Thermal annealing of Ag implanted silicon: Relationship between structural and optical properties

Low energy Ag ions were implanted into silicon and annealed at different temperatures in order to generate plasmonic active silicon hybrids. It was found that as the ion fluence of irradiation was increased, a monotonic decrease in the absorption spectra in the ultraviolet region occurs, due to amorphization and macrostructuring of the Si surface. At the same time, the optical spectra are characterized by a strong band after implantation presenting the contribution of the surface plasmon resonance (SPR) of Ag nanoparticles. After heat treatment at 500 and 600?C, the SPR peak shifts to lower wavelengths, as compared to as implanted samples, whereas the plasmon position shifts to higher wavelengths for annealing at 700?C. This observation can be explained by either an out-diffusion of Ag or by stress relaxation and recrystallization of silicon.</jats:p

Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia

Eradication of minimal residual disease (MRD) after allotransplantation in persons with chronic lymphocytic leukemia (CLL) is associated with lower rates of relapse. Rapid engraftment of donor lymphocyte elements may contribute to MRD control but it remains unclear if this strategy will benefit patients. Here we report incidence of MRD eradication and graft versus host disease (GvHD) in persons with rapid versus later donor T-lymphocyte engraftment after lymphodepleting chemotherapy and reduced intensity conditioning (RIC) allotransplantation. Twenty-seven subjects received lymphodepleting chemotherapy to facilitate donor engraftment followed by fludarabine and cyclophosphamide RIC and a blood cell allograft. MRD was monitored by multicolor flow cytometry post transplantation. Complete donor T-lymphoid (TLC) and myeloid (MC) chimerism were achieved in 25 subjects at a median of 28 days (range 14–60 days) and 21 days (range 14–180 days). Achieving complete donor TLC by day 14 versus day ≥28 correlated with occurrence of ≥grade-2 acute GvHD (90% [95% confidence interval (CI), 78–100%] versus 35% [95% CI, 16–54%], P=0.014) and better control of minimal residual disease in the bone marrow at day 100, median 0% (range, 0–0.1%) versus 8.5% (range, 0–92%; P=0.016). Among 11 persons with early donor TLC none had progressive disease (PD) and 7 died of treatment related mortality (TRM). In persons with later development of TLC 8 of 16 had PD and 2 died of TRM. Time to donor myeloid chimerism had no impact on outcomes. Rapid establishment of donor TLC results in more complete eradication of early MRD but greater incidence of acute GvHD and TRM in persons with CLL undergoing RIC allotransplantation

Allogeneic Hematopoetic Transplantation for CLL: Results of Combination Chemotherapy as Pre-Transplant Targeted Lymphocyte Depletion on Disease Response, Donor Chimerism, and Transplantation Outcomes.

Abstract Abstract 3476 The development of reduced intensity conditioning (RIC) regimens has increased the use of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with chronic lymphocytic leukemia (CLL). Despite decreased rates of transplant related mortality, RIC regimens confer slower rates of donor engraftment and increased relapse post-transplant. It has been reported that faster rates of conversion to donor chimerism after RIC alloHSCT result in lower rates of CLL relapse1. We hypothesized that systematic targeted host T-lymphocyte depletion (TLD) to a target level by serial administration of standard chemotherapy prior to RIC alloHSCT will result in more rapid donor engraftment and full donor chimerism, thereby enhancing graft versus leukemia activity. We evaluated the effects of TLD on host CD4 lymphocyte depletion, disease response, and toxicity as well as donor engraftment, non-relapse mortality, and disease control in 27 patients undergoing RIC alloHSCT for CLL from 1999 to 2010. All patients underwent TLD receiving 1–3 cycles of EPOCH-F±R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, fludarabine ± rituximab) prior to RIC (fludarabine/cyclophosphamide) and matched-related (N=17) or unrelated (N=10) donor transplantation followed by calcineurin inhibitor-based GVHD prophylaxis. The number of cycles administered (max of three cycles) was titrated to achieve an absolute CD4 count ≤ 100 cells/μL prior to RIC. The median number of EPOCH-F±R cycles given was 2. The median CD3+, CD4+, and CD8+ lymphocyte counts at baseline were 819, 443, and 269 cells/μL, respectively. The median CD3+, CD4+ and CD8+ lymphocyte counts after TLD were 124, 97, and 52 cells/μL, respectively. The overall response rate to EPOCH-F±R was 50% (9% CR, 41% PR), including 44% of patients who were refractory to their last treatment. The incidence of grade 3 and 4 non-hematologic toxicity with TLD was 72% and 32%, respectively. No patients failed to engraft. The median days to full donor peripheral blood lymphoid and myeloid chimerism were 28 (14-60) and 21 (14-180), respectively. Development of full lymphoid chimerism by day 14 (first evaluation point) versus day 28 or greater trended towards association with development of acute GVHD (90% vs. 35%, P=0.014) but not chronic GVHD (50% vs. 41%, P=0.71). Achievement of full lymphoid chimerism on day 14 as compared to day 28 or greater trended towards association with decreased CLL cells identified in the bone marrow by multicolor flow cytometry at day 100 (median 0% vs. 8.5%, P=0.016) but was not associated with (P=0.077) improved overall survival (OS). There was no association between rates of development of full myeloid chimerism and acute or chronic GVHD or disease control. The rates of acute (grade 2–4) and chronic GVHD were 52% and 44%, respectively. Non-relapse related mortality at one and two years was 21% and 30%, respectively. The rate of complete remission was 54% and the rate of minimal residual disease negativity after transplantation as assessed by multicolor flow cytometry was 55%. The incidence of disease progression after transplant was 33%. The three year event-free and OS probabilities were 56% and 57%, respectively. The median OS was 5.99 years (95% CI, 2.11-NR). In summary, the use of TLD resulted in a high rate of early donor engraftement after RIC alloHSCT in patients with CLL. Rapid donor engraftment was associated with better disease control and occurence of acute GVHD, but it did not appear to alter overall survival. These data suggest that methods resulting in faster donor chimerism may improve CLL control after RIC alloHSCT. Separation of antileukemic effects from severe GVHD remain a challenge. 1. Brown JR et al. Biol Blood Marrow Transplant. 2006 Oct;12(10):1056-64. Table 1: Patient characteristics at study entry N 27 Median age (range) 56 (37–71) Number male 21 (78%) Rai stage 3/4 16 (59%) Poor risk cytogenetics1 (n=25) 12 (44%) Bulky disease ≥5 cm (n=25) 6 (24%) ≥4 Prior regimens 16 (59%) Refractory to last regimen 14 (52%) Median time from diagnosis to HSCT (range) 58 m (17–205) Sorror comorbidity score2     0-2 20 (74%)     3+ 7 (26%) 1. Defined by deletion of 17p or 11q. 2. Sorror et al. Blood 2005;106:2912-2919. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology

Here we demonstrate that reprogramming steroid receptor coactivator-3 (SRC-3) function by changing its posttranslational modification (PTM) code drastically influences systems biology. These findings support the physiological importance of PTMs in directing in vivo functions of a master coregulator. We previously reported that the transactivation potential of SRC-3 is controlled in part by PTMs, although this data emanated from in vitro studies. To test the physiological implications of PTMs on SRC-3, we developed a knock-in mouse model containing mutations at four conserved phosphorylation sites. These mice displayed a systems biology phenotype with increased body weight and adiposity, coupled with reduced peripheral insulin sensitivity. Collectively, these phenotypes result from increased IGF1 signaling, due to elevated IGFBP3 levels. We provide convincing evidence that these mutations in SRC-3 promoted enhanced transcription of the IGFBP3 gene and globally influenced growth and metabolism. Consequently, these mice displayed increased liver tumorigenesis, which likely results from elevated IGF1 signaling

New national and regional bryophyte records, 31

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