Association between anti-Ro 60kDa (SS-A) autoantibodies and hypocomplementemia in systemic lupus erythematosus patients from Algiers prefectures

AbstractBackgroundSystemic lupus erythematosus (SLE) is characterized by a vicious cycle maintaining systemic inflammation. It starts by autoantibody production, immune complex formation and complement activation that contribute to inflammation, tissue damage and further autoantibody production.Aim of the workTo evaluate the association between the auto-antibodies (abs), circulating immune complexes (CIC), and complement activity in SLE patients.Patients and methodsThis study involved 30 female SLE patients analyzed for autoantibodies, complement profile including complement hemolytic 50 (CH50), alternative pathway 50, factor B, C1q, C2, C3 and C4 as well as C1q-CIC. SLE disease activity was assessed by the SLE Disease Activity Index (SLEDAI).ResultsThe age of patients was 34±12.8years, disease duration was 5.2±3.2years and their mean SLEDAI was 9.96±4.2. Anti-SSA, anti-dsDNA, anti-C1q abs, and CIC were detected in 36.7%, 50%, 50% and 30% of patients, respectively. Anti-SSA were higher in patients with lower compared to normal CH50 activity and C3 level (24.7 vs 88.6U/ml; p=0.002 and 118.6±25.18U/ml vs 15.9±7.3; p<0.0001 respectively) than the other autoantibodies. Increased CIC were higher in patients with lupus nephritis and were associated with anti-SSA, anti-SSB, anti-C1q, anti-Sm and in patients with low CH50 activity. The CIC significantly correlated with anti-C1q (r=0.69, p<0.0001), anti-SSA (r=0.5, p=0.005) and negatively with CH50 (r=−0.4, p=0.046).ConclusionsThe current study confirms that the etiopathogenic anti-SSA autoantibodies are the most associated with hypocomplementemia in SLE. This would stimulate future researches for validation of predictive biomarkers earlier than hypocomplementemia which is still the major unmet need in lupus research and patient care

First-principles study of the electrooptic effect in ferroelectric oxides

We present a method to compute the electrooptic tensor from first principles, explicitly taking into account the electronic, ionic and piezoelectric contributions. It allows us to study the non-linear optic behavior of three ferroelectric ABO_3 compounds : LiNbO_3, BaTiO_3 and PbTiO_3. Our calculations reveal the dominant contribution of the soft mode to the electrooptic coefficients in LiNbO_3 and BaTiO_3 and identify the coupling between the electric field and the polar atomic displacements along the B-O chains as the origin of the large electrooptic response in these compounds.Comment: accepted for publication in Phys. Rev. Let

DYNAMIC DISORDER AT INTERMEDIATE TEMPERATURE AND ITS EFFECT ON THE MAGNETIC PROPERTIES OF THE ORGANIC SUPERCONDUCTOR κ-(BEDTTTF)2Cu[N(CN)2]Br

The k-(BEDT-TTF)X superconducting salts, [where BEDT-TTF is bis(ethylenedithio)-tetrathiafulvalene, abbreviated as ET, and X is a monovalent anion like Cu[N(CN) ]Br 2 , and for either Cu[N(CN) ]Cl 2 or ( )2 Cu NCN and so on], exhibit interestinmagnetic and superconducting phase transitions [1]. They are quasi-two-dimensional and the interplane coupling is very weak. The basic structural unit is a dimer consisting of two BEDTTTF molecules stacked on top of one another. This layered structure leads to highly anisotropic electronic properties. These organic superconductors have similar characteristic superconducting properties including the intrinsic Josephson Effect and the mixed-state properties. This similarity suggests the existence of the vortex phase transition in the organic layered superconductors as observed in HTSC. Because the temperature scale is much lower in organic materials, the thermal fluctuation is expected to be small compared to HTSC. Thus, the comparison between the high-Tc and organic superconductors can give important clues as to the nature of vortex phase transitions. Besides these anomalies around 50 K, unusual time dependencies in magnetic and transport properties have been reported for both deuterated and hydrogenated k-Br near 80 K. For - H - Br 8 k , the superconducting properties have been found to depend on the thermal history, in particular on how fast the sample had been cooled through 80 K. As mentioned above, the ground state of - D - Br 8 k is strongly sample-dependent: both superconducting as well as non-superconducting crystals are found. Furthermore, superconducting as well as insulating (possibly antiferromagnetic) phases in separated volume parts of the same sample have been reported. Their relative volume fraction was found to depend on the cooling rate Vc employed at around 80 K[2-3-4]: in fast cooled samples, a strong decrease of the diamagnetic signal has been observed, which has been interpreted as indicating a suppression of the superconducting in favour of the magnetic phase

A study of sorghum production potential in the semi-arid tropic of Brazil.

The paper presents the application of a computerized agroclimatic system to the study ofsorghum production potential in the semi-arid tropic of Brazil. After a brief description of the system, the results obtainae for a sample of counties are discussed. In particular, the paper illustrates the use of clustering techniques in connection to agroclimatic zoning. The use of the system in relation to complementary irrigaton studies is also stressed.bitstream/item/179497/1/FL-06852.pd

Vortex phase transition and superconducting properties of organic quasi-two-dimensional k-(BEDT-TTF) 2 Cu[N(CN) 2 ]Br

International audienceWe report investigations of the low temperature dc susceptibility and the magnetization on the layered organic superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br near 80K and the effect of disorder on the superconducting transition temperature Tc. The shielding effect (S) and the critical current density Jc were studied (with H parallel to the c axis of the crystal). Jc can be estimated by analysis of magnetic hysteresis measurement using the Bean model. For each temperature value, we observed two regimes in the critical current density Jc(H). This result implies that there exists a first-order phase transition in the vortex system in this organic superconductor. Our results show that the magnetic properties of these compounds depend strongly on the cooling rate. The structural transformation which occurs at the vicinity of 80K very strongly influences the physics of vortex lattice and the associated magnetic behavior

Cucurbitacin B: A novel agent for inducing tumor-immune response.

Despite the emergence of immunotherapy as a potential breakthrough in cancer treatment, it showed only a marginal response in pancreatic and liver cancers. Thus, novel strategies are highly desirable to take full advantage of immunotherapy in the treatment of these cancers. One of the critical factors that influence the efficacy of immunotherapy is the increased infiltration of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAM) into tumors that alter the immune landscape and serve as facilitators of tumor proliferation, metastatic growth, and immunotherapy resistance. Thus, we believe that selecting a potent molecule that has the ability to suppress the function or revert the phenotypes of TAM and MDSCs will have a more significant impact in enhancing tumor immunotherapy response. Cucurbitacin B (Cuc B) is a potent inhibitor of Stat3, CSF-1R, and PI3Kγ and has shown its chemopreventive and therapeutic effects against various cancers but is limitedly explored for its application in modulating tumor immune response. In this study, we investigated the molecular effects and underlying molecular mechanisms of Cuc B on TAM and MDSCs. Cuc B significantly (P\u3c0.01) decreased the expression of M2 markers (Arginase I, YM1 FIZZ1, PPARγ and TGFβ in M2 polarized BMDMs and increased M1 markers (NOS2, IL-6, and CD11C) compared to IL-4 alone treatment group. It has been demonstrated that TAMs secrete PDL-1 which neutralizes the function of T-cells. Cuc B treatment significantly (P\u3c0.001) decreased PDL-1 expression in IL-4-treated RAW264.7 cells. Surprisingly, we observed that Cuc B treatment abolished the protein levels of PI3Kγ in IL-4 treated macrophages as determined by confocal microscopy and Western blot analysis. Cuc B treatment of bone marrow-derived MDSCs significantly (P\u3c0.01) decreased the expression of Arginase-1, IL-10, PDL-1, and Stat3. We observed that IL-4-treated BMDMs inhibited phagocytic capacity which was significantly restored upon Cuc B treatment. We observed that Cuc B is a more potent molecule than a pharmacological inhibitor of PI3Kγ (IPI-549) in suppressing key signaling components of TAM and MDSCs. We are performing in vivo study to investigate Cuc B potential to enhance checkpoint blockade immunotherapy response in clinically relevant mouse models of cancer. These results suggest that Cuc B is a novel therapeutic agent which has the potential to suppress or revert TAMs and MDSCs phenotypes. Cuc B may be used as an adjuvant drug molecule in combination with PD1 or CTLA-4 antibodies for improving immunotherapy response against less responsive tumors

Theoretical study of organic materials based on Thieno[2,3-b]thiophene as layer of bulk heterojunction solar cells

In this study, we report a theoretical investigations on the structural, optoelectronic and photovoltaic properties of a series of conjugated organic molecules containing thieno[2,3-b]thiophene, with different substituents. The DFT calculations were performed by using the quantum chemical methods using B3LYP [1] level with 6-31G(d) [2] basis set for all atoms. All calculations were realized by Gaussian 09 [3] program supported by GaussView 5.0.8 interface. Moreover, the optoelectronic properties (HOMO, LUMO, Egap…) were determined from the fully optimized structures. The absorption properties (λmax, Etr, OS) of these molecules are obtained by TD-B3LYP/6-31G(d) method [4].The studied oligomers can be subdivided in three categories; the first one constitutes by synthetized oligomers [5] but is characterized with the highest energy band values. Thanks to the effect of structural modifications in there chemical structures in the second and the third categories, the energy gap values have known a dramatic decrease. We conclude that these conjugated materials, especially of the third categories, are good candidates for bulk heterojunctions in organic solar cells applications.

Crescimento e produção do feijoeiro em resposta à profundidade de aplicação de adubo fosfatado

Several depths (0, 5, 10, 15, 20, 25 and 30 cm) of fertilizer application were studied to observe the growth and development of roots and aerial parts of bean plants (Phaseolus vulgaris L.) in a clayey texture Purple Latosol (Haplortox). Aerial parts were enhanced by fertilizer placed from 10 to 25 cm of depth. Grain yield, however, was equal in all of the treatments, due to an adequate water supply even in the dry season. Toot weight, which was evaluated in greenhouse in PVC tubes with openings each 5 cm up to 30 cm, was influenced by the fertilizer, being increased in those layers where it was applied.Foram estudados os efeitos de diversas profundidades (0, 5, 10, 15, 20, 25 e 30 cm) de aplicação de adubo fosfatado, no crescimento e desenvolvimento de raízes e partes aéreas do feijoeiro (Phaseolus vulgaris L.), em um Latossolo Roxo (Haplortox), textura argilosa. Na avaliação das partes aéreas das plantas notaram-se valores maiores nos tratamentos de 10 a 25 cm de profundidade de aplicação do adubo. Contudo, as produções de grãos se igualaram nos tratamentos, graças ao regime hídrico satisfatório, ocorrido, inclusive, no período da seca. O crescimento das raízes, que foi avaliado em casa de vegetação, em tubos de PVC com uma abertura a cada 5 cm até 30 cm, acusou aumento de peso nas secções adubadas

KAT Ligation for Rapid and Facile Covalent Attachment of Biomolecules to Surfaces

The efficient and bioorthogonal chemical ligation reaction between potassium acyltrifluoroborates (KATs) and hydroxylamines (HAs) was used for the surface functionalization of a self-assembled monolayer (SAM) with biomolecules. An alkane thioether molecule with one terminal KAT group (S-KAT) was synthesized and adsorbed onto a gold surface, placing a KAT group on the top of the monolayer (KAT-SAM). As an initial test case, an aqueous solution of a hydroxylamine (HA) derivative of poly(ethylene glycol) (PEG) (HA-PEG) was added to this KAT-SAM at room temperature to perform the surface KAT ligation. Quartz crystal microbalance with dissipation (QCM-D) monitoring confirmed the rapid attachment of the PEG moiety onto the SAM. By surface characterization methods such as contact angle and ellipsometry, the attachment of PEG layer was confirmed, and covalent amide-bond formation was established by X-ray photoelectron spectroscopy (XPS). In a proof-of-concept study, the applicability of this surface KAT ligation for the attachment of biomolecules to surfaces was tested using a model protein, green fluorescent protein (GFP). A GFP was chemically modified with an HA linker to synthesize HA-GFP and added to the KAT-SAM under aqueous dilute conditions. A rapid attachment of the GFP on the surface was observed in real time by QCM-D. Despite the fact that such biomolecules have a variety of unprotected functional groups within their structures, the surface KAT ligation proceeded rapidly in a chemoselective manner. Our results demonstrate the versatility of the KAT ligation for the covalent attachment of a variety of water-soluble molecules onto SAM surfaces under dilute and biocompatible conditions to form stable, natural amide bonds

Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.

Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo. In Cohort 1, CUB domain-containing protein-1 (CDCP1) was an independent negative prognostic factor for progression-free survival (hazard ratio of 1.79, p=0.0407) and overall survival (hazard ratio of 2.23, p=0.0192). A two-gene model based on AXL and CDCP1 expression was strongly associated with the clinical outcome to EGFR TKIs, in both cohorts of patients. Our preclinical experiments revealed that several RTKs and non-RTKs, were up-regulated at baseline or after treatment with gefitinib or osimertinib. TPX-0005 plus EGFR TKI suppressed expression and activation of RTKs and downstream signaling intermediates. Co-expression of CDCP1 and AXL is often observed in EGFR-mutation-positive tumors, limiting the efficacy of EGFR TKIs. Co-treatment with EGFR TKI and TPX-0005 warrants testing