NMR of TMV : nuclear magnetic resonance of tobacco mosaic virus

This Thesis describes the application of conventional 13 C and 1 H high resolution Fourier Transform Nuclear Magnetic resonance (HR FT NMR) to Tobacco Mosaic Virus (TMV) and its protein oligo- and polymers and some other largebiological systems. The rod-like (TMV) consists of 2200 identical protein subunits protecting one RNA chain (molecular weight 42 x 10 6 ). The most important protein oligo- and polymers are the trimer (molecular weight ≈50,000), rod-like polymer (molecular weight>10 6 ) and the double disk-like oligomer (molecular weight ≈0.6 x 10 6 ). This study could be carried out because these large biomolecules exhibit internal mobility. Apart from rotation of (TMV) and protein oligo- and polymers themselves several types of such internal mobility can be distinguished: rotational motions about carbon-carbonbonds in the polypeptide chain (backbone and side chains) within the protein subunits characterized by a rotational diffusion correlation time τ g -10 s, assumed to correspond to small-amplitude rotation extending over ≈40° ; translational and rotational motions of protein subunits within the protein oligomers about one or (more probably) two mutually perpendicularaxes with a correlation time τ p -8 s, temperature dependent rotational motions over a full 2πangle of both backbone and side chain about at least two carbon-carbon bonds of the section 57 to 62 of the polypeptide chain in the virus and of the section 57 to 62 and in the section 90 to 120 in the double disk-like oligomer on a time scale -7 s, The section 90-120 is known to constitute the RNA binding site. From the effect of proton binding to the rod-like polymers on internal mobility, it turns out that at least one aspartic, one arginine and probably a glumatic acid are involved in the anomalous titration behaviour of (TMV) protein rod-like polymers. These amino acids probably belong to the so called carboxyl cage which, based in ourresults, is expected to be hydrophobic. After the addition of the first proton the carboxyl cage is still incomplete, a result which follows from the fact that protein subunits with one bound proton, are still detectable.Based on the finding that protein subunits are mobile, it is shown that the stability of the double disk-like oligomer solely arises from entropy increase upon shielding of hydrophobic protein surfaces from water during the protein polymerization process to double disks, no specific protein-protein interactions being present. The positive ΔH and ΔS for this polymerization process led us to conclude that, if enough water is removed from the double disk protein surface, the double disk destabilizes and dissociates. From this conclusion a model for the assembly of (TMV) from double disk and (TMV) RNA has evolved.The first step in the assembly process, the formation of the initiation complex, is based on the double disk which specifically recognizes an RNA region. Summarizing, the model implies, that recognition takes place with an intact RNA hairpin; that the double disk dissociates at least at that surface which is approached by the RNA hairpin because of diminished water contact; that the heat released during double disk dissociation, because of the positive ΔH, is available for melting the RNA hairpin; that the initiation complex then can be completed and, finally, that the specificity arises from size and stability of the RNA hairpin, i.e. its secondary structure. It is reasonable to suppose that initiation is completed with both 3' and 5' end of RNA protruding from different sides of the initiation complex. The elongation process can be described similar as the formation of the initiation complex.Also a simple model for TMV dissociation, under physiological conditions in protein and RNA upon entering the plant cell, is presented. It is suggested that (TMV) dissociates when passing the cytoplasmic menbrane.In a small excursion to other large biological systems (plant viruses, phages, ribosomes) we show that the type of expirements described in this Thesis can be extended to many large biological systems. In this way proteins can be studied in their natural environment, close to the in vivo situation. Finally this Thesis shows that it is relatively simple to enrich these systems with stable isotopes against low material costs. For 13 C NMR measurements (TMV) was enriched with 13 C up to 12-15%.<p/

Multiresolution analysis of active region magnetic structure and its correlation with the Mt. Wilson classification and flaring activity

Two different multi-resolution analyses are used to decompose the structure of active region magnetic flux into concentrations of different size scales. Lines separating these opposite polarity regions of flux at each size scale are found. These lines are used as a mask on a map of the magnetic field gradient to sample the local gradient between opposite polarity regions of given scale sizes. It is shown that the maximum, average and standard deviation of the magnetic flux gradient for alpha, beta, beta-gamma and beta-gamma-delta active regions increase in the order listed, and that the order is maintained over all length-scales. This study demonstrates that, on average, the Mt. Wilson classification encodes the notion of activity over all length-scales in the active region, and not just those length-scales at which the strongest flux gradients are found. Further, it is also shown that the average gradients in the field, and the average length-scale at which they occur, also increase in the same order. Finally, there are significant differences in the gradient distribution, between flaring and non-flaring active regions, which are maintained over all length-scales. It is also shown that the average gradient content of active regions that have large flares (GOES class 'M' and above) is larger than that for active regions containing flares of all flare sizes; this difference is also maintained at all length-scales.Comment: Accepted for publication in Solar Physic

Risk for low pathogenicity avian influenza virus on poultry farms, The Netherlands, 2007–2013

Using annual serologic surveillance data from all poultry farms in the Netherlands during 2007–2013, we quantified the risk for the introduction of low pathogenicity avian influenza virus (LPAIV) in different types of poultry production farms and putative spatial-environmental risk factors: distance from poultry farms to clay soil, waterways, and wild waterfowl areas. Outdoor-layer, turkey (meat and breeder), and duck (meat and breeder) farms had a significantly higher risk for LPAIV introduction than did indoor-layer farms. Except for outdoor-layer, all poultry types (i.e., broilers, chicken breeders, ducks, and turkeys) are kept indoors. For all production types, LPAIV risk decreased significantly with increasing distance to medium-sized waterways and with increasing distance to areas with defined wild waterfowl, but only for outdoor-layer and turkey farms. Future research should focus not only on production types but also on distance to waterways and wild bird areas. In addition, settlement of new poultry farms in high-risk areas should be discouraged

Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

Background: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific. Objectives: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes. Methods: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF. Results: Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P &lt; 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. Conclusions: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.</p

Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

BACKGROUND: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific.OBJECTIVES: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes.METHODS: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF.RESULTS: Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P &lt; 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. CONCLUSIONS: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.</p

Non-universal Soft Parameters in Brane World and the Flavor Problem in Supergravity

We consider gravity mediated supersymmetry (SUSY) breaking in 5D spacetime with two 4D branes B1 and B2 separated in the extra dimension. Using an off-shell 5D supergravity (SUGRA) formalism, we argue that the SUSY breaking scales could be non-universal even at the fundamental scale in a brane world setting, since SUSY breaking effects could be effectively localized. As an application, we suggest a model in which the two light chiral MSSM generations reside on B1, while the third generation is located on B2, and the Higgs multiplets as well as gravity and gauge multiplets reside in the bulk. For SUSY breaking of the order of 10--20 TeV caused by a hidden sector localized at B1, the scalars belonging to the first two generations can become sufficiently heavy to overcome the SUSY flavor problem. SUSY breaking on B2 from a different localized hidden sector gives rise to the third generation soft scalar masses of the order of 1 TeV. Gaugino masses are also of the order of 1 TeV if the size of the extra dimension is $\sim 10^{-16}$ ${\rm GeV}^{-1}$. As in 4D effective supersymmetric theory, an adjustment of TeV scale parameters is needed to realize the 100 GeV electroweak symmetry breaking scale.Comment: 1+22 pages, Version to appear in PRD with additional comments and reference

Multiwavelength Studies of Young OB Associations

We discuss how contemporary multiwavelength observations of young OB-dominated clusters address long-standing astrophysical questions: Do clusters form rapidly or slowly with an age spread? When do clusters expand and disperse to constitute the field star population? Do rich clusters form by amalgamation of smaller subclusters? What is the pattern and duration of cluster formation in massive star forming regions (MSFRs)? Past observational difficulties in obtaining good stellar censuses of MSFRs have been alleviated in recent studies that combine X-ray and infrared surveys to obtain rich, though still incomplete, censuses of young stars in MSFRs. We describe here one of these efforts, the MYStIX project, that produced a catalog of 31,784 probable members of 20 MSFRs. We find that age spread within clusters are real in the sense that the stars in the core formed after the cluster halo. Cluster expansion is seen in the ensemble of (sub)clusters, and older dispersing populations are found across MSFRs. Direct evidence for subcluster merging is still unconvincing. Long-lived, asynchronous star formation is pervasive across MSFRs.Comment: 22 pages, 9 figures. To appear in "The Origin of Stellar Clusters", edited by Steven Stahler, Springer, 2017, in pres

High prevalence of non-accidental trauma among deceased children presenting at Level I trauma centers in the Netherlands

PURPOSE: Between 0.1—3% of injured children who present at a hospital emergency department ultimately die as a result of their injuries. These events are typically reported as unnatural causes of death and may result from either accidental or non-accidental trauma (NAT). Examples of the latter include trauma that is inflicted directly or resulting from neglect. Although consultation with a forensic physician is mandatory for all deceased children, the prevalence of fatal inflicted trauma or neglect among children is currently unclear. METHODS: This is a retrospective study that included children (0–18 years) who presented and died at one of the 11 Level I trauma centers in the Netherlands between January 1, 2014, and January 1, 2019. Outcomes were classified based on the conclusions of the Child Abuse and Neglect team or those of forensic pathologists and/or the court in cases referred for legally mandated autopsies. Cases in which conclusions were unavailable and there was no clear accidental cause of death were reviewed by an expert panel. RESULTS: The study included 175 cases of childhood death. Seventeen (9.7%) of these children died due to inflicted trauma (9.7%), 18 (10.3%) due to neglect, and 140 (80%) due to accidents. Preschool children (< 5 years old) were significantly more likely to present with injuries due to inflicted trauma and neglect compared to older children (44% versus 6%, p < 0.001, odds ratio [OR] 5.80, 95% confidence interval [CI] 2.66–12.65). Drowning accounted for 14 of the 18 (78%) pediatric deaths due to neglect, representing 8% of the total cases. Postmortem radiological studies and autopsies were performed on 37 (21%) of all cases of childhood death. CONCLUSION: One of every five pediatric deaths in our nationwide Level I trauma center study was attributed to NAT; 44% of these deaths were the result of trauma experienced by preschool-aged children. A remarkable number of fatal drownings were due to neglect. Postmortem radiological studies and autopsies were performed in only one-fifth of all deceased children. The limited use of postmortem investigations may have resulted in missed cases of NAT, which will result in an overall underestimation of fatal NAT experienced by children. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12024-021-00416-7

Different representations for the action principle in 4D N = 2 supergravity

Within the superspace formulation for four-dimensional N = 2 matter-coupled supergravity developed in arXiv:0805.4683, we elaborate two approaches to reduce the superfield action to components. One of them is based on the principle of projective invariance which is a purely N = 2 concept having no analogue in simple supergravity. In this approach, the component reduction of the action is performed without imposing any Wess-Zumino gauge condition, that is by keeping intact all the gauge symmetries of the superfield action, including the super-Weyl invariance. As a simple application, the c-map is derived for the first time from superfield supergravity. Our second approach to component reduction is based on the method of normal coordinates around a submanifold in a curved superspace, which we develop in detail. We derive differential equations which are obeyed by the vielbein and the connection in normal coordinates, and which can be used to reconstruct these objects, in principle in closed form. A separate equation is found for the super-determinant of the vielbein, which allows one to reconstruct it without a detailed knowledge of the vielbein. This approach is applicable to any supergravity theory in any number of space-time dimensions. As a simple application of this construction, we reduce an integral over the curved N = 2 superspace to that over the chiral subspace of the full superspace. We also give a new representation for the curved projective-superspace action principle as a chiral integral.Comment: 44 pages; V2: typos corrected, a comment added; V3: eq. (3.16) corrected, version published in JHEP; V4: more typos correcte