189 research outputs found
A variation norm Carleson theorem
We strengthen the Carleson-Hunt theorem by proving estimates for the
-variation of the partial sum operators for Fourier series and integrals,
for . Four appendices are concerned with transference, a
variation norm Menshov-Paley-Zygmund theorem, and applications to nonlinear
Fourier transforms and ergodic theory.Comment: 41 page
Mechanism for CCC DNA Synthesis in Hepadnaviruses
Hepadnavirus replication requires the synthesis of a covalently closed circular (CCC) DNA from the relaxed circular (RC) viral genome by an unknown mechanism. CCC DNA formation could require enzymatic activities of the viral reverse transcriptase (RT), or cellular DNA repair enzymes, or both. Physical mapping of the 5′ and 3′ ends of RC DNA and sequence analysis of CCC DNA revealed that CCC DNA synthesis requires the removal of the RT and an RNA oligomer from the 5′ ends of minus and plus strand DNA, respectively, removal of sequences from the terminally redundant minus strand, completion of the less than full-length plus strand, and ligation of the ends. Two models have been proposed that could explain CCC DNA formation. The first (model 1) invokes a role for the RT to catalyze a cleavage-ligation reaction leading to the formation of a unit length minus strand in CCC DNA and a DNA repair reaction for the completion and ligation of plus strand DNA; the second (model 2) predicts that CCC DNA formation depends entirely on cellular DNA repair enzymes. To determine which mechanism is utilized, we developed cell lines expressing duck hepatitis B virus genomes carrying mutations permitting us to follow the fate of viral DNA sequences during their conversion from RC to CCC DNA. Our results demonstrated that the oligomer at the 5′ end of minus strand DNA is completely or at least partially removed prior to CCC DNA synthesis. The results indicated that both RC DNA strands undergo DNA repair reactions carried out by the cellular DNA repair machinery as predicted by model 2. Thus, our study provided the basis for the identification of the cellular components required for CCC DNA formation
Onset of phase diffusion in high kinetic inductance granular aluminum micro-SQUIDs
Superconducting granular aluminum is attracting increasing interest due to its high kinetic inductance and low dissipation, favoring its use in kinetic inductance particle detectors, superconducting resonators or quantum bits. We perform switching current measurements on DC-SQUIDs, obtained by introducing two identical geometric constrictions in granular aluminum rings of various normal-state resistivities in the range from ρ n = 250–5550 μΩ cm. The relative high kinetic inductance of the SQUID loop, in the range of tens of nH, leads to a suppression of the modulation in the measured switching current versus magnetic flux, accompanied by a distortion towards a triangular shape. We observe a change in the temperature dependence of the switching current histograms with increasing normal-state film resistivity. This behavior suggests the onset of a diffusive motion of the superconducting phase across the constrictions in the two-dimensional washboard potential of the SQUIDs, which could be caused by a change of the local electromagnetic environment of films with increasing normal-state resistivities
Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort
Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pH 7.3 (7.18–7.31), HCO3− 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium
Evaluation of the prognostic value of electrocardiography parameters and heart rhythm in patients with pulmonary hypertension
Background: Several studies have analyzed arrhythmias in patients with pulmonary hypertension (PH) and increased P-wave duration was identified as a risk factor for development of atrial fibrillation (AF).
Methods: We retrospectively analyzed the incidence of arrhythmias in patients with an initial diagnosis of PH during long-term follow-up and assessed the prognostic value of electrocardiography (ECG) data. Data from 167 patients were analyzed (Dana Point Classification: Group 1: 59 patients, Group 2: 28 patients, Group 3: 39 patients, Group 4: 41 patients). Clinical, 6-minute walk distance test, echocardiography and right heart catheterization data were collected, and baseline/follow-up ECGs were analyzed.
Results: Baseline ECGs revealed sinus rhythm in 137 patients. Thirteen patients had newly onset AF during follow-up. In 30 patients, baseline ECG showed AF. Patients with baseline AF showed higher atrial diameters and higher right atrial pressure. Patients with P-wave duration > 0.11 s had shorter survival. Other ECG parameters (PQ-interval, QRS-width, QT-/ /QTc-interval) were not associated with survival. Mean survival times were 79.4 ± 5.4 months (sinus rhythm), 64.4 ± 12.9 months (baseline AF) and 58.8 ± 8.9 months (newly onset AF during follow-up) (p = 0.565).
Conclusions: Atrial fibrillation predict adverse prognosis in patients with PH and a longer P-wave (> 0.11 s) is associated with shorter survival time
MS Binding Assays with UNC0642 as reporter ligand for the MB327 binding site of the nicotinic acetylcholine receptor
Patterned immobilization of polyoxometalate-loaded mesoporous silica particles via amine-ene Michael additions on alkene functionalized surfaces
Polyoxometalates (POM) are anionic oxoclusters of early transition metals that are of great interest for a variety of applications, including the development of sensors and catalysts. A crucial step in the use of POM in functional materials is the production of composites that can be further processed into complex materials, e.g. by printing on different substrates. In this work, we present an immobilization approach for POMs that involves two key processes: first, the stable encapsulation of POMs in the pores of mesoporous silica nanoparticles (MSPs) and, second, the formation of microstructured arrays with these POM-loaded nanoparticles. Specifically, we have developed a strategy that leads to water-stable, POM-loaded mesoporous silica that can be covalently linked to alkene-bearing surfaces by amine-Michael addition and patterned into microarrays by scanning probe lithography (SPL). The immobilization strategy presented facilitates the printing of hybrid POM-loaded nanomaterials onto different surfaces and provides a versatile method for the fabrication of POM-based composites. Importantly, POM-loaded MSPs are useful in applications such as microfluidic systems and sensors that require frequent washing. Overall, this method is a promising way to produce surface-printed POM arrays that can be used for a wide range of applications
Synthesis and biological evaluation of novel MB327 analogs as resensitizers for desensitized nicotinic acetylcholine receptors after intoxication with nerve agents
Poisoning with organophosphorus compounds, which can lead to a cholinergic crisis due to the inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine (ACh) in the synaptic cleft, is a serious problem for which treatment options are currently insufficient. Our approach to broadening the therapeutic spectrum is to use agents that interact directly with desensitized nicotinic acetylcholine receptors (nAChRs) in order to induce functional recovery after ACh overstimulation. Although MB327, one of the most prominent compounds investigated in this context, has already shown positive properties in terms of muscle force recovery, this compound is not suitable for use as a therapeutic agent due to its insufficient potency. By means of in silico studies based on our recently presented allosteric binding pocket at the nAChR, i.e. the MB327-PAM-1 binding site, three promising MB327 analogs with a 4-aminopyridinium ion partial structure (PTM0056, PTM0062, and PTM0063) were identified. In this study, we present the synthesis and biological evaluation of a series of new analogs of the aforementioned compounds with a 4-aminopyridinium ion partial structure (PTM0064-PTM0072), as well as hydroxy-substituted analogs of MB327 (PTMD90–0012 and PTMD90–0015) designed to substitute entropically unfavorable water clusters identified during molecular dynamics simulations. The compounds were characterized in terms of their binding affinity towards the aforementioned binding site by applying the UNC0642 MS Binding Assays and in terms of their muscle force reactivation in rat diaphragm myography. More potent compounds were identified compared to MB327, as some of them showed a higher affinity towards MB327-PAM-1 and also a higher recovery of neuromuscular transmission at lower compound concentrations. To improve the treatment of organophosphate poisoning, direct targeting of nAChRs with appropriate compounds is a key step, and this study is an important contribution to this research
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