Primary ciliary dyskinesia: a big data genomics approach

How can the real-life frequency of a complicated condition that occurs irregularly, with a clinically variable presentation that is often difficult to diagnose, be calculated? This is a challenge for understanding the societal and medical impacts of an estimated 7000 rare disorders (those affecting more than one in 2000 people each) that can be poorly understood and often missed, especially if lacking clear-cut indicatory tests. The collective rare disease burden affects over one in 20 people, involving a disparate range of health-care services and creating unmet medical needs with potential for incorrect management. Better diagnostics and disease prevalence estimates are key to improving inequalities for millions of affected families worldwide

Sequential weak measurement

The notion of weak measurement provides a formalism for extracting information from a quantum system in the limit of vanishing disturbance to its state. Here we extend this formalism to the measurement of sequences of observables. When these observables do not commute, we may obtain information about joint properties of a quantum system that would be forbidden in the usual strong measurement scenario. As an application, we provide a physically compelling characterisation of the notion of counterfactual quantum computation

Examination of smears for tubercle bacilli by Fluorescence Microscopy

IN underdeveloped countries, laboratory facilities for the bacteriological diagnosis of tuberculosis are at present, very limited. Cultural methods are unlikely to be used on a large scale for many years to come. It is, therefore, important to investigate the most economical method of examining smears for tubercle bacilli. Fluorescence microscopy was introduced by Hagemann (1937) and has since been described by many authors, including Tanner (1941, 1948), Lind and Shaughnessy (1941), Lempert (1944), Norman and Jelks (1945), Clegg and Foster-Carter (1946), Wilson (1952), Von Haebler and Murray (1954), and Needham (1957). The great advantage claimed for this method is that stained bacilli can be detected using a much lower magnification than with the usual Ziehl-Neelsen method. Considerable time is saved in examining smears and larger areas can be searched. The method has not been widely employed for two reasons. In the first place, the light source must be very bright and many of the optical systems described previously have only supplied sufficient light if the equipment was used in a darkened room. Secondly, some workers (Ritterhoff and Bowman, 1945; Kuster, 1939; Holm and Plum, 1943) consider that false positive results can be obtained, since some smears may contain small naturally fluorescent particles which can be confused with bacilli. Equipment for fluorescence microscopy that can be used in normal daylight has been in use at the Tuberculosis Chemotherapy Centre, Madras, for over two years. When it was first introduced, a comparison between this method and the conventional Ziehl-Neelsen method was undertaken to test their relative sensitivities, and to see whether fluorescence microscopy yielded false positive results. The results of this comparison are described

Transport enhancement from incoherent coupling between one-dimensional quantum conductors

We study the non-equilibrium transport properties of a highly anisotropic two-dimensional lattice of spin-1/2 particles governed by a Heisenberg XXZ Hamiltonian. The anisotropy of the lattice allows us to approximate the system at finite temperature as an array of incoherently coupled one-dimensional chains. We show that in the regime of strong intrachain interactions, the weak interchain coupling considerably boosts spin transport in the driven system. Interestingly, we show that this enhancement increases with the length of the chains, which is related to superdiffusive spin transport. We describe the mechanism behind this effect, compare it to a similar phenomenon in single chains induced by dephasing, and explain why the former is much stronger

The Susceptibility to Hydrogen Peroxide of Indian and British Isoniazid-Sensitive and Isoniazid- Resistant Tubercle Bacilli

The present work describes an attempt to modify the method of Kreis and Le Joubioux (1957a) so that it would accurately estimate the relative proportions of catalase-positive and catalase-negative organisms in strains containing mixtures of the two types. A bactericidal test was chosen in preference to a bacteriostatic test, since it is difficult to obtain quantitative measurement with the latter technique. In performing a bactericidal test residual peroxide must be inactivated or removed by dilution so that it does not inhibit the growth of surviving organisms. Knox, Meadow and Worssam (1956) removed peroxide by centrifugation and washing, but this method was considered impracticable if this test were to be used on a large scale, and likely to produce inaccurate counts on the surviving organisms. In the present work the method of removal of peroxide was studied as well as the determination of the optimal peroxide concentration and period of exposure which would kill all catalase-negative organisms, but would leave catalase-positive organisms unaffected. In addition, the method of Kreis & Le Joubioux (1957a) was modified by reducing the inoculum of organisms exposed to peroxide so that catalase-positive bacilli would not be able to destroy peroxide during the test itself. The standardised bactericidal test was then employed in comparing the susceptibility to peroxide of isoniazid-sensitive strains from British and Indian patients, and in investigating the relationship between the peroxide susceptibility and the catalase activity of their isoniazid-resistant mutant strains

Nondestructive selective probing of phononic excitations in a cold Bose gas using impurities

We introduce a detector that selectively probes the phononic excitations of a cold Bose gas. The detector is composed of a single impurity atom confined by a double-well potential, where the two lowest eigenstates of the impurity form an effective probe qubit that is coupled to the phonons via density-density interactions with the bosons. The system is analogous to a two-level atom coupled to photons of the radiation field. We demonstrate that tracking the evolution of the qubit populations allows probing both thermal and coherent excitations in targeted phonon modes. The targeted modes are selected in both energy and momentum by adjusting the impurity's potential. We show how to use the detector to observe coherent density waves and to measure temperatures of the Bose gas down to the nano-Kelvin regime. We analyze how our scheme could be realized experimentally, including the possibility of using an array of multiple impurities to achieve greater precision from a single experimental run.Comment: 11+4 pages, 7 figure

Altered Cerebellar Short-Term Plasticity but No Change in Postsynaptic AMPA-Type Glutamate Receptors in a Mouse Model of Juvenile Batten Disease

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knockout mice. In Cln3Δex1–6 cells the amplitude of AMPA-evoked whole-cell currents was unchanged. Similarly, we found no change in the amplitude, kinetics, or rectification of synaptic currents evoked by individual quanta, or in their underlying single-channel conductance. We found no change in cerebellar expression of GluA2 or GluA4 protein. By contrast, we observed a reduced number of quantal events following mossy-fiber stimulation in Sr2+, altered short-term plasticity in conditions of reduced extracellular Ca2+, and reduced mossy fiber vesicle number. Thus, while our results suggest early presynaptic changes in the Cln3Δex1–6 mouse model of juvenile Batten disease, they reveal no evidence for altered postsynaptic AMPARs