Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya.

We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentially examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical malaria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of anti-peptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p<0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFB0145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current study substantiates further the potential of protein PFB0145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P. falciparum malaria

Shift of fibril‐forming ability of the designed α‐helical coiled‐coil peptides into the physiological pH region

Recently, we designed a short α‐helical fibril‐forming peptide (αFFP) that can form α‐helical nanofibrils at acid pH. The non‐physiological conditions of the fibril formation hamper biomedical application of αFFP. It was hypothesized that electrostatic repulsion between glutamic acid residues present at positions (g) of the αFFP coiled‐coil sequence prevent the fibrillogenesis at neutral pH, while their protonation below pH 5.5 triggers axial growth of the fibril. To test this hypothesis, we synthesized αFFPs where all glutamic acid residues were substituted by glutamines or serines. The electron microscopy study confirmed that the modified αFFPs form nanofibrils in a wider range of pH (2.5-11). Circular dichroism spectroscopy, sedimentation, diffusion and differential scanning calorimetry showed that the fibrils are α‐helical and have elongated and highly stable cooperative tertiary structures. This work leads to a better understanding of interactions that control the fibrillogenesis of the αFFPs and opens opportunities for their biomedical applicatio

Comparing magnetic triggering of ELMs in TCV and ASDEX Upgrade

Frequency locking of edge localized modes (ELMs) to the vertical plasma movements induced by magnetic perturbations first demonstrated in TCV was successfully repeated in ASDEX Upgrade. However, the ELMs were triggered in ASDEX Upgrade when the plasma was moving down towards the X-point with a consequent decrease in the plasma current density in the edge region, in contrast to the previous observation on TCV in which ELMs were triggered when the edge current was increased by an upward plasma movement. This opposite behaviour observed in the magnetic triggering of ELMs has been investigated by using a free-boundary tokamak simulator, DINA-CH. The passive stabilization loops (PSLs) located inside the vacuum vessel of ASDEX Upgrade produce similar external linking flux changes to those generated by the G-coil sets in TCV for opposite vertical plasma movements. Therefore, both plasmas experience similar local flux surface expansions near the upper G-coil set and PSL when the ELMs are triggered. In ASDEX Upgrade, however, the localized expansion of the plasma flux surfaces near the upper PSL is observed with the global shrinkage of the plasma column accompanied by the downward plasma movement

Radioactive decays at limits of nuclear stability

The last decades brought an impressive progress in synthesizing and studying properties of nuclides located very far from the beta stability line. Among the most fundamental properties of such exotic nuclides, usually established first, is the half-life, possible radioactive decay modes, and their relative probabilities. When approaching limits of nuclear stability, new decay modes set in. First, beta decays become accompanied by emission of nucleons from highly excited states of daughter nuclei. Second, when the nucleon separation energy becomes negative, nucleons start to be emitted from the ground state. Here, we present a review of the decay modes occurring close to the limits of stability. The experimental methods used to produce, identify and detect new species and their radiation are discussed. The current theoretical understanding of these decay processes is overviewed. The theoretical description of the most recently discovered and most complex radioactive process - the two-proton radioactivity - is discussed in more detail.Comment: Review, 68 pages, 39 figure

Linearized model Fokker-Planck collision operators for gyrokinetic simulations. II. Numerical implementation and tests

A set of key properties for an ideal dissipation scheme in gyrokinetic simulations is proposed, and implementation of a model collision operator satisfying these properties is described. This operator is based on the exact linearized test-particle collision operator, with approximations to the field-particle terms that preserve conservation laws and an H-Theorem. It includes energy diffusion, pitch-angle scattering, and finite Larmor radius effects corresponding to classical (real-space) diffusion. The numerical implementation in the continuum gyrokinetic code GS2 is fully implicit and guarantees exact satisfaction of conservation properties. Numerical results are presented showing that the correct physics is captured over the entire range of collisionalities, from the collisionless to the strongly collisional regimes, without recourse to artificial dissipation.Comment: 13 pages, 8 figures, submitted to Physics of Plasmas; typos fixe

Clinical significance of assertive community treatment among adolescents.

The efficacy of assertive community treatment for children and adolescents is proven in the United States, but remains controversial in Europe. Moreover, most studies showing positive outcomes of assertive community treatment are limited to statistically significant differences and do not consider whether the treatment is also subjectively clinically meaningful for the patient. Using a naturalistic sample, the present study aims to assess statistical and clinical significance of an assertive community treatment unit for adolescents in Europe. Linear mixed-effects models and reliable change indices were used to respectively assess the statistical and clinical significance of assertive community treatment in 179 adolescents (mean age = 15.76, SD = 1.76) with severe mental illnesses. Difficulties related to mental health (measured by the Health of the Nation Outcome Scales for Children and Adolescents, HoNOSCA) and overall functioning (measured by the Global Assessment of Functioning scale) statistically improved (all ps &lt; 0.001) from admission to discharge. Additionally, a considerable proportion of patients (from 14% to 21%) clinically recovered to functional levels. Our results support the fact that assertive community treatment can have convincing and positive clinical outcomes in European settings

Shift of fibril-forming ability of the designed alpha-helical coiled-coil peptides into the physiological pH region

Recently, we designed a short alpha-helical fibril-forming peptide (alphaFFP) that can form alpha-helical nanofibrils at acid pH. The non-physiological conditions of the fibril formation hamper biomedical application of alphaFFP. It was hypothesized that electrostatic repulsion between glutamic acid residues present at positions (g) of the alphaFFP coiled-coil sequence prevent the fibrillogenesis at neutral pH, while their protonation below pH 5.5 triggers axial growth of the fibril. To test this hypothesis, we synthesized alphaFFPs where all glutamic acid residues were substituted by glutamines or serines. The electron microscopy study confirmed that the modified alphaFFPs form nanofibrils in a wider range of pH (2.5-11). Circular dichroism spectroscopy, sedimentation, diffusion and differential scanning calorimetry showed that the fibrils are alpha-helical and have elongated and highly stable cooperative tertiary structures. This work leads to a better understanding of interactions that control the fibrillogenesis of the alphaFFPs and opens opportunities for their biomedical application

Anomalous peak in the superconducting condensate density of cuprate high T_{c} superconductors at a unique critical doping state

The doping dependence of the superconducting condensate density, n_{s}^{o}, has been studied by muon-spin-rotation for Y_{0.8}Ca_{0.2}Ba_{2}(Cu_{1-z}Zn_{z})_{3}O_{7-\delta} and Tl_{0.5-y}Pb_{0.5+y}Sr_{2}Ca_{1-x}Y_{x}Cu_{2}O_{7}. We find that n_{s}^{o} exhibits a pronounced peak at a unique doping state in the slightly overdoped regime. Its position coincides with the critical doping state where the normal state pseudogap first appears depleting the electronic density of states. A surprising correlation between n_{s}^{o} and the condensation energy U_{o} is observed which suggests unconventional behavior even in the overdoped region.Comment: 10 pages, 3 figure