In this work, we examined the effect of nanoparticle size on the thermal conductivity of mesoporous silica materials made from colloidal precursors. Porous thin films were synthesized using a ...polymer-templating method, employing commercial colloidal silica solutions containing nanoparticles 6, 9, and 22 nm in diameter as the silica source and poly(methyl methacrylate) colloids as the template. The ratio of polymer to silica was then varied to produce films with a range of porosities. The thermal conductivity of the films was measured using time domain thermal reflectance, and the results indicated that, for the particle sizes studied, there was a weak dependence of thermal conductivity on particle size. This weak dependence was associated with increased interfacial scattering of heat carriers at the boundaries of the smaller nanoparticles. This work adds to our understanding of the effect of nanostructuring on heat transport in amorphous material systems and improves our ability to design low thermal conductivity materials.
To describe and compare systemic and local pharmacokinetics (PK) and cervicovaginal (CV) pharmacodynamics (PD) of oral tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) with ...tenofovir (TFV) intravaginal ring (IVR).
Phase I, randomized, parallel-group study. Women (n = 22) used TDF/FTC oral tablets daily or TFV IVR continuously and were assessed at baseline and 14 days.
TFV and FTC concentrations were measured in plasma, CV fluid (CVF), and CV tissue. TFV-diphosphate and FTC-triphosphate were assessed in CV tissue. In vitro PD antiviral activities of TFV and FTC (using in vivo concentration ranges) were modeled in the CVF and by infecting CV tissue explants ex vivo with HIV-1BaL.
Adverse events (AEs) were more common with oral TDF/FTC use (P < 0.01). The median CVF TFV concentrations were 106 ng/mL after use of TFV IVR vs. 102 ng/mL for TDF/FTC. The median TFV and TFV-diphosphate concentrations in CV tissue were >100-fold higher among IVR users. The median CVF FTC concentrations were 103 ng/mL. FTC and FTC-triphosphate were detected in all CV tissues from TDF/FTC users. HIV inhibitory activity of CVF increased significantly with treatment in both cohorts (P < 0.01) but was higher in TFV IVR users (P < 0.01). In vitro inhibition of tissue infection with ex vivo administration of TFV and FTC was dose dependent, with maximal efficacy achieved with 10 µg/mL TFV, 1 µg/mL FTC, and 0.1 µg/mL of TFV and FTC combined.
Both products were safe and increased mucosal HIV inhibitory activity. In addition to systemic protection, oral TDF/FTC displays a PK/PD profile compatible with CV mucosal antiviral activity. TFV IVR resulted in fewer AEs, lower TFV plasma concentrations, higher CVF and tissue TFV and TFV-DP concentrations, and greater anti-HIV activity in CVF.
Introduction
Adherence to HIV prevention methods is a challenge, particularly for young women in Sub‐Saharan Africa. End‐user research during product development can inform modifiable factors to ...increase future uptake and adherence.
Methods
Preferences for four vaginally inserted placebo HIV prevention methods were assessed among Zimbabwean and South African young women using a crossover clinical design. For each of months 1 to 4, participants were asked to use a pre‐coitally inserted film, insert (vaginal tablet) and gel once/week for a month, and a monthly ring in a randomly assigned sequence. Participants subsequently chose one preferred product to use as directed for the final study month. Women ranked the four products from most preferred to least preferred at enrolment and after trying all products.
Results
A total of 200 women aged 18 to 30 (mean 23) were enrolled; 178 (89%) completed follow‐up. At baseline, 41% of participants selected the gel as their most preferred product and 61% selected the ring as least preferred. During the crossover period, most (82% to 85%) self‐reported using each product at least once a week, although only half the time with sex. Objective biomarker data confirmed adequate use of all products. After trying each product, rankings changed with the film, ring, insert and gel being selected by 29%, 28%, 26% and 16% respectively. Choice varied significantly by country (p < 0.001): More Zimbabweans chose the film (45%), and more South Africans chose the insert (34%). Among women choosing the ring, 88% reported using it every time with sex. By contrast, self‐reported adherence was lower for “on‐demand” (coitally associated) products, with 40% to 55% using them every time during sex (p < 0.001).
Conclusions
Preferences for these four dosage forms varied before and after use, and both within and across countries – there was no clear favourite – indicating the need for a range of options for end‐users. The ring's popularity increased the most with use, was the second most preferred delivery system, and per self‐report, provided more coverage during sex. These end‐user perspectives provide important information to product developers and funding agencies.
NH
, essential for producing artificial fertilizers and several military and commercial products, is being produced at a large scale to satisfy increasing demands. The inevitable leakage of NH
during ...its utilization, even in trace concentrations, poses significant environmental and health risks because of its highly toxic and reactive nature. Although numerous techniques have been developed for the removal of atmospheric NH
, conventional NH
abatement systems possess the disadvantages of high maintenance cost, low selectivity, and emission of secondary wastes. In this context, highly tunable porous materials such as metal-organic frameworks, covalent organic frameworks, hydrogen organic frameworks, porous organic polymers, and their composite materials have emerged as next-generation NH
adsorbents. Herein, recent progress in the development of porous NH
adsorbents is summarized; furthermore, factors affecting NH
capture are analyzed to provide a reasonable strategy for the design and synthesis of promising materials for NH
abatement.
The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted ...approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of ‘place’ and ‘timing’ in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products.
Introduction: Adherence to HIV prevention methods is a challenge, particularly for young women in Sub‐Saharan Africa. End‐user research during product development can inform modifiable factors to ...increase future uptake and adherence. Methods: Preferences for four vaginally inserted placebo HIV prevention methods were assessed among Zimbabwean and South African young women using a crossover clinical design. For each of months 1 to 4, participants were asked to use a pre‐coitally inserted film, insert (vaginal tablet) and gel once/week for a month, and a monthly ring in a randomly assigned sequence. Participants subsequently chose one preferred product to use as directed for the final study month. Women ranked the four products from most preferred to least preferred at enrolment and after trying all products. Results: A total of 200 women aged 18 to 30 (mean 23) were enrolled; 178 (89%) completed follow‐up. At baseline, 41% of participants selected the gel as their most preferred product and 61% selected the ring as least preferred. During the crossover period, most (82% to 85%) self‐reported using each product at least once a week, although only half the time with sex. Objective biomarker data confirmed adequate use of all products. After trying each product, rankings changed with the film, ring, insert and gel being selected by 29%, 28%, 26% and 16% respectively. Choice varied significantly by country (p < 0.001): More Zimbabweans chose the film (45%), and more South Africans chose the insert (34%). Among women choosing the ring, 88% reported using it every time with sex. By contrast, self‐reported adherence was lower for “on‐demand” (coitally associated) products, with 40% to 55% using them every time during sex (p < 0.001). Conclusions: Preferences for these four dosage forms varied before and after use, and both within and across countries – there was no clear favourite – indicating the need for a range of options for end‐users. The ring's popularity increased the most with use, was the second most preferred delivery system, and per self‐report, provided more coverage during sex. These end‐user perspectives provide important information to product developers and funding agencies.
Multipurpose prevention technologies (MPTs), which prevent sexually transmitted infection(s) and unintended pregnancy, are highly desirable to women. In this randomized, placebo-controlled, phase I ...study, women used a placebo or tenofovir (TFV) and levonorgestrel (LNG) intravaginal ring (IVR), either continuously or cyclically (three, 28-day cycles with a 3 day interruption in between each cycle), for 90 days. Sixty-eight women were screened; 47 were randomized to 4 arms: TFV/LNG or placebo IVRs used continuously or cyclically (4:4:1:1). Safety was assessed by adverse events and changes from baseline in mucosal histology and immune mediators. TFV concentrations were evaluated in multiple compartments. LNG concentration was determined in serum. Modeled TFV pharmacodynamic antiviral activity was evaluated in vaginal and rectal fluids and cervicovaginal tissue ex vivo. LNG pharmacodynamics was assessed with cervical mucus quality and anovulation. All IVRs were safe with no serious adverse events nor significant changes in genital tract histology, immune cell density or secreted soluble proteins from baseline. Median vaginal fluid TFV concentrations were >500 ng/mg throughout 90d. TFV-diphosphate tissue concentrations exceeded 1,000 fmol/mg within 72hrs of IVR insertion. Mean serum LNG concentrations exceeded 200 pg/mL within 2h of TFV/LNG use, decreasing quickly after IVR removal. Vaginal fluid of women using TFV-containing IVRs had significantly greater inhibitory activity (87–98% versus 10% at baseline; p<0.01) against HIV replication in vitro. There was a >10-fold reduction in HIV p24 antigen production from ectocervical tissues after TFV/LNG exposure. TFV/LNG IVR users had significantly higher rates of anovulation, lower Insler scores and poorer/abnormal cervical mucus sperm penetration. Most TFV/LNG IVR users reported no change in menstrual cycles or fewer days of and/or lighter bleeding. All IVRs were safe. Active rings delivered high TFV concentrations locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. Trial registration: ClinicalTrials.gov #NCT03279120.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The rapid modernization and densification of Taipei has resulted in a culturally and socially unsustainable society. The North American paradigm of high-rise condominiums disrupts the social pattern ...of the vernacular family, cultural activities and communities, isolating the city dwellers within their own homes. The physical city no longer reflects or supports its social and cultural condition, thus has led to the disintegration of traditional customs and lifestyle without a sustainable replacement. The hypothesis of this thesis is that high-density residential architecture can be reinvented through the reinterpretation of vernacular dwelling to accommodate cultural sustainable activities and a sociable, identifi able community. The first three chapters record and examine three branches of research: vernacular Taiwanese culture and architecture, high-density vernacular architecture, and the current condition of Taipei, Taiwan. The research deals with various disciplines, most importantly family and social structure, to provide a foundation for further discussion of dwelling condition versus culture. Chapter compares and analyzes the relationship between residential architecture and lifestyle of the vernacular and current dwelling. It argues for the importance of communities at different scales, bound together by a hierarchy of communal spaces. The condominium building is carefully reexamined under the categories of the unit, the floor, the building as a village, and the neighbourhood. The design project, Vertical Vernacular chapter v, presents a new typology of high-density residential architecture. It demonstrates the implantation of the theories and prototypes developed in the previous chapter, by consideration of current culture and family structure, including both traditional customs and modern lifestyle. A full range of unit plans are developed based on demographics, family structure, traditional custom, and adoption of tradition to modern imperatives. The co-operative living environment inspired by the vernacular dwelling creates friendly, strong and safe communities within the condominium. Furthermore, the project aims for the feasibility of the concept within the densest district of Taipei City from a developer's point-of-view.
The rapid modernization and densification of Taipei has resulted in a culturally and socially unsustainable society. The North American paradigm of high-rise condominiums disrupts the social pattern ...of the vernacular family, cultural activities and communities, isolating the city dwellers within their own homes. The physical city no longer reflects or supports its social and cultural condition, thus has led to the disintegration of traditional customs and lifestyle without a sustainable replacement. The hypothesis of this thesis is that high-density residential architecture can be reinvented through the reinterpretation of vernacular dwelling to accommodate cultural sustainable activities and a sociable, identifiable community.
The first three chapters record and examine three branches of research: vernacular Taiwanese culture and architecture, high-density vernacular architecture, and the current condition of Taipei, Taiwan. The research deals with various disciplines, most importantly family and social structure, to provide a foundation for further discussion of dwelling condition versus culture. Chapter iv compares and analyzes the relationship between residential architecture and lifestyle of the vernacular and current dwelling. It argues for the importance of communities at different scales, bound together by a hierarchy of communal spaces. The condominium building is carefully reexamined under the categories of the unit, the floor, the building as a village, and the neighbourhood.
The design project, Vertical Vernacular chapter v, presents a new typology of high-density residential architecture. It demonstrates the implantation of the theories and prototypes developed in the previous chapter, by consideration of current culture and family structure, including both traditional customs and modern lifestyle. A full range of unit plans are developed based on demographics, family structure, traditional custom, and adoption of tradition to modern imperatives. The co-operative living environment inspired by the vernacular dwelling creates friendly, strong and safe communities within the condominium. Furthermore, the project aims for the feasibility of the concept within the densest district of Taipei City from a developer's point-of-view.
Previous studies have shown that in vitro and in vivo zinc (Zn) deficiency result ultimately in cell death, while pretreatment of cells with Zn blocks apoptosis. Using a Zn chelator, we prepared Zn ...deficient medium and further characterized the events preceding Zn deficiency-induced cell death. Zn deficient 3T3 fibroblasts showed signs of oxidative stress, alterations in mitochondrial distribution and potential, and displayed apoptotic and necrotic cell death. Intracellular iron (Fe) levels were also found to be increased during Zn deficiency, a finding that is observed in most tissues in vivo as well. While investigators have suggested that Zn and Fe primarily interact at transport sites due to their chemical similarities, the increase in Fe levels observed in a Zn deficiency suggest an additional mechanism of accumulation. Therefore we hypothesized that Zn deficiency can trigger Fe accumulation via alterations in Iron Regulatory Proteins (IRPs), as these can be affected by increased reactive oxygen species, which is a consequence of Zn depletion. Our studies showed that during Zn deficiency, IRP-2 binding activity is increased, which was reflected in an increase in Transferrin Receptor (TfR) levels. Moreover, levels of Ferritin Light (FtL) Chain were increased while those of Ferritin Heavy (FtH) Chain remained unchanged, unexpectedly. In contrast, binding activity of IRP-1 was significantly decreased in the Zn deficient group. Next, we tested whether Zn deficiency increases PKC activity, as all PKC isoforms contain cysteine-rich finger motifs that bind to two Zn atoms. In turn, PKC can phosphorylate IRPs, which has been shown to increase the RNA-binding activity of IRPs. This mimics an Fe deficient state in the cell, which responds by increasing Fe uptake. For these experiments, we focused on two PKC isoforms: -α and -δ, which are ubiquitously expressed and have a role in cell proliferation and apoptosis, respectively. Zn deficient 3T3 cells had decreased PKC-α activity, which may contribute to cell death in this group. PKC-δ was proteolytically cleaved into a kinase-active fragment with pro-apoptosic activity in the mitochondria. Moreover, inhibition of PKC-δ resulted in decreased PKC-δ fragmentation and translocation to the mitochondria, thereby rescuing Zn deficient cells from apoptosis.
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