From statics of composites to acoustic metamaterials.

The Hashin-Shtrikman formalism for the static response of a composite is first summarized, in a form applicable to anisotropic media and arbitrary two-point correlations. Its extension to dynamic response is then explained and in particular the extra coupling, for stress with velocity as well as strain, and momentum density with strain as well as velocity that inevitably follows, is highlighted. The more recent dynamical formulations which incorporate extra flexibility through the use of a weighted mean displacement also receive mention. The article is concluded with an explicit analysis of a simple model random composite and some lessons are drawn from the solution, which exposes at least one clear gap in existing knowledge and requires further research. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

Post-exercise hypotension and skeletal muscle oxygenation is regulated by nitrate-reducing activity of oral bacteria.

Post-exercise hypotension (PEH) is a common physiological phenomenon leading to lower blood pressure after acute exercise, but it is not fully understood how this intriguing response occurs. This study investigated whether the nitrate-reducing activity of oral bacteria is a key mechanism to trigger PEH. Following a randomized, double blind and crossover design, twenty-three healthy individuals (15 males/8 females) completed two treadmill trials at moderate intensity. After exercise, participants rinsed their mouth with antibacterial mouthwash to inhibit the activity of oral bacteria or a placebo mouthwash. Blood pressure was measured before, 1h and 2 h after exercise. The microvascular response to a reactive hyperaemia test, as well as blood and salivary samples were taken before and 2 h after exercise to analyse nitrate and nitrite concentrations and the oral microbiome. As expected, systolic blood pressure (SBP) was lower (1 h: -5.2 ±â€¯1.0 mmHg; P < 0.001); 2 h: -3.8 ±â€¯1.1 mmHg, P = 0.005) after exercise compared to baseline in the placebo condition. This was accompanied by an increase of circulatory nitrite 2 h after exercise (2h: 100 ±â€¯13 nM) compared to baseline (59 ±â€¯9 nM; P = 0.013). Additionally, an increase in the peak of the tissue oxygenation index (TOI) during the reactive hyperaemia response was observed after exercise (86.1 ±â€¯0.6%) compared to baseline levels (84.8 ±â€¯0.5%; P = 0.010) in the placebo condition. On the other hand, the SBP-lowering effect of exercise was attenuated by 61% at 1 h in the recovery period, and it was fully attenuated 2 h after exercise with antibacterial mouthwash. This was associated with a lack of changes in circulatory nitrite (P > 0.05), and impaired microvascular response (peak TOI baseline: 85.1 ±â€¯3.1%; peak TOI post-exercise: 84.6 ±â€¯3.2%; P > 0.05). Diversity of oral bacteria did not change after exercise in any treatment. These findings show that nitrite synthesis by oral commensal bacteria is a key mechanism to induce the vascular response to exercise over the first period of recovery thereby promoting lower blood pressure and greater muscle oxygenation.

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users.

Location and length distribution of somatic hypermutation-associated DNA insertions and deletions reveals regions of antibody structural plasticity.

Following the initial diversity generated by V(D)J recombination, somatic hypermutation is the principal mechanism for producing further antibody repertoire diversity in antigen-experienced B cells. While somatic hypermutation typically results in single-nucleotide substitutions, the infrequent incorporation of genetic insertions and deletions has also been associated with the somatic hypermutation process. We used high-throughput antibody sequencing to determine the sequence of thousands of antibody genes containing somatic hypermutation-associated insertions and deletions (SHA indels), which revealed significant differences between the location of SHA indels and somatic mutations. Further, we identified a cluster of insertions and deletions in the antibody framework 3 region, which corresponds to the hypervariable region 4 (HV4) in T-cell receptors. We propose that this HV4-like region, identified by SHA indel analysis, represents a region of under-appreciated affinity maturation potential. Finally, through the analysis of both location and length distribution of SHA indels, we have determined regions of structural plasticity within the antibody protein.

High-throughput antibody sequencing reveals genetic evidence of global regulation of the naïve and memory repertoires that extends across individuals.

Vast diversity in the antibody repertoire is a key component of the adaptive immune response. This diversity is generated centrally through the assembly of variable, diversity and joining gene segments, and peripherally by somatic hypermutation and class-switch recombination. The peripheral diversification process is thought to only occur in response to antigenic stimulus, producing antigen-selected memory B cells. Surprisingly, analyses of the variable, diversity and joining gene segments have revealed that the naïve and memory subsets are composed of similar proportions of these elements. Lacking, however, is a more detailed study, analyzing the repertoires of naïve and memory subsets at the level of the complete V(D)J recombinant. This report presents a thorough examination of V(D)J recombinants in the human peripheral blood repertoire, revealing surprisingly large repertoire differences between circulating B-cell subsets and providing genetic evidence for global control of repertoire diversity in naïve and memory circulating B-cell subsets.

Repeated low-level formaldehyde exposure produces cross-sensitization to cocaine: possible relevance to chemical sensitivity in humans.

Sensitivity to chemicals in humans has been proposed to be an acquired disorder in which individuals become increasingly sensitive to chemicals in the environment. A possible link between the manifestation of psychiatric symptoms in individuals claiming sensitivity to chemicals was investigated based on a leading hypothesis put forth by Bell and co-workers (1992) to explain the amplification of symptoms after chemical exposure. The hypothesis is that chemical sensitivities may be akin to sensitization observed in rodents after repeated psychostimulants. Repeated exposure to psychostimulants enhances behavioral activity and the underlying neurochemical responses in specific limbic pathways; a similar sensitization of limbic pathways has been proposed to occur in individuals who become sensitive to chemicals. To test this hypothesis, female Sprague-Dawley rats were exposed to either air or formaldehyde (Form) for 1 h/day for 7 days or 20 days (5 days/week x 4 weeks). Two to 4 days after the last exposure, rats were given a cocaine challenge (= early withdrawal) followed by an additional cocaine challenge 4-6 weeks later (= late withdrawal). No differences in cocaine-induced locomotor activity were noted between groups after 7 days of exposure. However, after 20 days of exposure to Form, vertical activity was significantly elevated at both early and late withdrawal times. These studies demonstrate that behavioral sensitization occurs after long-term, but not short-term, low-level exposure to Form, and lends support to the limbic system sensitization hypothesis of sensitivity to chemicals in humans.

Enteroscopy-enteroclysis: experience with a combined endoscopic-radiographic technique.

BACKGROUND: Video enteroscopy provides high-quality diagnostic and therapeutic capabilities in the proximal small bowel. Enteroclysis remains an essential diagnostic technique in the distal small bowel. We report our experience with the combination of these techniques. METHODS: Seventy-one patients with obscure gastrointestinal bleeding (group A, 54 patients) or abnormal radiologic studies (group B, 17 patients) were evaluated with enteroscopy. Enteroclysis via a tube inserted on withdrawal of the enteroscope was performed in all patients with nondiagnostic enteroscopy. RESULTS: Enteroscopy identified bleeding sites in 29 of 54 (54%) group A patients (12 angiodysplasia, 10 ulcers, 7 gastric erosions, 1 vessel, 1 aortoenteric fistula), and lesions in 11 of 17 (65%) group B patients (7 ulcers, 3 benign strictures, 2 radiation enteritis, 1 mass). In group A, 13 (24%) patients had findings detectable by standard esophagogastroduodenoscopy. Enteroclysis identified masses in 2 of 24 (8%) group A patients, and lesions in 5 of 10 (50%) group B patients (3 strictures, 1 mass, 1 large diverticulum). No complications occurred. CONCLUSIONS: The combination of enteroscopy and enteroclysis is safe and offers quality small bowel examinations in more comfortable and convenient single diagnostic sittings. This combination detected bleeding sources in 57% and lesions in 70% of patients. Though enteroclysis identified bleeding sources in only 8% of patients, this study excluded lesions other than angiodysplasia.

Enteroscopy with enteroclysis.

The authors conclude that their experiences support the conclusion that the combination of enteroscopy and enterocysis is safe and offers quality small bowel examinations in a more comfortable and convenient single diagnostic setting. Although enteroclysis has identified bleeding sources in only 8% of patients who underwent this study, other lesions than angiodysplasia were confidently excluded in the remainder of patients. The combined procedure is well tolerated in the outpatient setting, more comfortable, and safer by decreasing radiation exposures than enteroclysis alone. Use of small bowel enteroscopy at an earlier stage in the evaluation of patients with obscure gastrointestinal bleeding increases cost effectiveness without compromising quality.

Proposed animal neurosensitization model for multiple chemical sensitivity in studies with formalin.

A potentially promising line of animal research relevant to multiple chemical sensitivity (MCS) is that of sensitization in the central nervous system (CNS), particularly limbic pathways in the brain. Sensitization is the progressive and enduring enhancement in behavioral and neurochemical responses that occurs after repeated exposure to psychostimulants or environmental stressors. Since the onset and progression of sensitization has many parallels with that of MCS, it has been proposed that MCS may be initiated through a mechanism similar to the sensitization of CNS components occurring in the rodent. To test this hypothesis, female Sprague-Dawley rats were exposed to formalin vapors (FORM, 11 ppm) or water vapor (control) 1 h/day for 7 days. The next day, a saline injection was given followed by a cocaine injection (15 mg/kg, i.p.) 24 h later, and locomotor activity was monitored. Animals pretreated with repeated FORM inhalation demonstrated a significantly enhanced locomotor response to cocaine compared to controls, an indicator that specific limbic pathways may have been sensitized. At 4 weeks of withdrawal from FORM exposure, a subset of animals remained sensitized to a cocaine challenge. No differences were found between groups after a saline injection. In a second experiment, animals were screened prior to FORM or water exposure for their response to a novel situation, a measure believed to reflect an animal's general responsiveness to stimuli. Rats were divided into high responders (HR) or low responders (LR), based on their locomotion in a novel cage. Results from three behavioral tests demonstrated that HR and LR were differentially affected by exposure to FORM. In a passive avoidance test, HR and LR appeared to be different in their distribution of responses, while HR and LR responses in the FORM group were nearly identical. On the elevated plus maze test of anxiety, HR spent more time on the open arms than LR in both treatment groups, with significant differences between HR and LR in the FORM, but not water, treated group. On a hot plate test to measure nociceptive levels, no differences occurred between HR and LR in the control group, whereas nociception of LR tended toward an increase compared to HR in the FORM-exposed group. Results from the second experiment suggest that the effects of FORM exposure may be obscured by examining behavior in a heterogeneous population (HR and LR). This approach using animal models may help define neural substrates that mediate the amplification of responses of a subpopulation of individuals to chemicals in the environment.