Dissipative quantum light field engineering

We put forward a dissipative preparation scheme for strongly correlated photon states. Our approach is based on a two-photon loss mechanism that is realised via a single four-level atom inside a bimodal optical cavity. Each elementary two-photon emission event removes one photon out of each of the two modes. The dark states of this loss mechanism are given by NOON states and arbitrary superpositions thereof. We find that the steady state of the two cavity modes exhibits entanglement and for certain parameters, a mixture of two coherent entangled states is produced. We discuss how the quantum correlations in the cavity modes and the output fields can be measured.Comment: 11 pages, 5 figure

Entangled states of trapped ions allow measuring the magnetic field gradient of a single atomic spin

Using trapped ions in an entangled state we propose detecting a magnetic dipole of a single atom at distance of a few $\mu$m. This requires a measurement of the magnetic field gradient at a level of about 10$^{-13}$ Tesla/$\mu$m. We discuss applications e.g. in determining a wide variation of ionic magnetic moments, for investigating the magnetic substructure of ions with a level structure not accessible for optical cooling and detection,and for studying exotic or rare ions, and molecular ions. The scheme may also be used for measureing spin imbalances of neutral atoms or atomic ensembles trapped by optical dipole forces. As the proposed method relies on techniques well established in ion trap quantum information processing it is within reach of current technology.Comment: 4 pages, 2 fi

Genomic and Phenotypic Characterization of Clostridium botulinum Isolates from an Infant Botulism Case Suggests Adaptation Signatures to the Gut

In early life, the immature human gut microbiota is prone to colonization by pathogens that are usually outcompeted by mature microbiota in the adult gut. Colonization and neurotoxin production by a vegetative Clostridium botulinum culture in the gut of an infant can lead to flaccid paralysis, resulting in a clinical outcome known as infant botulism, a potentially life-threatening condition. Beside host factors, little is known of the ecology, colonization, and adaptation of C. botulinum to the gut environment. In our previous report, an infant with intestinal botulism was shown to be colonized by neurotoxigenic C. botulinum culture for 7 months. In an effort to gain ecological and evolutionary insights into this unusually long gut colonization by C. botulinum, we analyzed and compared the genomes of C. botulinum isolates recovered from the infant feces during the course of intoxication and isolates from the infant household dust. A number of observed mutations and genomic alterations pinpointed at phenotypic traits that may have promoted colonization and adaptation to the gut environment and to the host. These traits include motility, quorum-sensing, sporulation, and carbohydrate metabolism. We provide novel perspectives and suggest a tentative model of the pathogenesis of C. botulinum in infant botulism. IMPORTANCE While the clinical aspects of infant botulism and the mode of action of BoNT have been thoroughly investigated, little is known on the pathogenesis and adaptive mechanisms of C. botulinum in the gut. Here, we provide for the first time a comprehensive view on the genomic dynamics and plasticity of C. botulinum over time in a case of infant botulism. The genomic and phenotypic analysis of C. botulinum isolates collected during the disease course offers an unprecedented view of C. botulinum ecology, evolution, and pathogenesis and may be instrumental in developing novel strategies for prevention and treatment of toxicoinfectious botulism. While the clinical aspects of infant botulism and the mode of action of BoNT have been thoroughly investigated, little is known on the pathogenesis and adaptive mechanisms of C. botulinum in the gut. Here, we provide for the first time a comprehensive view on the genomic dynamics and plasticity of C. botulinum over time in a case of infant botulism.Peer reviewe

Differentiation, Quantification and Identification of Abrin and Abrus precatorius Agglutinin

Abrin, the toxic lectin from the rosary pea plant Abrus precatorius, has gained considerable interest in the recent past due to its potential malevolent use. However, reliable and easy-to-use assays for the detection and discrimination of abrin from related plant proteins such as Abrus precatorius agglutinin or the homologous toxin ricin from Ricinus communis are sparse. To address this gap, a panel of highly specific monoclonal antibodies was generated against abrin and the related Abrus precatorius agglutinin. These antibodies were used to establish two sandwich ELISAs to preferentially detect abrin or A. precatorius agglutinin (limit of detection 22 pg/mL for abrin; 35 pg/mL for A. precatorius agglutinin). Furthermore, an abrin-specific lateral flow assay was developed for rapid on-site detection (limit of detection ~1 ng/mL abrin). Assays were validated for complex food, environmental and clinical matrices illustrating broad applicability in different threat scenarios. Additionally, the antibodies turned out to be suitable for immuno-enrichment strategies in combination with mass spectrometry-based approaches for unambiguous identification. Finally, we were able to demonstrate for the first time how the developed assays can be applied to detect, identify and quantify abrin from a clinical sample derived from an attempted suicide case involving A. precatorius.Peer Reviewe

Development of a Genus-Specific Antigen Capture ELISA for Orthopoxviruses – Target Selection and Optimized Screening

Orthopoxvirus species like cowpox, vaccinia and monkeypox virus cause zoonotic infections in humans worldwide. Infections often occur in rural areas lacking proper diagnostic infrastructure as exemplified by monkeypox, which is endemic in Western and Central Africa. While PCR detection requires demanding equipment and is restricted to genome detection, the evidence of virus particles can complement or replace PCR. Therefore, an easily distributable and manageable antigen capture enzyme-linked immunosorbent assay (ELISA) for the detection of orthopoxviruses was developed to facilitate particle detection. By comparing the virus particle binding properties of polyclonal antibodies developed against surface-exposed attachment or fusion proteins, the surface protein A27 was found to be a well-bound, highly immunogenic and exposed target for antibodies aiming at virus particle detection. Subsequently, eight monoclonal anti-A27 antibodies were generated and characterized by peptide epitope mapping and surface plasmon resonance measurements. All antibodies were found to bind with high affinity to two epitopes at the heparin binding site of A27, toward either the N- or C-terminal of the crucial KKEP-segment of A27. Two antibodies recognizing different epitopes were implemented in an antigen capture ELISA. Validation showed robust detection of virus particles from 11 different orthopoxvirus isolates pathogenic to humans, with the exception of MVA, which is apathogenic to humans. Most orthopoxviruses could be detected reliably for viral loads above 1 × 103 PFU/mL. To our knowledge, this is the first solely monoclonal and therefore reproducible antibody-based antigen capture ELISA able to detect all human pathogenic orthopoxviruses including monkeypox virus, except variola virus which was not included. Therefore, the newly developed antibody-based assay represents important progress towards feasible particle detection of this important genus of viruses

Construction and validation of safe Clostridium botulinum Group II surrogate strain producing inactive botulinum neurotoxin type E toxoid

Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.Peer reviewe

Origin of the large phonon band-gap in SrTiO3 and the vibrational signatures of ferroelectricity in ATiO3 perovskite: First principles lattice dynamics and inelastic neutron scattering of PbTiO3, BaTiO3 and SrTiO3

We report first principles density functional perturbation theory calculations and inelastic neutron scattering measurements of the phonon density of states, dispersion relations and electromechanical response of PbTiO3, BaTiO3 and SrTiO3. The phonon density-of-states of the quantum paraelectric SrTiO3 is found to be fundamentally distinct from that of ferroelectric PbTiO3 and BaTiO3 with a large 70-90 meV phonon band-gap. The phonon dispersion and electromechanical response of PbTiO3 reveal giant anisotropies. The interplay of covalent bonding and ferroelectricity, strongly modulates the electromechanical response and give rise to spectacular signatures in the phonon spectra. The computed charge densities have been used to study the bonding in these perovskites. Distinct bonding characteristics in the ferroelectric and paraelectric phases give rise to spectacular vibrational signatures. While a large phonon band-gap in ATiO3 perovskites seems a characteristic of quantum paraelectrics, anisotropy of the phonon spectra correlates well with ferroelectric strength. These correlations between the phonon spectra and ferroelectricity, can guide future efforts at custom designing still more effective piezoelectrics for applications. These results suggest that vibrational spectroscopy can help design novel materials.Comment: 11 pages, 4 color figures and 2 Table