4,476 research outputs found

    Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase.

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    Feline immunodeficiency virus (FIV) infection results in viral persistence, a prolonged asymptomatic phase, and progressive immunopathology. During the asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits features of viral latency in blood suggestive of inactive viral replication. We sought to investigate viral replication activity and genomic stability of the FIV proviral long terminal repeat (LTR) and the 5' aspect of gag over time. FIV-infected cats during the asymptomatic phase demonstrated undetectable plasma FIV gag RNA transcripts and intermittent to undetectable blood-derived cell-associated FIV gag RNA. The LTR sequence demonstrated instability in blood-derived cells over time, in spite of low to undetectable viral replication. Sequence variation in the LTR was identified in CD4+ and CD21+ leukocytes from blood and surgically removed lymph nodes. Three single nucleotide polymorphisms (SNPs) in the LTR were commonly identified. Promoter functionality of a common LTR SNP and rare U3 mutation were examined by reporter gene assays and demonstrated either no change or increased basal FIV promoter function, respectively. In conclusion, this cohort of asymptomatic FIV-infected cats demonstrated instability of the LTR and 5' gag sequences during the study period, in spite of undetectable plasma and rare to undetectable viral gag RNA, which suggests that blood may not accurately represent viral activity in asymptomatic FIV-infected cats

    Twisted Alexander polynomials detect the unknot

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    The group of a nontrivial knot admits a finite permutation representation such that the corresponding twisted Alexander polynomial is not a unit.Comment: This is the version published by Algebraic & Geometric Topology on 14 November 200

    Sustained inflation at birth did not alter lung injury from mechanical ventilation in surfactant-treated fetal lambs.

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    BackgroundSustained inflations (SI) are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation.HypothesisA 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs.MethodsThe head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline). Fetal lambs were randomized to one of four 15 minute interventions: 1) PEEP 8 cmH2O; 2) 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3) mechanical ventilation with 7 ml/kg tidal volume; or 4) 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention.ResultsSI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP) 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury.ConclusionIn surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation

    Alexander quandle lower bounds for link genera

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    We denote by Q_F the family of the Alexander quandle structures supported by finite fields. For every k-component oriented link L, every partition P of L into h:=|P| sublinks, and every labelling z of such a partition by the natural numbers z_1,...,z_n, the number of X-colorings of any diagram of (L,z) is a well-defined invariant of (L,P), of the form q^(a_X(L,P,z)+1) for some natural number a_X(L,P,z). Letting X and z vary in Q_F and among the labellings of P, we define a derived invariant A_Q(L,P)=sup a_X(L,P,z). If P_M is such that |P_M|=k, we show that A_Q(L,P_M) is a lower bound for t(L), where t(L) is the tunnel number of L. If P is a "boundary partition" of L and g(L,P) denotes the infimum among the sums of the genera of a system of disjoint Seifert surfaces for the L_j's, then we show that A_Q(L,P) is at most 2g(L,P)+2k-|P|-1. We set A_Q(L):=A_Q(L,P_m), where |P_m|=1. By elaborating on a suitable version of a result by Inoue, we show that when L=K is a knot then A_Q(K) is bounded above by A(K), where A(K) is the breadth of the Alexander polynomial of K. However, for every g we exhibit examples of genus-g knots having the same Alexander polynomial but different quandle invariants A_Q. Moreover, in such examples A_Q provides sharp lower bounds for the genera of the knots. On the other hand, A_Q(L) can give better lower bounds on the genus than A(L), when L has at least two components. We show that in order to compute A_Q(L) it is enough to consider only colorings with respect to the constant labelling z=1. In the case when L=K is a knot, if either A_Q(K)=A(K) or A_Q(K) provides a sharp lower bound for the knot genus, or if A_Q(K)=1, then A_Q(K) can be realized by means of the proper subfamily of quandles X=(F_p,*), where p varies among the odd prime numbers.Comment: 36 pages; 16 figure

    AN EXTENSION OF SOME RESULTS DUE TO JARDEN

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    This paper defines some generalized Fibonacci and Lucas sequences which satisfy arbitrary order linear recurrence relations and which answer a problem posed by Jarden in 1966 about generalizing an elegant result for a connection between even and odd subscripted Fibonacci and Lucas numbers

    ARBITRARY ORDER RECURSIVE SEQUENCES AND ASSOCIATED CONTINUED FRACTIONS

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    The essential idea in this paper it to generalize and synthesize some of the pioneering ideas of Bernstein, Lucas and Horadam on generalizations of basic and primordial Fibonacci numbers and their arbitrary order generalizations and their relation to generalized continued fractions with matrices as the unifying elements

    Innate immune pathways associated with lung radioprotection by soy isoflavones

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    Introduction: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radio- protection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury. Methods: BALB/c mice (5–6 weeks old) received a single 10 Gy dose of thoracic irra- diation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day. Arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 were detected in lung tissue by western blot analysis and immunohistochemistry. Lung MDSC subsets and their Arg-1 expression were analyzed by flow cytometry. Cytokine levels in the lungs were measured by ELISA. Results: At 1 week after radiation, CD11b+ cells expressing Arg-1 were decreased by radiation in lung tissue yet maintained in the lungs treated with radiation and soy isoflavones. Arg-1 was predominantly expressed by CD11b+Ly6ClowLy6G+ granulocytic MDSCs (gr-MDSCs). Arg-1 expression in gr-MDSCs was reduced by radiation and preserved by supplementation with soy isoflavones. A persistent increase in Arg-1+ cells was observed in lung tissue treated with combined radiation and soy isoflavones at early and late time points, compared to radiation alone. The increase in Arg-1 expression mediated by soy isoflavones could be associated with the inhibition of radiation-induced activation of NF-κB and the control of pro-inflammatory cytokine production demon- strated in this study. Conclusion: A radioprotective mechanism of soy isoflavones may involve the promotion of Arg-1-expressing gr-MDSCs that could play a role in downregulation of inflammation and lung radioprotection

    Some aspects of Fibonacci polynomial congruences

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    This paper formulates a definition of Fibonacci polynomials which is slightly different from the traditional definitions, but which is related to the classical polynomials of Bernoulli, Euler and Hermite. Some related congruence properties are developed and some unanswered questions are outlined. Keywords: Congruences, recurrence relations, Fibonacci sequence, Lucas sequences, umbral calculus

    The NMDA receptor GluN2C subunit controls cortical excitatoryinhibitory balance, neuronal oscillations and cognitive function

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    Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2Ccontaining NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs. In addition a greater number of perisomatic GAD67 puncta was observed suggesting a potential increase in parvalbumin interneuron inputs. At a network level the GluN2C knockout mice were found to have a more robust increase in power of oscillations in response to NMDAR blocker MK- 801. Furthermore, GluN2C heterozygous and knockout mice exhibited abnormalities in cognition and sensorimotor gating. Our results demonstrate that loss of GluN2C subunit leads to cortical excitatoryinhibitory imbalance and abnormal neuronal oscillations associated with neurodevelopmental disorders
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