Use of Z-pinch radiation sources for high-pressure shock wave studies

The authors are developing a new shock wave diagnostic using Z pinch sources for high-pressure equation of state (EOS) measurements. Specifically, they are employing VISAR interferometry to measure the particle velocity of shocked materials and fiber optic probes to measure the shock speed. Combination of these measurements will allow absolute EOS data with Z accelerators. This report is a progress report on the development of this new approach to EOS measurements; however, preliminary data obtained with the diagnostics are encouraging. With further development of Z pinch sources, it is envisioned that a variety of EOS and constitutive property measurements can be made. Time-resolved wave profile measurements will then provide a variety of EOS and material property data, such as isentropic EOS, initial compressive strength and shock-induced compressive strength, dynamic tensile strength, kinetics of phase transitions, and surface stability studies

Strawberry fruit resistance to simulated handling

Harvest operations are currently the main source of mechanical injury of strawberry (Fragaria x ananassa Duch.). Experiments were designed to simulate conditions encountered during commercial handling. Individual fruits were subjected to impact or compression forces with similar energy to determine the sensitivity to mechanical injury. Bruise volume was used as the measurement of injury. Bruise severity increased as a function of impact energy for both impact types. However, dropped fruits had larger bruise volume than fruits submitted to pendulum impactor at the same energy level. Doubling the impact energy (0.040 to 0.083 J) increased bruise volume by 7 times (13 to 91 mm³). Fruits dropped from 380 mm (0.075 J) showed 71% greater bruise volume than those dropped from either 130 mm (0.025 J) or 200 mm (0.040 J). Compressed fruits showed higher bruise volume than other tests. Some cultivars are more susceptible to compression forces than others. 'Sweet Charlie' berries showed bruise volume 40% higher than the others cultivars when subjected to compression. Fruits subjected to impact showed bruise volume lower than the compressed fruits, indicating the possibility to be handled and graded in a packing line.A etapa de colheita é a principal fonte de danos físicos ao morango (Fragaria x ananassa Duch.). Experimentos foram realizados para simular condições encontradas durante manuseio. Frutos foram submetidos individualmente às forças de impacto e compressão em energias similares para determinar sensibilidade dos frutos a danos físicos. Volume da injúria física foi utilizado para mensurar a incidência do dano físico ocorrido. Severidade da lesão aumenta, com incremento da energia, tanto para força de impacto como para compressão. Todavia, frutos submetidos à queda livre demonstraram maiores volumes de danos físicos do que frutos submetidos a danos ocasionados por pendulo no mesmo nível de energia. Dobrando a energia de impacto (0,040 para 0,083 J) ocorreu aumento no volume da injúria em sete vezes (13 para 91 mm³). Frutos submetidos à queda de 380 mm (0,075 J) demonstraram volumes de danos físicos 71% superiores do que aqueles ocasionados em queda de 130 mm (0,025 J) ou 200 mm (0,040 J). Frutos em teste de compressão mostraram maiores volumes de injúrias físicas do que outros testes. Alguns cultivares são mais sensíveis à força de compressão do que outros. Frutos cultivar 'Sweet Charlie' apresentaram volume de injúria 40% superiores do que outros quando submetidos à força de compressão. Morangos submetidos à força de impacto demonstraram volume de injúria inferior do que aqueles comprimidos, indicando a possibilidade dos morangos serem classificados e manuseados em uma linha de beneficiamento

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Factors associated with pain induced by orthodontic separators.

Pain resulting from the application of orthodontic forces varies markedly across individuals. The reasons of this variability are still largely unknown. To investigate factors that may be associated with orthodontic pain following the application of orthodontic separators. One hundred and seven participants were screened for pain response over 48 h following placement of orthodontic elastomeric separators. The highest (n = 10) and lowest (n = 10) pain responders were identified, and data collected on tooth pain sensitivity to electrical stimulation in conjunction with using the Pain Catastrophising Scale (PCS), Dental Anxiety Scale (DAS) and cold pressor test (CPT). There were statistically significant differences between high- and low-pain responders in catastrophising score (P ≤ 0·023). For every PCS magnification score of 1 unit higher, the relative risk of being a high-pain responder was 1·6 (P = 0·002); those scoring higher on helplessness had a lower risk of being so. DAS scores of high-pain responders were twice as high as those of low-pain responder (P = 0·043). During the first 2 min of CPT, the high-pain responders experienced more pain than the low-pain responders (P ≤ 0·029). Tooth pain thresholds did not differ between the two different pain responder groups. Pain catastrophising, dental anxiety and cold sensitivity appear to modify the pain experienced following placement of orthodontic separators. Further research is needed to determine the validity of screening questions to identify at-risk patients prior to commencing orthodontic treatment

The "Z" Pulsed Radiation Source: Recent Developments in Equation of State Measurement Capabilities

The Sandia Z machine is a source of intense radiation which can be used to drive ablative shocks for equation of state studies. In developing the capability to diagnose these types of studies on Z, techniques commonly used in conventional impact generated experiments were leveraged. The primary diagnostic transferred was velocity interferome~, VLSAR, [1] which not only provides Hugoniot particle velocity measurements, but also indications of shock stability and wave attenuation. In addition to a VISAR capability on the Z machine, methods for measuring shock velocity have been developed. When these measured parameters are used in conjunction with the Rankine-Hugoniot jump conditions, [2] material response at high temperatures and pressures can be inferred. With sample sizes used on Z being much smaller than those fielded in typical impact experiments, temporal resolution and methods of interfacing the diagnostics with the targets had to be improved. In this paper, a "standard" equation of state experiment, associated diagnostics, and some recent results in aluminum and beryllium will be discussed