Electron Glass Phase with Resilient Zhang-Rice Singlets in LiCu_{3}O_{3}.

LiCu_{3}O_{3} is an antiferromagnetic mixed valence cuprate where trilayers of edge-sharing Cu(II)O (3d^{9}) are sandwiched in between planes of Cu(I) (3d^{10}) ions, with Li stochastically substituting Cu(II). Angle-resolved photoemission spectroscopy (ARPES) and density functional theory reveal two insulating electronic subsystems that are segregated in spite of sharing common oxygen atoms: a Cu d_{z^{2}}/O p_{z} derived valence band (VB) dispersing on the Cu(I) plane, and a Cu 3d_{x^{2}-y^{2}}/O 2p_{x,y} derived Zhang-Rice singlet (ZRS) band dispersing on the Cu(II)O planes. First-principle analysis shows the Li substitution to stabilize the insulating ground state, but only if antiferromagnetic correlations are present. Li further induces substitutional disorder and a 2D electron glass behavior in charge transport, reflected in a large 530 meV Coulomb gap and a linear suppression of VB spectral weight at E_{F} that is observed by ARPES. Surprisingly, the disorder leaves the Cu(II)-derived ZRS largely unaffected. This indicates a local segregation of Li and Cu atoms onto the two separate corner-sharing Cu(II)O_{2} sub-lattices of the edge-sharing Cu(II)O planes, and highlights the ubiquitous resilience of the entangled two hole ZRS entity against impurity scattering.

Observation of Weakened V-V Dimers in the Monoclinic Metallic Phase of Strained VO_{2}.

Emergent order at mesoscopic length scales in condensed matter can provide fundamental insight into the underlying competing interactions and their relationship with the order parameter. Using spectromicroscopy, we show that mesoscopic stripe order near the metal-insulator transition (MIT) of strained VO_{2} represents periodic modulations in both crystal symmetry and V-V dimerization. Above the MIT, we unexpectedly find the long-range order of V-V dimer strength and crystal symmetry become dissociated beyond ≈200 nm, whereas the conductivity transition proceeds homogeneously in a narrow temperature range.

Analysis of T-cell clonality pattern in tumor samples of breast cancer patients.

PURPOSE AND METHODS: A large body of experimental evidence has confirmed that different tumors, including breast carcinomas, can stimulate specific T-cell-mediated immune responses. In this study we have analyzed patterns of T-cell clonality in tumor samples of 54 breast cancer patients classified as lymph node negative, N0 (n=16), or lymph node positive, N+ (n=38). The clonality of T-cells was analyzed by the PCR-PAGE method. RESULTS: Monoclonal/oligoclonal (M/O) T-cell populations were found in 15 breast cancer patients, nine N+ and six N0. In all analyzed groups (N+ + N0, N+, N0) the incidence of relapse was not significantly different between patients with M/O and patients with polyclonal T-cells. Comparison of disease-free interval (DFI) between patients divided according to the presence of TCRgamma monoclonality/oligoclonality showed a marginally significant difference only in the group of N+ patients within the first 24 months of follow-up. Patients with a M/O T-cell population had a shorter DFI than patients with a polyclonal T-cell population. This difference was not observed when the complete follow-up period was considered in the same group of patients. Furthermore, there was no significant difference in overall survival (OS) between patients with M/O and patients with polyclonal T-cells. CONCLUSION: Our results imply that tumor infiltrating T-cells are usually polyclonal. The pattern of T-cell clonality does not correlate with the incidence of relapse and the duration of DFI and OS in the analyzed groups of breast cancer patients, excluding N+ patients with M/O T-cells who had a shorter DFI in the first 24 months of follow-up. This observation suggests that polyclonal T-cell populations may provide a broader spectrum of T-cell-mediated antitumor response.

Selenium status in soils in Yugoslavia.

In the last 8 years, a number of data on selenium (Se) content and distribution in the soil of Yugoslavia (Serbia and Montenegro) became available. The Se content of the soil in Yugoslavia varies in a broad range 39 to 440 microg/kg (mean value 230 microg/kg; n = 284). The soil clay fraction is rich in Se (range 146 to 586 microg/kg) in relation to sand and silt fractions. The available Se content (after extraction with ammonium acetate and EDTA) varies in the range of 1.2 to 28.2% of the total Se content. The speciation of Se is shown for the soils derived from volcanic rocks in Serbia. In addition, the influence of some soil properties on the Se content, as well as its content in the rocks, sediment, and wild plants in Yugoslavia, is discussed. The geographical distribution of Se in the soil of Yugoslavia shows that it is found in inadequate amounts in many agricultural regions. Its low content in soil has been thought to be associated with a higher incidence of some diseases. The Se content of the soil in Yugoslavia is not fully known. There is a great need to make a systematic geochemical mapping for Se and other trace elements in the soil.

Selenium in soil, grass, and human serum in the Zlatibor mountain area (Serbia): geomedical aspects.

The Zlatibor district in Serbia has lower mortality rates of malignant and cardiovascular diseases (CVD) compared with other regions in Serbia. To better understand the influence of the geochemical environment, we collected and analyzed soil from various bedrocks and the grass growing on them. We also analyzed spring and stream waters, including large water supply accumulations, for major chemical elements and examined the serum of healthy adults in the large area of Zlatibor for selenium (Se) and magnesium (Mg). Our studies included villages, small towns, and the town of Uzice. Our results showed a variable Se content in the soil over different bedrocks. In general, soil in this area has a higher Se content than in other regions of Serbia. The Se content of the grass is influenced by bedrock and soil mineralogy, but mostly by soil pH and the date of collection. For example, in late summer, grass contains twice as much Se than in spring. Mg2+HCO3(-)-type waters occur in the ultramafic massif of Zlatibor in a concentration of 44 to 68 mgMg/L. The serum Se values were higher in the Zlatibor area than in other regions of Serbia (62.6 +/- 14.9 microgSe/L; n = 158). The serum Mg content (22.7 +/- 2.2 mg/L; n = 158) was in the uppermost part of the reference range. Taking into account their biological role, the Se and Mg levels in the human population in the Zlatibor area could influence the lower mortality rates of cancer and CVD in this region compared with other regions in Serbia.

Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha.

The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.

Impaired perforin-dependent NK cell cytotoxicity and proliferative activity of peripheral blood T cells is associated with metastatic melanoma.

AIMS AND BACKGROUND: Patients with metastatic melanoma often have defects in the percentage and function of peripheral blood NK cells, which are involved in the non-specific innate antitumor immune response, and T cells, which participate in the specific acquired antitumor immune response. The aim of this study was to investigate in more detail not only the percentage but also the activation status and function of NK and T cells in patients with metastatic melanoma prior to therapy. METHODS: The percentage of peripheral blood CD56+ NK cells, CD3+ T cells and their CD4+ and CD8+ subsets, as well as the expression of the activation antigens CD69, CD38 and HLA-DR were analyzed by flow cytometry. The functional capacity of NK cells was evaluated by the 51-chromium release cytotoxicity assay, while the proliferative activity of T cells was estimated by the lymphocyte transformation test to mitogen phytohemagglutinin. RESULTS: The results obtained in this study have revealed a new aspect of NK and T cell dysfunction that is not, as commonly reported, associated with a decrease in their percentage. Moreover, a significant number of the investigated patients had a higher percentage of NK cells that did not lead to improved NK cell cytotoxicity as a result of the detected defect in the NK cell perforin-mediated cytotoxic mechanism of tumor cell lysis. The impaired proliferative response of T cells was associated with a decreased expression of the activation antigen HLA-DR. CONCLUSION: The novel finding in this study of melanoma patients with metastatic disease is the impaired perforin-dependent NK cell cytotoxic mechanism, which was recently shown to be primarily responsible for preventing metastasis. Another interesting finding was the generally hyporeactive status of T cells, possibly resulting from persistent antigenic stimulation. The observed dysfunction of NK and T cells in patients with metastatic melanoma prior to therapy point to the need to supplement chemotherapy with appropriate immunotherapeutic agents in order to overcome the immunosuppression associated with advanced malignancy.

Selenium deficiency in Yugoslavia.

Data on selenium (Se) deficiency in Yugoslavia are presented. The results include Se content of soil, cereal crops, and garlic grown in these soils, and human serum and scalp hair from several towns and regions. All data indicate a serious Se deficiency: soil (n = 140), the mean value of 200 +/- 69.6 micrograms/kg Se; wheat, (58) mean = 20.5 +/- 12.4 micrograms/kg; corn, (79) mean = 13.7 +/- 13.6 micrograms/kg; and garlic, (66) mean = 13.7 +/- 17.1 micrograms/kg Se. Analyses of human tissue show a very low Se status of the Yugoslav population: serum, (n = 875) mean = 50.0 +/- 18.0 micrograms/L and scalp hair, (388) mean = 94 +/- 16 micrograms/kg Se. In some regions, Se contents of grain, garlic, and human serum and hair are approaching those in the low-Se belt in China. It is assumed that very low Se status of a human population could be a risk factor in the development of Balkan Endemic Nephropathy (BEN) and in a high incidence of urinary tract tumors (UTT) in endemic areas.

Hydrogen production by tuning the photonic band gap with the electronic band gap of TiO2.

Tuning the photonic band gap (PBG) to the electronic band gap (EBG) of Au/TiO2 catalysts resulted in considerable enhancement of the photocatalytic water splitting to hydrogen under direct sunlight. Au/TiO2 (PBG-357 nm) photocatalyst exhibited superior photocatalytic performance under both UV and sunlight compared to the Au/TiO2 (PBG-585 nm) photocatalyst and both are higher than Au/TiO2 without the 3 dimensionally ordered macro-porous structure materials. The very high photocatalytic activity is attributed to suppression of a fraction of electron-hole recombination route due to the co-incidence of the PBG with the EBG of TiO2 These materials that maintain their activity with very small amount of sacrificial agents (down to 0.5 vol.% of ethanol) are poised to find direct applications because of their high activity, low cost of the process, simplicity and stability.

CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma.

BACKGROUND: The few chemoimmunotherapy trials that together with dacarbazine (DTIC) and interferon-alpha 2a (IFNalpha), include retinoic acid (RA), did not include detailed immunological evaluation of functional and phenotypic natural killer (NK) cell characteristics, and have shown contradictory clinical results. MATERIALS AND METHODS: Malignant melanoma (MM) patients undergoing phase II-randomized chemoimmunotherapy trials were treated with DTIC, IFNalpha (Hoffmann-La Roche) (group A, n = 31), and with DTIC, IFNalpha and 13-cis-RA (Isotretinoin, Hoffmann-La Roche, Basel, Switzerland) (group B, n = 29). Patients and 42 healthy controls were evaluated by FACS flow analyses for CD3/CD56/CD69 positive cells, NK cytotoxicity in fresh peripheral blood lymphocytes (PBL) and for interferon regulatory factor-1 mRNA expression by reverse transcriptase polymerase chain reaction in treated PBL. RESULTS: The addition of RA to a DTIC-IFN regime did not bring any therapeutical benefit in terms of response or survival. Immunological follow-up on days 1, 6 and 27 of each therapy cycle shows a significant increase in NK cell activity in both groups, only on day 6 of the first cycle, while CD69+CD56+ expression increased significantly on day 6 of each therapy cycle, in both groups. Evaluation of the dynamics of expression of IRF-1 of in vitro treated PBL, shows its strong and prompt up-regulation by IFNalpha and synergistic effect of IFNalpha and RA combination. CONCLUSION: The dynamics of the increase in CD69 early activation antigen expression on CD56+ NK cells is systematic and serial with the increase being significantly higher on day six of the first cycle in group B patients with clinical response, compared to those without, indicating possible predictive value of CD69 expression for clinical response to chemoimmunotherapy.

Analysis of T-cell clonality pattern in tumor samples of breast cancer patients.

PURPOSE AND METHODS: A large body of experimental evidence has confirmed that different tumors, including breast carcinomas, can stimulate specific T-cell-mediated immune responses. In this study we have analyzed patterns of T-cell clonality in tumor samples of 54 breast cancer patients classified as lymph node negative, N0 (n=16), or lymph node positive, N+ (n=38). The clonality of T-cells was analyzed by the PCR-PAGE method. RESULTS: Monoclonal/oligoclonal (M/O) T-cell populations were found in 15 breast cancer patients, nine N+ and six N0. In all analyzed groups (N+ + N0, N+, N0) the incidence of relapse was not significantly different between patients with M/O and patients with polyclonal T-cells. Comparison of disease-free interval (DFI) between patients divided according to the presence of TCRg monoclonality/oligoclonality showed a marginally significant difference only in the group of N+ patients within the first 24 months of follow-up. Patients with a M/O T-cell population had a shorter DFI than patients with a polyclonal T-cell population. This difference was not observed when the complete follow-up period was considered in the same group of patients. Furthermore, there was no significant difference in overall survival (OS) between patients with M/O and patients with polyclonal T-cells. CONCLUSION: Our results imply that tumor infiltrating T-cells are usually polyclonal. The pattern of T-cell clonality does not correlate with the incidence of relapse and the duration of DFI and OS in the analyzed groups of breast cancer patients, excluding N+ patients with M/O T-cells who had a shorter DFI in the first 24 months of follow-up. This observation suggests that polyclonal T-cell populations may provide a broader spectrum of T-cell-mediated antitumor response. (Int J Biol Markers 2005; 20: 177-83).

Selenium deficiency in Yugoslavia and possible effects on health.

New data on Se-deficiency in Yugoslavia are presented. The results include Se contents of soils, cereal crops and garlic grown in the investigated soils, and human serum and scalp hair from several towns and regions in this country. All data indicate a serious Se-deficiency. Analyses of human tissues show a very low Se-status of the Yugoslav population. In some regions, Se contents of garlic, grains and human serum and hair are approaching those in the low-selenium zone in China. It is assumed that the very low Se-status of the human population could be a risk factor for the endemic nephropathy and the urinary tract tumours in endemic areas.

[Correlation between functional capability and phenotypic characteristics of peripheral blood lymphocytes in patients with malignant melanoma]. / Odnos funkcionalinih sposobnosti i fenotipskih karakteristika limfocita periferne krvi bolsnika sa malignim melanomima.

Malignant melanoma is well known for its poor response to chemotherapy, radiotherapy and its susceptibility to immunotherapy. Considering that dacarbazine (DTIC) and interferon alpha (IFNalpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFNalpha monotherapy, as well as with their combination in metastatic disease. Pre-therapy values of immunological parameters showed significantly decreased NK cell activity, altered in vitro production of TNFalpha, IL-2 and proliferative response of peripheral blood lymphocytes (PBL), while percentage of PBL subpopulations was unchanged. During therapy, NK cell activity was significantly increased after the 1st cycle of combined chemoimmunotherapy (DTIC + IFNalpha), followed by a significant decrease after the 2nd cycle of therapy. Furthermore, in this group, there was a significant increase in CD4+ T helper cell percentage after the 1st cycle of therapy. Serial monitoring of activation antigens also showed a significant increase in the expression of CD38 on CD8+ cytotoxic T cells, after the 1st and 2nd cycle in combined chemoimmunotherapy group and, after 30 days, in the group of patients treated with IFNalpha, only. The increase in the expression of HLA-DR activation antigen on CD3+ and CD8+ T cells had a gradual increase and significant rise after the 2nd cycle of combine chemoimmunotherapy, only. The dynamic of immunological changes, mostly observed in combined chemoimmunotherapy, and rarely in IFNalpha monotherapy gives valuable insight into induced immunomodulation, suggesting early, but transient favourable changes, that could be prolonged by timely introduction of other immunotherapeutic agents.