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Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. Method: Cross-sectional study with 1279 participants from the INMA cohorts. Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p = 0.026), for cop-per with excess body weight (p < 0.01), low social class (p = 0.03) and being multipara (p < 0.01), for magnesium with being over 35 years old (p = 0.001), high social class (p = 0.044), primiparous status (p = 0.002) and low daily intake of bread (p = 0.009) and legumes (p = 0.020); for zinc with university edu-cation (p = 0.039) and residence in Gipuzkoa (p < 0.01), and for selenium with residence in Valencia (p < 0.01), university education (p = 0.001), vitamin B6 supplementation (p = 0.006), fish intake (> 71 g/day) (p = 0.014) and having been born in Spain (p = 0.001). Further, lower iron levels were associated with being overweight (p = 0.021) or obese (p < 0.001) and vitamin B12 supplementation (p = 0.006). Conclusions: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables. This study is part of the INMA (Infancia y Medio Ambiente) project. It was supported by grants from Instituto de Salud Carlos III (FIS-FEDER: 06/0867, 09/00090, 13/1944, 16/1288, 19/1338; Miguel Servet-FEDER: CP15/0025; Miguel Servet-FSE: MS15/0025) , by the Council of Gipuzkoa (DFG15/009) and by the Health Department of the Basque Government.

The pozzolanic materials have the capacity to modify the performance of Portland cement (PC) mortars. When they are used as supplementary materials, the physical-chemical properties such as compressive-strength and resistance to aggressive environments (chloride, sulphate, acids) are improved. In this article, a study was carried out to evaluate the effects of the addition of two natural pozzolans: volcanic pumice and zeolite. Both used as substitutes for PC in mortars based on cement, considering mechanical strength and the aggressive effect of sulphate ions. Furthermore, the electrochemical behavior of the steel rebar embedded in these mortars was studied during 730 days of exposition to aggressive conditions. The results revealed that the development of the compressive strength of mortars with pozzolans added reached similar values to the reference mortar. It was possible to observe that the addition of the pozzolan suppresses the ettringite formation proportionally to the pozzolan content. The corrosion resistance of the steel improves with the addition of pozzolans after 730 days of exposition at sulphate environment. The results of this study revealed the feasibility to use natural pozzolan as an additive during the preparation of cement up to 25% without significant changes of the physical-chemical properties of the mortars.

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10-4, p-value = 5.87 × 10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10-7) in GRK1 and cg02212000 (β = -0.001, p-value = 8.13 × 10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations. INMA: Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03–1615, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338; Miguel Servet FEDER 15/0025 and 20/0006; FIS-FSE: 17/00260), Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat Valenciana BEST/2020/059, Fundacio ́ La Marato ́ de TV3 (090,430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn). Korean exposome study: This study was supported by the Korean Environment Industry & Technology Institute (KEITI) through “the Environmental Health Action Program”, funded by Korea Ministry of Environment (2017001360005). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and Norwegian Research Council/BIOBANK (grant no 221097). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club, all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA/Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND). Project Viva: The Project Viva cohort is funded by NIH grants R01HL111108, R01NR013945, and R37 HD034568. RHEA: The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014; ‘Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The work was also supported by MICINN (MTM2015-68140-R), Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII, the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)).

Microbial fermentation with lactic acid bacteria (LAB) is a natural food biopreservation method. Yellow mustard and milk whey are optimum substrates for LAB fermentation. The aim of the present study was to evaluate the bioaccessibility and bioavailability of bioactive compounds from yellow mustard flour and milk whey both with and without LAB fermentation. All extracts were subjected to a simulated digestion process. Total polyphenols, DL-3-phenyllactic acid (PLA), lactic acid, and the antioxidant activity were determined in the studied matrices before and after simulated digestion. Yellow mustard flour was significantly richer in total polyphenols, whereas significantly higher concentrations of PLA and lactic acid were observed in milk whey. Similar antioxidant activity was determined in both ingredients being in all cases strongly reduced after in vitro digestion. Higher bioaccessibility was found for polyphenols and PLA in milk whey. Transepithelial transport of total polyphenols was higher in yellow mustard flour compared to milk whey, reaching bioavailability values between 3-7% and 1-2%, respectively. PLA transepithelial transport was only significant in both fermented matrices with bioavailability around 4-6%. Transepithelial transport of lactic acid reached values of 31-34% (bioavailability ∼ 22%) and 15-78% (bioavailability ∼ 3%) in milk whey and yellow mustard flour, respectively. LAB fermentation showed beneficial effects on enriching extracts with PLA, lactic acid, and antioxidant activity, as well as increasing bioaccessibility of these acids in yellow mustard flour and total polyphenol bioavailability in milk whey. Results pointed to yellow mustard flour and milk whey as natural preservative ingredients used in the food industry, especially when fermented with LAB.

Although freezing is generally used to preserve the sensory and nutritional quality of fish and their products, it cannot mitigate physicochemical changes of the fish meat during storage. This study aimed to determine the cryoprotective effect of sorbitol incorporated into the yamú muscle (Brycon amazonicus), subjected to different storage times and temperatures. The methodology consisted of analyzing microstructural changes, protein profile, and physicochemical properties (texture, water holding capacity and pH) of the yamú’s meat under two temperatures (2±2 and -18±2 °C), two storage times (24 and 48 h) and the incorporation or not of 5% (w/w) of a 60% sorbitol solution. The microstructural changes were analyzed by optical microscopy and scanning electron microscopy, and the protein profile was analyzed by SDS PAGE electrophoresis. The physicochemical properties evaluated in yamú’s meat were affected mainly by the interaction between temperature and storage time. The myofibrillar proteins underwent a partial degradation, and changes in the connective tissue were observed concerning the loss of texture especially when the meat was not treated with sorbitol at freezing temperature (-18 °C). The use of sorbitol minimized the negative effects of freezing on the characteristics of the yamú muscle, maintaining the integrity of the muscular microstructure and generating a cryoprotective effect in comparison to untreated meat.

Background Prenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. Objectives To explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. Materials and methods Study subjects were 807 mother–child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4–5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). Results The geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) μg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. β [CI95%] = −1.37 [-2.33, −0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. Discussion An inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

Background: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. Objectives: To describe the urinary concentrations of the different As species and evaluate the methylation effi-ciency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. Methods: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003 & ndash;2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Socio-demographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. Results: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 lig/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., beta [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). Discussion: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood. This study was supported by grants from Instituto de Salud Carlos III, Spain [FIS-FEDER: 07/0314; FIS 11/01007, 13/1944, 16/1288, 19/1338; Miguel Servet-FEDER: CP15/0025, CPII20/00006; FIS-FSE: 17/00260; Miguel Servet-FSE: MS15/0025, MS20/0006; PI06/0867 and FIS-PI18/01142 incl. FEDER funds] , Generalitat Valenciana, Spain BEST/2020/059, Department of Health of the Basque Government, Spain (2005111093) , Provincial Government of Gipuzkoa (DFG06/002) , and annual agreements with the municipalities in the study area (Zumarraga, Urretxu, Legazpi, Azkoitia, Azpeitia and Beasain) .

Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.Pojedini mikotoksini poput bovericina (BEA), okratoksina A (OTA) i zearalenona (ZEA) prelaze krvno-moždanu barijeru, a to je i razlog zbog kojega smo istražili djelovanje ekstrakta karotenoida iz mesa bundeve protiv upalnih procesa izazvanih ovim mikotoksinima i njihovim kombinacijama (OTA+ZEA i OTA+ZEA+BEA) na modelu krvno-moždane barijere koji se sastojao od kultura stanica ECV304 i C6, oslanjajući se pritom na neciljani metabolomički pristup. Stanice su tretirane mikotoksinima u koncentraciji od 100 nmol/L po mikotoksinu odnosno ekstraktom karotenoida u koncentraciji od 500 nmol/L. Za kontrolu smo upotrijebili samo otapalo (stanična kontrola) odnosno otapalo s bundevinim ekstraktom (ekstraktna kontrola). Nakon dva sata tretmana uzorci su analizirani metodom tekućinske kromatografije / masene spektrometrije (HPLC-ESI-QTOF-MS), a dobiveni metaboliti identificirani su usporedbom s bazom podataka

Background: The interaction between obesity and genetic traits on high density lipoprotein (HDL) levels has been extensively studied. The variance of serum HDL has a strong genetic heritability, although the studied variant only explains a small part of this variation. The goal of this study was to investigate the associations between the apolipoprotein type 2 (APOA2) rs3813627 single nucleotide polymorphism (SNP) and anthropometric and biochemical variables, though body mass index (BMI). Methods: This study included 153 subjects (91 overweight/obese (BMI&sup3, 25 kg/m2) and 62 non-obese individuals (BMI &lt, 25 kg/m2)). The APOA2 rs3813627 SNP was selected and genotyped. Genotype analysis was performed to analyze the associations between APOA2 SNPs and anthropometric and biochemical variables through BMI. Results: The APOA2 rs3813627 TT genotype was associated with low HDL levels in comparison with the APOA2 rs3813627 GG and GT genotype in overweight/obese individuals, but not in the non-obese subjects (p &lt, 0.05). The same trend was observed in the apolipoprotein type 1 (APOA1) protein levels (p &lt, 0.05). Correlation analysis revealed a negative correlation between HDL and APOA1 levels and APOA2 rs3813627 SNP under recessive model (p &lt, 0.05). The odds ratio for low HDL levels was 3.76 and 3.94 for low APOA1 levels. The mediation analysis of APOA2 rs3813627 SNP through BMI showed a full mediation on HDL and partial mediation on APOA1 levels (p &lt, 0.05). Bioinformatic analysis showed that rs3813627 lies in the APOA2 promoter and overlaps motifs for several bound transcription factors. Conclusion: On the basis of these data, the APOA2 rs3813627 SNP is associated with low HDL and APOA1 levels susceptibility, and this effect was mediated by an increased BMI.

Purpose: To study the agreement between proton microdosimetric distributions measured with a silicon-based cylindrical microdosimeter and a previously published analytical microdosimetric model based on Geant4-DNA in-water Monte Carlo simulations for low energy proton beams. Methods and material: Distributions for lineal energy (y) are measured for four proton monoenergetic beams with nominal energies from 2.0 MeV to 4.5 MeV, with a tissue equivalent proportional counter (TEPC) and a silicon-based microdosimeter. The actual energy for protons traversing the silicon-based microdosimeter is simulated with SRIM. Monoenergetic beams with these energies are simulated with Geant4-DNA code by simulating a water cylinder site of dimensions equal to those of the microdosimeter. The microdosimeter response is calibrated by using the distribution peaks obtained from the TEPC. Analytical calculations for y‾F and y‾D using our methodology based on spherical sites are also performed choosing the equivalent sphere to be checked against experimental results. Results: Distributions for y at silicon are converted into tissue equivalent and compared to the Geant4-DNA simulated, yielding maximum deviations of 1.03% for y‾F and 1.17% for y‾D. Our analytical method generates maximum deviations of 1.29% and 3.33%, respectively, with respect to experimental results. Conclusion: Simulations in Geant4-DNA with ideal cylindrical sites in liquid water produce similar results to the measurements in an actual silicon-based cylindrical microdosimeter properly calibrated. The found agreement suggests the possibility to experimentally verify the calculated clinical y‾D with our analytical method. National Institute of Biomedical Imaging and Bioengineering 5P41 EB002033 European Union 745109, 675265 Gobierno de España RTI2018-098117-B-C21

In fire scenarios, the application and accuracy of traditional odontological methods are often limited. Crystalline studies and elemental profiling have been evaluated for their applicability in determining biological profiles (age and sex) from human dentition, particularly fire- and heat-affected dental remains. Thirty-seven teeth were paired according to tooth type and donor age/sex for the analysis of crown and root surfaces pre- and post-incineration using X-ray diffraction (XRD) and scanning electron microscopy (SEM/EDX). In unburned crowns, carbon (C) content showed a positive correlation with age, whereas phosphorus (P) and calcium (Ca) contents showed a negative correlation with age. In unburned roots, C, P and Ca contents also showed significant changes that were opposite of those observed in the crowns. In relation to sex, females exhibited a higher C ratio than males, whereas males showed significantly higher levels of oxygen (O), P and Ca in unburned roots. Incineration resulted in an increase in the crystallite size that correlated with increasing temperature. No differences in hydroxyapatite (HA) crystallite size were found between age groups; however, unburned teeth from females exhibited a larger crystallite size than did those from males. The challenges of using XRD with a 3D sample were overcome to allow analysis of whole teeth in a nondestructive manner. Further studies may be useful in helping predict the temperature of a fire.

Enniatins (ENs) are emerging mycotoxins produced by Fusarium fungi which are cytotoxic also at low concentrations due to its ionophoric properties. The aim of this study was to evaluate the hepatic toxicity of ENs exposure at different concentrations in Wistar rats through a proteomic approach. Animals were intoxicated by oral gavage with medium (EN A 256, ENA1 353, ENB 540, ENB1 296 μg/mL) and high concentrations (ENA 513, ENA1 706, ENB 1021, ENB1 593 μg/mL) of an ENs mixture and sacrificed after 8 h. Protein extraction was performed using powdered liver. Peptides were analyzed using a liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Proteins were filtered by abundance using Mass Professional Profiler software (Agilent Technologies) and 57 were differentially expressed when compared to the control. In terms of abundance, the liver biomarker Carboamoyl-phosphate synthase showed the highest levels in all conditions employed while actin-1 had the lowest. Bioinformatic analysis using DAVID platform reported acetylation, nucleotide phosphate-binding region:NAD and catalytic activity as the most represented terms. Furthermore, metabolism was the most significant and enriched pathway in Reactome overrepresentation. In conclusion, ENs acute exposure caused protein expression changes related to major cellular processes in rats, hinting its involvement in liver disturbance.

International audience; The commissioning of an ion beam for hadrontherapy requires the evaluation of the biologically weighted effective dose that results from the microdosimetric properties of the therapy beam. The spectra of the energy imparted at cellular and sub-cellular scales are fundamental to the determination of the biological effect of the beam. These magnitudes are related to the microdosimetric distributions of the ion beam at different points along the beam path. This work is dedicated to the measurement of microdosimetric spectra at several depths in the central axis of a 12C beam with an energy of 94.98 AMeV using a novel 3D ultrathin silicon diode detector. Data is compared with Monte Carlo calculations providing an excellent agreement (deviations are less than 2% for the most probable lineal energy value) up to the Bragg peak. The results show the feasibility to determine with high precision the lineal energy transfer spectrum of a hadrontherapy beam with these silicon devices.

A risk for developing progressive multifocal leukoencephalopathy is a major barrier to natalizumab use. Extended dosing intervals have been proposed as a way to maintain therapeutic efficacy and reduce progressive multifocal leukoencephalopathy incidence. This is the first reported case of progressive multifocal leukoencephalopathy in a patient using an extended dosing regimen (300 mg/6 weeks). A close clinical and imaging monitoring allowed early detection, which is a major prognostic factor. A favorable outcome was seen with a therapy comprising plasma exchange therapy, mirtazapine, mefloquine and cidofovir. Further studies will be needed to assess the potential role of extended dosing intervals to improve prognosis in patients receiving natalizumab and also to measure its impact clinically and/or radiologically.

Background/objectives: Dyslipidemia is a public health problem. The main causes of dyslipidemia are sedentary lifestyle, excessive intake of saturated fats and low intake of dietary fiber. Opuntia Cactaceae contains high levels of fiber, which is known to decrease intestinal absorption of lipids. The objective of this study is to determine the lipid-lowering effect of a normal-calorie diet supplemented with Opuntia Cactaceae in patients with dyslipidemia. Subjects/methods: From a 160 patients with dyslipidemia group we randomly assigned two groups according to the criteria established by the World Health Organization, a control group and an experimental group. Baseline levels of cholesterol, triglycerides and fasting glucose were obtained, secondly, a Harris-Benedict normocaloric diet was calculated and anthropometric measurements were performed in both groups. The experimental group received 100g of Opuntia Cactaceae supplementation in their diet for a month. Results: We compared cholesterol and triglycerides levels at baseline and at the end of the study on both groups. There was a statistically significant difference (P

Journal of Instrumentation 12(05), P05015 - P05015 (2017). doi:10.1088/1748-0221/12/05/P05015, For the High-Luminosity upgrade of the Large Hadron Collider an increased instantaneous luminosity of up to 7.5 ⋅ 10$^{34}$ cm$^{−2}$ s$^{−1}$, leading to a total integrated luminosity of up to 3000 fb$^{−1}$, is foreseen. The current silicon and transition radiation tracking detectors of the ATLAS experiment will be unable to cope with the increased track densities and radiation levels, and will need to be replaced. The new tracking detector will consist entirely of silicon pixel and strip detectors. In this paper, results on the development and tests of prototype components for the new silicon strip detector in the forward regions (end-caps) of the ATLAS detector are presented. Flex-printed readout boards with fast readout chips, referred to as hybrids, and silicon detector modules are investigated. The modules consist of a hybrid glued onto a silicon strip sensor. The channels on both are connected via wire-bonds for readout and powering. Measurements of important performance parameters and a comparison of two possible readout schemes are presented. In addition, the assembly procedure is described and recommendations for further prototyping are derived., Published by Inst. of Physics, London

AC-coupled silicon strip sensors can be damaged in case of a beam loss due to the possibility of a large charge accumulation in the bulk, developing very high voltages across the coupling capacitors which can destroy them. Punch-through structures are currently used to avoid this problem helping to evacuate the accumulated charge as large voltages are developing. Nevertheless, previous experiments, performed with laser pulses, have shown that these structures can become ineffective in relatively long strips. The large value of the implant resistance can effectively isolate the “far” end of the strip from the punch-through structure leading to large voltages. We present here our developments to fabricate low-resistance strip sensors to avoid this problem. The deposition of a conducting material in contact with the implants drastically reduces the strip resistance, assuring the effectiveness of the punch-through structures. First devices have been fabricated with this new technology. Initial results with laser tests show the expected reduction in peak voltages on the low resistivity implants. Other aspects of the sensor performance, including the signal formation, are not affected by the new technology.

Charge multiplication in severely irradiated silicon detectors is now a well proven effect that enhances their charge collection and makes them operable up to the doses anticipated for future super-colliders (like the high luminosity LHC at CERN). The effect is well documented but not completely understood. The multiplication is caused by impact ionisation due to hot electrons moving in the high electric field that develops near the junction in the irradiated sensors. The details of the electric field profile in the silicon bulk are not available due to the unknown spatial distribution of the inhomogeneous effective space charge in the hadron irradiated silicon bulk. The gradient of the effective space charge distribution is crucial for the formation of high electric field regions where the multiplication takes place. The electric field might be influenced by the implant forming the n–p junction and by a non-homogenous bulk space charge near the junction. Deep n+ structures (junction) could enhance or reduce the multiplication effect. Also an altered doping gradient (obtainable for example by a graded p-doping between the junction and the p-bulk) could achieve the same results. In order to achieve enhanced charge multiplication in microstrip detectors the junction has been shaped by mean of deep p-doping diffusion and of trenches etched in the silicon bulk and filled with n+ doped polysilicon to create a deep junction. We report here the result obtained with these methods before and after various doses of neutron irradiation.

Current techniques of cancer treatment using protons and heavy ions (hadrons) are an expanding branch of the external radiation therapy. Characterization of radiobiological efficiency of the hadron beams depends on the knowledge of the energy deposition distributions associated to their track structure. Novel manufacturing techniques led to the fabrication of micrometer-scale instruments for the measurement of such quantities. A 3D diode microdosimeter was tested under radiation sources, proton and carbon beams. The results are consistent with Monte Carlo simulations showing great agreement between them.

International audience; This is the first study where graphene is used as a MALDI adjuvant in combination with the traditional matrix α-cyano-4-hydroxycinnamic acid (CHCA) to improve the signal intensity of peptide samples. Use of this amended matrix not only leads to increased signals but also to a higher number of peaks detected in complex samples. Additionally, the use of graphene has a stabilizing effect that can also be exploited to improve the detection of easily cleavable molecules.

Silicon detectors in 3D technology are a candidate for applications in environments requiring an extreme radiation hardness, as in the innermost layers of the detectors at the proposed High-Luminosity LHC. In 3D detectors, the electrodes are made of columns etched into the silicon perpendicular to the surface. This leads to higher electric fields, a smaller depletion voltage and a reduced trapping probability of the charge carriers compared to standard planar detectors. In this article, the signal and the noise of irradiated n-in-p and p-in-n 3D silicon strip detectors are compared. The devices under test have been irradiated up to a fluence of 2×1016 1 MeV neutron equivalent particles per square centimetre (neq/cm2), which corresponds to the fluence expected for the inner pixel detector layers at the High-Luminosity LHC. A relative charge collection efficiency of approximately 70% was obtained even after the highest irradiation fluence with both detector types. The influence of different temperatures on the signal and the noise is investigated and results of annealing measurements are reported.

The planned luminosity upgrade of the CERN LHC to the super LHC (sLHC) requires investigation of new radiation hard tracking detectors. Compared to the LHC, tracking detectors must withstand a 5-10 times higher radiation fluence. Promising radiation hard options are planar silicon detectors with n-side readout and silicon detectors in 3D technology, where columnar electrodes are etched into the silicon substrate. This article presents beam test measurements per formed with planar and 3D n-in-p silicon strip detectors. The detectors were irradiated to different fluences, where the maximum fluence was 3 × 1015 1 MeV neutron equivalent particles per square centimeter (neq/cm2) for the planar detectors and 2 × 1015 neq/cm2 for the 3D detectors. In addition to signal measurements, charge sharing and resolution of both detector technologies are compared. An increased signal from the irradiated 3D detectors at high bias voltages compared to the signal from the unirradiated detector indicates that charge multiplication effects occur in the 3D detectors. At a bias voltage of 260 V, the 3D detector irradiated to 2 × 1015 neq/cm2 yields a signal almost twice as high as the signal of the unirradiated detector. Only 30% of the signal of an unirradiated detector could be measured with the planar detector irradiated to 3 × 1015 neq/cm2 at a bias voltage of 600 V, which was the highest bias voltage applied to this sensor.

Thermal stability of bovine α-lactalbumin in the presence of three different calcium concentrations in aqueous solutions of several concentrations of erythritol, xylitol, sorbitol, and inositol at pH 6.5 was evaluated by UV absorbance, fluorescence spectroscopy, and circular dichroism spectroscopy. At the selected conditions, the thermal denaturation process is reversible and is well described by a two-state model. Results show a higher stability for the holo form of the protein in the presence of calcium, followed by the holo- and the apo-lactalbumin, respectively. The stabilizing effect of the polyols increases with polyol concentration and it is higher for the apo-lactalbumin than holo-lactalbumin and is very small for the protein in the presence of a calcium excess.

For the planned luminosity upgrade of the CERN LHC to the sLHC new radiation hard technologies for the tracking detectors are investigated. Corresponding to the luminosity increase, the radiation dose will be approximately a factor of ten higher than for the detectors currently installed in the LHC experiments. One option for radiation tolerant detectors are 3D silicon detectors with columnar electrodes penetrating into the silicon bulk. This article reports results of beam test measurements performed with 3D-DDTC (Double-Sided, Double Type Column) silicon strip detectors, where the columns do not pass through the detector completely. The devices were produced by IMB-CNM (Barcelona, Spain) and by FBK-irst (Trento, Italy). Important properties like space-resolved charge collection and efficiency are investigated.

The differential in vitro antimicrobial activity of a 12-residue-long arginine-rich peptide derived from protamine was examined against bacterial and parasite microbes. A design of discrete peptide fragments based on the thermolysin-digestion map allowed us to propose three peptide fragments to be further assessed regarding their biological and secondary structural properties. Peptide structure allowed designing three arginine-rich fragments. All peptide fragments were assessed regarding their antimicrobial activity against Gram-positive and Gram-negative bacteria and a human malaria strain. Qualitative and quantitative assays carried out for determining all peptides' antibacterial activity at different concentration levels included radial diffusion and a time-controlled technique. Tests demonstrated that all assessed molecules inhibited invasion of Plasmodium falciparum parasites to human red blood cells. Cytolytic activity of the parent protamine peptide was completely abolished by strategically fragmenting its aminoacid sequence. Remarkably, the cationic C-fragment exhibited stronger biological activity than its parent peptide. Interestingly, the peptide fragment denoted as 2077 displays a typical ?-helix profile according to its CD spectrum. The results support proposing the protamine C-terminal fragment as a potential new antimicrobial peptide. © 2009 Elsevier Inc. All rights reserved.

Proton irradiation results are shown here for three different SiGe:C HBT technologies from IHP Microelectronics. High damages are observed although the transistors remain usable for their application on the Super-LHC. Considerations on the ionization and displacement effects additivity are also presented in order to validate parameterized experiments. This study shows a reasonable agreement between proton irradiations and previous gamma and neutron irradiations.

Thermal stability of bovine α-lactalbumin in buffer and dilute aqueous solutions of erythritol, xylitol, sorbitol, inositol and glucose was evaluated by fluorescence spectroscopy and circular dichroism. Results show that at the selected conditions, the transition is reversible and is well described by a two-state model. At low concentration the cosolutes do not show a structure stabilizing effect, and some of them even destabilize the protein. At higher concentration, all of them stabilize the native protein conformation; however, the extent of stabilization is lower than the effect shown with other proteins, presumably due to the lactalbumin incomplete unfolding.

Silicon edgeless detectors represent a novel type of detector that are being developed for close-to-beam applications in high-energy physics and for large-scale tiled 1D and 2D arrays used in radiation imaging. In this work, the electric field and potential distributions on the device cut side, key factors in detector performance, have been investigated using two methods—the Conductive Microprobe Technique and the Scanning Transient Current Technique. It has been found that the behaviour of the potential distribution at the edge indicates a significant presence of positively charged states, with the charge density changing with the applied voltage. This work will predict, to a first approximation, the trend of the electric field at the edge of these devices after irradiation to high fluences. This prediction will provide key inputs in the development of edgeless radiation hard detectors.

3D detectors are photodiode detectors with n- and p-type electrode columns passing through a silicon substrate. This structure gives a much smaller spacing between the electrodes than in a standard photodiode, greatly reducing the detector's operating voltage and collection time. The device structure also reduces charge sharing between adjacent pixels. This improves the image quality, making these detectors potentially useful for applications such as X-ray diffraction experiments in synchrotrons. A set of silicon detectors with a simplified “double-sided” 3D structure have been fabricated. After being bump-bonded to Medipix2 single-photon-counting readout chips, they have been tested using X-rays and alpha particles. The test results show that the 3D detectors have substantially lower charge sharing than a planar detector of the same thickness.

Particle-tracking detectors made on high-resistivity (HR) float zone (FZ) silicon are widely used in high-energy physics experiments. It is known that the incorporation of oxygen in the FZ Si can lead to some improvement in the radiation hardness of the material. In this contribution we investigate the effects of 2 MeV electron irradiation, up to a fluence of 5×1016 e/cm2, on the electrical and carrier lifetime properties of p-on-n silicon diodes fabricated on different substrate materials, including HR standard and oxygenated FZ, as well as HR magnetic Czochralski silicon, with a higher intrinsic oxygen contents. A progressive degradation of the characteristics is observed for all devices, pointing to a generation of bulk damage. Interestingly, a significant increase of the effective carrier concentration is observed after the highest fluences for all materials. Under the limited experimental conditions studied, no significant changes are observed for diode characteristics subjected to a thermal annealing treatment at 80 °C. This degradation in the electrical properties should be taken into account for the use of such HR Si materials under high-energy electron environments. © 2009 Elsevier B.V. All rights reserved.

Leaves and wood of Peltostigma guatemalense, a novel species of the family Rutaceae, yielded a total of 14 secondary metabolites, i.e. methyl p-hydroxy benzoate, phenylacetic acid, beta-sitosterol, lupeol, syringaresinol, scopoletin, gardenin B (1), and seven alkaloids: gamma-fagarine (2), skimmianine (3), kokusaginine (4), 7-O-isopentenyl-gamma-fagarine (5), anhydro-evoxine (6), evoxine (7) and 4-methoxy-1-methyl-quinolin-2-one (8). The compounds have been identified by spectroscopic methods. Antibacterial and antimalarial in vitro activity of the isolated compounds were also determined. Methyl p-hydroxy benzoate and quinolone (8) were the most effective on Plasmodium falciparium strains.

A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.

3D detectors are photodiode radiation detectors with n- and p-type electrode columns passing through a silicon substrate. This structure makes it possible to achieve a very small electrode spacing without reducing the sensitive thickness. This greatly reduces the detector's depletion voltage and collection time, and hence improves its radiation hardness. This could make 3D detectors useful as pixel detectors for future high-luminosity colliders, such as the Super-LHC. The research institute IMB-CNM (Centro Nacional de Microelectronica, Barcelona) have produced 3D pad, pixel and strip detectors with a “double-sided 3D” structure. This fabrication has been done alongside design and simulation work at the University of Glasgow. The first devices produced by CNM have been successfully IV and CV tested, and source tests are ongoing. Additionally, this conference record discusses work done by other 3D detector collaborations: Stanford, Manchester University and Sintef; FBK (Trento); and Glasgow, Diamond Light Source and IceMOS Ltd.

Experimental densities and viscosities of dilute aqueous binary mixtures of 1-butanol, 1,2-butanediol, 1,4-butanediol, 1,2,4-butanetriol, and 1,2,3,4-butanetetrol (erythritol) were measured in the temperature range from 283.15 to 323.15 K. Apparent molar volumes were determined as a function of composition from density measurements. The limiting partial molar volumes of alcohols in aqueous solution were evaluated through extrapolation. The relative viscosity values were adjusted by least-squares to a second order equation to obtain the viscosity B coefficient which has been related to the size and shape of the solute molecule. The temperature dependence of the partial molar volume at infinite dilution and the viscosity B coefficient are discussed in terms of the relationship among polar and non polar groups on water structure and the effect of the position of hydroxyl groups in the molecule.

A simple and useful method for β-lactoglobulin isolation from bovine whey is presented in this work. Differential precipitation with ammonium sulfate was used to isolate β-lactoglobulin from other whey proteins using 50% ammonium sulfate. The precipitate was dissolved and separated again using 70% ammonium sulfate, leaving a supernatant liquid enriched in β-lactoglobulin. After dialysis and lyophilization, isolation of the protein was performed by ion-exchange chromatography. This is a rapid, efficient and inexpensive two-step method that allows high homogeneous protein yield and has advantages over other methods since it preserves the native structure of β-lactoglobulin. The isolated product was compared with a commercial β-lactoglobulin standard that was also employed to induce mice polyclonal antibodies. Such antibodies were the tools for identifying the natural isolated β-lactoglobulin from bovine whey. Physicochemical and structural characterization of purified β-lactoglobulin is presented in this work.

An advance in the selective acylation of polyamines having identical or similar amine functions is reported. While nucleophilicity differences between the various amine functions are slight, the corresponding conjugate acids exhibit pKa values over a significant range. We have used proton as polyamine protecting group: the monoamine resulting from single deprotonation of a polyammonium compound has allowed for high yields of selective acylation.

In order to identify an appropriate low-temperature surface passivation that could be used for bulk lifetime estimation of high resistivity (HR) (> 1 k·cm) silicon for radiation detectors, different passivating layers were evaluated on n-type and p-type standard Czochralski (CZ), HR magnetic CZ and HR float zone (FZ) substrates. Minority carrier lifetime measurements were performed by means of a μW-PCD set-up. The results show that SiNx PECVD layers deposited at low temperatures (≤ 250°C) may be used to evaluate the impact of different processing steps and treatments on the substrate characteristics for radiation detectors. First results are obtained about a preliminary thermal treatment experiment to evaluate the thermal stability of the passivating layers, as well as the potential impact of the generation of thermal donors on minority carrier lifetime.

A technology for the fabrication of p-type microstrip silicon radiation detectors using p-spray implant insulation has been developed at CNM-IMB within the RD50 collaboration framework. The p-spray insulation has been designed to withstand the ionising irradiation dose expected in the middle region of the ATLAS tracking system for the future Super-LHC. Detectors have been fabricated with Float Zone and Magnetic Czochralski p-type high resistivity silicon substrates in the Clean Room facility of CNM-IMB, irradiated with neutrons up to a fluence of 10 15 neutrons cm - 2 and characterised at IFIC-Valencia. The results show a charge collection efficiency below 40% at 1000 V bias voltage.

Twenty years ago we reported the first synthetic peptide-based anti-malarial vaccine named SPf66, which conferred limited protective efficacy in large-scale human field-trials. Our efforts towards a second vaccine generation based on the rational selection of conserved high activity binding peptides (HABPs) whose critical binding residues have to be precisely replaced by others. Introducing peptide bond isosters on these HABPs' critical binding residues constitutes also an important approach. Our results suggest that knowing a parasite's immunologically active peptides, their 3D structure, and their interaction for properly stabilizing MHC-II peptide-TCR complexes constitutes the basis for rationally designing a fully effective, multi-component, multistage subunit-based anti-malarial vaccine.

This work reports on an optimization study of the p-spray profile for the fabrication of n-in-p microstrip silicon detectors. A thorough simulation process of the expected electrical performance of different p-spray technologies was carried out. The best technological options for the p-spray implantation were chosen for the fabrication of miniature n-in-p microstrip detectors on high resistivity FZ wafers at the IMB-CNM clean room. The main conclusions derived from the simulations, and the electrical performance of a sample of the fabricated devices is presented.

A further development of a new technological solution to improve the beam-loss protection of silicon strip sensors used in large High Energy Physics experiments is presented. Previous studies show that the high strip resistance limits the beneficial effect of full Punch-Through protection (PTP) structures to the area near the structures. In our approach, we extended the PTP protection to the full active area of the sensor by lowering the strip resistance. This is achieved by the addition of a low-resistivity layer connected along the whole strip implant. We have previously demonstrated that such sensors performed as expected, and that other sensor performance factors are not compromised due to the technological modification. The current studies are focused on two aspects of practical application: manufacturability of the sensors with high yield, and their radiation tolerance. To that extend we have made devices with alternative methods of making low-resistivity layers that with better technological performance, and we have irradiated them with protons in the range expected for upgraded ATLAS strips system. The results show that the sensors fabricated with these alternative technological methods remain within specs and that the strip resistance is properly reduced. On the other hand, radiation does not affect the reduced strip resistance.

This paper reports on the fabrication, simulation, and charge collection characteristics of a new generation of cylindrical silicon microdosimeters fabricated on SOI wafers. The devices consist of an array of p+ electrodes surrounded by trench n+ electrodes creating well defined, cylindrical sensitive volumes. A first batch of microsensors with 5.4 μm active thickness has been successfully fabricated. The devices are fully functional with good diode behavior and a depletion voltage of only 3 V. Their charge collection characteristics have been investigated using the IBIC technique with protons and alpha particles. The IBIC maps show a 100% yield of active cells in a microdosimeter array and full charge collection efficiency in the active area of the unit microsensors. These devices constitute an step forward in the current status of microdosimeters based on silicon technologies.

The very high radiation fluence expected at LHC (Large Hadron Collider) at CERN will induce serious changes in the electrical properties of the silicon detectors that will be used in the internal layers of the experiments (ATLAS, CMS, LHCb). To understand the influence of the fabrication technology in the radiation-induced degradation, silicon detectors were fabricated simultaneously with the three different possible technologies, P-in-N, N-in-N, and N-in-P, on standard and oxygenated float-zone silicon wafers. The diodes were irradiated with protons to fluences up to 10/sup 15/ cm/sup -2/. The measurements of the electrical characteristics, current-voltage and capacitance-voltage, are presented for the detectors manufactured with the three technologies. In terms of alpha factor (leakage current) the three technologies behave similarly. In terms of beta factor (effective doping concentration) N-in-P devices show the best performances.

Silicon wafers grown by the Magnetic Czochralski (MCZ) method have been processed in form of pad diodes at Instituto de Microelectronica de Barcelona (IMB-CNM) facilities. The n-type MCZ wafers were manufactured by Okmetic OYJ and they have a nominal resistivity of 1 kΩ cm. Concentrations of oxygen and carbon in MCZ wafers were measured by Secondary Ion Mass Spectroscopy (SIMS) technique to be compared to standard and oxygenated float zone (FZ) silicon material. The diodes were characterized by leakage current and capacitance measurements. The average full depletion voltage, V FD, of the pad detectors is 290±10 V, while the leakage current density at V FD +20 V is 7±3 nA/cm 2 . Minority carrier lifetime of MCZ, standard FZ and oxygenated FZ substrates was measured by using a quasi steady-state photoconductance technique. The uniformity of the MCZ wafers was studied before the fabrication by mapping the resistivity of the wafer and after the fabrication process by measuring the full depletion voltage and leakage current as a function of diode position on the wafer. It was found that the fabrication process did not change the resistivity of the material although no donor-killing heat treatment was performed on the wafers.

The C-terminal portion of the Plasmodium falciparum blood stage MSP-1 antigen plays a key role in invasion of human erythrocytes. The MSP-1 1282–1301 non-polymorphic 1585 peptide, from the processed MSP-1 42 fragment, is poorly immunogenic and highly α-helical [Angew. Chem. Int. Ed. 40 (2001) 4654]. Assessing the α-carbon asymmetry and its implication in the host immune response is proposed in this work to overcome the 1585 peptide’s immunological properties. Accordingly, the effect of incorporating single d -amino acids and ψ-[CH 2 –NH] isoster bonds into the 1585 peptide was examined both at the immunogenic and 3D-structure levels. Therefore, specific binding to RBCs is promoted by site-directed chiral modifications on the native peptide as well as by simultaneously combining specific d -substitutions with ψ-[CH 2 –NH] isoster bonds transforming this molecule into a high specific HLAβ1*1101 allele binder. d -analog pseudopeptide immunized animals induced antibodies selectively recognizing a recombinant as well as native MSP-1 42 and MSP-1 33 fragments. Protection and low parasitemia levels were induced in Aotus monkeys immunized with the EVLYL( d K)PLAGVYRSLKKQLE analog. Peptide α-carbon chiral transformation is therefore an important target for structural modulation and, consequently, represents a novel approach towards designing multi-component subunit-based malarial vaccines.

Use of synthetic peptides as vaccine components is hampered by their susceptibility to enzymatic degradation and rapid clearance from biological fluids. Introduction of non-natural structural modifications can render peptides more resistant to enzymatic degradation, encouraging attempts to profile such non-natural ligands as components of synthetic sub-unit vaccines. We have compared the antigenic and immunogenic properties of a series of non-natural peptide analogues derived from a promiscuous T cell epitope of the major Plasmodium falciparum malaria vaccine candidate merozoite surface protein 1 (MSP-1). A series of HLA class II restricted MSP-1(38-58)-specific TCC established from three volunteers were characterized for their minimal epitope and fine specificity. T cell stimulatory activities of a series of pseudo-peptide analogues with single reduced peptide bond Psi-[CH2-NH] modifications were compared with those of single d-amino acid replacement analogues. Compared to reduced peptide bond analogues the single d-amino acid replacement analogues turned out to be less suitable for stimulation of TCC. In particular, the reduced peptide analogue carrying a Psi-[CH2-NH] backbone modification between positions V52 and L53 of MSP-1(38-58) demonstrated properties that would make it a more suitable vaccine component than the unmodified parent peptide. First, the pseudo-peptide stimulated a number of TCC restricted by a range of HLA class II alleles. Second, trypsin treatment in combination with T cell stimulation assays provided evidence for increased resistance to proteolytic digestion. Third, the parasite-binding anti-MSP-1 mAb 7.27 recognized best this particular pseudo-peptide in competition ELISA experiments and its immunogenicity in out-bred Aotus monkeys was superior to that of the parent peptide eliciting antibodies cross-reactive with native MSP-1.