Molecular Biodynamers:Dynamic Covalent Analogues of Biopolymers

Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications. In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of molecular biodynamers as structural or functional biomimetics of biopolymers, including DyNAs, glycodynamers, and dynamic proteoids. We introduce how chemists utilize various reversible reactions to generate molecular biodynamers with specific sequences and well-ordered structures in aqueous medium. We also discuss and list their potential applications in various research fields, such as drug delivery, drug discovery, gene sensing, cancer diagnosis, and treatment

A doubly hermaphroditic chiral crown ether

A single-crystal structure determination on the S-protected form of a chiral 18-crown-6 derivative known to be a selective catalyst for thiolysis reactions of amino acid derivatives has shown the molecule to crystallise in an unsolvated form where the macrocyclic ring has a conformation in which the dipoles of substituent amide units are aligned parallel. The resulting polar entities are linked through NH center dot center dot center dot O H-bonds and weaker interactions which can be considered to result in doubly hermaphroditic links, the whole crystal proving to be polar. The possible consequences of the observed secondary interactions, some being intramolecular, are considered in relation to the mechanism of catalysis by the isolated molecule

Magnetic and pair correlations of the Hubbard model with next-nearest-neighbor hopping

A combination of analytical approaches and quantum Monte Carlo simulations is used to study both magnetic and pairing correlations for a version of the Hubbard model that includes second-neighbor hopping $t^{\prime }=-0.35t$ as a model for high-temperature superconductors. Magnetic properties are analyzed using the Two-Particle Self-Consistent approach. The maximum in magnetic susceptibility as a function of doping appears both at finite $$ and at $t^{\prime }=0$ but for two totally different physical reasons. When $t^{\prime }=0$, it is induced by antiferromagnetic correlations while at $t^{\prime }=-0.35t$ it is a band structure effect amplified by interactions. Finally, pairing fluctuations are compared with $$-matrix results to disentangle the effects of van Hove singularity and of nesting on superconducting correlations. The addition of antiferromagnetic fluctuations increases slightly the $d$-wave superconducting correlations despite the presence of a van Hove singularity which tends to decrease them in the repulsive model. Some aspects of the phase diagram and some subtleties of finite-size scaling in Monte Carlo simulations, such as inverted finite-size dependence, are also discussed.Comment: Revtex, 8 pages + 15 uuencoded postcript figure

Magnetic properties of the three-dimensional Hubbard model at half filling

We study the magnetic properties of the 3d Hubbard model at half-filling in the TPSC formalism, previously developed for the 2d model. We focus on the N\'eel transition approached from the disordered side and on the paramagnetic phase. We find a very good quantitative agreement with Dynamical Mean-Field results for the isotropic 3d model. Calculations on finite size lattices also provide satisfactory comparisons with Monte Carlo results up to the intermediate coupling regime. We point out a qualitative difference between the isotropic 3d case, and the 2d or anisotropic 3d cases for the double occupation factor. Even for this local correlation function, 2d or anisotropic 3d cases are out of reach of DMF: this comes from the inability of DMF to account for antiferromagnetic fluctuations, which are crucial.Comment: RevTex, 9 pages +10 figure

Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.Open access funding provided by Projekt DEA

Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.

Autoantibodies neutralizing type I interferons (IFN-Is) can underlie infection severity. Here, we trace the development of these autoantibodies at high-resolution using longitudinal samples from 1,876 well-treated individuals living with HIV over a 35-year period. Similar to general populations, ∼1.9% of individuals acquired anti-IFN-I autoantibodies as they aged (median onset ∼63 years). Once detected, anti-IFN-I autoantibodies persisted lifelong, and titers increased over decades. Individuals developed distinct neutralizing and non-neutralizing autoantibody repertoires at discrete times that selectively targeted combinations of IFNα, IFNβ, and IFNω. Emergence of neutralizing anti-IFNα autoantibodies correlated with reduced baseline IFN-stimulated gene levels and was associated with subsequent susceptibility to severe COVID-19 several years later. Retrospective measurements revealed enrichment of pre-existing autoreactivity against other autoantigens in individuals who later developed anti-IFN-I autoantibodies, and there was evidence for prior viral infections or increased IFN at the time of anti-IFN-I autoantibody triggering. These analyses suggest that age-related loss of self-tolerance prior to IFN-I immune-triggering poses a risk of developing lifelong functional IFN-I deficiency

“Nanostandardization” in action: implementing standardization processes in a multidisciplinary nanoparticle-based research and development project

Nanomaterials have attracted much interest in the medical field and related applications as their distinct properties in the nano-range enable new and improved diagnosis and therapies. Owing to these properties and their potential interactions with the human body and the environment, the impact of nanomaterials on humans and their potential toxicity have been regarded a very significant issue. Consequently, nanomaterials are the subject of a wide range of cutting-edge research efforts in the medical and related fields to thoroughly probe their potential beneficial utilizations and their more negative effects. We posit that the lack of standardization in the field is a serious shortcoming as it has led to the establishment of methods and results that do not ensure sufficient consistency and thus in our view can possibly result in research outputs that are not as robust as they should be. The main aim of this article is to present how NanoDiaRA, a large FP7 European multidisciplinary project that seeks to investigate and develop nanotechnology-based diagnostic systems, has developed and implemented robust, standardized methods to support research practices involving the engineering and manipulation of nanomaterials. First, to contextualize this research, an overview of the measures defined by different regulatory bodies concerning nano-safety is presented. Although these authorities have been very active in the past several years, many questions remain unanswered in our view. Second, a number of national and international projects that attempted to ensure more reliable exchanges of methods and results are discussed. However, the frequent lack of publication of procedures and protocols in research can often be a hindrance for sharing those good practices. Subsequently, the efforts made through NanoDiaRA to introduce standardized methods and techniques to support the development and utilization of nanomaterials are discussed in depth. A series of semi-structured interviews were conducted with the partners of this project, and the interviews were analyzed thematically to highlight the determined efforts of the researchers to standardize their methods. Finally, some recommendations are made towards the setting up of well-defined methods to support the high-quality work of collaborative nanoparticle-based research and development projects and to enhance standardization processes

Pion-Xi correlations in Au-Au collisions at STAR

We present pion-Xi correlation analysis in Au-Au collisions at sqrt(s_NN)= 200 GeV and sqrt(s_NN) = 62.4 GeV, performed using the STAR detector at RHIC. A Xi*(1530) resonance signal is observed for the first time in Au-Au collisions. Experimental data are compared with theoretical predictions. The strength of the Xi* peak is reproduced in the correlation function assuming that pions and Xis emerge from a system in collective expansion.Comment: To appear in the proceedings of 18th Nuclear Physics Division Conference of the EPS (NPDC18),Prague, 23.8.-29.8. 200

Inclusive pi0 spectra at high transverse momentum in d-Au collisions at RHIC

Preliminary results on inclusive neutral pion production in d-Au collisions at sqrt(s_NN) = 200 GeV in the pseudo-rapidity range 0<eta<1 are presented. The measurement is performed using the STAR Barrel Electromagnetic calorimeter (BEMC). In this paper, the analysis of the first BEMC hadron measurement is described and the results are compared with earlier RHIC findings. The pi0 invariant differential cross sections show good agreement with next-to-leading order (NLO) perturbative QCD calculations.Comment: 4 pages, 5 figures, 18th Nuclear Physics Division Conference of the EPS, Prague, submitted to Nucl. Phys.

The Feasibility of performing resistance exercise with acutely ill hospitalized older adults

BACKGROUND: For older adults, hospitalization frequently results in deterioration of mobility and function. Nevertheless, there are little data about how older adults exercise in the hospital and definitive studies are not yet available to determine what type of physical activity will prevent hospital related decline. Strengthening exercise may prevent deconditioning and Pilates exercise, which focuses on proper body mechanics and posture, may promote safety. METHODS: A hospital-based resistance exercise program, which incorporates principles of resistance training and Pilates exercise, was developed and administered to intervention subjects to determine whether acutely-ill older patients can perform resistance exercise while in the hospital. Exercises were designed to be reproducible and easily performed in bed. The primary outcome measures were adherence and participation. RESULTS: Thirty-nine ill patients, recently admitted to an acute care hospital, who were over age 70 [mean age of 82.0 (SD= 7.3)] and ambulatory prior to admission, were randomized to the resistance exercise group (19) or passive range of motion (ROM) group (20). For the resistance exercise group, participation was 71% (p = 0.004) and adherence was 63% (p = 0.020). Participation and adherence for ROM exercises was 96% and 95%, respectively. CONCLUSION: Using a standardized and simple exercise regimen, selected, ill, older adults in the hospital are able to comply with resistance exercise. Further studies are needed to determine if resistance exercise can prevent or treat hospital-related deterioration in mobility and function