Academic literature on the topic 'Ca 2686-ca 2181 B C'

Convolvulus austroaegyptiacus Abdallah & Sa’ad (CA) and Convolvulus pilosellifolius Desr. (CP) are commonly used in the Saudi Arabia folk medicine. They are potent in treating the ulcers and skin diseases. The lack of information about their biological activities led us to investigate the possible biological activities by determination of antibacterial and antioxidant activities of total ethanolic extracts and various fractions. Total flavonoid contents of the plants were determined by colorimetric method while total phenols were determined by using Folin-Ciocalteu method. In vitro antibacterial activity was studied against E. coli, P. aeruginosa, and B. subtilis, and the total antioxidant capacity was evaluated by radical scavenging method. IC50 were found to be 21.81, 17.62, and 3.31 μg/mL for CA, CP, and vitamin C, respectively, while the lowest MIC value of 0.25 mg/mL was recorded with CP extract against B. subtilis. Around 21 compounds are tentatively elucidated from both plants using rapid, simple, and high-resolution analytical technique for chemical profiling of natural compounds by direct analysis in real-time of flight-mass spectrometry, of which 17 were not isolated or reported previously.

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

Interleukin (IL)-6, one of the cytokines released from inflammatory cells, stimulates insulin secretion in a physiological concentration (1-100 pg/ml), but the exact mechanism is still unknown. The present studies were undertaken to investigate the mechanism of IL-6-induced stimulation of insulin secretion in HIT-T 15 cells. The effects of the addition of nifedipine on the IL-6 (100 pg/ml)-induced stimulation of insulin secretion were investigated. We also examined the possibility that IL-6 (1-100 pg/ml) may stimulate insulin messenger ribonucleic acid (mRNA) expression, using the reverse transcription-polymerase chain reaction method. The addition of 100 and 1000 nM nifedipine significantly attenuated the stimulatory effects of 100 pg/ml IL-6 on insulin secretion. The addition of 1-100 pg/ml IL-6 dose-dependently increased preproinsulin mRNA expression relative to beta-actin mRNA. IL-6 increased insulin gene promoter activity of fragments A (-2188 to +337 bp) and B (-1782 to +270 bp) but not fragments C (-1275 to +270 bp), D (-1138 to +270 bp), E (-880 to +236 bp) or F (-356 to +252 bp). The addition of 10 nM nifedipine completely abolished the stimulatory effect of 10-100 pg/ml IL-6 on relative preproinsulin mRNA expression. These data raised the possibility that IL-6 increased preproinsulin mRNA expression via the stimulation of Ca(2+) influx which enhances insulin gene expression.

AbstractSveinbergeite, Ca(Fe2+6Fe3+)Ti2(Si4O12)2O2(OH)5(H2O)4, is a new astrophyllite-group mineral discovered in a syenite pegmatite at Buer on the Vesteroya peninsula, Sandefjord, Oslo Region, Norway. The mineral occurs in pegmatite cavities as 0.01—0.05 mm thick lamellar (0.2—0.5×5—10 mm) crystals forming rosette-like divergent groups and spherical aggregates, which are covered by brown coatings of iron (and possibly manganese) oxides, associated with magnesiokatophorite, aegirine, microcline, albite. calcite, fluorapatite, molybdenite, galena and a hochelagaite-like mineral. Crystals of sveinbergeite are deep green with a pale green streak and a vitreous and pearly lustre. Sveinbergeite has perfect cleavage on ﹛001﹜ and a Mohs hardness of 3. Its calculated density is 3.152 g/cm3. It is biaxial positive with α 1.745(2), β 1.746(2), γ 1.753(2), 2V(meas.) = 20(3)°. The mineral is pleochroic according to the scheme Z > X ∽ Y : Z is deep green, X and Y are brownish green. Orientation is as follows: X ┴ L (001), Y ᶺ b = 12°, Z = a, elongation positive. Sveinbergeite is triclinic, space group P1̄, a = 5.329(4), b = 11.803(8), c = 11.822(8) Å; α = 101.140(8)°, β = 98.224(8)°, γ = 102.442(8)°; V = 699.0(8) Å3; Z = 1. The nine strongest lines in the X-ray powder diffraction pattern [d in Å(I)(hkl)] are: 11.395(100)(001,010). 2.880(38)(004), 2.640(31)(2̄10,l̄41), 1.643(24)(07̄1,072), 2.492(20)(2l̄l), 1.616(15)(070), 1.573(14)(3̄2̄2), 2.270(13)(1̄3̄4) and 2.757(12)(1̄40,1̄3̄2). Chemical analysis by electron microprobe gave Nb2O5 0.55, TiO2 10.76, ZrO2 0.48, SiO2 34.41, A12O3 0.34, Fe2O3 5.57, FeO 29.39, MnO 1.27, CaO 3.87, MgO 0.52, K2O 0.49, Na2O 0.27, F 0.24, H2O 8.05, O=F -0.10, sum 96.11 wt.%, the amount of H2O was determined from structure refinement, and the valence state of Fe was calculated from structure refinement in accord with Mossbauer spectroscopy. The empirical formula, calculated on the basis of eight (Si + Al) p.f.u., is (Ca0.95Na0.12K0.14)Σ1.21(Fe2+5.65Fe3+0.93Mn0.25Mg0.18)Σ7.01(Ti1.86Nb0.06Zr0.05Fe3+)Σ2 (Si7091Al0.09)Σ8O34.61H12.34F0.17, Z = 1. The infrared spectrum of the mineral contains the following absorption frequencies: 3588, ∽3398 (broad), ∽3204 (broad), 1628, 1069, 1009, 942, 702, 655 and 560 cm–1. The crystal structure of the mineral was solved by direct methods and refined to an R1 index of 21.81%. The main structural unit in the sveinbergeite structure is an HOH layer which is topologically identical to that in the astrophyllite structure. Sveinbergeite differs from all other minerals of the astrophyllite group in the composition and topology of the interstitial A and B sites and linkage of adjacent HOH layers. The mineral is named in honour of Svein Arne Berge (b. 1949), a noted Norwegian amateur mineralogist and collector who was the first to observe and record this mineral from its type locality as a potential new species.

4125 Background: Both gemcitabine and 5FU-based chemotherapy have demonstrated efficacy in MPC. Alternating regimens may 1) reduce toxicity 2) slow resistant cancer biology emergence and 3) provide a broader platform for addition of other therapeutic agents. Alternating GA and FOLFIRI in MPC has been previously reported as part of the SEENA -1 trial,our own institution, and elsewhere (Picozzi et.al. GI Cancer Symposium 2017, Picozzi et.al, ASCO 2018 Assenat et,al, ASCO 2018). An extension of our institutional observations are reported here. Methods: Pt eligibility required the following: 1) biopsy proven de novo MPC, 2) no prior evidence MPC on CT, 3) ECOG performance status ≤ 2, and 4) bi-dimensionally measurable disease. Treatment (Rx) entailed gemcitabine 1000mg/m2 and nab-paclitaxel 125mg/m2 1, (8), 15 alternating every 8 wks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 wks. Rx was continued up to 48 wks; Rx thereafter decided by pt/MD. Results: 108 pts met eligibility requirements from 10/2015 and 12/2020. Pt characteristics included median age 68 ( range 35-81), ECOG PS 0/≥1 54%/46%, # diseases sites 1/≥1 62%/38%, liver /non-liver 76%/24%, biliary obstruction yes/no 40%/60%, C 19.9 NL/ < 59XNL/ > 59X NL 12%/32%/56%; median Ca 19.9 4598 With median f/u of 19.7 mo, 17 pts remain on Rx < 48 wks, 35/91 (38%) completed 48 wks Rx, 56/91 (62%) pts progressed prior to 48 wks. Median # mos on Rx was 8.9. ≥ grade 3 heme toxicity included anemia 7%, neutropenia 9%, thrombocytopenia 5%. Neutrophil growth factors were not used in this pt cohort. ≥ 3 non-hem toxicity included neuropathy1%, nausea/vomiting 2%, mucositis 2%, diarrhea 1%. Disease control at 16 wks was 81% (35% PR/46% SD/16% PD, 95% CI 72-87%). Median OS was 13.7 mo (95% CI 10.9-18.7 mo). 6 /12/18/24 mo OS were 87%/55%/41%/ 20% respectively. Prognostic significance was seen with Rx > vs < 48 wks (21.1 vs 8.0 mo, p <.0001), and ECOG PS 0 vs. ≥1 ( 17.8 vs. 10.9 mo, p = 0.03) Age, # metastatic sites, liver involvement, biliary obstruction and magnitude of CA 19.9 elevation all failed to achieve prognostic significance at the p <.05 level. Conclusions: 1) Alternating GA/ FOLFIRI in MPC has a more favorable toxicity profile than standard regimens 2) Med OS appears superior to GA and competitive with FOLFIRINOX ; longer term (18/24 mo ) OS seemed particularly encouraging 3) ≥ 48 wks Rx and ECOG PS 0 were prognostically significant 4) Further investigation using this regimen including a) randomized comparisons, b) incorporation of molecular data and c) addition of additional agents seems indicated Updated survival data will be presented at the meeting

En el cultivo de Agave tequilana, los estudios se han restringido a una parte de su largo ciclo y a periodos cortos de tiempo, por tal razón, con el objetivo de evaluar las características agronómicas en planta y piña en un ciclo completo de la planta, se establecieron hijuelos provenientes de Jalisco en el sur de Tamaulipas en tres condiciones: a) en temporal y sin fertilizante (TA); b) fertigación, además de la precipitación, recibieron agua y nutrimentos (N, P, K, Ca, Mg, y micronutrimentos) mediante un sistema de riego por goteo; y c) FB+fertigación, adicional a lo anterior, éstas plantas recibieron fertilización de base (FB), con N, P, K y micronutrimentos, cada tratamiento tuvo tres repeticiones. Se realizaron ocho evaluaciones destructivas utilizando una planta por unidad experimental, septiembre 2004, febrero del 2005, octubre de 2005, 2006, 2007, 2008, 2009 y 2010. Las plantas desarrolladas con fertigación y fb+fertigación, en promedio superaron en 26% y 57% la altura y número de hojas de plantas del TA, respectivamente; la mayor producción de Materia Seca (MS) anual fue 51.8 t ha-1, estimándose un total de biomasa por planta de 491.4 y 456.1 t ha-1 y 218.1 y 252.4 t ha-1 en la piña, respectivamente. En plantas del TA la biomasa total fue 97 t ha-1 y un rendimiento de piña de 46.5 t ha-1. En piña los azúcares evaluados en oBrix y azúcares reductores totales (ART) no fueron afectados por los tratamientos. La concentración de ART en la piña fluctuó entre 26.8 y 29%. La concentración de glucosa y fructosa fue similar en etapas iniciales de desarrollo de la piña; Sin embargo, al final del ciclo durante la etapa de máximo crecimiento el valor medio en la concentración de fructosa fue de 246.8 g por kg MS de piña y representó 88% de los dos monosacáridos solubles evaluados, la glucosa presentó un comportamiento inverso y representó el restante 12%.

Variations in the interatomic distances lead to altered d-band centre for a given metal, and provide an elegant way to control its activity towards (electro)catalytic reactions (“strain-engineering” approach). The effect of strain was rationalized within the frame of the d-band theory of Hammer and Nørskov in the late 1990s [1,2]. The authors predicted that the rate of the sluggish oxygen reduction reaction (ORR) can be enhanced on catalysts binding *OH ca. 0.10 - 0.15 eV more weakly than Pt(111), [1, 2] and this prediction was experimentally verified using a Pt3Ni(111)-skin surface.[3] Nevertheless, these predictions hardly translated to nanomaterials, because of the wide variety of catalytic sites configurations. Also, the d-band theory mostly considers catalytic surfaces in vacuum, without any effect related to the electrical double layer and adsorption/desorption processes. Hence, an in situ picture of how strain develops on Pt-based surfaces is still lacking. In this contribution, we took benefit of recent advances in Bragg Coherent Diffraction Imaging (BCDI) [4, 5]and of the fourth generation Extremely Brilliant Source of the European Synchrotron (ESRF-EBS, Grenoble, France) to map strain over Pt nanoparticles in situ. Our results show that adsorption of anions causes appearance of compressive strain at under-coordinated (edges and corners) atoms and tensile strain at highly-coordinated ({001} and {111} facets) atoms. Strain heterogeneity increases with the electrode potential and reaches as large as 0.08 %. at ORR-relevant potential. These results provide direct insights into the dynamics of Pt nanoparticles in an electrochemical environment, and have direct consequences for electrocatalysis in general, and for ORR electrocatalysis in particular. Ackowledgements This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant n° 818823). FM acknowledges the financial support from the French National Research Agency in the frame of the BRIDGE project (grant n° ANR-19-ENER-0008-01). References [1] B. Hammer, J. K. Nørskov, Surf. Sci. 1995, 343, 211. [2] B. Hammer, Y. Morikawa, J. K. Nørskov, Phys. Rev. Lett. 1996, 76, 2141. [3] V. R. Stamenkovic, B. Fowler, B. S. Mun, G. Wang, P. N. Ross, C. A. Lucas, N. M. Markovic, Science 2007, 315, 493. [4] I. Robinson, R. Harder, Nat. Mater. 2009, 8, 291. [5] J. Carnis, A. R. Kshirsagar, L. Wu, M. Dupraz, S. Labat, M. Texier, L. Favre, L. Gao, F. E. Oropeza, N. Gazit, E. Almog, A. Campos, J.-S. Micha, E. J. M. Hensen, S. J. Leake, T. U. Schülli, E. Rabkin, O. Thomas, R. Poloni, J. P. Hofmann, M.-I. Richard, Nat. Commun. 2021, 12, 5385. Figure 1. Schematic representation of observed strain distribution over a Pt nanoparticle in 0.05 M H2SO4. Figure 1

Progesterone (P4) is an important component of oestrous cyclicity and is critical to fertility. A concentration >1 ng mL−1 reflects the function of the corpus luteum (CL) and is considered indicative of a cyclic cow. Recent publications have shown that P4 at the onset of synchronization programs is critical to pregnancy outcomes in primiparous cows (Stevenson et al. 2015 J. Anim. Sci. 93, 2111-2123) and cows with P4 <5 ng mL−1 on Day 14 could predict pregnancy loss (Kenyon et al. 2013 Anim. Reprod. Sci. 136, 223-230). Currently, the gold standard technique to quantify P4 is radioimmunoassay (RIA). However, new techniques are emerging. The objective of this study was to evaluate a new commercial in vitro diagnostic assay to quantify P4 based on enzyme immunoassay by competition with detection of final fluorescence (enzyme-linked fluorescence assay, ELFA). A total of 30 cows were synchronized on Day 0 with an intravaginal device (IVD) containing 500 mg of P4 (Cronipres, Biogénesis Bagó, Argentina). On Day 7 and Day 8 all cows received 150 mg of prostaglandin F2α (Enzaprost, Biogénesis Bagó). All IVD were removed on Day 8. A total of 95 blood samples were taken at Days 0, 9, 9.5, and 10 using BD Vacutainer (Becton-Dickinson, Franklin Lakes, NJ, USA) with sodium heparin by jugular venipuncture and centrifuged at 3000 × g for 30 min for plasma separation, which was frozen at –20°C until analysis. Samples were measured in duplicate by IM1188-Progesterone-RIA (Beckman Coulter, Brea, CA, USA) and VIDAS-PRG-ELFA (Biomerieux, Marcy l’Étoile, France). Concentrations of P4 obtained by RIA were classified in 2 groups: (A) P4 <1 ng mL−1, and (B) P4 ≥1 ng mL−1 and matched with P4 concentrations obtained by ELFA. Kappa (κ) test was used to determine agreement between both techniques, intra-assay coefficients of variation was determined for RIA and ELFA; and sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were determined for ELFA. There was very good agreement between the RIA and ELFA techniques, κ = 0.95, to determine P4 concentrations for group A (62 and 62 samples, respectively) and group B (33 and 33 samples, respectively). The intra-assay coefficients of variation were 5% (RIA) and 2.9% (ELFA). Values for SE = 0.97, SP = 0.98, PPV = 0.97, and NPV = 0.98 were obtained for ELFA. We were able to quantify P4 in bovine plasma in all samples using the ELFA technique with similar reliability to the RIA technique. Only 2 samples (2.1%) differed in their concentrations and clinical interpretation. There was a slight discrepancy between the results found for both techniques with an excellent SE and SP in ELFA compared with RIA. Based on the analytical results, we believe that this in vitro diagnostic assay developed for use with an autoanalyzer could be useful for routine bovine reproduction programs. Further studies should be carried out to strengthen these conclusions.

BackgroundGastric cancer is the sixth most common cancer and second-leading cause of cancer-related mortality worldwide.1 The heterogenous and genetically complex nature of this disease underlies the challenges in developing effective therapies for metastatic gastric cancer. In the majority of cases, stomach tumors evolve from intestinal metaplasia resulting in ectopic expression of the enterocyte differentiation antigen guanylyl cyclase C (GUCY2C) by ~50% of primary and metastatic gastric cancers.2–4 In the context of the efficacy of GUCY2C-directed chimeric antigen receptor (CAR)-T cells against metastatic colorectal cancer in animal models,5,6 we hypothesized that this adoptive cell therapy may be effective against metastatic gastric cancer.MethodsHere, we explored the efficacy of GUCY2C-directed CAR-T cells for gastric cancer in a patient derived xenograft (PDX) tumor model. Also, we interrogated translational GUCY2C biomarker assays using RT-qPCR, immunoblot analysis, and immunohistochemistry (IHC) for the intended purpose of identifying patients whose tumors express GUCY2C and could benefit from GUCY2C-directed CAR-T cell therapy.ResultsGUCY2C-directed CAR-T cells significantly reduced subcutaneous T84 colorectal tumor growth, producing a 5-fold reduction in tumor volume, compared to control treated tumors. GUCY2C-directed CAR-T cells produced no response in tumors produced from the GUCY2C-deficient colorectal cancer cell line, SW480. Importantly, GUCY2C-directed CAR-T cells controlled gastric cancer PDX growth, maintaining a >12-fold reduction in tumor volume compared to control and in some cases produced complete tumor elimination. Furthermore, IHC based assays, indicate that antibodies developed in our laboratory may be suitable for development of a companion diagnostic for GUCY2C-directed CAR-T cells. Indeed, the commercial polyclonal antibody demonstrated robust, non-specific staining regardless of tissue type or GUCY2C mRNA profile, while novel monoclonal antibodies produced in our laboratory primarily detected protein localized to the membrane of glandular epithelial cells, demonstrating antigen specificity, and indicating their potential for further development in diagnostic companion assays to identify gastric cancer patients who may benefit from GUCY2C-directed CAR-T cell therapy.ConclusionsGUCY2C-directed CAR-T cells prevented the growth of, and at times eliminated, a subcutaneous gastric cancer PDX model. In the context of previously established safety in mouse models, additional studies defining the efficacy of GUCY2C-directed CAR-T cells in gastric cancer models may allow future translation of this therapy to patients with advanced gastric cancers. Concurrent development of a novel companion diagnostic IHC assay would permit identification of the ~50% of gastric cancer patients whose tumors express GUCY2C and could benefit from this therapy.AcknowledgementsThis work was supported by a DeGregorio Family Foundation Award and by the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-17-1-0299, W81XWH-191-0263, and W81XWH-19-1-0067) to AES. SAW is supported by the National Institutes of Health (NIH) (R01 CA204881, R01 CA206026, and P30 CA56036), the Defense Congressionally Directed Medical Research Program W81XWH-17-PRCRP-TTSA, and Targeted Diagnostic & Therapeutics. SAW and AES were also supported by a grant from The Courtney Ann Diacont Memorial Foundation. SAW is the Samuel M.V. Hamilton Professor of Thomas Jefferson University. AZ was supported by NIH institutional award T32 GM008562 for Postdoctoral Training in Clinical Pharmacology.The authors thank the NCI Patient-Derived Models Repository for their support and resources to make this research possible. The authors also thank the Sidney Kimmel Cancer Center Translational Research & Pathology Core Facility, and the Office of Animal Resources at Thomas Jefferson University for their continued technical assistance and support in this research.Ethics ApprovalThis study was approved by the Thomas Jefferson University Institutional Review Board (#14.0204) and the Instituational Animal Care and Use Commitee (Protocol #01529).ReferencesBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin2018;68:394–424. doi:10.3322/caac.21492.Park J, Schulz S, Haaf J, Kairys JC, Waldman SA. Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach. Cancer Epidemiol Biomarkers Prev 2002;11:739–44.Birbe R, Palazzo JP, Walters R, Weinberg D, Schulz S, Waldman SA. Guanylyl cyclase C is a marker of intestinal metaplasia, dysplasia, and adenocarcinoma of the gastrointestinal tract. Hum Pathol. 2005;36:170–9. doi:10.1016/j.humpath.2004.12.002.Mathur D, Root AR, Bugaj-Gaweda B, Bisulco S, Tan X, Fang W, et al. A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers. Clin Cancer Res 2020;26:2188–202. doi:10.1158/1078-0432.CCR-19-3275.Magee MS, Kraft CL, Abraham TS, Baybutt TR, Marszalowicz GP, Li P, et al. GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity. Oncoimmunology 2016;5:e1227897. doi:10.1080/2162402X.2016.1227897.Magee MS, Abraham TS, Baybutt TR, Flickinger JC, Ridge NA, Marszalowicz GP, et al. Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases. Cancer Immunol Res 2018;6:509–16. doi:10.1158/2326-6066.CIR-16-0362.

BackgroundAging is the biggest risk factor for cancer, yet there are limited pre-clinical/clinical data regarding aging effects on immune checkpoint (IC) inhibition (ICI) outcomes. αPD-1 can potentially block PD-L1 and PD-L2 while αPD-L1 can block PD-1 and CD80. Melanoma response to αPD-1/αPD-L1 correlates with CD8+TCF-1+ T cell stem cell (TCSC) generation.1 Lack of host IL-17 can lead to increased IFN-γ production.2 3MethodsWe tested αPD-1 (200 μg/mouse), αPD-L1 (100 μg/mouse) or αPD-L2 (200 μg/mouse) in aged (18–33 months) and young (3–8 months) mice challenged orthotopically with B16 (WT or PD-L1ko) or TPN61R melanoma (NRAS mutation melanoma model)4 (αPD-L2 only) (SQ). Tumors were analyzed by flow. We tested αPD-L2 (20 μg/ml) effects by co-culturing young or aged T cells ± young or aged myeloid cells.ResultsWe reported that αPD-1 treats young and aged with B16 whereas αPD-L1 treats young not aged.5 αPD-L2 treated B16 and TPN61R melanoma in aged but, remarkably, not young, the first single agent anti-cancer immunotherapy exhibiting this property (figure 1). B16 tumors from aged had differential IC content (PD-1, PD-L1, CD80, PD-L2) versus tumors from young (e.g., more PD-L2+ tumor and stroma cells in aged mice; figure 2). Efficacy in young (αPD-1, αPD-L1) and aged (αPD-L2) correlated with increased tumor TCSC content (figure 3). αPD-L2 efficacy against B16 in aged mice required host IFN-γ and IL-17 (figure 4). αPD-1 efficacy against B16 in aged appeared to be host and tumor PD-L1 independent (figure 5). PD-L1KO B16 response to αPD-1 in aged also correlated with increased tumor TCSC content. Myeloid cell PD-L2 signaling inhibited aged but not young CD8+ T cell IL-2 production in vitro (figure 6).Abstract 234 Figure 1Abstract 234 Figure 2Abstract 234 Figure 3Abstract 234 Figure 4Abstract 234 Figure 5Abstract 234 Figure 6ConclusionsTreatment differences in aged versus young could depend on IC, TCSC and/or host cytokine differences (IL-17/IFN-γ). αPD-1 efficacy in aged PD-L1KO mice challenged with PD-L1KO B16 suggests that PD-L2 block is sufficient for αPD-1 efficacy in aged. PD-L2 expression differences in the tumor microenvironment could also contribute to treatment efficacy differences. PD-L2 inhibitory signaling on aged but not young CD8+ T cells is a likely mechanism for αPD-L2 efficacy in aged but not young. We are now testing the role of IL-17 in αPD-L2 efficacy as it could be upstream of IFN-γ effects, and TCSC effects in aged versus young. Our work can improve cancer immunotherapy in aged hosts and provides insights into treatment failure, including in young hosts.AcknowledgementsSouth Texas MSTP training grant (NIH T32GM113896), TL1TR002647, NIH T32AI138944, R01 CA231325, Waxman Grant, UL1 TR001120ReferencesMiller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, Yates KB, Lako A, Felt K, Naik GS, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol 2019;20(3):326–336.Moroda M, Takamoto M, Iwakura Y, Nakayama J, Aosai F. Interleukin-17A-deficient mice are highly susceptible to toxoplasma gondii infection due to excessively induced T. gondii HSP70 and interferon gamma production. Infection and immunity 2017;85(12):e00399–00317.Yi T, Zhao D, Lin C-L, Zhang C, Chen Y, Todorov I, LeBon T, Kandeel F, Forman S, Zeng D. Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease. Blood, The Journal of the American Society of Hematology 2008;112(5):2101–2110.Burd CE, Liu W, Huynh MV, Waqas MA, Gillahan JE, Clark KS, Fu K, Martin BL, Jeck WR, Souroullas GP. Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma. Cancer discovery 2014;4(12):1418–1429.Padron A, Hurez V, Gupta HB, Clark CA, Pandeswara SL, Yuan B, Svatek RS, Turk MJ, Drerup JM, Li R, et al. Age effects of distinct immune checkpoint blockade treatments in a mouse melanoma model. Exp Gerontol 2018;105:146–154.Ethics ApprovalAll animal studies are approved by UTHSA IACUC.

Cette étude porte sur les noms des particuliers au IIIème millénaire avant J. -C. , soit de l’époque thinite à la fin de la Première Période Intermédiaire. Le terme de « particuliers » comprend tous les Egyptiens, à l’exception du roi qui reste un être à part, au-delà de tout critère strictement humain. Ce travail vise d’abord à dresser un tableau des anthroponymes du IIIème millénaire. Il ne s’agit pourtant pas d’un simple dictionnaire. Celui-ci est la base d’une réflexion à la fois sur la construction graphique et grammaticale des noms de personnes et sur la portée sociale et anthropologique du nom chez les anciens Égyptiens. Une telle étude montre que les données anthroponymiques de cette période s’accordent en partie avec ce que l’on en sait pour les époques ultérieures. Toutefois, que ce soit sur le plan grammatical et anthropologique, les noms de personnes du IIIème millénaire révèlent des particularités qui reflètent un système de pensée bien différent de celui des époques subséquentes
This study deals with the names of the private individuals in the IIIrd millennium BC, it is to say from thinite period to the end of the First Intermediate Period. "Private individuals" term includes all the Egyptians, with the exception of king who remains a being in part, beyond any strictly human criterion. This work aims at first at having a general view of the Egyptian names of the IIIth millennium. It is not nevertheless about a simple dictionary. This one is the base of a reflection at the same moment on the graphic and grammatical construction of the personal names and on the social and anthropological reach of the name to the ancient Egyptians. Such a study shows that the anthroponymic data of this period agree partially with what we know about it for later times. However, whether it is on the grammatical and anthropological plan, the personal names of the IIIrd millennium reveal peculiarities which reflect a system of thought very different from that of later times

L'étude du matériel prosopographique permet d'esquisser une reconstitution des instances judiciaires et de leur personnel entre l'Ancien et la fin du Moyen Empire égyptien (2700-1710 avant notre ère). Le croisement de ces données avec celles recueillies dans d'autres sources (procès-verbaux, contrats, testaments, donations, décrets royaux , autobiographies, correspondances épistolaires,. . . ) favorise la compréhension des attributions accordées à ces juridictions, des fonctions exercées par leurs agents mais encore l'étude de ces deux types de procédure, ordinaire et extraordinaire, observées par ces cours grâce à l'analyse de quelques cas pratiques. Ainsi, sur le plan des structures, il est possible de suivre l'instauration d'un département de la justice sous l'Ancien Empire, sa disparition lors de la "révolution sociale", connue sous le nom de première période intermédiaire, puis sa restructuration sous la forme d'une section dépendant du bureau viziral au Moyen Empire. Sur le plan des mécanismes, si l'ensemble des litiges que nous qualifions de "civil" et de "pénal" relève de la procédure ordinaire, les affaires liées à la Couronne ou impliquant les personnages les plus éminents de l'État suscitent le déclenchement d'une procédure inquisitoire conduite par le roi oupar les agents qu'il désigne

Le titre sm désigne, à l’Ancien Empire, un officiant au service du roi ou un prêtre de Sokar, les deux fonctions étant distinguées à cette époque par des graphies différentes. Le premier intervient principalement dans le pr dw“t où il s’occupe de l’habillement et de la préparation du souverain alors que les attributions du second se rapportent à la fabrication des attributs royaux et des insignes métalliques, dont il était très probablement responsable de la conception. Les interventions du prêtre s’étendent alors à d’autres domaines et notamment au domaine funéraire. Dans ce cadre, il est chargé de la récitation des formules rituelles, de la mise en place d’accessoires pendant le rituel de l’embaumement et de toutes les autres opérations en rapport avec la renaissance du défunt dans les officines funéraires. Ces fonctions procèdent de son association avec Sokar. En effet, le dieu et sa barque-Ìnw étaient perçus comme la matrice gestationnelle où le corps du défunt, assimilé à Osiris démembré, était régénéré avant de reprendre sa course comme Rê triomphant. Les attributions du prêtre-sm font écho à cette fonction. À partir d’Amenhotep III, un prêtre-sm officiait dans les châteaux des millions d’années pour la survie post mortem du souverain ainsi que dans le temple d’Amon, au sein d’un ensemble de chapelles et de temples consacrés à des formes divines originaires de la région memphito-héliopolitaine, pour le maintien de son essence divine sur terre. L’un et l’autre intervenaient dans un environnement cultuel où Sokar constituait un principe actif de la renaissance du roi associé à des conceptions solaires en rapport avec la réapparition de Rê
The title sm refers at the Old Kingdom to a celebrant at the service of king or a priest of Sokar, the two functions are distinguished at this time by different spellings. The first is mainly involved in the pr dw“t where he is responsible for the clothing and the preparation of sovereign insigna while the second relates to the manufacture of metallic regalia and insignia, and was probably responsible for the design. The interventions of the priest extend to other areas, including the funerals ceremonies. In this context, he is responsible for the recitation of ritual formulas, the introduction of accessories for the ritual of embalming and all other operations in connection with the rebirth of the deceased in the funeral tent. These functions are based on its association with Sokar. In fact, the god and his boat-Ìnw were perceived as gestational matrix where the body of the deceased, assimilated to Osiris dismembered, was regenerated before resuming his course as Ra triumphant. From Amenhotep III, a sm priest officiated in the « châteaux des millions d’années » for the post-mortem survival of the sovereign and in the temple of Amon, in a series of chapels and temples dedicated to divine forms from thee memphito-helipolitan region, to maintain its divinity on earth. The both were involved in a cult where Sokar was an active ingredient of the renaissance king associated with solar designs in connection with the reappearance of Ra

Ce travail a pour but de clarifier le role de la famille royale dans la royaute et les institutions de l'egypte d'ancien empire (environ 2700-2200 av j. -c. ). La precision necessaire dans la datation des personnages conduit a une analyse critique des methodes habituellement employees, en particulier celles qui utilisent des criteres figures (ch. 1). Sur ces bases, l'etude de la chronologie des tombes du site de dahchour, aux nombreux fils royaux, est renouvelee (ch. 2). Les contours de la famille royale sont ensuite examines, par categories (fils, epouses, meres, etc), qu'il s'agisse de paren te fictive ou reelle (ch. 3); une large place est faite a l'historiographie du sujet. Le ch. 4, selon ces categories, anal yse chaque groupe dans ses rapports au pouvoir: fils royaux et administration; reines et royautes; filles royales et politiques matrimoniale de la monarchei. La fin du chapitre est consacree aux problemes de la succession au trone et du rapport entre dynastie et lignee. Les fiches-personnages (un peu moins de 30) sont presentees dans un corpus qui rassemble les informations sur la date (selon les principes du ch. 1), les titres, la genealogie
The present study aims at clarifying the role of the royal family in the kingship and institutions of the old kingdom egypt (about 2700-2200 b. C. ). The need of a precise dating of the individuals leads to a critical analysis of the usual methods, especially those which use figurative criteria (ch. 1). On this basis, the study of the chronology of the tombs of dahshur necropolis, with numerous royal sons, is reappraised (ch. 2). The boudaries of the royal family group is then investigated, by categories (sons, queens, royal mothers, etc), the kinship being fictive or real. The historiography of the topic is fully investigated. Ch. 4, divided according to the avovementioned categories, is a precise analysis of the relations between those groups and the power. Royal sons and administration, queens and kingship , royal daughters and the matrimonial policy of the monarchy. The end of the chapter is devoted to the problems pf the royal succession to the throne, and the link between dynasty and lineage. The files about the individuals (a little less than 300) are in a separate corpus, and gather together informations about dating (according to the principles set up in ch. 1), titles and genealogy

"Le plateau de Giza, proche de la ville moderne du Caire, est un des sites les plus célèbres, sinon des mieux connus, de l'Égypte. Son histoire débute avec le commencement de la civilisation égyptienne et les premières dynasties et se poursuit pratiquement sans solution de continuité jusqu'à l'époque gréco-romaine. Si les pyramides de la IVe dynastie, bâties par Chéops, Chephren et Mykérinos, ainsi que le Grand sphinx, en sont les éléments les plus remarquables, le site n'en connut pas moins une activité intense au cours des deux millénaires qui suivirent l'ancien empire. Des cultes nouveaux avaient surgi. Celui d'Harmachis, incarné dans la statue colossale du Grand sphinx, et son pèlerinage, nés durant le nouvel empire, se poursuivirent au cours du premier millénaire. Cette période vit le développement du culte d’Isis sous sa forme locale et spécifique de "dame des pyramides", qui protégeait le site tout entier. Une ancienne chapelle funéraire d'une petite pyramide subsidiaire à l'est de celle de Chéops, fut restaurée, transformée et agrandie pour servir de lieu de culte, où les desservants de la déesse et ses dévots ont laissé un nombre important d'inscriptions et d'objets, stèles, statues, etc. C'est à partir de ces témoignages, inédits pour la plupart jusqu'à présent, qu'il a été possible de reconstituer l'histoire du site. "
The plateau of Giza is one of the most famous, if not most well-known, sites of Egypt, not far from Cairo. The history of the site is linked with the beginnings of the history of Egypt and the first dynasties. It will last, almost without any gap, until the Greco-Roman period. The pyramids of the IVth dynasty, erected by Khufu, Khephren and Mykerinos and the great sphinx, appear obviously as the most striking features of the site. Nevertheless its life will survive for two other millenniums after the end of the old kingdom. New cults appeared. The worshipping of Harmachis, as the Egyptians called the great sphinx, and his pilgrimage began during the 18th dynasty and lasted during the first millennium. At that time, the devotion to Isis was increasing; the goddess was known as the "mistress of the pyramids" who protected the whole site. The funerary chapel of the southern subsidiary pyramid, east of Khufu's pyramid, was restored and enlarged to be used as a cult chapel for Isis. Inscriptions and artefacts, stelae, statues, etc. Have been left by the priests and the worshippers of the goddess. A good part of them have not been published before. Owing to these new data, it has been possible to reconstruct the history of the site

Cette thèse a pour sujet un groupe religieux égyptien, principalement féminin, connu sous le nom de hnr. L’étude ici menée propose de comprendre l’évolution, la structure hiérarchique et les pratiques rituelles de ce groupe de façon diachronique en se fondant à la fois sur les sources textuelles et iconographiques. La période concernée va du début de l’Ancien Empire à la fin du Nouvel Empire. La thèse est divisée en deux volumes, le premier étant dédié à la présentations des résultats de l’enquête et le second regroupant l’ensemble des sources rassemblées et sur lesquelles se fonde l’analyse. Les résultats de cette enquête montrent d’abord les évolutions du hnr à travers les époques concernées avant de discuter la structure hiérarchique ainsi que l’éventail des rites et rituels du groupe. La thèse propose en outre une analyse des relations entre les genres au sein du hnr et interroge également sur les liens entre ce groupe religieux la royauté et l’élite. Enfin, la signification-même du terme hnr est discutée et envisagée sous l’angle des sources rassemblées ici. Cette thèse propose de comprendre le hnr dans le contexte plus large de l’évolution des clergés féminins égyptiens afin de saisir sa singularité
This thesis is about an Egyptian religious group, mainly feminine, known as hnr. The study carried out here proposes to understand the evolution, of the hierarchical structure and the ritual practices of this group in a diachronic way based on both textual and iconographic sources. The period covered ranges from the start of the Old Kingdom to the end of the New Kingdom. The thesis is divided into two volumes, the first being dedicated to the presentation of the results and the second bringing together all the sources collected and on which the analysis is based. The results of this investigation first show the evolution of hnr through the periods concerned before discussing the hierarchical structure as well as the scope of rites and rituals of the group. The thesis also offers an analysis of gender relations within the hnr and also questions the links between this religious group, royalty and the elite. Finally, the very meaning of the term hnr is discussed and re onsidered in regard of the sources gathered here. This thesis proposes to understand the hnr in the broader context of the evolution of Egyptian female priesthood in order to grasp its singularity

La « dissimilation graphique » est une particularité récurrente des écritures égyptiennes, en particulier à l’Ancien Empire (IIIe-VIe dynasties, env. 2700/2150 av. J. C.). À cette époque, la pluralité (aussi bien grammaticale que lexicale) était indiquée par le triplement des sémogrammes, signes investis d’une valeur sémantique et censés permettre la compréhension des lexèmes. De ce fait, si les idéogrammes et classificateurs étaient d’ordinaire répétés trois fois à l’identique, la « dissimilation » désigne les occurrences dans lesquelles ces trois signes sont distincts. Par exemple, si un mot comme bAk.w, « serviteurs », est traditionnellement accompagné de trois hommes assis, l’un d’entre eux pourra être remplacé par une femme en cas de dissimilation. De même, si mHy.t, « poissons », comprend habituellement trois poissons de même espèce, sa version dissimilée offrira trois espèces différentes. Cette thèse se donne pour objectif d’analyser de façon systématique la dissimilation graphique, majoritairement attestée dans les inscriptions hiéroglyphes des tombes royales et privées, mais également dans certains documents hiératiques. À travers cette étude, les raisons supposées de l’existence de la dissimilation graphique sont exposées. En conséquence, la classification égyptienne se voit placée sous de nouveaux éclairages. De plus, par l’examen d’un nombre important de textes égyptiens de l’Ancien Empire, de nouvelles analyses des fonctions des signes qui les composent seront proposées afin d’éclaircir certaines zones d’ombres de la linguistique égyptologique
The peculiarity called “dissimilation graphique” is recurrent in Egyptian writing systems, particularly during Old Kingdom (Dyn. III-VI, ca. 2700-2150 BC). At this time, plurality (grammatical and lexical) is indicated by the threefold of semograms, signs that have a semantic value and allow to understand the lexemes. Thus, if ideograms and classifiers are ordinary reproduced three times identically, “dissimilation” refers to occurrences where these three signs are different. For example, if bAk.w, “servants”, is usually followed by three men, in case of dissimilation, one of them can be replaced by a woman. In the same way, if mHy.t, “fish”, habitually takes three identical fish, a dissimilated version will show three different species. This Ph.D Thesis aims to analyse in a systematic way the process of “dissimilation graphique”, mostly found in hieroglyphic inscriptions of royal and private tombs, but also in some hieratic documents. Through this study, the supposed reasons of dissimilation are exposed. Consequently, Egyptian classification is newly enlightened. Moreover, in examining a great number of Old Kingdom texts, new analysis of the signs functions are proposed to clarify some unclear elements of egyptological Linguistics

Cette étude s’intéresse aux modes de transport terrestre utilisés pour les biens et marchandises dans l’ancienne Égypte. On en dénombre plusieurs, dont les plus importants sont la palanche, la barre de portage, le traîneau, et le transport à dos d’âne. Cette recherche s’appuie principalement sur des ressources documentaires iconographiques et plastiques, provenant de mastabas et d’hypogées datés de l’Ancien et du Moyen Empire. Elle a pour enjeu de préciser les conditions d’utilisation des différents modes de transport, tant sur un plan chronologique, que sociologique, ou topographique
This study deals with means of land transport used for goods and merchandises in ancient Egypt. We can count a few, among which the most important are yoke, carrying pole, sledge and donkeys. This research is mainly based on iconographic and sculptural documentary resources from mastabas and hypogea dating from the Old and Middle Kingdom. Its main concern is to explain the conditions of use of the different means of land transport, on a chronological, sociological as well as on a topographical level

Cette étude retrace l’évolution de certains traitements réservés aux cadavres et aux restes humains en Égypte en se concentrant sur l’époque prédynastique et les six premières dynasties. Les cimetières contemporains de cette période de formation et d’affirmation des principaux éléments constitutifs de la civilisation pharaonique témoignent de la coexistence de pratiques funéraires associées à l’émergence de la momification artificielle et de pratiques mortuaires intervenant sur des corps partiellement ou totalement décomposés. L’objectif est de réévaluer par une approche archéothanatologique la documentation relative à ces deux catégories de traitements du corps, afin d’appréhender la diversité des pratiques de cette période. Cette étude vise donc à replacer le corps du défunt au centre de la discussion sur les pratiques mortuaires égyptiennes en prenant en compte deux ères chronologiques souvent considérées séparément. La relecture des publications archéologiques et de certaines archives de fouilles dans cette perspective a permis de proposer une sélection hétérogène de sépultures et de dépôts de restes humains provenant de 27 cimetières de la vallée égyptienne du Nil. Cette sélection d’inhumations offre une vision d’ensemble de la manière dont pouvaient être traités les défunts, ce qui permet de discuter de la continuité entre les pratiques prédynastiques et dynastiques et de confronter les données recueillies aux différentes interprétations possibles des gestes identifiés
This study examines the evolution of practices pertaining to the treatment of human bodies and remains in Egypt from the Predynastic era through the first six dynasties. Burial grounds contemporaneous with the formation and affirmation of the principal constituents of the pharaonic civilization indicate the coexistence of funerary practices related to the emergence of artificial mummification, and mortuary practices involving partially or fully decomposed bodies. The purpose is to reevaluate, through the lens of archaeothanatology, the existing documentation regarding these two body treatment categories to better understand the diversity of practices over this period. The study aims to see the body of the deceased as the focal point of the discussion on Egyptian mortuary practices by taking into consideration two chronological eras often examined separately. Studying archaeological publications and archival documents of past excavations from this perspective provides a heterogeneous set of human sepultures and deposits found in 27 cemeteries throughout the Egyptian Nile valley. The cases chosen for the purpose of this study offer a comprehensive outlook into how the deceased were treated, which gives the grounds for discussing the continuity between predynastic and dynastic practices and for confronting the collected materials with diverse possible interpretations of these treatments

Les prêtres sont une partie indissociable de l’organisation et du fonctionnement de la société égyptienne. Parmi eux les prophètes avaient une grande importance dans le clergé égyptien. Leur étude nous permet non seulement une meilleure compréhension du sacerdoce égyptien, mais aussi une meilleure connaissance de la religion égyptienne. Concentrée sur l’époque thinite et l’Ancien Empire, notre recherche a fait l’examen exhaustif des titulaires des prêtrises divines afin de comprendre les mécanismes de l’obtention de celle-ci et les fonctions déléguées aux prophètes. L’examen de sources nous a parmi d’attester une relation entre fonction civile et prêtrise divine qui est étudiée en détail. Nous discuterons la chronologie des prêtrises, les divinités concernées et la nature de ses titulaires. Nous interrogeons sur l’obtention et la transmission de la prêtrise divine. Enfin, nous poserons la question sur les lieux d’exercice de la fonction sacerdotale, ainsi que sur ce que celle-ci devait être
The priests were an inseparable part of the organisation and functioning of the Egyptian society. Among them the prophets were one of the most important for the Egyptian clergy. The study of them allows us not only a better comprehension ofthe Egyptian priesthood but also a better knowledge of the Egyptian religion. Focused on the Early dynastic period and the Old Kingdom our research examinedthe holders of the divine priesthoods in order to understand the ways of having andobtaining it. The study of the sources allowed us to attest a relation between the civil service and the divine priesthood. We discussed the priesthood’s chronology, the mentioned gods and its holders. We question about its obtainment and transmission. At last, we focused on finding the place of exercise of the priesthood and its significance