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Bladder cancer remains a leading cause of death and one of the most expensive cancers to treat in the United States. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) is a personalized therapeutic approach that has the potential to treat bladder cancer at every stage of disease. We have previously demonstrated the ability to expand tumor reactive T cells from transurethral resection, radical cystectomy, and metastatic lymph node tumor specimens collected from bladder cancer patients. In this study, our goal is to investigate different delivery approaches of ACT in vivo to determine the best strategy to decrease tumor burden and advise clinical trial design. Experiments were performed using MB49 murine bladder cancer cells transfected to express ovalbumin (MB49OVA). MB49OVA cells are recognized by OVA-specific OT-I T cells as determined by IFN-gamma production in vitro. Our methods include both subcutaneous and orthotopic bladder tumor models. In vivo, we first tested systemic delivery of OT-I T cells (5.0 × 10e6) by tail vein injection after lymphodepletion with a regimen of cyclophosphamide followed by fludarabine in mice bearing subcutaneous MB49OVA tumors. ACT-treated mice experienced significant tumor regression (p=0.02), improved survival (median survival PBS=47 days, ACT=undefined, p=0.01), and increased tumor infiltration of CD3+, CD4+, and CD8+ T cells. OT-I T cells as well as endogenous OVA-specific CD8+ T cells were detectable in the spleens and tumors of treated mice. Next we tested the efficacy of intravesical delivery of OT-I T cells in mice bearing orthotopic MB49OVA tumors, without prior lymphodepletion. OT-I T cells (4.0 × 10e6) were delivered directly to the bladder via catherization and tumor growth was monitored weekly via ultrasound imaging. Infiltration of CellTrace Violet-labeled OT-I T cells into orthotopic tumors was detected after 3 hours of incubation by flow cytometry analysis of resected tumor. Orthotopic bladder tumor growth was significantly abrogated in ACT-treated mice compared with PBS control-treated mice (p=0.001) and improved survival was observed (median survival PBS=35 days, ACT=undefined). An increase in CD8+ T-cell infiltration was measured in tumors of mice at day 60 post treatment. In order to evaluate the efficacy of TIL transfer in these bladder tumor models, T cells infiltrating subcutaneous MB49OVA tumors were isolated and cultured in vitro in media containing IL-2. After 1 week, bladder TIL demonstrated reactivity against MB49OVA and MB49 parental cells as determined by IFN-gamma production. Future work will implement the adoptive transfer of MB49 TIL for the treatment of orthotopic bladder tumors alone or in combination with anti-PD-L1 therapy. Taken together, these data suggest that ACT using bladder tumor-specific T cells has the potential to reduce bladder tumor burden when given either systemically or intravesically directly into the bladder. Citation Format: Brittany L. Bunch, Jennifer Morse, Sarah Asby, Michael Poch, Shari Pilon-Thomas. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for the treatment of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A01.

Immunotherapy, including adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TIL) predominantly targets improvement in MHC Class I-mediated anti-tumor immune responses. The primary objective of this study is to better understand the role of CD4+ TIL in ACT as a complementary avenue for therapeutic efficacy. Briefly, CD4+ TIL were isolated by negative selection from metastatic melanoma patients who received TIL therapy at Moffitt Cancer Center on IRB approved protocols. Individual T cell clones were tracked by TCRbeta sequencing to quantify clonal persistence in patients. CD4+ TIL clones were found to be decidedly persistent in a candidate patient who achieved a complete response (CR) after infusion of 88% CD4+ T cells. CD4+ TIL from additional patients were stimulated with anti-CD3/CD28 in vitro and those who were clinical responders demonstrated a pleiotropic cytokine profile marked by an elevated ratio of Th1:Th2 cytokines (p=0.07, n=13). When cultured with APCs loaded with autologous tumor (AT), CD4+ TIL produced high levels of IFN-gamma in an MHC Class II-dependent manner. Induction of MHC Class II on melanoma cell lines and AT determined that CD4+ TIL secreted IFNg and TNFa directly in response to AT. ACT of tumor-reactive CD4+ TIL in immunodeficient (NSG) mice provided significant control of AT growth when compared to non-reactive CD4+ TIL. Preliminary data in syngeneic mouse models also suggests that antigen-specific CD4+ T cells aid in initial tumor rejection, memory formation and epitope spreading, resulting in an overall increased therapeutic efficacy during ACT. This data supports the conclusion that CD4+ TIL are tumor-reactive and instrumental to an effective anti-tumor immune response in cancer patients.

We introduce a type $A$ crystal structure on decreasing factorizations of fully-commutative elements in the 0-Hecke monoid which we call $\star$-crystal. This crystal is a $K$-theoretic generalization of the crystal on decreasing factorizations in the symmetric group of the first and last author. We prove that under the residue map the $\star$-crystal intertwines with the crystal on set-valued tableaux recently introduced by Monical, Pechenik and Scrimshaw. We also define a new insertion from decreasing factorization to pairs of semistandard Young tableaux and prove several properties, such as its relation to the Hecke insertion and the uncrowding algorithm. The new insertion also intertwines with the crystal operators., Comment: 37 pages; in revision 1 Sections 3.1, 4.3 and 4.4 were updated; in revision 2 the phrase 321-avoiding is replaced by fully-commutative, typos are fixed, reference added

Intralesional (IL) injection of Rose Bengal (PV-10) induces regression of injected and uninjected lesions in several murine tumor models. In this study, we investigated the anti-tumor response of combining IL PV-10 with blockade of the PD-1 / PD-L1 pathway and the role of immune cell populations in eliciting this response. To investigate the role of T cell subsets in mediating an immune response, B16 or M05 melanoma-bearing mice received combination therapy as well as CD8+, CD4+, or CD25+ depleting antibodies. Tumor growth was measured. T cells were collected from spleens or tumors, and phenotype, activation markers, and reactivity were measured. Splenocytes from mice treated with combination therapy had increased OVA antigen-specific CD8+ T cells in M05-tumor-bearing mice. Depletion of CD4+ T cells or regulatory T cells (Tregs) in combination with IL PV-10 and anti-PD-1 antibody treatment resulted in an enhanced anti-tumor effect. Treatment with CD8+ depleting antibody abrogated anti-tumor immunity. These results support a clinical study for the safety and anti-tumor immune responses with combination therapy of IL PV-10 and PD-1/PD-L1 blockade.

4-1BB (CD137) is a co-stimulatory receptor expressed on activated T cells and other immune cells and is associated with enhanced T cell proliferation, survival, and increased cytokine production upon engagement with its ligand (4-1BBL). We have previously shown that addition of agonistic 4-1BB antibody to tumor fragments increased tumor infiltrating lymphocyte (TIL) expansion in human melanoma and pancreatic tumors. Furthermore, agonistic 4-1BB antibody led to increased expression of maturation markers in resident dendritic cells (DCs) present within tumor fragments. While the role of 4-1BB in T cell biology is well described, little is known about 4-1BB signaling in tumor-resident DCs. We hypothesized that 4-1BB agonism in tumor-resident DCs would promote anti-tumor T cell immune responses. To evaluate the role of 4-1BB signaling on dendritic cells, murine bone marrow derived-DCs were cultured with agonistic 4-1BB antibody and loaded with OVA protein. Treatment with agonistic 4-1BB in vitro led to increased OVA-FITC uptake by DCs (32.6% compared to 15.9% in DCs treated with control antibody). DCs treated with agonistic 4-1BB antibody demonstrated increased T cell stimulatory capacity upon co-culture with OVA-specific OT-I and OT-II T cells. We next compared systemic and intralesional (IL) treatment with agonistic 4-1BB antibody. For the systemic model, mice were injected subcutaneously (SC) with B16 melanoma or Panc02 pancreatic tumor cells and treated by intraperitoneal injection of control or anti-4-1BB antibodies. Mice treated systemically with agonistic 4-1BB antibody exhibited a minimal reduction in tumor growth. In contrast, IL injection of agonistic 4-1BB antibody led to dramatic decreases in tumor growth. Next, we wanted to determine whether IL treatment with agonistic 4-1BB antibody would improve DC stimulatory capacity. Mice bearing B16 or Panc02 tumors were treated IL with normal control or anti-4-1BB antibody. After 7 days, tumor-resident CD11b+ DCs exhibited enhanced in vivo antigen uptake. In addition, an increased number of CD8+ T cells was measured within tumors treated with agonistic 4-1BB antibody (28.1% compared to 20% in NrIgG-treated Panc02OVA tumors and 19.45% compared to 7.3% in NrIgG treated B16-OVA tumors; p=0.0059). Together, these studies demonstrate that agonistic 4-1BB can enhance the ability of DCs to stimulate T cells and IL administration of agonistic 4-1BB antibody can significantly reduce tumor growth. This suggests that IL treatment of agonistic 4-1BB may yield greater efficacy than systemic therapy in patients with melanoma or pancreatic cancer. Citation Format: Amy Mackay Weber, Patrick Innamarato, Jennifer Morse, Scott Kidd, Sarah Asby, Amod Sarnaik, Shari Pilon-Thomas. Targeting 4-1BB in tumors enhances anti-tumor immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2403.

Establishing a program to monitor waste anesthetic gas (WAG) in order to limit personnel exposure requires measuring the levels of WAG emitted and determining the effectiveness of scavenging methods to reduce such levels. In this study, the authors used infrared spectroscopy to measure levels of WAG emitted while anesthetizing mice with isoflurane for 15 min. They evaluated four different WAG scavenging conditions during induction and maintenance anesthesia: two conditions that used passive techniques and two that used active techniques. Isoflurane concentrations were measured at three different locations: in the operator's vicinity, at the mouse-facemask interface and in the room environment. Passive scavenging of WAG improved when chambers were purged with oxygen after induction and when a diaphragm-sealed facemask delivered a reduced anesthetic flow rate during maintenance anesthesia. Active scavenging of WAG improved when a relief intake opening was provided in the induction chamber's vacuum line, vacuum draw after induction was regulated and the anesthetic flow rate and vacuum scavenging draw were balanced during maintenance anesthesia using a facemask that separated the breathing space from the scavenging zone. Additionally, time-weighted average isoflurane WAG levels detected by personal dosimeters correlated with real-time measurements made using infrared spectroscopy. These observations contribute to the development of a substantiated program for monitoring WAG air quality.

Prognostic uncertainty is one barrier to engaging in goals-of-care discussions in chronic kidney disease (CKD). The surprise question ("Would you be surprised if this patient died in the next 12 months?") is a tool to assist in prognostication. However, it has not been studied in non-dialysis-dependent CKD and its reliability is unknown.Observational study.388 patients at least 60 years of age with non-dialysis-dependent CKD stages 4 to 5 who were seen at an outpatient nephrology clinic.Trinary (ie, Yes, Neutral, or No) and binary (Yes or No) surprise question response.Mortality, test-retest reliability, and blinded inter-rater reliability.Baseline comorbid conditions, Charlson Comorbidity Index, cause of CKD, and baseline laboratory values (ie, serum creatinine/estimated glomerular filtration rate, serum albumin, and hemoglobin).Median patient age was 71 years with median follow-up of 1.4 years, during which time 52 (13%) patients died. Using the trinary surprise question, providers responded Yes, Neutral, and No for 202 (52%), 80 (21%), and 106 (27%) patients, respectively. About 5%, 15%, and 27% of Yes, Neutral, and No patients died, respectively (P0.001). Trinary surprise question inter-rater reliability was 0.58 (95% CI, 0.42-0.72), and test-retest reliability was 0.63 (95% CI, 0.54-0.72). The trinary surprise question No response had sensitivity and specificity of 55% and 76%, respectively (95% CIs, 38%-71% and 71%-80%, respectively). The binary surprise question had sensitivity of 66% (95% CI, 49%-80%; P=0.3 vs trinary), but lower specificity of 68% (95% CI, 63%-73%; P=0.02 vs trinary).Single center, small number of deaths.The surprise question associates with mortality in CKD stages 4 to 5 and demonstrates moderate to good reliability. Future studies should examine how best to deploy the surprise question to facilitate advance care planning in advanced non-dialysis-dependent CKD.

The non-negative integer cocharge statistic on words was introduced in the 1970's by Lascoux and Sch\"utzenberger to combinatorially characterize the Hall-Littlewood polynomials. Cocharge has since been used to explain phenomena ranging from the graded decomposition of Garsia-Procesi modules to the cohomology structure of the Grassman variety. Although its application to contemporary variations of these problems had been deemed intractable, we prove that the two-parameter, symmetric Macdonald polynomials are generating functions of a distinguished family of colored words. Cocharge adorns one parameter and the second measures its deviation from cocharge on words without color. We use the same framework to expand the plactic monoid, apply Kashiwara's crystal theory to various Garsia-Haiman modules, and to address problems in K-theoretic Schubert calculus., Comment: 25 pages

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been linked to acute kidney injury (AKI), chronic kidney disease (CKD) and cardiovascular disease (CVD). Patients who survive an AKI episode are at risk for future adverse kidney and cardiovascular outcomes. The objective of our study was to examine the prevalence and predictors of NSAID use among AKI survivors. Methods The Southern Community Cohort Study is a prospective study of low-income adults aged 40–79 in the southeastern US. Through linkage with Centers for Medicare and Medicaid Services, 826 participants with an AKI diagnosis (ICD-9 584.5-584.9) at any age prior to cohort enrollment were identified. At baseline, data were collected on regular use of prescription and over-the-counter NSAIDs, as well as demographic, medical and other characteristics. Additional comorbidities were ascertained via linkage with CMS or the US Renal Data System. Results One hundred fifty-four AKI survivors (19%) reported regular NSAID use at cohort enrollment (52 prescription, 81 OTC, 21 both) and the percentage of NSAID users did not vary by time since AKI event. Over 58% of users were taking NSAIDS regularly both before and after their AKI event. Hypertension (83%), arthritis (71%), heart failure (44%), CKD (36%) and diabetes (35%) were prevalent among NSAID users. In a multivariable model, history of arthritis (OR: 3.00; 95% CI: 1.92, 4.68) and acetaminophen use (OR: 2.43; 95% CI: 1.50, 3.93) were significantly associated with NSAID use, while prevalent CKD (OR: 0.63; 95% CI: 0.41, 0.98) and diabetes (OR: 0.44; 95% CI: 0.29, 0.69) were significantly inversely associated. Conclusions NSAID use among AKI survivors is common and highlights the need to understand physician and patient decision-making around NSAIDs and to develop effective strategies to reduce NSAID use in this vulnerable population. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0411-7) contains supplementary material, which is available to authorized users.

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Background Delirium affects 20–30% of patients after cardiac surgery and is associated with increased mortality and persistent cognitive decline. Hyperoxic reperfusion of ischemic tissues increases oxidative injury, but oxygen administration remains high during cardiac surgery. We tested the hypothesis that intraoperative hyperoxic cerebral reperfusion is associated with increased postoperative delirium and that oxidative injury mediates this association. Methods We prospectively measured cerebral oxygenation with bilateral oximetry monitors in 310 cardiac surgery patients, quantified intraoperative hyperoxic cerebral reperfusion by measuring the magnitude of cerebral oxygenation above baseline after any ischemic event, and assessed patients for delirium twice daily in the ICU following surgery using the confusion assessment method for ICU (CAM-ICU). We examined the association between hyperoxic cerebral reperfusion and postoperative delirium, adjusted for the extent of cerebral hypoxia, the extent of cerebral hyperoxia prior to any ischemia, and additional potential confounders and risk factors for delirium. To assess oxidative injury mediation, we examined the association between hyperoxic cerebral reperfusion and delirium after further adjusting for plasma levels of F 2 -isoprostanes and isofurans at baseline and ICU admission, the association between hyperoxic cerebral reperfusion and these markers of oxidative injury, and the association between these markers and delirium. Results Ninety of the 310 patients developed delirium following surgery. Every 10%·hour of intraoperative hyperoxic cerebral reperfusion was independently associated with a 65% increase in the odds of delirium (OR, 1.65 [95% CI, 1.12–2.44]; P=0.01). Hyperoxia prior to ischemia was also independently associated with delirium (1.10 [1.01–1.19]; P=0.02), but hypoxia was not (1.12 [0.97–1.29]; P=0.11). Increased hyperoxic cerebral reperfusion was associated with increased concentrations of F 2 -isoprostanes and isofurans at ICU admission, increased concentrations of these markers were associated with increased delirium, and the association between hyperoxic cerebral reperfusion and delirium was weaker after adjusting for these markers of oxidative injury. Conclusions Intraoperative hyperoxic cerebral reperfusion was associated with increased postoperative delirium, and increased oxidative injury following hyperoxic cerebral reperfusion may partially mediate this association. Further research is needed to assess the potential deleterious role of cerebral hyper-oxygenation during surgery.

We introduce a family of tableaux that simultaneously generalizes the tableaux used to characterize Grothendieck polynomials and k -Schur functions. We prove that the polynomials drawn from these tableaux are the affine Grothendieck polynomials and k - K -Schur functions – Schubert representatives for the K -theory of affine Grassmannians and their dual in the nil Hecke ring. We prove a number of combinatorial properties including Pieri rules.

OBJECTIVES/SPECIFIC AIMS: The Life’s Simple 7 (LS7) metric was created by the American Heart Association with the goal of educating the public on seven modifiable factors that contribute to heart health. While it is well documented that these ideal health behaviors lower risk of cardiovascular disease (CVD) in the general population, the association between the LS7 ideal health metrics and end stage renal disease (ESRD) risk has not been examined in a lower socioeconomic population at high risk for both ESRD and CVD. Our objective is to examine the association between the LS7 score and incident ESRD in a cohort of white and black men and women in the southeastern US, where rates of CVD and ESRD are high. METHODS/STUDY POPULATION: The Southern Community Cohort Study recruited ~86,000 low-income blacks and whites in the southeastern US (2002-2009). Utilizing a nested case-control design, our analysis included 1628 incident cases of ESRD identified via linkage of the cohort with the United States Renal Data System (USRDS) from January 1, 2002 to March 31, 2015. Controls (n = 4884) were individually matched 3:1 with ESRD cases based on age, sex, and race. Demographic, medical, and lifestyle information were obtained via baseline questionnaire. The AHA definitions for ideal health were used for non-smoking (never or quit >12 months), body mass index (BMI75 min/week of vigorous physical activity or >150min/week of moderate/vigorous activity). Modified definitions were used for consuming a healthy diet [Healthy Eating Index (HEI10) score>70] and for blood pressure, fasting plasma glucose, and total cholesterol, based on self-reported no history of diagnosis of hypertension, diabetes, and hypercholesterolemia, respectively. The number of ideal health parameters were summed to generate the LS7 score, which ranged from 0-7 with higher scores indicating more ideal health. Adjusted odds ratios (95% confidence intervals) for incident ESRD associated with LS7 score were calculated using conditional logistic regression models, adjusting for income and education. The SCCS ESRD case-cohort dataset will be available by TS 2019 and analyses will be completed to adjust for baseline estimated glomerular filtration rate (eGFR) as a marker of kidney function and to examine whether eGFR modifies the relationship between LS7 and incident ESRD. RESULTS/ANTICIPATED RESULTS: At baseline, mean age was 54 years, 55% (3600) of participants were women, and 87% (5656) were black. A total of 58% (943) of ESRD cases were non-smokers compared to 54% (2633) of controls. ESRD cases had higher prevalence of BMI>25 kg/m2 (81% vs. 74%), hypertension (84% vs. 59%), hypercholesterolemia (48% vs. 34%), and diabetes (66% vs. 22%) compared to controls. A total of 18% (839) of controls and 12% (194) of ESRD cases met ideal exercise recommendations, and 20% of either cases (302) or controls (916) had a HEI10 score above 70. The median LS7 score for controls and ESRD cases was 3 and 2, respectively, and 17% (983) of participants had a low score (0-1) while 2% (105) met 6 or 7 ideal health metrics. Higher LS7 score was associated with lower odds of ESRD (P-trend3 (above median) had 75% reduced odds of ESRD (OR 0.25; 95% CI 0.22, 0.29) compared to those with a score of 2 or less. DISCUSSION/SIGNIFICANCE OF IMPACT: In the SCCS population, the presence of any 3 or more ideal health behaviors is associated with reduced odds of developing ESRD. The components of the LS7 represent important modifiable risk factors that may be targets for future interventions driven by the patient. The attributable risk due to each factor is needed to dissect which ideal behaviors are the most beneficial.

The problem of computing products of Schubert classes in the cohomology ring can be formulated as the problem of expanding skew Schur polynomials into the basis of ordinary Schur polynomials. In contrast, the problem of computing the structure constants of the Grothendieck ring of a Grassmannian variety with respect to its basis of Schubert structure sheaves is not equivalent to expanding skew stable Grothendieck polynomials into the basis of ordinary stable Grothendiecks. Instead, we show that the appropriate K-theoretic analogy is through the expansion of skew reverse plane partitions into the basis of polynomials which are Hopf-dual to stable Grothendieck polynomials. We combinatorially prove this expansion is determined by Yamanouchi set-valued tableaux. A by-product of our results is a dual approach proof for Buch's K-theoretic Littlewood-Richardson rule for the product of stable Grothendieck polynomials., 18 pages; references added; minor revisions

We give a new description of the Pieri rule for $k$-Schur functions using the Bruhat order on the affine type-$A$ Weyl group. In doing so, we prove a new combinatorial formula for representatives of the Schubert classes for the cohomology of affine Grassmannians. We show how new combinatorics involved in our formulas gives the Kostka-Foulkes polynomials and discuss how this can be applied to study the transition matrices between Hall-Littlewood and $k$-Schur functions., Nous présentons une nouvelle description, issue de l'ordre de Bruhat du groupe de Weyl affine de type $A$, de la règle de Pieri pour les fonctions $k$-Schur. Ce faisant, nous obtenons une nouvelle formule combinatoire pour les représentants des classes de Schubert de la cohomologie des Grassmannienne affines. Nous décrivons aussi comment notre approche permet d'obtenir les polynômes de Kostka-Foulkes et comment elle peut être appliquée à l’étude des matrices de transition entre les polynômes de Hall-Littlewood et les fonctions $k$-Schur.

We prove that structure constants related to Hecke algebras at roots of unity are special cases of k k -Littlewood-Richardson coefficients associated to a product of k k -Schur functions. As a consequence, both the 3-point Gromov-Witten invariants appearing in the quantum cohomology of the Grassmannian, and the fusion coefficients for the WZW conformal field theories associated to s u ^ ( ℓ ) \widehat {su}(\ell ) are shown to be k k -Littlewood-Richardson coefficients. From this, Mark Shimozono conjectured that the k k -Schur functions form the Schubert basis for the homology of the loop Grassmannian, whereas k k -Schur coproducts correspond to the integral cohomology of the loop Grassmannian. We introduce dual k k -Schur functions defined on weights of k k -tableaux that, given Shimozono’s conjecture, form the Schubert basis for the cohomology of the loop Grassmannian. We derive several properties of these functions that extend those of skew Schur functions.

The transcription factor NF-kappaB is believed to play a key pathophysiological role in chronic intestinal inflammation. Further characterization of its mechanism of regulation, predominantly through cell signaling pathways, may provide clues as to the means of its intervention. One such potential signaling candidate is the protein kinase CK2. Despite its known ability to influence NF-kappaB activation, it has received no attention in this particular setting.To characterize the aspects of its activation in response to IL-1beta in the colonic cell lines Caco2 and HCT116.A biochemical analysis of kinase activation was performed using phospho-specific antibodies as well as immune complex kinase assays; transcription factor activity was measured by transient transfection and luciferase-based NF-kappaB reporter assays; pro-inflammatory molecule expression was determined using RT-PCR.In this report, we show an enhanced activation of CK2 bound to IKKgamma or the p65 subunit of the NF-kappaB in response to IL-1beta stimulation of intestinal epithelial cells. Using two established NF-kappaB reporters, we demonstrate that CK2 is involved in NF-kappaB regulation through the p65 serine 529 site. Using co-immunoprecipitation studies, we also show that p65 is bound to CK2 predominantly in the nucleus. From a functional perspective, two CK2 specific inhibitors were then shown to attenuate IL-8 reporter activation. Finally, the expression of a series of pro-inflammatory molecules including IL-8, GRO-alpha, MCP-1, TNFalpha and iNOS were variably affected in response to CK2 inhibition.CK2 plays an active role in NF-kappaB signaling in intestinal epithelial cell lines and may represent a possible target for intervention.

The k-Young lattice Y k is a weak subposet of the Young lattice containing partitions whose first part is bounded by an integer k > 0. The Y k poset was introduced in connection with generalized Schur functions and later shown to be isomorphic to the weak order on the quotient of the affine symmetric group Sk + 1 by a maximal parabolic subgroup. We prove a number of properties for Y k including that the covering relation is preserved when elements are translated by rectangular partitions with hook-length k. We highlight the order ideal generated by an m x n rectangular shape. This order ideal, L k (m, n), reduces to L(m, n) for large k, and we prove it is isomorphic to the induced subposet of L(m, n) whose vertex set is restricted to elements with no more than k - m + 1 parts smaller than m. We provide explicit formulas for the number of elements and the rank-generating function of L k (m, n). We conclude with unimodality conjectures involving q-binomial coefficients and discuss how implications connect to recent work on sieved q-binomial coefficients.

We obtain general identities for the product of two Schur functions in the case where one of the functions is indexed by a rectangular partition, and give their t-analogs using vertex operators. We study subspaces forming a filtration for the symmetric function space that lends itself to generalizing the theory of Schur functions and also provides a convenient environment for studying the Macdonald polynomials. We use our identities to prove that the vertex operators leave such subspaces invariant. We finish by showing that these operators act simply on the k-Schur functions, thus leading to a concept of irreducibility for these functions., Comment: 18 pages

We apply crystal theory to affine Schubert calculus, Gromov-Witten invariants for the complete flag manifold, and the positroid stratification of the positive Grassmannian. We introduce operators on decompositions of elements in the type-$A$ affine Weyl group and produce a crystal reflecting the internal structure of the generalized Young modules whose Frobenius image is represented by stable Schubert polynomials. We apply the crystal framework to products of a Schur function with a $k$-Schur function, consequently proving that a subclass of 3-point Gromov-Witten invariants of complete flag varieties for $\mathbb C^n$ enumerate the highest weight elements under these operators. Included in this class are the Schubert structure constants in the (quantum) product of a Schubert polynomial with a Schur function $s_\lambda$ for all $|\lambda^\vee|< n$. Another by-product gives a highest weight formulation for various fusion coefficients of the Verlinde algebra and for the Schubert decomposition of certain positroid classes., Comment: 42 pages; version to appear in IMRN

This purpose of this chapter is to introduce Stanley symmetric functions and affine Stanley symmetric functions from the combinatorial and algebraic point of view. The presentation roughly follows three lectures I gave at a conference titled “Affine Schubert Calculus” held in July of 2010 at the Fields Institute in Toronto.

The purpose of this chapter is to outline some of the results and open problems related to k-Schur functions, mostly in the setting of symmetric function theory. This chapter roughly follows the outline of several talks given by Luc Lapointe and Jennifer Morse at a conference titled “Affine Schubert Calculus” held in July of 2010 at the Fields Institute in Toronto.

This book is an exposition of the current state of research of affine Schubert calculus and $k$-Schur functions. This text is based on a series of lectures given at a workshop titled "Affine Schubert Calculus" that took place in July 2010 at the Fields Institute in Toronto, Ontario. The story of this research is told in three parts: 1. Primer on $k$-Schur Functions 2. Stanley symmetric functions and Peterson algebras 3. Affine Schubert calculus

This chapter discusses how k-Schur and dual k-Schur functions can be defined for all types. This is done via some combinatorial problems that come from the geometry of a very large family of generalized flag varieties. They apply to the expansion of products of Schur functions, k-Schur functions and their dual basis, and Schubert polynomials. Despite the geometric origin of these problems, concrete algebraic models will be given for the relevant cohomology rings and their Schubert bases.

Continuously monitoring vital signs on general care units may provide earlier detection and intervention of instabilities in patients. These earlier interventions could prevent deaths and admission to critical care units, thereby increasing patient safety and improving patient outcomes.

We introduce a $q,t$-enumeration of Dyck paths which are forced to touch the main diagonal at specific points and forbidden to touch elsewhere and conjecture that it describes the action of the Macdonald theory $\nabla$ operator applied to a Hall-Littlewood polynomial. Our conjecture refines several earlier conjectures concerning the space of diagonal harmonics including the "shuffle conjecture" (Duke J. Math. $\mathbf {126}$ (2005), pp. 195-232) for $\nabla e_n[X]$. We bring to light that certain generalized Hall-Littlewood polynomials indexed by compositions are the building blocks for the algebraic combinatorial theory of $q,t$-Catalan sequences and we prove a number of identities involving these functions., 20 pages

A combinatorial expansion of the Hall-Littlewood functions into the Schur basis of symmetric functions was first given by Lascoux and Schützenberger, with their discovery of the charge statistic. A combinatorial expansion of stable Grassmannian Grothendieck polynomials into monomials was first given by Buch, using set-valued tableaux. The dual basis of the stable Grothendieck polynomials was given a combinatorial expansion into monomials by Lam and Pylyavskyy using reverse plane partitions. We generalize charge to set-valued tableaux and use all of these combinatorial ideas to give a nice expansion of Hall-Littlewood polynomials into the dual Grothendieck basis. \par, En associant une charge à un tableau, une formule combinatoire donnant le développement des polynômes de Hall-Littlewood en termes des fonctions de Schur a été obtenue par Lascoux et Schützenberger. Une formule combinatoire donnant le développement des polynômes de Grothendieck Grassmanniens stables en termes des fonctions monomiales a quant à elle été obtenue par Buch à l'aide de tableaux à valeurs sur des ensembles. Finalement, une formule faisant intervenir des partitions planaires inverses a été obtenue par Lam et Pylyavskyy pour donner le développement de la base duale aux polynômes de Grothendieck stables en termes de monômes. Nous généralisons le concept de charge aux tableaux à valeurs sur des ensembles et, en nous servant de toutes ces notions combinatoires, nous obtenons une formule élégante donnant le développement des polynômes de Hall-Littlewood en termes de la base de Grothendieck duale.

Although, stratifin (SFN) is externalized by keratinocytes and stimulates the expression of matrix metalloproteinase-1 (MMP-1) in fibroblasts, its mechanism of externalization is not known. Here, we hypothesize that keratinocytes have a capacity to release stratifin through externalization of exosomes. To test this hypothesis, exosomes were purified from human keratinocyte conditioned medium (KCM) and analyzed for the presence of SFN by Western blot analysis using lysosomal-associated membrane protein 2 (LAMP-2) and heat shock cognate 70 (hsc70) as exosomal markers. The results showed the presence of SFN in keratinocyte lysate, concentrated KCM and exosomes, but not in concentrated unconditioned medium. Transmission electron microscopic examination revealed the presence of unique "saucer-like" structures characteristic of exosomes whose diameters were

We study combinatorial aspects of the Schubert calculus of the affine Grassmannian Gr associated with SL(n,C). Our main results are: 1) Pieri rules for the Schubert bases of H^*(Gr) and H_*(Gr), which expresses the product of a special Schubert class and an arbitrary Schubert class in terms of Schubert classes. 2) A new combinatorial definition for k-Schur functions, which represent the Schubert basis of H_*(Gr). 3) A combinatorial interpretation of the pairing between homology and cohomology of the affine Grassmannian. These results are obtained by interpreting the Schubert bases of Gr combinatorially as generating functions of objects we call strong and weak tableaux, which are respectively defined using the strong and weak orders on the affine symmetric group. We define a bijection called affine insertion, generalizing the Robinson-Schensted Knuth correspondence, which sends certain biwords to pairs of tableaux of the same shape, one strong and one weak. Affine insertion offers a duality between the weak and strong orders which does not seem to have been noticed previously. Our cohomology Pieri rule conjecturally extends to the affine flag manifold, and we give a series of related combinatorial conjectures., Comment: 98 pages

We study k-Schur functions characterized by k-tableaux, proving combinatorial properties such as a k-Pieri rule and a k-conjugation. This new approach relies on developing the theory of k-tableaux, and includes the introduction of a weight-permuting involution on these tableaux that generalizes the Bender-Knuth involution. This work lays the groundwork needed to prove that the set of k-Schur Littlewood-Richardson coefficients contains the 3-point Gromov-Witten invariants; structure constants for the quantum cohomology ring., 19 pages

The $k$-Young lattice $Y^k$ is a partial order on partitions with no part larger than $k$. This weak subposet of the Young lattice originated from the study of the $k$-Schur functions(atoms) $s_\lambda^{(k)}$, symmetric functions that form a natural basis of the space spanned by homogeneous functions indexed by $k$-bounded partitions. The chains in the $k$-Young lattice are induced by a Pieri-type rule experimentally satisfied by the $k$-Schur functions. Here, using a natural bijection between $k$-bounded partitions and $k+1$-cores, we establish an algorithm for identifying chains in the $k$-Young lattice with certain tableaux on $k+1$ cores. This algorithm reveals that the $k$-Young lattice is isomorphic to the weak order on the quotient of the affine symmetric group $\tilde S_{k+1}$ by a maximal parabolic subgroup. From this, the conjectured $k$-Pieri rule implies that the $k$-Kostka matrix connecting the homogeneous basis $\{h_\la\}_{\la\in\CY^k}$ to $\{s_\la^{(k)}\}_{\la\in\CY^k}$ may now be obtained by counting appropriate classes of tableaux on $k+1$-cores. This suggests that the conjecturally positive $k$-Schur expansion coefficients for Macdonald polynomials (reducing to $q,t$-Kostka polynomials for large $k$) could be described by a $q,t$-statistic on these tableaux, or equivalently on reduced words for affine permutations., Comment: 30 pages, 1 figure

We consider semisimple triangular operators acting in the symmetric component of the group algebra over the weight lattice of a root system. We present a determinantal formula for the eigenbasis of such triangular operators. This determinantal formula gives rise to an explicit construction of the Macdonald polynomials and of the Heckman-Opdam generalized Jacobi polynomials., 28 pages

Let $\Lambda$ be the space of symmetric functions and $V_k$ be the subspace spanned by the modified Schur functions $\{S_\lambda[X/(1-t)]\}_{\lambda_1\leq k}$. We introduce a new family of symmetric polynomials, $\{A_{\lambda}^{(k)}[X;t]\}_{\lambda_1\leq k}$, constructed from sums of tableaux using the charge statistic. We conjecture that the polynomials $A_{\lambda}^{(k)}[X;t]$ form a basis for $V_k$ and that the Macdonald polynomials indexed by partitions whose first part is not larger than $k$ expand positively in terms of our polynomials. A proof of this conjecture would not only imply the Macdonald positivity conjecture, but would substantially refine it. Our construction of the $A_\lambda^{(k)}[X;t]$ relies on the use of tableaux combinatorics and yields various properties and conjectures on the nature of these polynomials. Another important development following from our investigation is that the $A_{\lambda}^{(k)}[X;t]$ seem to play the same role for $V_k$ as the Schur functions do for $\Lambda$. In particular, this has led us to the discovery of many generalizations of properties held by the Schur functions, such as Pieri and Littlewood-Richardson type coefficients., Comment: 38 pages, 7 figures. New version, with minor modifications, of "A filtration of the symmetric function space and a refinement of the Macdonald positivity conjecture"

Lab Anim. (NY) 42, 371–379 (2013). The machined facemask used for maintenance anesthesia in Condition 4 and shown in Figure 5 (left) was incorrectly identified in the Methods (page 375, first column, sixth sentence). The facemask is a product of VetEquip, Inc. (Pleasanton, CA).

We show that the action of classical operators associated to the Macdonald polynomials on the basis of Schur functions, S_{\lambda}[X(t-1)/(q-1)], can be reduced to addition in \lambda-rings. This provides explicit formulas for the Macdonald polynomials expanded in this basis as well as in the ordinary Schur basis, S_{\lambda}[X], and the monomial basis, m_{\lambda}[X].