Host and pathogen genetic diversity shape vaccine-mediated protection to .

To investigate how host and pathogen diversity govern immunity against (Mtb), we performed a large-scale screen of vaccine-mediated protection against aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] and three Mtb strains (H37Rv, CDC1551, SA161) representing two lineages and distinct virulence properties. We compared three protective modalities, all of which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, and concomitant Mtb infection (CoMtb), a model of pre-existing immunity in which a low-level Mtb infection is established in the cervical lymph node following intradermal inoculation. We examined lung bacterial burdens at early (Day 28) and late (Day 98) time points after aerosol Mtb challenge and histopathology at Day 98.

Development, synthesis and evaluation of novel fluorescent Endothelin-B receptor probes.

The endothelin (ET) signaling system is comprised of three endothelin peptides (ET-1, -2 and -3) and two corresponding endothelin-A and -B receptors (ETR and ETR), which belong to the G-protein coupled receptor (GPCR) superfamily. The endothelin axis, as this system is also referred to, contributes to the maintenance of vascular tone, functions as regulator of inflammation and proliferation and helps in balancing water homeostasis. In pathological settings, the ET axis is known to contribute to endothelial activation in cardiovascular diseases, to cell proliferation, chemoresistance and metastasis in cancer and to inflammation and fibrosis in renal disease.

Electron glass signatures up to room temperature in disordered insulators.

This paper describes the observation of non-equilibrium field effects at room temperature in four disordered insulating systems: granular Al, discontinuous Au, amorphous NbSi and amorphous indium oxide thin films. The use of wide enough gate voltage ranges and a cautious analysis of the data allow us to uncover memory dips (MDs), the advocated hallmark of the electron glass, in the four systems. These MDs are found to relax slowly over days of measurements under gate voltage changes, reflecting the impossibility for the systems to reach an equilibrium state within experimentally accessible times.

Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis.

Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum.

Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.

Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although the M72/ASOE1 trial yielded encouraging results (54% efficacy in subjects with prior exposure to Mtb), a highly effective vaccine against adult tuberculosis remains elusive. We show that in a mouse model, establishment of a contained and persistent yet non-pathogenic infection with Mtb ("contained Mtb infection", CMTB) rapidly and durably reduces tuberculosis disease burden after re-exposure through aerosol challenge.

Cutting Edge: Bacillus Calmette-Guérin-Induced T Cells Shape Infection before Reducing the Bacterial Burden.

Growing evidence suggests the outcome of infection is established rapidly after exposure, but how the current tuberculosis vaccine, bacillus Calmette-Guérin (BCG), impacts early immunity is poorly understood. In this study, we found that murine BCG immunization promotes a dramatic shift in infected cell types. Although alveolar macrophages are the major infected cell for the first 2 weeks in unimmunized animals, BCG promotes the accelerated recruitment and infection of lung-infiltrating phagocytes.

Doppler ultrasonography devices, including elastography, allow for accurate diagnosis of severe liver fibrosis.

Objectives: Advanced chronic liver disease is frequent yet largely underdiagnosed. Doppler-US is a common examination and we recently identified three simple Doppler-US signs associated with severe liver fibrosis. Recent Doppler-US devices include elastography modules, allowing for liver stiffness measurement (LSM).

Alveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination.

Mycobacterium tuberculosis (Mtb) infection is initiated in the distal airways, but the bacteria ultimately disseminate to the lung interstitium. Although various cell types, including alveolar macrophages (AM), neutrophils, and permissive monocytes, are known to be infected with Mtb, the initially infected cells as well as those that mediate dissemination from the alveoli to the lung interstitium are unknown. In this study, using a murine infection model, we reveal that early, productive Mtb infection occurs almost exclusively within airway-resident AM.

Evidence for thermal activation in the glassy dynamics of insulating granular aluminum conductance.

Insulating granular aluminum is one of the proto-typical disordered insulators whose low temperature electrical conductance exhibits ubiquitous non-equilibrium phenomena. These include slow responses to temperature or gate voltage changes, characteristic field effect anomalies and ageing phenomena typical of a glass. In this system the influence of temperature on the glassy dynamics has remained elusive.

Generalized Benford's Law as a Lie Detector.

The first significant (leftmost nonzero) digit of seemingly random numbers often appears to conform to a logarithmic distribution, with more 1s than 2s, more 2s than 3s, and so forth, a phenomenon known as . When humans try to produce random numbers, they often fail to conform to this distribution. This feature grounds the so-called , aiming at detecting fabricated data.

Human behavioral complexity peaks at age 25.

Random Item Generation tasks (RIG) are commonly used to assess high cognitive abilities such as inhibition or sustained attention. They also draw upon our approximate sense of complexity. A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks, but little is as yet known about the developmental curve of cognitive complexity over the lifespan.

Publisher's Note: Glassy Dynamics in Disordered Electronic Systems Reveal Striking Thermal Memory Effects [Phys. Rev. Lett. 117, 116601 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.

Glassy Dynamics in Disordered Electronic Systems Reveal Striking Thermal Memory Effects.

Memory is one of the unique qualities of a glassy system. The relaxation of a glass to equilibrium contains information on the sample's excitation history, an effect often refer to as "aging." We demonstrate that under the right conditions a glass can also possess a different type of memory.

High-field plasma acceleration in a high-ionization-potential gas.

Plasma accelerators driven by particle beams are a very promising future accelerator technology as they can sustain high accelerating fields over long distances with high energy efficiency. They rely on the excitation of a plasma wave in the wake of a drive beam. To generate the plasma, a neutral gas can be field-ionized by the head of the drive beam, in which case the distance of acceleration and energy gain can be strongly limited by head erosion.

Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator.

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces.

Health Care Transition Services for Youth With Autism Spectrum Disorders: Perspectives of Caregivers.

Background And Objective: This paper seeks to describe the experience of youth with autism spectrum disorder (ASD) in making the health care transition (HCT) to adult care.

Methods: We surveyed 183 parents and guardians of youth with ASD, assessing the extent to which youth and families experienced and desired HCT services, their satisfaction with services, and obstacles to transition. Descriptive statistics were used to examine HCT measures and Fisher's exact and t tests assessed whether demographic or health measures were associated with service receipt.

Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield.

Electrical breakdown sets a limit on the kinetic energy that particles in a conventional radio-frequency accelerator can reach. New accelerator concepts must be developed to achieve higher energies and to make future particle colliders more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one such concept, in which the electric field of a plasma wake excited by a bunch of charged particles (such as electrons) is used to accelerate a trailing bunch of particles.

Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders.

Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These enzymes convert sphingolipid and lysolipid substrates to cyclic phosphates by activating a hydroxyl nucleophile present in both classes of lipid. The most medically relevant substrates are thought to be sphingomyelin and/or lysophosphatidylcholine.

Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD).

We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this care. Qualitative data were gathered by phone using a structured interview guide and analyzed using the framework approach.

Health-Related Quality of Life of Adolescent and Young Adult Survivors of Central Nervous System Tumors: Identifying Domains From a Survivor Perspective.

This article uses qualitative methods to describe the domains of health-related quality of life (HRQoL) that adolescent and young adult (AYA) survivors of central nervous system (CNS) tumors identify as important. Survivors clearly attributed aspects of their current HRQoL to their disease or its treatment. We identified 7 key domains of AYA CNS tumor survivorship: physical health, social well-being, mental health, cognitive functioning, health behaviors, sexual and reproductive health, and support systems.

High-efficiency acceleration of an electron beam in a plasma wakefield accelerator.

High-efficiency acceleration of charged particle beams at high gradients of energy gain per unit length is necessary to achieve an affordable and compact high-energy collider. The plasma wakefield accelerator is one concept being developed for this purpose. In plasma wakefield acceleration, a charge-density wake with high accelerating fields is driven by the passage of an ultra-relativistic bunch of charged particles (the drive bunch) through a plasma.

Quality of life outcomes in proton and photon treated pediatric brain tumor survivors.

Background: Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors.

Methods: HRQoL data were prospectively collected on PRT-treated patients aged 2-18 treated at Massachusetts General Hospital (MGH).

Calculating Kolmogorov complexity from the output frequency distributions of small Turing machines.

Drawing on various notions from theoretical computer science, we present a novel numerical approach, motivated by the notion of algorithmic probability, to the problem of approximating the Kolmogorov-Chaitin complexity of short strings. The method is an alternative to the traditional lossless compression algorithms, which it may complement, the two being serviceable for different string lengths. We provide a thorough analysis for all Σ(n=1)(11) 2(n) binary strings of length n<12 and for most strings of length 12≤n≤16 by running all ~2.

Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1.

As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome-lysosome fusion and the consumption of AP-3-containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type-specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor.

Pediatric provider's perspectives on the transition to adult health care for youth with autism spectrum disorder: current strategies and promising new directions.

Few youth with autism spectrum disorder (ASD) nationally report receiving services to help them transition from the pediatric health care system to the adult health care system. For example, only one-fifth (21.1%) of youth with ASD receive any transition planning services.