Temporal characterization of individual harmonics of an attosecond pulse train by THz streaking

We report on the global temporal pulse characteristics of individual harmonics in an attosecond pulse train by means of photo-electron streaking in a strong low-frequency transient. The scheme allows direct retrieval of pulse durations and first order chirp of individual harmonics without the need of temporal scanning. The measurements were performed using an intense THz field generated by tilted phase front technique in LiNbO_3 . Pulse properties for harmonics of order 23, 25 and 27 show that the individual pulse durations and linear chirp are decreasing by the harmonic order

Antiproliferativna aktivnost glutarimidnih derivata iz baze podataka Nacionalnog instituta za rak, SAD - 3D odnos strukture i aktivnosti nezavisan od poravnavanja molekula

Alignment-free, three dimensional structure-activity relationships (3D QSAR) of the antiproliferative potency of twenty-two glutarimide-containing compounds, taken from National Cancer Institute Developmental therapeutics Program database, toward eight representative human tumour cell lines are reported. The descriptors used in the QSAR study were derived from GRID molecular interaction fields. The obtained models readily detect structural motifs positively or negatively correlated with the potency of the studied compounds toward each cell line. In this way, the pharmacophoric pattern required for high potency of compounds is reported. This pattern can serve as guidance for the design and syntheses of novel congeners, planned to be tested toward human tumour cell lines.U tekstu je opisan odnos strukture i antiproliferativne aktivnosti 22 glutarimidna derivata prema osam reprezentativnih linija humanih tumora. Podaci o strukturi jedinjenja i njihovoj aktivnosti su preuzeti iz baze podataka Nacionalnog Instituta za rak, SAD. Deskriptori, nezavisni od poravnavanja molekula (GRIND-2), korišćeni u proučavanju odnosa strukture i aktivnosti su dobijeni upotrebom programa GRID. Modeli jasno prikazuju strukturne elemente jedinjenja koji se pozitivno ili negativno korelišu sa biološkom aktivnošću. Farmakoforna slika dobijena iz modela će biti korišćena za planiranje novih analoga koji sadrže glutarimidni prsten i za koje se očekuje da će pokazati značajnu antiproliferativnu aktivnost

Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

© 2017 J. Serb. Chem. Soc. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).Redox properties of a set of aryldiketo acids (ADKs), small organic molecules that comprise 2,4-dioxobutanoic acid moiety, were studied. Along with well-known HIV-1 integrase (IN) inhibition, ADKs exert widespread biological activities. The aim of this work was to evaluate effects of aryl substitutions on properties of dioxobutanoic moiety that is involved in key interactions with metal ions within active sites of target enzymes. The effect of pH on electronic properties of nine congeners was examined using cyclic voltammetry and differential pulse polarography. Compounds were chosen as a simple set of congeners, bearing Me-groups on phenyl ring which should not be involved in electrochemical reactions, leaving diketo moiety as sole electrophore. Substitution pattern was systematically varied, yielding a set having different torsion between phenyl ring and aryl keto group (Ar-C(O)). Protonation state of ADKs at different pH values was determined from experimentally obtained pKas. The results showed that the equal number of protons and electrons is involved in the oxidation and reduction reactions at the surface of electrode. Quantitative linear correlations between reduction potentials and energies of frontier orbitals, calculated for neutral, monoanionic and corresponding radical anionic species, and steric parameter were found.Peer reviewe

Noninvasive technique of preventing thrombin escape into the systemic circulation during ultrasound-guided thrombin injection (UGTI) of the postcatheterization pseudoaneurysms

Introduction Iatrogenic, postcatheterization pseudoaneurysms (PSA) of the femoral artery are a common complication after diagnostic and interventional procedures, with up to 7.7% incidence. Treatment includes surgical repair, ultrasound-guided compression (USGC) repair of the tract of the PSA, or recently ultrasound-guided thrombin injection (UGTI). Large ([1.8 cm) PSA sac with short (\3 mm) and/or wide ([3 mm) tract has higher complication ratio such as thromboembolic events after UGTI. Those cases are considered for protective balloon inflation during thrombin injection. The aim of our study was to evaluate the success rate of preventing escape of the thrombin during UGTI with simultaneous manual compression on ipsilateral iliac artery. Methods and results We reported 46 patients, 17 males and 29 females, aged 53–74 years, with iatrogenic, postcatheterization femoral artery PSA. Out of 46 patients, 7 were successfully treated with USGC. The rest of the patients were treated with UGTI with simultaneous manual compression on ipsilateral iliac artery to stop the flow in PSA, and to avoid thrombin escape into the native circulation. Success rate of UGTI with manual compression of ipsilateral iliac artery was 97% with the complication rate of 2.6%. Conclusion Our study confirms that UGTI treatment of the PSA of the femoral artery combined with compression of the ipsilateral iliac artery could be a safe and reliable method of the thrombin escape prevention into the systemic circulation, as good as more invasive and demanding methods

The antitumor immune response in HER-2 positive, metastatic breast cancer patients

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. We observed a significant increase in PBMC-dependent cytotoxicity when autologous serum was introduced in the assay. Furthermore, the addition of Herceptin significantly increases their cytotoxicity. These data suggest that autologous serum constitutively contains factors that might affect PBMC-dependent cytotoxic activity against HER-2 positive cancer cells

Sinteza, NMR i DFT proračunavanja i ispitivanje antimikrobne aktivnosti Zn(II) kompleksa sa N-benziloksikarbonil-S-alaninom

In this study, the first complexes of Zn(II) with the N-benzyloxycarbonyl-S-alaninato ligand (N-Boc-S-ala) were synthesized. The new complexes were characterized by elemental analysis, conductometric measurements, IR. (1)H-NMR, (13)C-NMR and 2D-NMR spectroscopy. On the basis of the experimental data, tetrahedral geometry of the Zn(II) complexes was proposed. A very good agreement between the NMR and DFT calculated data was obtained. Investigation of antimicrobial activity of the newly synthesized complexes was also performed. It was established that [Zn(N-Boc-S-ala)(2)] was selective and acts only on Candida aibicans.U ovom radu su sintetizovani prvi kompleksi Zn(II) sa N-benziloksikarbonil-S-alaninato ligandom (N-Boc-S-ala). Kompleksi su okarakterisani elementalnom analizom, konduktometrijskim merenjem, IR, 1H-NMR, 13C-NMR i 2D-NMR spektroskopijom. Tetraedarska geometrija Zn(II) kompleksa pretpostavljena je na osnovu eksperimentalnih podataka. Dobijeno je veoma dobro slaganje između NMR i DFT podataka. Ispitivana je antimikrobna aktivnost novosintetizovanih kompleksa. Ustanovljeno je da je [Zn(N-Boc-S-ala)2] kompleks selektivan i da deluje samo na gljivu Candida albicans

Different levels of humoral immunoreactivity to different wheat cultivars gliadin are present in patients with celiac disease and in patients with multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Immunity to food antigens (gliadin, cow's milk proteins) is in the centre of the attention of modern medicine focused on the prevention of diseases, prevention which is based on the use of appropriate restriction diet. Detection of the enhanced levels of the immune reactions to antigen(s) present in food is from this point of view of great importance because there are reports that some of health disturbances, like celiac disease (CD) and some premalignant conditions, like monoclonal gammopathy of undetermined significance (MGUS), were vanished after the appropriate restriction diets.</p> <p>It is well known that gliadin is toxic to small bowel mucosa of relatively small population of genetically predisposed individuals, who under this toxic action develop celiac disease (CD). As the quantity of immunogenic gliadin could vary between different wheat species, the first aim of this work was to determine the percentage of immunogenic gliadin in ten bread wheat cultivars and in three commercially grown durum wheat cultivars. The second part of the study was initiated by results of previous publication, reporting that sera of some of multiple myeloma (MM) patients showed the presence of elevated levels of anti-gliadin IgA, without the enhanced levels of anti-gliadin IgG antibodies, determined with commercial ELISA test. It was designed to assess is it possible to reveal is there any hidden, especially anti-gliadin IgG immunoreactivity, in serum of mentioned group of patients. For this purpose we tested MM patients sera, as well as celiac disease (CD) patients sera for the immunoreaction with the native gliadin isolated from wheat species used for bread and pasta making in corresponding geographic region.</p> <p>Results</p> <p>Gliadin was isolated from wheat flour by two step 60% ehanolic extraction. Its content was determined by commercial R5 Mendez Elisa using PWG gliadin as the standard. Results obtained showed that immunogenic gliadin content varies between 50.4 and 65.4 mg/g in bread wheat cultivars and between 20 and 25.6 mg/g in durum wheat cultivars.</p> <p>Anti-gliadin IgA and IgG immunoreactivity of patients' sera in (IU/ml) was firstly determined by commercial diagnostic Binding Site ELISA test, and then additionally by non-commercial ELISA tests, using standardized ethanol wheat extracts -gliadin as the antigen.</p> <p>In both patients groups IgA immunoreactivity to gliadin from different cultivars was almost homogenous and in correlation with results from commercial test (except for one patient with IgA(λ) myeloma, they were more then five times higher). But, results for IgG immunoreactivity were more frequently inhomogeneous, and especially for few MM patients, they were more then five times higher and did not correlate with results obtained using Binding Site test.</p> <p>Conclusion</p> <p>Results obtained showed different content of immunogenic gliadin epitopes in various species of wheat.</p> <p>They also point for new effort to elucidate is there a need to develop new standard antigen, the representative mixture of gliadin isolated from local wheat species used for bread production in corresponding geographic region for ELISA diagnostic tests.</p

Anti-CD26 autoantibodies are involved in rheumatoid arthritis and show potential clinical interest

Objectives Rheumatoid arthritis (RA) patients show low serum levels of the Ag dipeptidyl peptidase IV (DPP-IV/CD26), both soluble CD26 (sCD26) concentration and its DPP-IV activity. The aim of this study was to test if anti-DPP-IV/CD26 Abs (Anti-CD26) cleared sCD26. Design & methods Serum Anti-CD26 and Total titers (as comparison) of isotypes IgA, IgM and IgG as well as sCD26 concentration and DPP-IV activity were measured in a cohort of RA patients undergoing different biological and non-biological therapies (n = 105) and controls (n = 50). Results Anti-CD26 levels were increased approximately two-fold for each isotype in RA, were not related to the sCD26 clearance, showed several correlations with disease activity parameters, were significantly higher in smokers and they were not ACPA. Anti-CD26 Igs showed high diagnostic power (82% sensitivity and 96% specificity) and their levels differed amongst the different groups of patients stratified by the type of therapy. Conclusions As DPP-IV/CD26 is associated to factors triggering RA in the lung and periodontal tissue, these results suggest that Anti-CD26 isotypes may participate in pathogenesis and may be useful as biomarkers for earlier diagnosis and/or precision medicineThis work was supported by an unrestricted medical grant from Pfizer Spain (WS1541122). Dr. Pego has support from the European Union Seventh Framework Programme [FP7/REGPOT-2012-2013.1] under grant agreement no 316265, BIOCAPS. The funding organization (s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.S

Cytomegalovirus protein m154 perturbs the adaptor protein-1 compartment mediating broad-spectrum immune evasion

Cytomegaloviruses (CMVs) are ubiquitous pathogens known to employ numerous immunoevasive strategies that significantly impair the ability of the immune system to eliminate the infected cells. Here, we report that the single mouse CMV (MCMV) protein, m154, downregulates multiple surface molecules involved in the activation and costimulation of the immune cells. We demonstrate that m154 uses its cytoplasmic tail motif, DD, to interfere with the adaptor protein-1 (AP-1) complex, implicated in intracellular protein sorting and packaging. As a consequence of the perturbed AP-1 sorting, m154 promotes lysosomal degradation of several proteins involved in T cell costimulation, thus impairing virus-specific CD8+ T cell response and virus control in vivo. Additionally, we show that HCMV infection similarly interferes with the AP-1 complex. Altogether, we identify the robust mechanism employed by single viral immunomodulatory protein targeting a broad spectrum of cell surface molecules involved in the antiviral immune response