High-harmonic generation (HHG) is widely used for up-conversion of amplified (near) infrared ultrafast laser pulses to short wavelengths. We demonstrate that Ramsey-comb spectroscopy, based on two ...such pulses derived from a frequency-comb laser, enables us to observe phase effects in this process with a few mrad precision. As a result, we could perform the most accurate spectroscopic measurement based on light from HHG, illustrated with a determination of the 5p6→5p58s23/21 transition at 110 nm in Xe132. We improve its relative accuracy 104 times to a value of 2.3×10−10. This is 3.6 times better than shown before involving HHG, and promising to enable 1S−2S spectroscopy of He+ for fundamental tests.
The energy levels of hydrogen-like atomic systems can be calculated with great precision. Starting from their quantum mechanical solution, they have been refined over the years to include the ...electron spin, the relativistic and quantum field effects, and tiny energy shifts related to the complex structure of the nucleus. These energy shifts caused by the nuclear structure are vastly magnified in hydrogen-like systems formed by a negative muon and a nucleus, so spectroscopy of these muonic ions can be used to investigate the nuclear structure with high precision. Here we present the measurement of two 2S-2P transitions in the muonic helium-4 ion that yields a precise determination of the root-mean-square charge radius of the α particle of 1.67824(83) femtometres. This determination from atomic spectroscopy is in excellent agreement with the value from electron scattering
, but a factor of 4.8 more precise, providing a benchmark for few-nucleon theories, lattice quantum chromodynamics and electron scattering. This agreement also constrains several beyond-standard-model theories proposed to explain the proton-radius puzzle
, in line with recent determinations of the proton charge radius
, and establishes spectroscopy of light muonic atoms and ions as a precise tool for studies of nuclear properties.
An accurate diagnosis of helminth infection is important to improve patient management. However, there is considerable intra- and inter-specimen variation of helminth egg counts in human feces. ...Homogenization of stool samples has been suggested to improve diagnostic accuracy, but there are no detailed investigations. Rapid disintegration of hookworm eggs constitutes another problem in epidemiological surveys. We studied the spatial distribution of Schistosoma mansoni and hookworm eggs in stool samples, the effect of homogenization, and determined egg counts over time in stool samples stored under different conditions.
Whole-stool samples were collected from 222 individuals in a rural part of south Côte d'Ivoire. Samples were cut into four pieces and helminth egg locations from the front to the back and from the center to the surface were analyzed. Some samples were homogenized and fecal egg counts (FECs) compared before and after homogenization. The effect of stool storing methods on FECs was investigated over time, comparing stool storage on ice, covering stool samples with a water-soaked tissue, or keeping stool samples in the shade.
We found no clear spatial pattern of S. mansoni and hookworm eggs in fecal samples. Homogenization decreased S. mansoni FECs (p = 0.026), while no effect was observed for hookworm and other soil-transmitted helminths. Hookworm FECs decreased over time. Storing stool samples on ice or covered with a moist tissue slowed down hookworm egg decay (p<0.005).
Our findings have important implications for helminth diagnosis at the individual patient level and for epidemiological surveys, anthelmintic drug efficacy studies and monitoring of control programs. Specifically, homogenization of fecal samples is recommended for an accurate detection of S. mansoni eggs, while keeping collected stool samples cool and moist delayed the disintegration of hookworm eggs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Results from animal toxicology studies are critical to evaluating the potential harm from exposure to environmental chemicals or the safety of drugs prior to human testing. However, there is ...significant debate about how to evaluate the methodology and potential biases of the animal studies. There is no agreed-upon approach, and a systematic evaluation of current best practices is lacking.
We performed a systematic review to identify and evaluate instruments for assessing the risk of bias and/or other methodological criteria of animal studies.
We searched Medline (January 1966-November 2011) to identify all relevant articles. We extracted data on risk of bias criteria (e.g., randomization, blinding, allocation concealment) and other study design features included in each assessment instrument.
Thirty distinct instruments were identified, with the total number of assessed risk of bias, methodological, and/or reporting criteria ranging from 2 to 25. The most common criteria assessed were randomization (25/30, 83%), investigator blinding (23/30, 77%), and sample size calculation (18/30, 60%). In general, authors failed to empirically justify why these or other criteria were included. Nearly all (28/30, 93%) of the instruments have not been rigorously tested for validity or reliability.
Our review highlights a number of risk of bias assessment criteria that have been empirically tested for animal research, including randomization, concealment of allocation, blinding, and accounting for all animals. In addition, there is a need for empirically testing additional methodological criteria and assessing the validity and reliability of a standard risk of bias assessment instrument.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Precision spectroscopy of light muonic atoms provides unique information about the atomic and nuclear structure of these systems and thus represents a way to access fundamental interactions, ...properties and constants. One application comprises the determination of absolute nuclear charge radii with unprecedented accuracy from measurements of the 2S - 2P Lamb shift. Here, we review recent results of nuclear charge radii extracted from muonic hydrogen and helium spectroscopy and present experiment proposals to access light muonic atoms with Z ≥ 3. In addition, our approaches towards a precise measurement of the Zemach radii in muonic hydrogen (μp) and helium (μ3He+) are discussed. These results will provide new tests of bound-state quantum-electrodynamics in hydrogen-like systems and can be used as benchmarks for nuclear structure theories.
In the course of our investigations on the antitrypanosomal potential of sesquiterpene lactones (STL), we have recently reported on the exceptionally strong activity of 4,15-
-Atriplicolide tiglate, ...which demonstrated an IC
value of 15 nM against
, the etiologic agent responsible for East African human trypanosomiasis (HAT). Since STLs are known to often interact with their biological targets (e.g., in anti-inflammatory and anti-tumor activity) by means of the covalent modification of biological nucleophiles-most prominently free cysteine thiol groups in proteins-it was a straightforward assumption that such compounds might interfere with the trypanothione-associated detoxification system of trypanosomes. This system heavily relies on thiol groups in the form of the dithiol trypanothione (T(SH)
) and in the active centers of enzymes involved in trypanothione metabolism and homeostasis. Indeed, we found in the present study that 4,15-
-atriplicolide tiglate, as well as its structural homologues, the corresponding methacrylate and isobutyrate, are inhibitors of trypanothione reductase (TR), the enzyme serving the parasites to keep T(SH)
in the dithiol state. The TR inhibitory activity was demonstrated to be time-dependent and irreversible. Quite interestingly, of the several further STLs with different core structures that were also tested, none inhibited TR at a significant level. Thus, the TR inhibitory effect by the 4,15-
-atriplicolide esters appears to be specific for this particular type of furanoheliangolide-type STL. Some structure-activity relationships can already be deduced on the basis of the data reported here, which may serve as the starting point for searching further, possibly more potent, TR inhibitors.
IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of ...the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.
Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone ...marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.
The house dust mite (HDM) Dermatophagoides pteronyssinus is a major allergen source eliciting allergic asthma. The aim of the study was to identify new important HDM allergens associated with ...allergic asthma. A cDNA coding for a new mite allergen, designated Der p 21, was isolated using immunoglobulin E (IgE) antibodies from patients with allergic asthma out of a D. pteronyssinus expression cDNA library and expressed in Escherichia coli. Circular dichroism analysis of the purified allergen showed that rDer p 21 (14 726 Da) is one of the few mite allergens with an α-helical secondary structure. The protein exhibited high thermal stability and refolding capacity, and, as determined by small angle X-ray scattering, formed a dimer consisting of two flat triangles. rDer p 21 bound high levels of patients' IgE antibodies and showed high allergenic activity in basophil activation experiments. Rabbit anti-Der p 21 IgG antibodies inhibited mite-allergic patients' IgE binding and allowed the ultrastructural localization of the allergen in the midgut (epithelium, lumen and faeces) of D. pteronyssinus by immunogold electron microscopy. Der p 21 revealed sequence homology with group 5 mite allergens, but IgE and IgG reactivity data and cross-inhibition studies identified it as a new mite allergen. Der p 21 is a new important mite allergen which is liberated into the environment via faecal particles and hence may be associated with allergic asthma.
Summary
Background
The process of gastro‐duodenal digestion may play a role in determining the allergenic properties of food proteins. The sensitizing and allergenic potential of digestion products ...of highly degraded allergens, such as the major peanut allergen Ara h 1, is currently under debate. We evaluated the effect of in vitro gastro‐duodenal digestion of Ara h 1 on T cell reactivity and basophil histamine release.
Methods
An in vitro model of gastro‐duodenal digestion was used to investigate changes in the allergenic properties of Ara h 1 using in vitro assays monitoring T cell reactivity (proliferation, cytokine production) and histamine release of basophils from peanut allergic individuals. The digestion process was monitored using an SDS‐PAGE gel.
Results
In vitro gastric digestion led to rapid degradation of Ara h 1 into small fragments Mr L5600. Gastric digestion did not affect the ability of Ara h 1 to stimulate cellular proliferation. Gastro‐duodenal digestion significantly reduced its ability to stimulate clonal expansion (P<0,05; Wilxocon's signed rank test). The Th‐2 type cytokine polarization of T cells from peanut allergic donors (IFN‐γ/IL‐13 ratio and IFN‐γ/IL‐4 ratio of CFSElow CD4+ T cells) remained unchanged regardless of the level of digestion. Histamine release of basophils from peanut allergic individuals was induced to the same extent by native Ara h 1 and its digestion products.
Conclusion
Gastro‐duodenal digestion fragments of Ara h 1 retain T cell stimulatory and IgE‐binding and cross‐linking properties of the intact protein.
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