220 research outputs found
Network theory approach for data evaluation in the dynamic force spectroscopy of biomolecular interactions
Investigations of molecular bonds between single molecules and molecular
complexes by the dynamic force spectroscopy are subject to large fluctuations
at nanoscale and possible other aspecific binding, which mask the experimental
output. Big efforts are devoted to develop methods for effective selection of
the relevant experimental data, before taking the quantitative analysis of bond
parameters. Here we present a methodology which is based on the application of
graph theory. The force-distance curves corresponding to repeated pulling
events are mapped onto their correlation network (mathematical graph). On these
graphs the groups of similar curves appear as topological modules, which are
identified using the spectral analysis of graphs. We demonstrate the approach
by analyzing a large ensemble of the force-distance curves measured on:
ssDNA-ssDNA, peptide-RNA (system from HIV1), and peptide-Au surface. Within our
data sets the methodology systematically separates subgroups of curves which
are related to different intermolecular interactions and to spatial
arrangements in which the molecules are brought together and/or pulling speeds.
This demonstrates the sensitivity of the method to the spatial degrees of
freedom, suggesting potential applications in the case of large molecular
complexes and situations with multiple binding sites
Monitoring core temperature of firefighters to validate a wearable non-invasive core thermometer in different types of protective clothing:Concurrent in-vivo validation
This study aims (1) to test the validity of a new non-invasive core thermometer, CosinussĀ°, in rest and (2) during firefighting simulation tasks, against invasive temperature pill and inner-ear temperature and (3) to compare the change in core temperature of firefighters when working in two types of protective clothing (traditional turnout gear versus new concept). 11 active firefighters performed twice a selection of tasks during their periodic preventive medical examination and a fire-extinguishing task. Without correction no correlation between the CosinussĀ° and thermometer pill (ICCā¤0.09, p ā„ 0.154, LoAā„1.37) and a moderate correlation between CosinussĀ° and inner-ear infrared (ICC = 0.40, p = 0.044, LoAĀ±1.20) was observed. With individual correction both correlations were excellent (ICCā„0.84, p = 0.000, LoAā¤0.30). However, during and after working all correlations were poor and non-significant (ICCā¤0.38, p ā„ 0.091, LoAā„1.71). During firefighting tasks, the CosinussĀ° is invalid for measuring the core temperature. No differences in heat development in the two types of protective clothing was proven
Pulmonary involvement in primary Sjogren's syndrome, as measured by the ESSDAI
Objective: Systemic features influence disease prognosis and choice of treatment in primary Sjogren's syndrome (pSS). Our aim was to investigate the prevalence of pulmonary involvement in pSS patients and to classify patients according to the pulmonary domain of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). Methods: This retrospective cohort study included consecutive pSS patients, fulfilling American-European Consensus Group/American College of Rheumatology classification criteria, who visited the Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, in 2015. Data on pulmonary complaints and pulmonary tests were obtained from electronic patient records. Pulmonary involvement was recorded if therapy was needed or follow-up was recommended, and when it was possibly or assumed to be related to pSS instead of coincidental factors. Results: Of the 262 included pSS patients, 88 (34%) had pulmonary complaints, mostly cough or dyspnoea on exertion. Pulmonary diagnostics were performed in 225 patients (86%). Pulmonary involvement was present and assumed to be related to pSS in 25 patients (10%) and possibly related to pSS in 14 (5%). Interstitial lung disease (ILD, n = 15), especially non-specific interstitial pneumonia (n = 7), was present most commonly. In total, 16 patients (6%) were scored as low (n = 4), moderate (n = 11), or high activity (n = 1) on the ESSDAI pulmonary domain. Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was present in 10-15% of pSS patients, of which ILD was most common. Of all pSS patients, 6% were scored as active on the pulmonary domain of the ESSDAI
Challenges and controversies patients and (health care) professionals experience in managing vaginal, vulvar, penile or anal cancer:The SILENCE study
Bone health in children with Angelman syndrome at the ENCORE Expertise Center
Angelman syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD), or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are observed frequently in our clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS. In this prospective cohort study, we describe bone health in 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the bone health index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication use, mobility, body mass index (BMI), and onset of puberty. Children with AS had a mean BHI of ā1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (ā2.24 SDS) versus non-deletion (ā1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (ā2.60 vs ā1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes. Conclusions: Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age. What is Known: ā¢ Children with neurological disorders often have a low bone health and higher risk of fractures. ā¢ Little is known about bone health in children with Angelman syndrome (AS). What is New: ā¢ Children with AS showed a reduced bone health and this was significantly associated with having a deletion, not being able to walk independently, and late onset of puberty. ā¢ Longitudinal analysis showed a significant decrease in bone health as children got older.</p
1H and 13C resonance assignments of a guanine sensing riboswitchās terminator hairpin
Here we report the nearly complete base assignments and partial sugar assignments of the 35-residue terminator hairpin of the Bacillus subtilisxpt-pbuX-mRNA guanine sensing riboswitch
Formulation of the Dutch Atmospheric Large-Eddy Simulation (DALES) and Overview of Its Applications
The current version of the Dutch Atmospheric Large-Eddy Simulation (DALES) is presented. DALES is a large-eddy simulation code designed for studies of the physics of the atmospheric boundary layer, including convective and stable boundary layers as well as cloudy boundary layers. In addition, DALES can be used for studies of more specific cases, such as flow over sloping or heterogeneous terrain, and dispersion of inert and chemically active species. This paper contains an extensive description of the physical and numerical formulation of the code, and gives an overview of its applications and accomplishments in recent years
Multiple segmental and selective isotope labeling of large RNA for NMR structural studies
Multiple segmental and selective isotope labeling of RNA with three segments has been demonstrated by introducing an RNA segment, selectively labeled with 13C9/15N2/2H(1ā², 3ā², 4ā², 5ā², 5ā²ā²)-labeled uridine residues, into the central position of the 20 kDa Īµ-RNA of Duck Hepatitis B Virus. The RNA molecules were produced via two efficient protocols: a two-step protocol, which uses T4 DNA ligase and T4 RNA ligase 1, and a one-pot protocol, which uses T4 RNA ligase 1 alone. With T4 RNA ligase 1 all not-to-be-ligated termini are usually protected to prevent formation of side products. We show that such labor-intensive protection of termini is not required, provided segmentation sites can be chosen such that the segments fold into the target structure or target-like structures and thus are not trapped into stable alternate structures. These sites can be reliably predicted via DINAMelt. The simplified NMR spectrum provided evidence for the presence of a U28 H3-imino resonance, previously obscured in the fully labeled sample, and thus of the non-canonical base pair U28:C37. The demonstrated multiple segmental labeling protocols are generally applicable to large RNA molecules and can be extended to more than three segments
Adverse drug reactions to tocolytic treatment for preterm labour: Prospective cohort study
Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. Design Prospective cohort study. Setting 28 hospitals in the Netherlands and Belgium. Participants 1920 consecutive women treated with tocolytics for threatened preterm labour. Main outcome measures Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. Results An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a (3 adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drugtocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. Conclusions The use of (3 adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious a
Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study
Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations
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