Trapping and cooling of rf-dressed atoms in a quadrupole magnetic field

6 pages, 6 figures; to appear in J. Phys. BInternational audienceWe observe the spontaneous evaporation of atoms confined in a bubble-like rf-dressed trap (Zobay and Garraway, 2001). The atoms are confined in a quadrupole magnetic trap and are dressed by a linearly polarized rf field. The evaporation is related to the presence of holes in the trap, at the positions where the rf coupling vanishes, due to its vectorial character. The final temperature results from a competition between residual heating and evaporation efficiency, which is controlled via the height of the holes with respect to the bottom of the trap. The experimental data are modeled by a Monte-Carlo simulation predicting a small increase in phase space density limited by the heating rate. This increase was within the phase space density determination uncertainty of the experiment

Source laser intense pour le refroidissement du 87Rb par doublement de fréquence d'un laser fibré télécom

to appear in EPJ-ST; COLOQ11 ProceedingsWe built a frequency-doubled laser for 87Rb laser cooling, from a Telecom fiber laser. Thanks to intense technological development, telecom fiber lasers exhibit outstanding properties regarding relative intensity noise and modulation bandwidth. The enhanced doubling efficiency of periodically poled crystals allowed to obtain up to 1.8 W at 780 nm from 10 W at 1560 nm, with a simple pass configuration in a 50-mm long crystal of ppLN:MgO. This technique can also be applied at the wavelength of potassium (767 nm) (Bourdel, 2009) and could be of great interest for the realization of dipole traps

Structural basis of IL-23 antagonism by an Alphabody protein scaffold

Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies

Influence of the Radio-Frequency source properties on RF-based atom traps

We discuss the quality required for the RF source used to trap neutral atoms in RF-dressed potentials. We illustrate this discussion with experimental results obtained on a Bose-Einstein condensation experiment with different RF sources.Comment: 5 figures, 7 page

Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting

The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating protein antagonist against induced myeloid leukemia cell differentiation protein MCL-1, an intracellular target in cancer, by grafting the critical B-cell lymphoma 2 homology 3 helix of MCL-1 onto the Alphabody and tagging the scaffold’s termini with designed cell-penetration polypeptides. Introduction of an albumin-binding moiety extended the serum half-life of the engineered Alphabody to therapeutically relevant levels, and administration thereof in mouse tumor xenografts based on myeloma cell lines reduced tumor burden. Crystal structures of such a designed Alphabody in complex with MCL-1 and serum albumin provided the structural blueprint of the applied design principles. Collectively, we provide proof of concept for the use of Alphabodies against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics

A BEAT-PCD consensus statement:a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

BACKGROUND: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD).METHODS: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts.RESULTS: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS.CONCLUSION: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.</p

Lack of Correlation of Sinonasal and Otologic Reported Symptoms With Objective Measurements Among Patients With Primary Ciliary Dyskinesia: An International Study.

peer reviewedSinonasal and otologic symptoms are common among patients with primary ciliary dyskinesia (PCD) of all ages. We used baseline data from the ENT Prospective International Cohort of PCD patients (EPIC-PCD), the first PCD cohort focused on ENT disease manifestations. We assessed agreement between patient- or parent-reported symptoms and relevant examination findings, and calculated unweighted Cohen’s kappa to adjust for agreement by chance. We included 404 participants, from 12 centres. We found no correlation between patient-reported sinonasal symptoms and relevant clinical examination findings. Otologic symptoms correlated poorly or weakly with otoscopy and audiometry findings, with age and centre identified as determinants of agreement

Development and Notch Signaling Requirements of the Zebrafish Choroid Plexus

The choroid plexus (CP) is an epithelial and vascular structure in the ventricular system of the brain that is a critical part of the blood-brain barrier. The CP has two primary functions, 1) to produce and regulate components of the cerebral spinal fluid, and 2) to inhibit entry into the brain of exogenous substances. Despite its importance in neurobiology, little is known about how this structure forms.Here we show that the transposon-mediated enhancer trap zebrafish line Et(Mn16) expresses green fluorescent protein within a population of cells that migrate toward the midline and coalesce to form the definitive CP. We further demonstrate the development of the integral vascular network of the definitive CP. Utilizing pharmacologic pan-notch inhibition and specific morpholino-mediated knockdown, we demonstrate a requirement for Notch signaling in choroid plexus development. We identify three Notch signaling pathway members as mediating this effect, notch1b, deltaA, and deltaD.This work is the first to identify the zebrafish choroid plexus and to characterize its epithelial and vasculature integration. This study, in the context of other comparative anatomical studies, strongly indicates a conserved mechanism for development of the CP. Finally, we characterize a requirement for Notch signaling in the developing CP. This establishes the zebrafish CP as an important new system for the determination of key signaling pathways in the formation of this essential component of the vertebrate brain

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients