Recombinants between Deformed wing virus and Varroa destructor virus-1 may prevail in Varroa destructor-infested honeybee colonies

We have used high-throughput Illumina sequencing to identify novel recombinants between deformed wing virus (DWV) and Varroa destructor virus-1 (VDV-1), which accumulate to higher levels than DWV in both honeybees and Varroa destructor mites. The recombinants, VDV-1VVD and VDV-1DVD, exhibit crossovers between the 5’-untranslated region (5’-UTR), and/or the regions encoding the structural (capsid) and non-structural viral proteins. This implies the genomes are modular and that each region may evolve independently, as demonstrated in human enteroviruses. Individual honeybee pupae were infected with a mixture of observed recombinants and DWV. The strong correlation between VDV-1DVD levels in honeybee pupae and the associated mites was observed, suggesting that this recombinant, with a DWV-derived 5’-UTR and non-structural protein region flanking VDV- 1-derived capsid encoding region, is better adapted to transmission between V. destructor and honeybees than the parental DWV or a recombinant bearing the VDV-1-derived 5’-UTR (VDV-1VVD)

Combinatorial Hopf algebras and Towers of Algebras

Bergeron and Li have introduced a set of axioms which guarantee that the Grothendieck groups of a tower of algebras $\bigoplus_{n\ge0}A_n$ can be endowed with the structure of graded dual Hopf algebras. Hivert and Nzeutzhap, and independently Lam and Shimozono constructed dual graded graphs from primitive elements in Hopf algebras. In this paper we apply the composition of these constructions to towers of algebras. We show that if a tower $\bigoplus_{n\ge0}A_n$ gives rise to graded dual Hopf algebras then we must have $\dim(A_n)=r^nn!$ where $r = \dim(A_1)$.Comment: 7 page

Role of 1q21 in multiple myeloma: From pathogenesis to possible therapeutic targets

Multiple myeloma (MM) is characterized by an accumulation of malignant plasma cells (PCs) in the bone marrow (BM). The amplification of 1q21 is one of the most common cytogenetic abnormalities occurring in around 40% of de novo patients and 70% of relapsed/refractory MM. Patients with this unfavorable cytogenetic abnormality are considered to be high risk with a poor response to standard therapies. The gene(s) driving amplification of the 1q21 amplicon has not been fully studied. A number of clear candidates are under investigation, and some of them (IL6R, ILF2, MCL-1, CKS1B and BCL9) have been recently proposed to be potential drivers of this region. However, much remains to be learned about the biology of the genes driving the disease progression in MM patients with 1q21 amp. Understanding the mechanisms of these genes is important for the development of effective targeted therapeutic approaches to treat these patients for whom effective therapies are currently lacking. In this paper, we review the current knowledge about the pathological features, the mechanism of 1q21 amplification, and the signal pathway of the most relevant candidate genes that have been suggested as possible therapeutic targets for the 1q21 amplicon

Large Scale Optimization Problems for Central Energy Facilities with Distributed Energy Storage

On large campuses, energy facilities are used to serve the heating and cooling needs of all the buildings, while utilizing cost savings strategies to manage operational cost. Strategies range from shifting loads to participating in utility programs that offer payouts. Among available strategies are central plant optimization, electrical energy storage, participation in utility demand response programs, and manipulating the temperature setpoints in the campus buildings. However, simultaneously optimizing all of the central plant assets, temperature setpoints and participation in utility programs can be a daunting task even for a powerful computer if the desire is real time control. These strategies may be implemented separately across several optimization systems without a coordinating algorithm. Due to system interactions, decentralized control may be far from optimal and worse yet may try to use the same asset for different goals. In this work, a hierarchal optimization system has been created to coordinate the optimization of the central plant, the battery, participation in demand response programs, and temperature setpoints. In the hierarchal controller, the high level coordinator determines the load allocations across the campus or facility. The coordinator also determines the participation in utility incentive programs. It is shown that these incentive programs can be grouped into reservation programs and price adjustment programs. The second tier of control is split into 3 portions: control of the central energy facility, control of the battery system, and control of the temperature setpoints. The second tier is responsible for converting load allocations into central plant temperature setpoints and flows, battery charge and discharge setpoints, and temperature setpoints, which are delivered to the Building Automation System for execution. It is shown that the whole system can be coordinated by representing the second tier controllers with a smaller set of data that can be used by the coordinating controller. The central plant optimizer must supply an operational domain which constrains how each group of equipment can operate. The high level controller uses this information to send down loadings for each resource a group of equipment in the plant produces or consumes. For battery storage, the coordinating controller uses a simple integrator model of the battery and is responsible for providing a demand target and the amount of participation in any incentive programs. Finally, to perform temperature setpoint optimization a dynamic model of the zone is provided to the coordinating controller. This information is used to determine load allocations for groups of zones. The hierarchal control strategy is successful at optimizing the entire energy facility fast enough to allow the algorithms to control the energy facility, building setpoints, and program bids in real-time

Solitons from Dressing in an Algebraic Approach to the Constrained KP Hierarchy

The algebraic matrix hierarchy approach based on affine Lie $sl (n)$ algebras leads to a variety of 1+1 soliton equations. By varying the rank of the underlying $sl (n)$ algebra as well as its gradation in the affine setting, one encompasses the set of the soliton equations of the constrained KP hierarchy. The soliton solutions are then obtained as elements of the orbits of the dressing transformations constructed in terms of representations of the vertex operators of the affine $sl (n)$ algebras realized in the unconventional gradations. Such soliton solutions exhibit non-trivial dependence on the KdV (odd) time flows and KP (odd and even) time flows which distinguishes them from the conventional structure of the Darboux-B\"{a}cklund Wronskian solutions of the constrained KP hierarchy.Comment: LaTeX, 13pg

Fermionic Coset, Critical Level W^(2)_4-Algebra and Higher Spins

The fermionic coset is a limit of the pure spinor formulation of the AdS5xS5 sigma model as well as a limit of a nonlinear topological A-model, introduced by Berkovits. We study the latter, especially its symmetries, and map them to higher spin algebras. We show the following. The linear A-model possesses affine \AKMSA{pgl}{4}{4}_0 symmetry at critical level and its \AKMSA{psl}{4}{4}_0 current-current perturbation is the nonlinear model. We find that the perturbation preserves $\mathcal{W}^{(2)}_4$-algebra symmetry at critical level. There is a topological algebra associated to \AKMSA{pgl}{4}{4}_0 with the properties that the perturbation is BRST-exact. Further, the BRST-cohomology contains world-sheet supersymmetric symplectic fermions and the non-trivial generators of the $\mathcal{W}^{(2)}_4$-algebra. The Zhu functor maps the linear model to a higher spin theory. We analyze its \SLSA{psl}{4}{4} action and find finite dimensional short multiplets.Comment: 25 page

q-Analogue of Am−1⊕An−1⊂Amn−1A_{m-1}\oplus A_{n-1}\subset A_{mn-1}

A natural embedding $A_{m-1}\oplus A_{n-1}\subset A_{mn-1}$ for the corresponding quantum algebras is constructed through the appropriate comultiplication on the generators of each of the $A_{m-1}$ and $A_{n-1}$ algebras. The above embedding is proved in their $q$-boson realization by means of the isomorphism between the $\mathcal{A}_q^{-}$ (mn)$\sim {\otimes} ^n \mathcal{A}_q^{-}$(m)$\sim {\otimes}^m\mathcal{A}_q^{-}$(n) algebras.Comment: 11 pages, no figures. In memory of professor R. P. Rousse

Selective serotonin reuptake inhibitors and clozapine: Clinically relevant interactions and considerations

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic im-provements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, show-ing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

Background: The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies. Methods: The PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients. Results: First, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16− cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between Í14+PD-L1+ and Í8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells. Conclusions: Our data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment

Spectral extension of the quantum group cotangent bundle

The structure of a cotangent bundle is investigated for quantum linear groups GLq(n) and SLq(n). Using a q-version of the Cayley-Hamilton theorem we construct an extension of the algebra of differential operators on SLq(n) (otherwise called the Heisenberg double) by spectral values of the matrix of right invariant vector fields. We consider two applications for the spectral extension. First, we describe the extended Heisenberg double in terms of a new set of generators -- the Weyl partners of the spectral variables. Calculating defining relations in terms of these generators allows us to derive SLq(n) type dynamical R-matrices in a surprisingly simple way. Second, we calculate an evolution operator for the model of q-deformed isotropic top introduced by A.Alekseev and L.Faddeev. The evolution operator is not uniquely defined and we present two possible expressions for it. The first one is a Riemann theta function in the spectral variables. The second one is an almost free motion evolution operator in terms of logarithms of the spectral variables. Relation between the two operators is given by a modular functional equation for Riemann theta function.Comment: 38 pages, no figure