Comparing the Influence of Residual Stress on Composite Materials Made of Polyhydroxybutyrate (PHB) and Amorphous Hydrogenated Carbon (a-C:H) Layers: Differences Caused by Single Side and Full Substrate Film Attachment during Plasma Coating.

Polyhydroxybutyrate (PHB) is a bio-based, biodegradable and commercially used polymer, which in its native form is unfortunately not generally applicable. A widely used technique to adapt polymers to a wider range of applications is the surface modification with amorphous hydrogenated carbon (a-C:H) layers, realized by plasma-enhanced chemical vapor deposition (PE-CVD). However, this process creates intrinsic stress in the layer-polymer system which can even lead to full layer failure. The aim of this study was to investigate how the carbon layer is affected when the basic polymer film to be coated can follow the stress and bend (single side attachment) and when it cannot do so because it is firmly clamped (full attachment). For both attachment methods, the a-C:H layers were simultaneously deposited on PHB samples. Ex-situ characterization was performed using a scanning electron microscope (SEM) for surface morphology and contact angle (CA) measurements for wettability. In addition, the stress prevailing in the layer was calculated using the Stoney equation. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) measurements were used to investigate the chemical composition of the coating surface.

Plasma Supported Deposition of Amorphous Hydrogenated Carbon (a-C:H) on Polyamide 6: Determining Interlayer Completion and Dehydrogenation Effects during Layer Growth.

Polyamide 6 (PA6) is a commonly used material in many different sectors of modern industry. Herein, PA6 samples were coated with amorphous carbon layers (a-C:H) with increasing thickness up to 2 µm using radio frequency plasma enhanced chemical vapor deposition for surface adjustment. The morphology of the carbon coatings was inspected by ex situ atomic force microscopy and scanning electron microscopy. Surface wettability was checked by contact angle measurements. The chemical composition was analyzed using the surface sensitive synchrotron X-ray-based techniques near-edge X-ray absorption fine structure and X-ray photoelectron spectroscopy, supported by diffuse reflectance infrared Fourier transform spectroscopy. Particular attention was paid to the coating interval from 0 to 100 nm, to specify the interlayer thickness between the PA6 polymer and a-C:H coating, and the region between 1000 and 2000 nm, where dehydrogenation of the a-C:H layer occurs. The interlayer is decisive for the linkage of the deposited carbon layer on the polymer: the more pronounced it is, the better the adhesion. The thickness of the interlayer could be narrowed down to 40 nm in all used methods, and the dehydrogenation process takes place at a layer thickness of 1500 nm.

Refinement of Sustainable Polybutylene Adipate Terephthalate (PBAT) with Amorphous Hydrogenated Carbon Films (a-C:H) Revealing Film Instabilities Influenced by a Thickness-Dependent Change of sp2/sp3 Ratio.

The increasing use of polymers is related to a growing disposal problem. Switching to biodegradable polymers such as polybutylene adipate terephthalate (PBAT) is a feasible possibility, but after industrial production of commercially available material PBAT is not suitable for every application. Therefore, surface refinements with amorphous hydrogenated carbon films (a-C:H) produced by plasma-assisted chemical vapor deposition (PE-CVD) changing the top layer characteristics are used. Here, 50 µm-thick PBAT films are coated with a-C:H layers up to 500 nm in 50 nm steps. The top surface sp2/sp3 bonding ratios are analyzed by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) both synchrotron-based. In addition, measurements using diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) were performed for detailed chemical composition. Surface topography was analyzed by scanning electron microscopy (SEM) and the surface wettability by contact angle measurements. With increasing a-C:H layer thickness not only does the topography change but also the sp2 to sp3 ratio, which in combination indicates internal stress-induced phenomena. The results obtained provide a more detailed understanding of the mostly inorganic a-C:H coatings on the biodegradable organic polymer PBAT via in situ growth and stepwise height-dependent analysis.

In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIV-infected patients.

Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4CD45ROCD25 cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4CD45ROCD25 cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45ROCD25 or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25 cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45ROCD25 cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4CD45ROCD25 cells that express high levels of foxP3 but exert weak suppressive function. These CD4CD25 cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4 T cell pool.

Paradox of precision: bright tobacco as technology of transfer, 1880-1937.

This article compares two episodes of technology transfer in the 1890s: the movement of bright tobacco production technology to south-central Africa with the spread of the crop to eastern North Carolina and South Carolina. It finds similarities in the people who introduced the crop, but significant differences in the methods used to produce it. This is troubling because the type is defined by the cultivation and especially the curing techniques used to produce it; it is also often described in the historical literature as "Virginia tobacco," even when grown elsewhere. the technological differences are the product of different environments, which include not only the climate but also many elements of the technological system beyond immediate human control: the availability and organization of labor, differences in market structures and marketing institutions, and the government incentives provided to buyers. Therefore, this essay takes as its subject the paradox inherent in the official classification of tobacco types regulated by the USDA and argues that varietal types represent a form of market regulation disguised as botanical taxonomy.

Must We Embody Context?

The essays in this forum brace this meditation on the historiography of technology. Understanding devices incorporates the context of any particular hardware, as John Staudenmaier showed by quantifying the contents of the first decades of Technology and Culture. As contextualist approaches have widened from systems theory through social construction and into the assemblages of actor-network theory, the discipline has kept artifacts at the analytical center: it is the history of technology that scholars seek to understand. Even recognizing that the machine only embodies the technology, the discipline has long sought to explain the machine. These essays invite consideration of how the history of technology might apply to non-corporeal things-methods as well as machines, and all the worldly phenomena that function in technological ways even without physicality. Materiality is financial as well as corporeal, the history of capitalism reminds us, and this essay urges scholars to apply history-of-technology approaches more broadly.

Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation.

OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose. Various patterns of fluorodeoxyglucose accumulation in HIV-positive patients have been described previously and hypothesized potentially to represent regions of active HIV replication or nodal activation. We evaluated the utility of fluorodeoxyglucose scanning as a tool to study HIV pathogenesis. DESIGN: We evaluated fluorodeoxyglucose biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected patients to determine the impact on the pattern of nodal activation of HIV infection, the stage of HIV infection and degree of viremia, and HAART. In addition, we attempted to image anatomical site(s) of ongoing HIV replication in patients with suppressed HIV viremia on HAART, but subsequently discontinued HAART. METHOD: We performed fluorodeoxyglucose imaging on five groups: HIV-negative, HIV-positive individuals with early infection, HIV-positive patients with advanced disease, HIV-positive patients with suppressed viral loads, and HIV-positive patients who stopped HAART. RESULTS: Healthy HIV patients with suppressed viral loads and HIV-negative individuals had no or little fluorodeoxyglucose nodal accumulation or any other hypermetabolic areas, whereas viremic individuals with early and advanced HIV had increased fluorodeoxyglucose in the peripheral nodes, indicating that fluorodeoxyglucose potentially identifies areas of HIV replication. Fluorodeoxyglucose biodistribution was similar between early and advanced-stage disease. Four of five patients taken off HAART had negative baseline scans but developed nodal uptake and increases in viral loads. CONCLUSION: Abnormal fluorodeoxyglucose accumulation occurs in the nodes of individuals with detectable viral loads. Interruption of effective HAART results in the activation of previously quiescent nodal areas.

Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation.

OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose (FDG). Various patterns of FDG accumulation in HIV-positive subjects have been described previously and hypothesized to potentially represent regions of active HIV replication and or nodal activation. We evaluated the utility of FDG scanning as a tool to study HIV pathogenesis. DESIGN: We evaluated FDG biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected subjects to determine the impact on pattern of nodal activation of: HIV infection; stage of HIV infection and degree of viremia; and HAART. In addition, we attempted to image anatomical site(s) of on-going HIV replication in subjects with suppressed HIV viremia on ART, but who subsequently discontinued ART. METHOD: We performed FDG imaging on five groups: HIV-negative, HIV-positive with early infection, HIV-positive with advanced disease, HIV-positive with suppressed viral loads, and HIV-positive who stopped ART. RESULTS: Healthy HIV subjects with suppressed viral loads and HIV-negative individuals had no or little FDG nodal accumulation or any other hypermetabolic areas, whereas viremic subjects with early and advanced HIV had increased FDG in peripheral nodes, indicating that FDG potentially identifies areas of HIV replication. FDG biodistribution was similar between early and advanced-stage. Four of five subjects taken off ART had negative baseline scans but developed nodal uptake and increases in viral load. CONCLUSIONS: Abnormal FDG accumulation occurs in nodes of subjects with detectable viral loads. Interruption of effective ART results in activation of previously quiescent nodal areas.

Interruption of antiretroviral therapy blunts but does not abrogate CD4 T-cell responses to interleukin-2 administration in HIV infected patients.

BACKGROUND: Intermittent administration of interleukin (IL)-2 to HIV infected patients leads to CD4 T-cell expansions that are associated with decreased CD4 T-cell turnover. IL-2 is under evaluation in antiretroviral therapy (ART) interruption studies, but it is unclear how the emergence of viremia may affect CD4 expansions. METHODS: CD4 T-cell responses were evaluated in 27 HIV infected patients on long-term intermittent IL-2 therapy who underwent ART interruption immediately after an IL-2 cycle ('IL-2/off') and compared with responses from a previous IL-2 cycle while on continuous ART ('IL-2/on'). Immunophenotypic analysis, including intracellular Ki67 staining, of cryopreserved peripheral blood mononuclear cells was performed. RESULTS: CD4 T-cell increases, in naive and central memory CD4 T-cell subsets, were observed in the IL-2/on (106 and 327 cells/microl, respectively) and IL-2/off (84 and 184 cells/microl, respectively) cycles 1 month following IL-2 administration. These increases were greater during the IL-2/on cycle (P = 0.05, P = 0.01, respectively). In both cycles, the change in CD4 T-cell count correlated with the change in CD4/CD25 T cells. In the IL-2/off cycle, the change in the proportion of CD4 T cells expressing Ki67 was associated with both the changes in viral load (r = 0.64, P = 0.001) and the changes in CD4 T cells (r = -0.56, P = 0.01). CONCLUSIONS: IL-2 administration followed by ART interruption led to significant, although blunted, CD4 T-cell increases. IL-2 induced CD4 T-cell increases in the setting of emergent viremia were associated with decreased CD4 T-cell activation that counteracted the viremia-induced increases in CD4 T-cell activation.

Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial.

OBJECTIVE: To evaluate whether interleukin (IL)-2 in patients with chronic HIV infection can maintain CD4 T cell counts during 6 months of HAART interruption. DESIGN: Prospective, randomized, controlled, open-label phase II noninferiority trial comparing IL-2 with HAART interruption or continuous HAART. METHODS: Forty-one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4 cell count at least 500 cells/microl were randomized in the ratio 2: 1 to interrupted (I = 27) or continuous (C = 14) HAART for 6 months following an initial IL-2 cycle. Subsequent IL-2 cycles were triggered by CD4 T cell counts less than 90% of baseline. Immune, metabolic, and quality of life indices were compared (Mann-Whitney and Fisher's exact tests), defining noninferiority as a percentage difference (C- I) in treatment success (CD4 T cells > or =90% of baseline at 6 months) with a 95% confidence interval (CI) lower limit greater than -20%. RESULTS: Demographic and immune parameters were similar between the groups at baseline. Median CD4 T cell count, HIV viral load, and treatment success differed significantly at 6 months (I: 866 cells/microl, 39,389 copies/ml, 48.1%; C: 1246 cells/microl, <50 copies/ml, 92.3%; P < or = 0.001). Group I was inferior to C (% difference = -44.2%; 95% CI: -64.2%, -11.2%; P = 0.013). Minor statistically significant differences in HgbA1c and energy level occurred at 6 months (I > C). Following HAART interruption, single cases of acute retroviral syndrome, secondary syphilis, non-Hodgkin's lymphoma, and Kaposi's sarcoma recurrence were observed. CONCLUSION: IL-2 alone was inferior to IL-2 with HAART in maintaining baseline CD4 T cell counts. HAART interruption had a small impact on metabolic parameters and quality of life.

The effect of continuous versus pericycle antiretroviral therapy on IL-2 responsiveness.

BACKGROUND: Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HIV)- infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. METHODS: CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. RESULTS: C cycles resulted in a significantly greater CD4 gain than P cycles (Delta156 cells/microL, 95% CI = 68-243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38+, CD8/DR+, and CD4 Ki67+ phenotype were not predictive. CONCLUSIONS: Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies.

Prolonged oral hydroxyurea and concurrent 3d-conformal radiation in patients with progressive or recurrent meningioma: results of a pilot study.

PURPOSE: Treatment of recurrent and progressive meningiomas remains a challenge in clinical neurooncology. This study was designed to evaluate the efficacy of the simultaneous application of 3d-conformal radiotherapy and chemotherapy with hydroxyurea (HU). PATIENTS AND METHODS: Twenty-one patients with recurrent or progressive meningiomas (13 benign, 4 atypical and malignant, 4 with unproven histology) received treatment by fractionated 3d-conformal radiation (55.8-59.4 Gy) and concurrent HU, administered for a median time of three months with a daily dosage of 20 mg/kg. Response was evaluated using clinical and neuro-imaging data. RESULTS: Disease stabilization was achieved in 14/21 patients (pts). Three pts had significant improvement of tumor associated neurological symptoms with imaging criteria of minor response. Progression free survival rates 1 year and 2 years after the initiation of radio-chemotherapy were 84% and 77%, respectively. At the time of analysis a total of 6/21 pts presented with progressive disease with a median time to progression of 59 weeks. Documented radio- and chemotherapy associated toxicity was minimal; only one patient discontinued HU treatment due to gastrointestinal symptoms such as anorexia and weight loss. CONCLUSION: Results obtained in this study indicate that treatment with HU and simultaneous radiotherapy is safe and effective with disease stabilization in the majority of patients. Randomized trials comparing radiosurgery versus radiochemotherapy versus fractionated radiotherapy are warranted.

Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection.

Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy can lead to substantial CD4 cell increases in many HIV-infected patients have generally been of limited duration. We studied 77 patients participating in active longitudinal studies of subcutaneous IL-2 therapy at our center in order to determine the long-term feasibility of this approach. Following initial induction, patients in each trial were eligible to receive intermittent 5-day cycles of subcutaneous IL-2 treatment at individualized doses and frequencies capable of maintaining CD4 counts at postinduction levels. The mean duration of study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline CD4 cell count and CD4 percent values of 0.521 x 10(9)/L (521 cells/microL) and 27% have risen to 1.005 x 10(9)/L (1005 cells/microL) and 38%, respectively, at 90 months. The mean number of subcutaneous IL-2 cycles required to achieve and maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean interval of cycling required to maintain these elevations is 39 months (median, 35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is capable of maintaining CD4 cell increases for an extended period using a remarkably low frequency of intermittent cycling. These observations may contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term treatment strategy.

Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4(+)/CD25(+) T cells.

The long-term immunologic effects of intermittent interleukin 2 (IL-2) therapy were evaluated in a cross-sectional study by comparing 3 groups: HIV-seronegative volunteers, HIV-infected (HIV(+)) patients receiving highly active antiretroviral therapy (HAART), and HIV(+) patients receiving HAART and intermittent IL-2. Whole-blood immunophenotyping was performed to study expression of the IL-2 receptor chains on T lymphocytes and natural killer cells and to further characterize CD4(+)/CD25(+) T cells. Increased CD25 expression, especially in CD4(+) T cells but also in CD8(+) T cells, without increases in expression of the beta and gamma chains of the IL-2 receptor was detected in the IL-2 group. Up to 79% of naive CD4(+) T cells (median, 61%) from patients in the IL-2 group expressed CD25, and the number of naive CD4(+)/CD25(+) T cells correlated positively with both the total and naive CD4(+) T-cell counts. A discrete population of CD45 double intermediate RA(+)/RO(+) CD4(+) cells was also preferentially expanded in the IL-2 group, and the number of these cells strongly correlated with the total CD4(+) count. Despite increases in CD25 expression, T lymphocytes from patients treated with IL-2 did not have increased expression of early (CD69) or late (CD95) activation markers or evidence of recent proliferation (Ki67). Both CD4(+)/CD25(+) and CD4(+)/CD25(-) cells from IL-2-treated HIV(+) patients proliferated in response to mitogens, specific antigens, and T-cell-receptor-mediated stimuli. Thus, intermittent administration of IL-2 in HIV(+) patients leads to preferential expansion of a unique subset of CD4(+) T cells that may represent a critical population in T-cell homeostasis.

A randomized, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus.

Intermittent administration of interleukin (IL)-2 produces significant and sustained increases in CD4(+) T lymphocyte count in human immunodeficiency virus (HIV)-infected subjects but can be associated with dose-limiting toxicities. The primary objective of this study was to determine whether concomitant administration of prednisone could decrease these toxicities. HIV-seropositive adults receiving highly active antiretroviral therapy (HAART) were randomized to receive either (1) intermittent subcutaneous IL-2 and placebo, (2) intermittent subcutaneous IL-2 and prednisone, (3) intermittent prednisone, or (4) intermittent placebo. Prednisone decreased levels of proinflammatory cytokines during IL-2 cycles but, despite induction of expression of CD25, blunted increases in IL-2-associated CD4(+) T lymphocyte count. Whereas intermittent administration of IL-2 reduced basal proliferation of CD4(+) T cells, this effect was inhibited by prednisone, suggesting that prednisone potentially interferes with IL-2's long-term effects on survival of T lymphocytes.