Exact Wave Solutions to 6D Gauged Chiral Supergravity

We describe a broad class of time-dependent exact wave solutions to 6D gauged chiral supergravity with two compact dimensions. These 6D solutions are nontrivial warped generalizations of 4D pp-waves and Kundt class solutions and describe how a broad class of previously-static compactifications from 6D to 4D (sourced by two 3-branes) respond to waves moving along one of the uncompactified directions. Because our methods are generally applicable to any higher dimensional supergravity they are likely to be of use for finding the supergravity limit of time-dependent solutions in string theory. The 6D solutions are interesting in their own right, describing 6D shock waves induced by high energy particles on the branes, and as descriptions of the near-brane limit of the transient wavefront arising from a local bubble-nucleation event on one of the branes, such as might occur if a tension-changing phase transition were to occur.Comment: 22 pages, 1 figure. Minor clarifications added. Accepted in JHE

The Polonnaruwa meteorite: oxygen isotope, crystalline and biological composition

Results of X-Ray Diffraction (XRD) analysis, Triple Oxygen Isotope analysis and Scanning Electron Microscopic (SEM) studies are presented for stone fragments recovered from the North Central Province of Sri Lanka following a witnessed fireball event on 29 December 2012. The existence of numerous nitrogen depleted highly carbonaceous fossilized biological structures fused into the rock matrix is inconsistent with recent terrestrial contamination. Oxygen isotope results compare well with those of CI and CI-like chondrites but are inconsistent with the fulgurite hypothesis.Comment: 7 pages, 7 figures, 4 table

Carbon superatom thin films

Assembling clusters on surfaces has emerged as a novel way to grow thin films with targeted properties. In particular, it has been proposed from experimental findings that fullerenes deposited on surfaces could give rise to thin films retaining the bonding properties of the incident clusters. However the microscopic structure of such films is still unclear. By performing quantum molecular dynamics simulations, we show that C_28 fullerenes can be deposited on a surface to form a thin film of nearly defect free molecules, which act as carbon superatoms. Our findings help clarify the structure of disordered small fullerene films and also support the recently proposed hyperdiamond model for solid C_28.Comment: 13 pages, RevTeX, 2 figures available as black and white PostScript files; color PostScript and/or gif files available upon reques

Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer

BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer. METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models. RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model. CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies

Predicting non-native insect impact: focusing on the trees to see the forest

Non-native organisms have invaded novel ecosystems for centuries, yet we have only a limited understanding of why their impacts vary widely from minor to severe. Predicting the impact of non-established or newly detected species could help focus biosecurity measures on species with the highest potential to cause widespread damage. However, predictive models require an understanding of potential drivers of impact and the appropriate level at which these drivers should be evaluated. Here, we used non-native, specialist herbivorous insects of forest ecosystems to test which factors drive impact and if there were differences based on whether they used woody angiosperms or conifers as hosts. We identified convergent and divergent patterns between the two host types indicating fundamental similarities and differences in their interactions with non-native insects. Evolutionary divergence time between native and novel hosts was a significant driver of insect impact for both host types but was modulated by different factors in the two systems. Beetles in the subfamily Scolytinae posed the highest risk to woody angiosperms, and different host traits influenced impact of specialists on conifers and woody angiosperms. Tree wood density was a significant predictor of host impact for woody angiosperms with intermediate densities (0.5–0.6 mg/mm3) associated with highest risk, whereas risk of impact was highest for conifers that coupled shade tolerance with drought intolerance. These results underscore the importance of identifying the relevant levels of biological organization and ecological interactions needed to develop accurate risk models for species that may arrive in novel ecosystems

Apple skin patterning is associated with differential expression of MYB10

Background: Some apple (Malus × domestica Borkh.) varieties have attractive striping patterns, a quality attribute that is important for determining apple fruit market acceptance. Most apple cultivars (e.g. ‘Royal Gala’) produce fruit with a defined fruit pigment pattern, but in the case of ‘Honeycrisp’ apple, trees can produce fruits of two different kinds: striped and blushed. The causes of this phenomenon are unknown. Results: Here we show that striped areas of ‘Honeycrisp’ and ‘Royal Gala’ are due to sectorial increases in anthocyanin concentration. Transcript levels of the major biosynthetic genes and MYB10, a transcription factor that upregulates apple anthocyanin production, correlated with increased anthocyanin concentration in stripes. However, nucleotide changes in the promoter and coding sequence of MYB10 do not correlate with skin pattern in ‘Honeycrisp’ and other cultivars differing in peel pigmentation patterns. A survey of methylation levels throughout the coding region of MYB10 and a 2.5 Kb region 5’ of the ATG translation start site indicated that an area 900 bp long, starting 1400 bp upstream of the translation start site, is highly methylated. Cytosine methylation was present in all three contexts, with higher methylation levels observed for CHH and CHG (where H is A, C or T) than for CG. Comparisons of methylation levels of the MYB10 promoter in ‘Honeycrisp’ red and green stripes indicated that they correlate with peel phenotypes, with an enrichment of methylation observed in green stripes. Conclusions: Differences in anthocyanin levels between red and green stripes can be explained by differential transcript accumulation of MYB10. Different levels of MYB10 transcript in red versus green stripes are inversely associated with methylation levels in the promoter region. Although observed methylation differences are modest, trends are consistent across years and differences are statistically significant. Methylation may be associated with the presence of a TRIM retrotransposon within the promoter region, but the presence of the TRIM element alone cannot explain the phenotypic variability observed in ‘Honeycrisp’. We suggest that methylation in the MYB10 promoter is more variable in ‘Honeycrisp’ than in ‘Royal Gala’, leading to more variable color patterns in the peel of this cultivar.https://doi.org/10.1186/1471-2229-11-9

The Use of a Pipeline Embolization Device for Treatment of a Ruptured Dissecting Middle Cerebral Artery M3/M4 Aneurysm: Challenges and Technical Considerations

Prompt, effective treatment is necessary following aneurysmal subarachnoid hemorrhage to prevent recurrent rupture, which is thought to double mortality. Atypical ruptured aneurysms, such as blister or dissecting pseudoaneurysms, or those that are unusually distal in the middle cerebral artery (MCA) are challenging to treat with either open or endovascular options, though the pipeline embolization device (PED) has shown promise in multiple case series. We present a case of a ruptured dissecting pseudoaneurysm in the distal MCA (distal M3/proximal M4) prefrontal division in an healthy young patient (<60 years) successfully treated with a PED. The PED was chosen both as the only vessel sparing option in the young patient as well as for its potential as a vessel sacrifice tool if the pseudoaneurysm was felt to be incompletely treated, which in this case was not necessary—though would have leveraged the thrombogenicity of the device as a therapeutic advantage

FORUM:Remote testing for psychological and physiological acoustics

Acoustics research involving human participants typically takes place in specialized laboratory settings. Listening studies, for example, may present controlled sounds using calibrated transducers in sound-attenuating or anechoic chambers. In contrast, remote testing takes place outside of the laboratory in everyday settings (e.g., participants' homes). Remote testing could provide greater access to participants, larger sample sizes, and opportunities to characterize performance in typical listening environments at the cost of reduced control of environmental conditions, less precise calibration, and inconsistency in attentional state and/or response behaviors from relatively smaller sample sizes and unintuitive experimental tasks. The Acoustical Society of America Technical Committee on Psychological and Physiological Acoustics launched the Task Force on Remote Testing (https://tcppasa.org/remotetesting/) in May 2020 with goals of surveying approaches and platforms available to support remote testing and identifying challenges and considerations for prospective investigators. The results of this task force survey were made available online in the form of a set of Wiki pages and summarized in this report. This report outlines the state-of-the-art of remote testing in auditory-related research as of August 2021, which is based on the Wiki and a literature search of papers published in this area since 2020, and provides three case studies to demonstrate feasibility during practice

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

PIM kinase expression in human lymphomas can influence the outcome of chemotherapy, and blocking cap-dependent translation can reverse PIM-mediated rapamycin resistance in murine lymphomas

Neuroacanthocytosis associated with a defect of the 4.1R membrane protein

BACKGROUND: Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density. We report clinical, biochemical, and genetic features in four patients from four unrelated families with NA in order to explain the cause of morphological abnormalities and the relationship with neurodegenerative processes. CASE PRESENTATION: All patients were characterised by atypical NA with a novel alteration of the erythrocyte membrane: a 4.1R protein deficiency. The 4.1R protein content was significantly lower in patients (3.40 ± 0.42) than in controls (4.41 ± 0.40, P < 0.0001), reflecting weakened interactions of the cytoskeleton with the membrane. In patients IV:1 (RM23), IV:3 (RM15), and IV:6 (RM16) the 4.1 deficiency seemed to affect the horizontal interactions of spectrin and an impairment of the dimer self-association into tetramers was detected. In patient IV:1 (RM16) the 4.1 deficiency seemed to affect the skeletal attachment to membrane and the protein band 3 was partially reduced. CONCLUSION: A decreased expression pattern of the 4.1R protein was observed in the erythrocytes from patients with atypical NA, which might reflect the expression pattern in the central nervous system, especially basal ganglia, and might lead to dysfunction of AMPA-mediated glutamate transmission