular structures of all bisphenols studied here exhibit distorted aromatic moieties. Hence, the substituents studied here prevent proximal positioning of phenolic units and the formation of strong O-H···O hydrogen bonds. In the packing of the underivatized bisphenol we found a strand-like molecular arrangement featuring strong O-H···O hydrogen bonds and extensive edge-to-face contacts (C-H···π) between the bisphenol molecules. The introduction of EWGs to the aromatic moieties changes these intermolecular interactions into face-to-face contacts resulting either in bisphenol stacks or handshake-like motifs between two bisphenol molecules. In both cases, the C-H···π interactions are more or less replaced by C-H···O contacts as the prevalent non-covalent interaction. In the packing of two nitro bisphenols in their DMSO inclusion compounds an exciting layered arrangement is observed, which also matches with the pronounced foliated habitus of their crystals. Additionally, proton NMR was used to establish the binding coefficients between the respective bisphenols and DMSO in solution
The Rho-Family GTPase Rac1 Regulates Integrin Localization in Drosophila Immunosurveillance Cells
BACKGROUND: When the parasitoid wasp Leptopilina boulardi lays an egg in a Drosophila larva, phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. The Drosophila β-integrin Myospheroid (Mys) is necessary for lamellocytes to adhere to the cellular capsule surrounding L. boulardi eggs. Integrins are heterodimeric adhesion receptors consisting of α and β subunits, and similar to other plasma membrane receptors undergo ligand-dependent endocytosis. In mammalian cells it is known that integrin binding to the extracellular matrix induces the activation of Rac GTPases, and we have previously shown that Rac1 and Rac2 are necessary for a proper encapsulation response in Drosophila larvae. We wanted to test the possibility that Myospheroid and Rac GTPases interact during the Drosophila anti-parasitoid immune response. RESULTS: In the current study we demonstrate that Rac1 is required for the proper localization of Myospheroid to the cell periphery of haemocytes after parasitization. Interestingly, the mislocalization of Myospheroid in Rac1 mutants is rescued by hyperthermia, involving the heat shock protein Hsp83. From these results we conclude that Rac1 and Hsp83 are required for the proper localization of Mys after parasitization. SIGNIFICANCE: We show for the first time that the small GTPase Rac1 is required for Mysopheroid localization. Interestingly, the necessity of Rac1 in Mys localization was negated by hyperthermia. This presents a problem, in Drosophila we quite often raise larvae at 29°C when using the GAL4/UAS misexpression system. If hyperthermia rescues receptor endosomal recycling defects, raising larvae in hyperthermic conditions may mask potentially interesting phenotypes
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