Seconds-scale coherence in a tweezer-array optical clock

Optical clocks based on atoms and ions achieve exceptional precision and accuracy, with applications to relativistic geodesy, tests of relativity, and searches for dark matter. Achieving such performance requires balancing competing desirable features, including a high particle number, isolation of atoms from collisions, insensitivity to motional effects, and high duty-cycle operation. Here we demonstrate a new platform based on arrays of ultracold strontium atoms confined within optical tweezers that realizes a novel combination of these features by providing a scalable platform for isolated atoms that can be interrogated multiple times. With this tweezer-array clock, we achieve greater than 3 second coherence times and record duty cycles up to 96%, as well as stability commensurate with leading platforms. By using optical tweezer arrays --- a proven platform for the controlled creation of entanglement through microscopic control --- this work further promises a new path toward combining entanglement enhanced sensitivities with the most precise optical clock transitions

Local-flexural interactive buckling of standard and optimised cold-formed steel columns

This paper aims to study the interaction of local and overall flexural buckling in cold-formed steel (CFS) channels under axial compression. Detailed nonlinear FE models were developed and validated against a total of 36 axial compression tests on CFS plain and lipped channel columns with pin-ended boundary conditions. The numerical models incorporated the non-linear stress-strain behaviour of CFS material and enhanced properties of cold-worked corner regions obtained from coupon tests. The effects of initial geometric imperfections of the specimens measured by a specially designed set-up with laser displacement transducers were also taken into account. The developed FE models produced excellent predictions of the ultimate strength of the specimens obtained from experimental tests. The validated FE models and experimental results were then used to assess the adequacy of the effective width method in Eurocode 3 (EC3) and Direct Strength Method (DSM) in estimating the design capacity of a wide range of conventional and optimised design CFS channel column sections. The results indicate that Eurocode 3 provides conservative predictions (on average 21% deviation) for the compressive capacity of plain and lipped channel sections, while in general DSM predictions are more accurate for lipped channels. A comparison between FE predictions and tested results show that geometric imperfections can change the FE predictions by up to 20% and 40%, respectively, for lipped and plain channel columns, while the strain hardening effect at the rounded corner regions of the cross-sections is negligible. The results also confirmed that the proposed numerical model is able to provide a consistent and reliable prediction on the efficiency of a previously proposed optimisation methodology

Ultrafast Electron Microscopy Integrated with a Direct Electron Detection Camera

In the past decade, we have witnessed the rapid growth of the field of ultrafast electron microscopy (UEM), which provides intuitive means to watch atomic and molecular motions of matter. Yet, because of the limited current of the pulsed electron beam resulting from space-charge effects, observations have been mainly made to periodic motions of the crystalline structure of hundreds of nanometers or higher by stroboscopic imaging at high repetition rates. Here, we develop an advanced UEM with robust capabilities for circumventing the present limitations by integrating a direct electron detection camera for the first time which allows for imaging at low repetition rates. This approach is expected to promote UEM to a more powerful platform to visualize molecular and collective motions and dissect fundamental physical, chemical, and materials phenomena in space and time.ope

The Use of Omalizumab in Chronic Urticaria: Available Data and Future Aspects of Anti-IgE Treatment

Chronic urticaria (CU) defined as repeatedly occurred itchy wheals and/or angioedema for at least 6 weeks. Due to the unpredictability, recurrent and disabling symptoms, and a considerably impaired quality of life, effective and tolerable treatment for CU patients is crucial. Almost a half of patients with CU are refractory to H1-antihistamines, even though the dose of antihistamines is increased up to 4-fold. Recently treatment modulating IgE levels and activities provides an efficient therapeutic approach. Omalizumab, the only approved anti-IgE treatment for chronic spontaneous urticaria (CSU) patients until now, with a strong evidence of the efficacy and safety, opened a new horizon in the care of the patients whose urticaria is not controlled with antihistamines. Recent international guidelines recommend omalizumab as the first choice of treatment for antihistamine-refractory CSU. However, as it is not curative neither disease-modifying agent, there is a subpopulation of CSU patients responding partly or never to omalizumab. The other things to be solved in the treatment of CU is that clinical evidence is still limited on chronic inducible urticaria (CIndU) and special populations. Thus, a new anti-IgE treatment, ligelizumab is actively evaluated in the efficacy compared with both placebo and omalizumab. Further understandings on the pathogenesis of CU can lead to the development of new mechanism-based therapeutics for CU patients

Newly designed coil tube for bowel decompression in patients with small bowel obstructions

AbstractBackgroundThe purpose of this study was to clinically evaluate a coil tube that we recently designed for bowel decompression in patients with a small bowel obstruction.MethodsThe coil tube was composed of a stainless steel coil, a polyolefin tube, and a rubber adaptor. The tube was inserted under fluoroscopic guidance in 14 consecutive patients with small bowel obstructions. Technical success was defined as insertion of the distal end of the tube into at least the proximal jejunum, and clinical success was defined as intestinal decompression and relief of obstructive symptoms.ResultsThe technical success rate was 100%. Clinical success was achieved in 12 patients (86%). The clinical failures were a patient with peritoneal carcinomatosis and an ileocolic fistula, and a patient with bezoars following intestinal hemorrhage. No coil-related complications occurred.ConclusionOur newly designed coil tube was safe and effective in patients with bowel decompression associated with a small bowel obstruction. In addition, our tube has several advantages over other currently used tube types

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

The metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality-control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout the opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate Bag6, a unique metazoan factor. While TRC35 and its fungal homolog, guided entry of tail-anchored protein 4 (Get4), utilize a conserved hydrophobic patch to bind their respective partners, Bag6 wraps around TRC35 on the opposite face relative to the Get4–5 interface. We further demonstrate that TRC35 binding is critical not only for occluding the Bag6 nuclear localization sequence from karyopherin α to retain Bag6 in the cytosol but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol

Antigen-binding Characteristics of Circulating IgG Autoantibodies to Cytokeratin 18 Protein in Patients with Nonallergic Asthma

Cytokeratin 18 (CK18) protein was identified as an airway epithelial cell autoantigen associated with nonallergic asthma. Cleavage of CK18 protein by caspase-3 is a marker of early apoptosis in epithelial cells. It has been shown that the expression of active caspase-3 was increased in bronchial epithelial cells of asthmatic patients, when compared with healthy controls. To investigate the antigen-binding characteristics of IgG autoantibodies to CK18 protein in nonallergic asthma, the bindings of IgG autoantibodies to the fragments of CK18 protein cleaved by caspase-3 were analyzed by Western blot using serum samples from three patients with nonallergic asthma. Recombinant human CK18 protein was treated by caspase-3 and cleaved into N-terminal fragment (1-397 amino acids) and C-terminal fragment (398-430 amino acids). The binding capacity of IgG autoantibodies to N-terminal fragment of CK18 was maintained in one patient and reduced in other two patients. IgG autoantibodies from all three patients did not bind to C-terminal fragment of CK18. In conclusion, IgG autoantibodies to CK18 protein from patients with nonallergic asthma seems to preferentially bind to the whole molecule of CK18 protein and their antigen-binding characteristics were heterogeneous among the patients with nonallergic asthma