Measurement of Dark Ice-Ablator Mix in Inertial Confinement Fusion.

We present measurements of ice-ablator mix at stagnation of inertially confined, cryogenically layered capsule implosions. An ice layer thickness scan with layers significantly thinner than used in ignition experiments enables us to investigate mix near the inner ablator interface. Our experiments reveal for the first time that the majority of atomically mixed ablator material is "dark" mix. It is seeded by the ice-ablator interface instability and located in the relatively cooler, denser region of the fuel assembly surrounding the fusion hot spot. The amount of dark mix is an important quantity as it is thought to affect both fusion fuel compression and burn propagation when it turns into hot mix as the burn wave propagates through the initially colder fuel region surrounding an igniting hot spot. We demonstrate a significant reduction in ice-ablator mix in the hot-spot boundary region when we increase the initial ice layer thickness.

Record Energetics for an Inertial Fusion Implosion at NIF.

Inertial confinement fusion seeks to create burning plasma conditions in a spherical capsule implosion, which requires efficiently absorbing the driver energy in the capsule, transferring that energy into kinetic energy of the imploding DT fuel and then into internal energy of the fuel at stagnation. We report new implosions conducted on the National Ignition Facility (NIF) with several improvements on recent work [Phys. Rev. Lett. 120, 245003 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.245003; Phys. Rev. E 102, 023210 (2020)PRESCM2470-004510.1103/PhysRevE.102.023210]: larger capsules, thicker fuel layers to mitigate fuel-ablator mix, and new symmetry control via cross-beam energy transfer; at modest velocities, these experiments achieve record values for the implosion energetics figures of merit as well as fusion yield for a NIF experiment.

Evidence of Three-Dimensional Asymmetries Seeded by High-Density Carbon-Ablator Nonuniformity in Experiments at the National Ignition Facility.

Inertial confinement fusion implosions must achieve high in-flight shell velocity, sufficient energy coupling between the hot spot and imploding shell, and high areal density (ρR=∫ρdr) at stagnation. Asymmetries in ρR degrade the coupling of shell kinetic energy to the hot spot and reduce the confinement of that energy. We present the first evidence that nonuniformity in the ablator shell thickness (∼0.5% of the total thickness) in high-density carbon experiments is a significant cause for observed 3D ρR asymmetries at the National Ignition Facility. These shell-thickness nonuniformities have significantly impacted some recent experiments leading to ρR asymmetries on the order of ∼25% of the average ρR and hot spot velocities of ∼100 km/s. This work reveals the origin of a significant implosion performance degradation in ignition experiments and places stringent new requirements on capsule thickness metrology and symmetry.

Fusion Energy Output Greater than the Kinetic Energy of an Imploding Shell at the National Ignition Facility.

A series of cryogenic, layered deuterium-tritium (DT) implosions have produced, for the first time, fusion energy output twice the peak kinetic energy of the imploding shell. These experiments at the National Ignition Facility utilized high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums, resulting in a peak hohlraum radiative temperature ∼290 eV. The imploding shell, composed of the nonablated high density carbon and the DT cryogenic layer, is, thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic energy of ∼21 kJ, which once stagnated produced a total DT neutron yield of 1.9×10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ. Time dependent low mode asymmetries that limited further progress of implosions have now been controlled, leading to an increased compression of the hot spot. It resulted in hot spot areal density (ρr∼0.3 g/cm^{2}) and stagnation pressure (∼360 Gbar) never before achieved in a laboratory experiment.

Point Prevalence of Adult Intestinal Failure in Republic Of Ireland.

Parenteral Nutrition (PN) is a life-saving treatment used for patients with Intestinal Failure (IF). PN is complex and demands highly specialised care to avoid serious complications in the home setting. All tertiary centres in the Republic of Ireland (ROI) were contacted to assess the prevalence of IF requiring PN and complications, over a one year period. Sixty-seven patients were treated across 15 centres: a period prevalence of 14.6 and 9.6 patients per million for long-term PN and home PN respectively. Three-quarters of patients experienced at least one major complication with 18% mortality rate over the study period. There were 2.86 admissions per HPN patient, each lasting mean 13.4 days. One-third experienced catheter-related infections. There was a reduced length of stay during emergency re-admissions in high volume centres (mean 31 v 43 days, p=0.17). The establishment of a National Centre for IF/HPN in ROI is integral to reducing PN-associated complications.

Potential of Earlier Detection and Treatment of Disease-Related Malnutrition with Oral Nutrition Supplements to Release Acute Care Bed Capacity.

A recent systematic review and meta-analysis shows that appropriate use of oral nutrition supplements (ONS) in community patients is associated with a significant reduction in hospitalisations. Given higher use of acute care resource by malnourished versus normally nourished patients, this paper examines the potential to reduce bed utilisation by applying these results to Irish inpatient and malnutrition prevalence data. In 2013, adults admitted to hospital with medium or high malnutrition risk scores used an estimated 36% of adult acute inpatient bed days. Targeted use of ONS in community patients might reduce hospitalisation by 168,438 adult bed days per year, equivalent to 460 beds per day. This is particularly important, given high bed occupancy rates and twelve month daily averages of 254 patients on trolleys. Relevant stakeholders should consider strategies to ensure effective ONS use with a view to improving outcomes and reducing pressure on the acute care system.

Initial experience with a rapid access blackouts triage clinic.

Transient loss of consciousness (T-LOC), or blackout, is common in acute medicine. Clinical skills are not done well, with at least 74,000 patients misdiagnosed and mistreated for epilepsy in England alone. The aim of this study was to provide a rapid, structured assessment and an electrocardiogram (ECG) for patients with blackouts, aiming to identify high risk, reduce misdiagnoses, reduce hospital admission rates for low-risk patients, diagnose and treat where appropriate, and also provide onward specialist referral. The majority of patients had syncope, and very few had epilepsy. A high proportion had an abnormal ECG. A specialist-nurse-led rapid access blackouts triage clinic (RABTC) provided rapid effective triage for risk, a comprehensive assessment format, direct treatment for many patients, and otherwise a prompt appropriate onward referral. Rapid assessment through a RABTC reduced re-admissions with blackouts. Widespread use of the web-based blackouts tool could provide the NHS with a performance map. The U.K. has low rates of pacing compared to Western Europe, which RABTCs might help correct. The RABTC sits between first responders and specialist referral, providing clinical assessment and ECG in all cases, and referral where appropriate.

Female In-Class Participation and Performance Increase with More Female Peers and/or a Female Instructor in Life Sciences Courses.

As we strive to make science education more inclusive, more research is needed to fully understand gender gaps in academic performance and in-class participation in the life sciences. Studies suggest that male voices dominate introductory biology courses, but no studies have been done on upper-level courses. Results on achievement gender gaps in biology vary and often conflict, and no studies have been done on the correlation between participation and academic performance gaps. We observed 34 life sciences courses at all levels at a large private university. Overall, males were more likely to participate than their female peers, but these gender gaps varied from class to class. Females participated more in classes in which the instructor called on most hands that were raised or in classes with more females in attendance. Performance gender gaps also varied by classroom, but female final course grades were as much as 0.2 SD higher in classes with a female instructor and/or a female student majority. Gender gaps in participation and final course grades were positively correlated, but this could be solely because female students are more likely to both participate more and earn higher grades in classes with many females in attendance.

Circulating beta-carotene levels and type 2 diabetes-cause or effect?

AIMS/HYPOTHESIS: Circulating beta-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes. METHODS: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 10(-24)), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between beta-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. RESULTS: A 0.27 standard deviation increase in beta-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p = 0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.

Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus.

Comparison of HTLV-III, the putative AIDS virus, with other related viruses, may help to reveal more about the origin of AIDS in humans. In this study, the nucleotide sequence of the gag and pol genes of an equine infectious anemia virus (EIAV) proviral DNA clone was determined. The sequence was compared with that of HTLV-III and of visna, a pathogenic lentivirus of sheep. The results show that these viruses constitute a family clearly distinct from that of the type C viruses or the BLV-HTLV-I and -II group. Within the family, EIAV, HTLV-III, and visna appear to be equally divergent from a common evolutionary ancestor.

Isolation and characterization of an endogenous type C virus of rhesus monkeys.

A type C retrovirus was isolated from a continuous cell line established from a spontaneous esophageal carcinoma of a rhesus monkey (Macaca mulata) by prolonged cocultivation with canine cells. A DNA transcript of the viral RNA hybridized to a high level and kinetic analysis indicated the presence of multiple copies of the viral genome in rhesus monkey DNA, showing that the virus is endogenous in this species. The rhesus monkey virus closely resembles, in several respects, an endogenous type C virus previously isolated from stumptailed macques (Macaca arctoides), aa species closely related to rhesus monkeys.

Investigation of ecological and environmental determinants for the presence of questing Ixodes ricinus (Acari: Ixodidae) on Gower, South Wales.

The spatial heterogeneity of questing Ixodes ricinus (L.) (Acari: Ixodidae) within endemic areas in Great Britain is well established. Their presence is acutely responsive to blood host availability and their ability to maintain water balance, which are in turn governed by a variety of ecological and environmental factors. This article details the findings of a 3-yr study on the Gower peninsula, south Wales, which investigated the contribution of such factors (both ground- and geographic information systems [GIS] -derived) for predicting the presence of questing I. ricinus (Q(P)), at a local scale. Statistically significant univariate associations were found between Q(P) and calcareous/ neutral grassland and heathland habitats, particularly those grazed by livestock, and various factors that intuitively promote tick survival. For example, topographical features, such as certain aspects, that reduce exposure to cold northerly winds and the hot midday sun, favored Q(P). Similarly, positive associations were found with substrata composed of less permeable soil types and less permeable superficial/bedrock geologies that promote a moist microhabitat and reduce the likelihood of desiccation. Q(P) was also higher in areas of high soil moisture. This study highlighted a number of GIS-derived data sets that could be applied in the development of local and national predictive maps for I. ricinus in Great Britain. An understanding of the influence of these factors on questing I. ricinus can aid targeted tick control programs and help to educate the public, and those occupationally exposed, in understanding likely I. ricinus prolific areas within an I. ricinus endemic region.

Learning Gains from a Recurring "Teach and Question" Homework Assignment in a General Biology Course: Using Reciprocal Peer Tutoring Outside Class.

Providing students with one-on-one interaction with instructors is a big challenge in large courses. One solution is to have students interact with their peers during class. Reciprocal peer tutoring (RPT) is a more involved interaction that requires peers to alternate the roles of "teacher" and "student." Theoretically, advantages for peer tutoring include the verbalization and questioning of information and the scaffolded exploration of material through social and cognitive interaction. Studies on RPT vary in their execution, but most require elaborate planning and take up valuable class time. We tested the effectiveness of a "teach and question" (TQ) assignment that required student pairs to engage in RPT regularly outside class. A quasi-experimental design was implemented: one section of a general biology course completed TQ assignments, while another section completed a substitute assignment requiring individuals to review course material. The TQ section outperformed the other section by ∼6% on exams. Session recordings were coded to investigate correlation between TQ quality and student performance. Asking more questions was the characteristic that best predicted exam performance, and this was more predictive than most aspects of the course. We propose the TQ as an easy assignment to implement with large performance gains.

Expression of NFAT-family proteins in normal human T cells.

NFAT proteins constitute a family of transcription factors involved in mediating signal transduction. Using a panel of specific antisera in immunoprecipitation assays, we found that NFATp (135 kDa) is constitutively expressed in normal human T cells, while synthesis of NFATc (predominant form of 86 kDa) is induced by ionomycin treatment. NFAT4/x was very weakly expressed in unstimulated cells, and its level did not increase upon treatment with activating agents. NFAT3 protein was not observed under any conditions. Higher-molecular-weight species of NFATc (of 110 and 140 kDa) were also detected. In addition, translation of NFATc mRNA apparently initiates at two different AUG codons, giving rise to proteins that differ in size by 36 amino acids. Additional size heterogeneity of both NFATc and NFATp results from phosphorylation. In contrast to ionomycin treatment, exposure of cells to phorbol myristate acetate (PMA) plus anti-CD28 did not induce NFATc, indicating that under these conditions, interleukin-2 synthesis by these cells is apparently independent of NFATc. In DNA binding assays, both PMA plus anti-CD28 and PMA plus ionomycin resulted in nuclear NFAT. Surprisingly, the PMA-ionomycin-induced synthesis of NFATc that was detected by immunoprecipitation was not mirrored in the DNA binding assays: nearly all of the activity was due to NFATp. This is the first study of expression of all family members at the protein level in normal human T cells.

The PEST-like sequence of I kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA homodimers.

In most cells, proteins belonging to the Rel/NF-kappa B family of transcription factors are held in inactive form in the cytoplasm by an inhibitor protein, I kappa B alpha. Stimulation of the cells leads to degradation of the inhibitor and transit of active DNA-binding Rel/NF-kappa B dimers to the nucleus. I kappa B alpha is also able to inhibit DNA binding by Rel/NF-kappa B dimers in vitro, suggesting that it may perform the same function in cells when the activating signal is no longer present. Structurally, the human I kappa B alpha molecule can be divided into three sections: a 70-amino-acid N terminus with no known function, a 205-residue midsection composed of six ankyrin-like repeats, and a very acidic 42-amino-acid C terminus that resembles a PEST sequence. In this study we examined how the structural elements of the I kappa B alpha protein correlate with its functional capabilities both in vitro and in vivo. Using a battery of I kappa B alpha mutants, we show that (i) a dimer binds a single I kappa B alpha molecule, (ii) the acidic C-terminal region of I kappa B alpha is not required for protein-protein binding and does not mask the nuclear localization signal of the dimer, (iii) the same C-terminal region is required for inhibition of DNA binding, and (iv) this inhibition may be accomplished by direct interaction between the PEST-like region and the DNA-binding region of one of the subunits of the dimer.

Genetic characterization of human c-rel sequences.

We isolated and sequenced a human genomic-DNA segment that is homologous to a portion of v-rel, the transforming gene of reticuloendotheliosis virus (strain T). We also localized the human rel sequences to human chromosome 2 by screening a panel of rodent X human somatic-cell hybrids with the newly described human rel segment.

The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers.

Members of the Rel/NF-kappaB family of transcription factors are related to each other over a region of about 300 amino acids called the Rel Homology Domain (RHD), which governs DNA binding, dimerization, and binding to inhibitor. At the C-terminal end of the RHD, each protein has a nuclear localization signal (NLS). The crystal structures of the p50 and RelA family members show that the RHD consists of two regions: an N-terminal section which contains some of the DNA contacts and a C-terminal section which contains the remaining DNA contacts and controls dimerization. In unstimulated cells, the homo- or heterodimeric Rel/NF-kappaB proteins are cytoplasmic by virtue of binding to an inhibitor protein (IkappaB) which somehow masks the NLS of each member of the dimer. The IkappaB proteins consist of an ankyrin-repeat-containing domain that is required for binding to dimers and N- and C-terminal domains that are dispensable for binding to most dimers. In this study, we examined the interaction between IkappaB alpha and Rel family homodimers by mutational analysis. We show that (i) the dimerization regions of p50, RelA, and c-Rel are sufficient for binding to IkappaB alpha, (ii) the NLSs of RelA and c-Rel are not required for binding to IkappaB alpha but do stabilize the interaction, (iii) the NLS of p50 is required for binding to IkappaB alpha, (iv) only certain residues within the p50 NLS are required for binding, and (v) in a p50-IkappaB alpha complex or a c-Rel-IkappaB alpha complex, the N terminus of IkappaB alpha either directly or indirectly masks one or both of the dimer NLSs.

N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity.

The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression.

Detection of c-rel-related transcripts in mouse hematopoietic tissues, fractionated lymphocyte populations, and cell lines.

A portion of the human cellular homolog of v-rel, the transforming gene of the leukemogenic retrovirus reticuloendotheliosis virus, strain T, was used to survey RNAs from several mouse tissues, selected lymphocyte populations, and hematopoietic cell lines for c-rel expression. Relatively high levels of a high-molecular-weight transcript were observed in peripheral B and T cells, whereas lower levels were detectable in functionally immature thymocytes. These results suggested that, unlike c-myb and c-ets, the c-rel proto-oncogene plays a role in later stages of lymphocyte differentiation.

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.

Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (RelA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of Il-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of I kappa B alpha following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.