577 research outputs found
Зміна роздільної здатності зображень на основі власних векторів матриць-операторів індукованих з піксельних наборів
The method of problem solving increase resolution image sets provided that the
dimension of the set. The method is to build a matrix operator and find its
eigenvectors. Using sets of eigenvectors and matrix color images developed a practical set of algorithm changes the resolution
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Evolution of resistance in paediatric patients with failure on antiretroviral therapy
On the Nature of Memory and Rejuvenation in Glassy Systems
The memory effect in a single crystal spin glass
() has been measured using ac susceptibility techniques over a reduced temperature range of
and a model of the memory effect has been developed. A
double-waiting-time protocol is carried out where the spin glass is first
allowed to age at a temperature below , followed by a second aging at a
lower temperature after it has fully rejuvenated. The model is based on
calculating typical coincidences between the growth of correlated regions at
the two temperatures. It accounts for the absolute magnitude of the memory
effect as a function of both waiting times and temperatures. The data can be
explained by the memory loss being a function of the relative change in the
correlated volume at the first waiting temperature because of the growth in the
correlations at the second waiting temperature.Comment: 11 pages, 6 figure
Hadamard magnetization transfers achieve dramatic sensitivity enhancements in homonuclear multidimensional NMR correlations of labile sites in proteins, polysaccharides and nucleic acids
EXSY, TOCSY and NOESY lie at the foundation of homonuclear NMR experiments in
organic and pharmaceutical chemistry, as well as in structural biology. Limited
magnetization transfer efficiency is an intrinsic downside of these methods,
particularly when targeting rapidly exchanging species such as labile protons
ubiquitous in polysaccharides, sidechains and backbones of proteins, and in
bases and sugars of nucleic acids: the fast decoherence imparted on these
protons through solvent exchanges, greatly reduces their involvement in
homonuclear correlation experiments. We have recently discussed how these
decoherences can be visualized as an Anti-Zeno Effect, that can be harnessed to
enhance the efficiency of homonuclear transfers within Looped PROjected
SpectroscopY (L-PROSY) leading to 200-300% enhancements in NOESY and TOCSY
cross-peaks for amide groups in biomolecules. This study demonstrates that even
larger sensitivity gains per unit time, equivalent to reductions by several
hundred-folds in the duration of experiments, can be achieved by looping
inversion or using saturation procedures. In the ensuing experiments a priori
selected frequencies are encoded according to Hadamard recipes, and
subsequently resolved along the indirect dimension via linear combinations.
Magnetization-transfer (MT) processes reminiscent of those occurring in CEST
provide significant enhancements in the resulting cross-peaks, in only a
fraction of acquisition time of a normal 2D experiment. The effectiveness of
the ensuing three-way polarization transfer interplay between water, labile and
non-labile protons was corroborated experimentally for proteins,
homo-oligosaccharides and nucleic acids. In all cases, cross-peaks barely
detectable in conventional 2D NMR counterparts, were measured ca. 10-fold
faster and with 200-600% signal enhancements by the Hadamard MT counterparts
Loss to follow-up in a community clinic in South Africa – roles of gender, pregnancy and CD4 count
Background. Faith-based organisations have expanded antiretroviral therapy (ART) in community clinics across South Africa. Loss to follow-up (LTFU), however, limits the potential individual and population treatment benefits and optimal care. Objective. To identify patient characteristics associated with LTFU 6 months after starting ART in a large community clinic. Methods. Patients initiating ART between April 2004 and October 2006 in one South African Catholic Bishops’ Conference HIV treatment clinic who had at least one follow-up visit were included and routinely monitored every 6 months after ART initiation. Standardised instruments were used to collect data. Rates of LTFU over time were estimated by the Kaplan-Meier method. The Cox proportional hazard regression examined the impact of age, baseline CD4 count, baseline HIV RNA, gender and pregnancy status on LTFU. Results. Data from 925 patients (age >14 years, median age 36 years, 70% female, of whom 16% were pregnant) were included: 51 (6%) were lost to follow-up 6 months after ART initiation. Younger age (≤30 years) (hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.05 - 4.38) and pregnancy for women (HR 3.75, 95% CI 1.53 - 9.16) were significantly associated with higher LTFU rates. When stratified by baseline CD4 count, gender and pregnancy status, pregnant women with lower baseline CD4 counts (≤200 cells/ μl) had 6.06 times the hazard (95% CI 2.20 - 16.71) of LTFU at 6 months compared with men. Conclusions. HIV-infected pregnant women initiating ART were significantly more likely to be lost to follow-up in a community clinic in South Africa. Urgent interventions to successfully retain pregnant women in care are needed
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Novel regulation of keratin gene expression by thyroid hormone and retinoid receptors
Expression of keratin proteins, markers of epidermal differentiation and pathology, is uniquely regulated by the nuclear receptors for retinoic acid (RAR) and thyroid hormone (T3R) and their ligands: it is constitutively activated by unliganded T3R, but it is suppressed by ligand-occupied T3R or RAR. This regulation was studied using gel mobility shift assays with purified receptors and transient transfection assays with vectors expressing various receptor mutants. Regulation of keratin gene expression by RAR and T3R occurs through direct binding of these receptors to receptor response elements of the keratin gene promoters. The DNA binding C domain of these receptors is essential for both ligand-dependent and -independent regulation. However, the NH2-terminal A/B domain of T3R is not required for either mode of regulation of keratin gene expression. Furthermore, v-ErbA, an oncogenic derivative of cT3R, also activates keratin gene expression. In contrast to the previously described mechanism of gene regulation by T3R, heterodimerization with the retinoid X receptor is not essential for activation of keratin gene expression by unliganded T3R. These findings indicate that the mechanism of regulation of keratin genes by RAR and T3R differs significantly from the mechanisms described for other genes modulated by these receptors
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The Survival Benefits of Antiretroviral Therapy in South Africa
Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa
Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability
Background
In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods
In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results
At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions
In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions
Climate and predation dominate juvenile and adult recruitment in a turtle with temperature-dependent sex determination
Conditions experienced early in life can influence phenotypes in ecologically important ways, as exemplified by organisms with environmental sex determination. For organisms with temperature-dependent sex determination (TSD), variation in nest temperatures induces phenotypic variation that could impact population growth rates. In environments that vary over space and time, how does this variation influence key demographic parameters (cohort sex ratio and hatchling recruitment) in early life stages of populations exhibiting TSD? We leverage a 17-year data set on a population of painted turtles, Chrysemys picta, to investigate how spatial variation in nest vegetation cover and temporal variation in climate influence early life-history demography. We found that spatial variation in nest cover strongly influenced nest temperature and sex ratio, but was not correlated with clutch size, nest predation, total nest failure, or hatching success. Temporal variation in climate influenced percentage of total nest failure and cohort sex ratio, but not depredation rate, mean clutch size, or mean hatching success. Total hatchling recruitment in a year was influenced primarily by temporal variation in climate-independent factors, number of nests constructed, and depredation rate. Recruitment of female hatchlings was determined by stochastic variation in nest depredation and annual climate and also by the total nest production. Overall population demography depends more strongly on annual variation in climate and predation than it does on the intricacies of nest-specific biology. Finally, we demonstrate that recruitment of female hatchlings translates into recruitment of breeding females into the population, thus linking climate (and other) effects on early life stages to adult demographics
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