General Principles for the Design of Visible-Light-Responsive Photoswitches:Tetra-ortho-Chloro-Azobenzenes

Molecular photoswitches enable reversible external control of biological systems, nanomachines, and smart materials. Their development is driven by the need for low energy (green-red-NIR) light switching, to allow non-invasive operation with deep tissue penetration. The lack of clear design principles for the adaptation and optimization of such systems limits further applications. Here we provide a design rulebook for tetra-ortho-chloroazobenzenes, an emerging class of visible-light-responsive photochromes, by elucidating the role that substituents play in defining their key characteristics: absorption spectra, band overlap, photoswitching efficiencies, and half-lives of the unstable cis isomers. This is achieved through joint photochemical and theoretical analyses of a representative library of molecules featuring substituents of varying electronic nature. A set of guidelines is presented that enables tuning of properties to the desired application through informed photochrome engineering

Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography

IntroductionBacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria.Methods[18F]FB-NHS and [18F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [18F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites.Results[18F]FB-vancomycin, [18F]BODIPY-FL-vancomycin, and [18F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [18F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [18F]PQ-VE1-vancomycin and [18F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones.ConclusionHere we present the synthesis and first evaluation of the vancomycin-based PET tracers [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin

Phenylimino Indolinone:A Green-Light-Responsive T-Type Photoswitch Exhibiting Negative Photochromism

Imines are photoaddressable motifs useful in the development of new generations of molecular switches, but their operation with low-energy photons and control over isomer stability remain challenging. Based on a computational design, we developed phenylimino indolinone (PIO), a green-light-addressable T-type photoswitch showing negative photochromism. The isomerization behavior of this photoactuator of the iminothioindoxyl (ITI) class was studied using time-resolved spectroscopies on time scales from femtoseconds to the steady state and by quantum-chemical analyses. The understanding of the isomerization properties and substituent effects governing these photoswitches opens new avenues for the development of novel T-type visible-light-addressable photoactuators based on C=N bonds

A microscopic Kondo lattice model for the heavy fermion antiferromagnet CeIn3_3

Electrons at the border of localization generate exotic states of matter across all classes of strongly correlated electron materials and many other quantum materials with emergent functionality. Heavy electron metals are a model example, in which magnetic interactions arise from the opposing limits of localized and itinerant electrons. This remarkable duality is intimately related to the emergence of a plethora of novel quantum matter states such as unconventional superconductivity, electronic-nematic states, hidden order and most recently topological states of matter such as topological Kondo insulators and Kondo semimetals and putative chiral superconductors. The outstanding challenge is that the archetypal Kondo lattice model that captures the underlying electronic dichotomy is notoriously difficult to solve for real materials. Here we show, using the prototypical strongly-correlated antiferromagnet CeIn$_{3}$, that a multi-orbital periodic Anderson model embedded with input from ab initio bandstructure calculations can be reduced to a simple Kondo-Heisenberg model, which captures the magnetic interactions quantitatively. We validate this tractable Hamiltonian via high-resolution neutron spectroscopy that reproduces accurately the magnetic soft modes in CeIn$_{3}$, which are believed to mediate unconventional superconductivity. Our study paves the way for a quantitative understanding of metallic quantum states such as unconventional superconductivity

A microscopic Kondo lattice model for the heavy fermion antiferromagnet CeIn3_3

Electrons at the border of localization generate exotic states of matter across all classes of strongly correlated electron materials and many other quantum materials with emergent functionality. Heavy electron metals are a model example, in which magnetic interactions arise from the opposing limits of localized and itinerant electrons. This remarkable duality is intimately related to the emergence of a plethora of novel quantum matter states such as unconventional superconductivity, electronic-nematic states, hidden order and most recently topological states of matter such as topological Kondo insulators and Kondo semimetals and putative chiral superconductors. The outstanding challenge is that the archetypal Kondo lattice model that captures the underlying electronic dichotomy is notoriously difficult to solve for real materials. Here we show, using the prototypical strongly-correlated antiferromagnet CeIn$_3$, that a multi-orbital periodic Anderson model embedded with input from ab initio bandstructure calculations can be reduced to a simple Kondo-Heisenberg model, which captures the magnetic interactions quantitatively. We validate this tractable Hamiltonian via high-resolution neutron spectroscopy that reproduces accurately the magnetic soft modes in CeIn$_3$, which are believed to mediate unconventional superconductivity. Our study paves the way for a quantitative understanding of metallic quantum states such as unconventional superconductivity

The synaptic vesicle cluster as a controller of pre‐ and postsynaptic structure and function

The synaptic vesicle cluster (SVC) is an essential component of chemical synapses, which provides neurotransmitter-loaded vesicles during synaptic activity, at the same time as also controlling the local concentrations of numerous exo- and endocytosis cofactors. In addition, the SVC hosts molecules that participate in other aspects of synaptic function, from cytoskeletal components to adhesion proteins, and affects the location and function of organelles such as mitochondria and the endoplasmic reticulum. We argue here that these features extend the functional involvement of the SVC in synapse formation, signalling and plasticity, as well as synapse stabilization and metabolism. We also propose that changes in the size of the SVC coalesce with changes in the postsynaptic compartment, supporting the interplay between pre- and postsynaptic dynamics. Thereby, the SVC could be seen as an 'all-in-one' regulator of synaptic structure and function, which should be investigated in more detail, to reveal molecular mechanisms that control synaptic function and heterogeneity

Why do technology firms publish scientific papers? The strategic use of science by small and midsize enterprises in nanotechnology

In the emerging technology domain of nanotechnology, a significant portion of small and midsize enterprises have contributed to the scientific literature by publishing their research and development results. However, while considerable attention has been paid to patenting by small and midsize technology firms, the underlying business motivations for such firms to publish scientific papers are not well understood. This paper investigates the scientific publishing patterns of smaller firms engaged in nanotechnology and the factors that underlie this phenomenon. Based on an analysis of 85 US small and midsize enterprises with a minimum of four nanotechnology patents or publications, we test three hypotheses about corporate publishing: reputational gains, absorptive capacity, and strategic spillovers. We find that the small and midsize firms in our sample are more likely to publish when their work is associated with public science and when it involves a greater technological focus, but having a university collaborator is not a significant factor. The results from this study of nanotechnology enterprises suggest that small and midsize technology firms selectively manage and disclose their research based on internal developmental and capacity drivers

Unraveling the Thermal Isomerization Mechanisms of Heteroaryl Azoswitches: Phenylazoindoles as Case Study

The research on heteroaromatic azoswitches has been blossoming in recent years due to their astonishingly broad range of properties. Minimal chemical modifications can drastically change the demeanor of these switches, regarding photophysical and (photo)­chemical properties, promoting them as ideal scaffolds for a vast variety of applications based on bistable light-addressable systems. However, most of the characteristics exhibited by heteroaryl azoswitches were found empirically, and only a few works focus on their rationalization. Herein we report on a mechanistic study employing phenylazoindoles as a model reference, combining spectroscopic experiments with comprehensive computational analysis. This approach will elucidate the intrinsic correlations between the molecular structure of the switch and its thermal behavior, allowing a more rational design transferable to various heteroaryl azoswitches

Short- and Long-Term Efficacy of Intragastric Air-Filled Balloon (Heliosphere\uae BAG) Among Obese Patients

Abstract Background Obesity is an increasing health problem worldwide. The intragastric balloon as a temporary endoscopic treatment of obesity can play an important role among the aforementioned group of obese individuals. It can also be used as a preoperative test before subjecting patients to restrictive bariatric surgery. Furthermore, the intragastric device may be applied to patients affected by severe obesity as a \u201cbridge treatment\u201d before they undergo major surgery in order to reduce chances of operation-related risks. To date, there are insufficient data in the literature on the long-term results of the intragastric balloon. Methods Our study includes an analysis of our experience with Heliosphere\uae BAG from 2006 through to 2010, concerning early weight loss and weight loss maintenance over at least 18 months since the device\u2019s removal. The 32 patients who completed the 6-month treatment had recorded a mean weight loss of 12.66 kg and a mean overweight loss of 24.37 % (SD, 12.74). Results A total of 16 patients are subjected to an 18-month follow-up. Their pretreatment and long-term body mass index (BMI) were calculated: 6 months later, when devices were removed, they showed a mean weight of 99.75 kg (SD, 17.90; p<0.001) and a mean weight loss of 13.62 kg and 26.14 % (SD, 12.79). 18 months after removing Heliosphere \uae BAG, the 16 patients\u2019 mean BMI was 37.28 kg/m\ub2 (SD, 5.41; p=0.004), with a mean weight of 103.56 kg (SD 17.25; p=0.0125), and a mean weight loss of 9.8 kg or 18.2 % (SD, 12.07). Conclusions Heliosphere\uae BAG enables modest short-term weight loss with little side effects, although mid/long-term follow-up may entail partial weight gain. We believe it can be considered a useful bridge treatment in bariatric surgery in order to reduce chances of preoperative risks