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The article discusses the release of Goldfinger, the James Bond film that introduced the iconic Aston Martin DB5, marking a key moment in cinematic history. Topics include the creation of the DB5's gadget-filled design by Q Branch, its impact on the Bond franchise, and the collaboration between producers and filmmakers in choosing the car as Bond's vehicle.

There is a myriad of variables that must be considered when designing a superconducting magnet. Two of these are: the local magnetic field, dictating the response of the superconductor, and the mutual inductance matrix, dictating the generated voltage. These issues may be resolved with the help of finite element analysis tools, but this is not practical at the very beginning of coil design or when many concepts must be analysed quickly. Then comes the problem of robustly constructing the coil's winding pack such that it will operate as required. Analytical Python Electromagnetic Coil Simulator (APECS) offers one solution to the above. It uses accepted analytical and semi-numerical methods to calculate, at any point in space, the magnetic field generated by circular loop coils, such as a tokamak's poloidal field magnets, as well as straight-edge loop coils, such as a rectangular toroidal field magnet in a spherical tokamak. Combined with knowledge about the performance of the superconducting material and a user-specified cable design, APECS can construct a “minimum viable” winding pack for each poloidal field magnet to aid further analysis and design iteration. Despite that it cannot presently optimize the cable design or the thermo-hydraulics, superconductor/copper content, or the stress and failure, it is an invaluable tool used extensively in the design and analysis of the poloidal field (PF) magnet system on U.K.’s Spherical Tokamak for Energy Production (STEP).

PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME that can be targeted therapeutically in cancer.

Kimberlites are volatile-rich, occasionally diamond-bearing magmas that have erupted explosively at Earth’s surface in the geologic past1–3. These enigmatic magmas, originating from depths exceeding 150 km in Earth’s mantle1, occur in stable cratons and in pulses broadly synchronous with supercontinent cyclicity4. Whether their mobilization is driven by mantle plumes5or by mechanical weakening of cratonic lithosphere4,6remains unclear. Here we show that most kimberlites spanning the past billion years erupted about 30 million years (Myr) after continental breakup, suggesting an association with rifting processes. Our dynamical and analytical models show that physically steep lithosphere–asthenosphere boundaries (LABs) formed during rifting generate convective instabilities in the asthenosphere that slowly migrate many hundreds to thousands of kilometres inboard of rift zones. These instabilities endure many tens of millions of years after continental breakup and destabilize the basal tens of kilometres of the cratonic lithosphere, or keel. Displaced keel is replaced by a hot, upwelling mixture of asthenosphere and recycled volatile-rich keel in the return flow, causing decompressional partial melting. Our calculations show that this process can generate small-volume, low-degree, volatile-rich melts, closely matching the characteristics expected of kimberlites1–3. Together, these results provide a quantitative and mechanistic link between kimberlite episodicity and supercontinent cycles through progressive disruption of cratonic keels.

Scleractinian corals are crucially important to the health of some of the world’s most biodiverse, productive, and economically important marine habitats. Despite this importance, analysis of coral peptidomes is still in its infancy. Here we show that the tentacle extract from the stony coral Heliofungia actiniformisis rich in peptides with diverse and novel structures. We have characterized the sequences and three-dimensional structures of four new peptides, three of which have no known homologues. We show that a 2 kDa peptide, Hact-2, promotes significant cell proliferation on human cells and speculate this peptide may be involved in the remarkable regenerative capacity of corals. We found a 3 kDa peptide, Hact-3, encoded within a fascin-like domain, and homologues of Hact-3 are present in the genomes of other coral species. Two additional peptides, Hact-4 and Hact-SCRiP1, with limited sequence similarity, both contain a beta-defensin-like fold and highlight a structural link with the small cysteine-rich proteins (SCRiP) family of proteins found predominantly in corals. Our results provide a first glimpse into the remarkable and unexplored structural diversity of coral peptides, providing insight into their diversity and putative functions and, given the ancient lineage of corals, potential insight into the evolution of structural motifs.

Two-dimensional (2D) crystals are promising materials for developing future nano-enabled technologies1–6. The cleavage of weak, interlayer van der Waals bonds in layered bulk crystals enables the production of high-quality 2D, atomically thin monolayers7–10. Nonetheless, as earth-abundant compounds, metal oxides are rarely accessible as pure and fully stoichiometric monolayers owing to their ion-stabilized ‘lamellar’ bulk structure11–14. Here, we report the discovery of a layered planar hexagonal phase of oxides from elements across the transition metals, post-transition metals, lanthanides and metalloids, derived from strictly controlled oxidation at the metal–gas interface. The highly crystalline monolayers, without the support of ionic dopants or vacancies, can easily be mechanically exfoliated by stamping them onto substrates. Monolayer and few-layered hexagonal TiO2are characterized as examples, showing p-type semiconducting properties with hole mobilities of up to 950 cm2V−1s−1at room temperature. The strategy can be readily extended to a variety of elements, possibly expanding the exploration of metal oxides in the 2D quantum regime.

THE LIFE LITTLE EPHEMERA from filming The Italian Job survived production. The Flaminia had been styled by Carrozzeria Touring of Milan, which had also designed the Aston Martin DB4, making the Lancia a passable double. After The Italian Job, the production company sold the hero Aston Martin DB4. [Extracted from the article]

To determine genetic mutational profiles in patients with Ocular Surface Squamous Neoplasia (OSSN) using whole exome sequencing.

The orientation-specific immobilization of antibodies onto nanoparticles, to preserve antibody–antigen recognition, is a key challenge in developing targeted nanomedicines. Herein, we report the targeting ability of metal–phenolic network (MPN)-coated gold nanoparticles with surface-physisorbed antibodies against respective antigens. The MPN coatings were self-assembled from metal ions (FeIII, CoII, CuII, NiII, or ZnII) cross-linked with tannic acid. Upon physisorption of antibodies, all particle systems exhibited enhanced association with target antigens, with CoIIsystems demonstrating more than 2-fold greater association. These systems contained more metal atoms distributed in a way to specifically interact with antibodies, which were investigated by molecular dynamics simulations. A model antibody fragment crystallizable (Fc) region in solution with CoII-tannic acid complexes revealed that the solvent-exposed CoIIcan directly coordinate to the histidine-rich portion of the Fc region. This one-pot interaction suggests anchoring of the antibody Fc region to the MPN on nanoparticles, allowing for enhanced targeting.

I got cars off friends, cars out of I got the cheapest Aston Martin DB4 Convertible I could find. Had wanted more cars, but the British car giant failed to grasp Fresh from prison, he's here to collect his Aston Martin DB4 Two Aston Martin DB4 Convertibles. [Extracted from the article]

In this report, the gas sensing performance of zinc titanate (ZnTiO3) nanoarrays (NAs) synthesized by coating hydrothermally formed zinc oxide (ZnO) NAs with TiO2using low-temperature chemical vapor deposition is presented. By controlling the annealing temperature, diffusion of ZnO into TiO2forms a mixed oxide of ZnTiO3NAs. The uniformity and the electrical properties of ZnTiO3NAs made them ideal for light-activated acetone gas sensing applications for which such materials are not well studied. The acetone sensing performance of the ZnTiO3NAs is tested by biasing the sensor with voltages from 0.1 to 9 V dc in an amperometric mode. An increase in the applied bias was found to increase the sensitivity of the device toward acetone under photoinduced and nonphotoinduced (dark) conditions. When illuminated with 365 nm UV light, the sensitivity was observed to increase by 3.4 times toward 12.5 ppm acetone at 350 °C with an applied bias of 9 V, as compared to dark conditions. The sensor was also observed to have significantly reduced the adsorption time, desorption time, and limit of detection (LoD) when excited by the light source. For example, LoD of the sensor in the dark and under UV light at 350 °C with a 9 V bias is found to be 80 and 10 ppb, respectively. The described approach also enabled acetone sensing at an operating temperature down to 45 °C with a repeatability of >99% and a LoD of 90 ppb when operated under light, thus indicating that the ZnTiO3NAs are a promising material for low concentration acetone gas sensing applications.

Two-dimensional (2D) transition metal dichalcogenide semiconductors offer unique electronic and optical properties, which are significantly different from their bulk counterparts. It is known that the electronic structure of 2D MoS2, which is the most popular member of the family, depends on the number of layers. Its electronic structure alters dramatically at near atomically thin morphologies, producing strong photoluminescence (PL). Developing processes for controlling the 2D MoS2PL is essential to efficiently harness many of its optical capabilities. So far, it has been shown that this PL can be electrically or mechanically gated. Here, we introduce an electrochemical approach to actively control the PL of liquid-phase-exfoliated 2D MoS2nanoflakes by manipulating the amount of intercalated ions including Li+, Na+, and K+into and out of the 2D crystal structure. These ions are selected as they are crucial components in many bioprocesses. We show that this controlled intercalation allows for large PL modulations. The introduced electrochemically controlled PL will find significant applications in future chemical and bio-optical sensors as well as optical modulators/switches.

Susie Linfield warns us against "telling lies" [Letters, April 6], then proceeds to demonstrate her commitment to exactly that by claiming, falsely, that I have manufactured "entirely fictitious claims." Not true, but a useful illustration of how extreme was Israel's concern that a two-state solution might be endorsed by the UN. The country's formal reaction was presented by Prime Minister Yitzhak Rabin: Israel must "vehemently oppose any tendency to establish a third state in the area between it and Jordan.". [Extracted from the article]

Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in two separate kindreds in whom probands presented with immune dysregulation, combined T and B cell deficiency, inflammation, and epithelial defects. IKBKB encodes IKK2, which activates NF-κB signaling. IKK2V203I results in enhanced NF-κB signaling, as well as T and B cell functional defects. IKK2V203 is a highly conserved residue, and to prove causation, we generated an accurate mouse model by introducing the precise orthologous codon change in Ikbkb using CRISPR/Cas9. Mice and humans carrying this missense mutation exhibit remarkably similar cellular and biochemical phenotypes. Accurate mouse models engineered by CRISPR/Cas9 can help characterize novel syndromes arising from de novo germline mutations and yield insight into pathogenesis.

Additional Sex Combs-Like 1 (ASXL1) is mutated at a high frequency in all forms of myeloid malignancies associated with poor prognosis. We generated a Vav1 promoter-driven Flag-Asxl1Y588X transgenic mouse model, Asxl1Y588XTg, to express a truncated FLAG-ASXL1aa1-587 protein in the hematopoietic system. The Asxl1Y588XTg mice had an enlarged hematopoietic stem cell (HSC) pool, shortened survival, and predisposition to a spectrum of myeloid malignancies, thereby recapitulating the characteristics of myeloid malignancy patients with ASXL1 mutations. ATAC- and RNA-sequencing analyses revealed that the ASXL1aa1-587 truncating protein expression results in more open chromatin in cKit+ cells compared with wild-type cells, accompanied by dysregulated expression of genes critical for HSC self-renewal and differentiation. Liquid chromatography–tandem mass spectrometry and coimmunoprecipitation experiments showed that ASXL1aa1-587 acquired an interaction with BRD4. An epigenetic drug screening demonstrated a hypersensitivity of Asxl1Y588XTg bone marrow cells to BET bromodomain inhibitors. This study demonstrates that ASXL1aa1-587 plays a gain-of-function role in promoting myeloid malignancies. Our model provides a powerful platform to test therapeutic approaches of targeting the ASXL1 truncation mutations in myeloid malignancies.

IMPORTANCE: Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood. OBJECTIVE: To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES). DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline. MAIN OUTCOMES AND MEASURES: Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures. RESULTS: The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p. CONCLUSIONS AND RELEVANCE: In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.

Detonation nanodiamonds (DNDs) have unique physical and chemical properties that make them invaluable in many applications. However, DNDs are generally assumed to show weak fluorescence, if any, unless chemically modified with organic molecules. We demonstrate that detonation nanodiamonds exhibit significant and excitation-wavelength-dependent fluorescence from the visible to the near-infrared spectral region above 800 nm, even without the engraftment of organic molecules to their surfaces. We show that this fluorescence depends on the surface functionality of the DND particles. The investigated functionalized DNDs, produced from the same purified DND as well as the as-received polyfunctional starting material, are hydrogen, hydroxyl, carboxyl, ethylenediamine, and octadecylamine-terminated. All DNDs are investigated in solution and on a silicon wafer substrate and compared to fluorescent high-pressure high-temperature nanodiamonds. The brightest fluorescence is observed from octadecylamine-functionalized particles and is more than 100 times brighter than the least fluorescent particles, carboxylated DNDs. The majority of photons emitted by all particle types likely originates from non-diamond carbon. However, we locally find bright and photostable fluorescence from nitrogen-vacancy centers in diamond in hydrogenated, hydroxylated, and carboxylated detonation nanodiamonds. Our results contribute to understanding the effects of surface chemistry on the fluorescence of DNDs and enable the exploration of the fluorescent properties of DNDs for applications in theranostics as nontoxic fluorescent labels, sensors, nanoscale tracers, and many others where chemically stable and brightly fluorescent nanoparticles with tailorable surface chemistry are needed.

IMPORTANCE: Uveal melanoma (UM) is an intraocular primary malignant neoplasm that often gives rise to metastatic disease for which there are no effective therapies. A substantial proportion of UMs express the cancer-testis antigen PRAME (preferentially expressed antigen in melanoma), which can potentially be targeted by adoptive T-cell therapy. OBJECTIVE: To determine whether there may be a rationale for PRAME-directed T-cell therapy for metastatic UM. DESIGN, SETTING, AND PARTICIPANTS: An experimental study using a retrospective cohort of 64 patients with UM (median follow-up, 62 months) was conducted from January 8, 2015, to November 20, 2016, at the Leiden University Medical Center. Clinical, histopathologic, and genetic parameters were compared between 64 PRAME-positive and PRAME-negative UMs. HLA class I restricted, PRAME-specific T cells were stimulated with UM cell lines to measure their antigen-specific reactivity against these cell lines, which were analyzed for PRAME expression by real-time quantitative polymerase chain reaction. Uveal melanoma metastases from 16 unrelated patients were assessed for PRAME expression by messenger RNA fluorescence in situ hybridization and for HLA class I expression by immunofluorescence staining. MAIN OUTCOMES AND MEASURES: Interferon γ production for antigen-specific reactivity and detection of PRAME and HLA class I expression in primary and metastatic UM. RESULTS: Of the 64 patients in the study (31 women and 33 men; mean [SD] age at the time of enucleation, 60.6 [15.6] years), PRAME expression was negative in 35 primary UMs and positive in 29 primary UMs. Positive PRAME expression was associated with a high largest basal diameter (15.0 vs 12.0 mm; P = .005), ciliary body involvement (59% vs 26%; P = .008), and amplification of chromosome 8q (66% vs 23%; P = .002). PRAME-specific T cells reacted against 4 of 7 UM cell lines, demonstrating that T-cell reactivity correlated with PRAME expression. Metastatic UM samples were positive for PRAME messenger RNA in 11 of 16 patients and for HLA class I in 10 of 16 patients, with 8 of 16 patients demonstrating coexpression of both PRAME and HLA class I. CONCLUSIONS AND RELEVANCE: PRAME is expressed in many primary and metastatic UMs, and about half of the metastatic UMs coexpress PRAME and HLA class I. The finding that PRAME-specific T cells in this study reacted against PRAME-positive UM cell lines suggests a potential role for PRAME-directed immunotherapy for selected patients with metastatic UM.

Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis.

IMPORTANCE: Frequent mutations have been described in the following 5 genes in uveal melanoma (UM): BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. Understanding the prognostic significance of these mutations could facilitate their use in precision medicine. OBJECTIVE: To determine the associations between driver mutations, gene expression profile (GEP) classification, clinicopathologic features, and patient outcomes in UM. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of patients with UM treated by enucleation by a single ocular oncologist between November 1, 1998, and July 31, 2014. MAIN OUTCOMES AND MEASURES: Clinicopathologic features, patient outcomes, GEP classification (class 1 or class 2), and mutation status were recorded. RESULTS: The study cohort comprised 81 participants. Their mean age was 61.5 years, and 37% (30 of 81) were female. The GEP classification was class 1 in 35 of 81 (43%), class 2 in 42 of 81 (52%), and unknown in 4 of 81 (5%). BAP1 mutations were identified in 29 of 64 (45%), GNAQ mutations in 36 of 81 (44%), GNA11 mutations in 36 of 81 (44%), SF3B1 mutations in 19 of 81 (24%), and EIF1AX mutations in 14 of 81 (17%). Sixteen of the mutations in BAP1 and 6 of the mutations in EIF1AX were previously unreported in UM. GNAQ and GNA11 mutations were mutually exclusive. BAP1, SF3B1, and EIF1AX mutations were almost mutually exclusive with each other. Using multiple regression analysis, BAP1 mutations were associated with class 2 GEP and older patient. EIF1AX mutations were associated with class 1 GEP and the absence of ciliary body involvement. SF3B1 mutations were associated with younger patient age. GNAQ mutations were associated with the absence of ciliary body involvement and greater largest basal diameter. GNA11 mutations were not associated with any of the analyzed features. Using Cox proportional hazards modeling, class 2 GEP was the prognostic factor most strongly associated with metastasis (relative risk, 9.4; 95% CI, 3.1-28.5) and melanoma-specific mortality (relative risk, 15.7; 95% CI, 3.6-69.1) (P < .001 for both). After excluding GEP class, the presence of BAP1 mutations was the factor most strongly associated with metastasis (relative risk, 10.6; 95% CI, 3.4-33.5) and melanoma-specific mortality (relative risk, 9.0; 95% CI, 2.8-29.2) (P < .001 for both). CONCLUSIONS AND RELEVANCE: BAP1, SF3B1, and EIF1AX mutations occur during UM tumor progression in an almost mutually exclusive manner and are associated with different levels of metastatic risk. These mutations may have value as prognostic markers in UM.

Few-layer two-dimensional (2D) molybdenum oxide nanoflakes are exfoliated using a grinding assisted liquid phase sonication exfoliation method. The sonication process is carried out in five different mixtures of water with both aprotic and protic solvents. We found that surface energy and solubility of mixtures play important roles in changing the thickness, lateral dimension, and synthetic yield of the nanoflakes. We demonstrate an increase in proton intercalation in 2D nanoflakes upon simulated solar light exposure. This results in substoichiometric flakes and a subsequent enhancement in free electron concentrations, producing plasmon resonances. Two plasmon resonance peaks associated with the thickness and the lateral dimension axes are observable in the samples, in which the plasmonic peak positions could be tuned by the choice of the solvent in exfoliating 2D molybdenum oxide. The extinction coefficients of the plasmonic absorption bands of 2D molybdenum oxide nanoflakes in all samples are found to be high (ε > 109L mol–1cm–1). It is expected that the tunable plasmon resonances of 2D molybdenum oxide nanoflakes presented in this work can be used in future electronic, optical, and sensing devices.

The article focuses on differentiation between uveal melanoma and cutaneous melanoma along with informations uveal melanoma arises in the iris, using micrometastasis for treatment, and metastatic risk revealed by using gene expression profiling.

Whole genome sequencing (WGS) of cancer patients’ tumours offers the most comprehensive method of identifying both novel and known clinically-actionable genomic targets. However, the practicalities of performing WGS on clinical samples are poorly defined. This study was designed to test sample preparation, sequencing specifications and bioinformatic algorithms for their effect on accuracy and cost-efficiency in a large WGS analysis of human melanoma samples. WGS was performed on melanoma cell lines (n=15) and melanoma fresh frozen tumours (n=222). The appropriate level of coverage and the optimal mutation detection algorithm for the project pipeline were determined. An incremental increase in sequencing coverage from 36X to 132X in melanoma tissue samples and 30X to 103X for cell lines only resulted in a small increase (1–2%) in the number of mutations detected, and the quality scores of the additional mutations indicated a low probability that the mutations were real. The results suggest that 60X coverage for melanoma tissue and 40X for melanoma cell lines empower the detection of 98–99% of informative single nucleotide variants (SNVs), a sensitivity level at which clinical decision making or landscape research projects can be carried out with a high degree of confidence in the results. Likewise the bioinformatic mutation analysis methodology strongly influenced the number and quality of SNVs detected. Detecting mutations in the blood genomes separate to the tumour genomes generated 41% more SNVs than if the blood and melanoma tissue genomes were analysed simultaneously. Therefore, simultaneous analysis should be employed on matched melanoma tissue and blood genomes to reduce errors in mutation detection. This study provided valuable insights into the accuracy of SNV with WGS at various coverage levels in human clinical cancer specimens. Additionally, we investigated the accuracy of the publicly available mutation detection algorithms to detect cancer specific SNVs which will aid researchers and clinicians in study design and implementation of WGS for the identification of somatic mutations in other cancers.

The use of membranes for gas permeation and phase separation offers many distinct advantages over other more energy-dependent processes. The operational efficiencies of these membranes rely heavily on high gas permeability. Here, we report membranes with significantly increased permeability without a considerable decrease in mechanical strength or selectivity, synthesized from a polymer nanocomposite that incorporates graphene and polydimethylsiloxane (PDMS). These graphene–PDMS nanocomposite membranes were able to enhance the gas permeation of N2, CO2, Ar, and CH4in reference to pristine PDMS membranes. This is achieved by creating interfacial voids between the graphene flakes and polymer chains, which increases the fractional free volume within the nanocomposites, giving rise to an increase in permeation. An optimal loading of graphene was found to be 0.25 wt%, while greater loading created agglomeration of the graphene flakes, hence reducing the effective surface area. We present the enhancements that the membranes can provide to sensing and phase separation applications. We show that these nanocomposites are near transparent to CO2gas molecules in sensing measurements. This study offers a new area of research for graphene-based nanocomposites.

Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor κB pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency.

Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor κB pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency.

To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma.

In this paper, we present H2gas sensors based on hollow and filled, well-aligned electrospun SnO2nanofibers, operating at a low temperature of 150 °C. SnO2nanofibers with diameters ranging from 80 to 400 nm have been successfully synthesized in which the diameter of the nanofibers can be controlled by adjusting the concentration of polyacrylonitrile in the solution for electrospinning. The presence of this polymer results in the formation of granular walls for the nanofibers. We discussed the correlation between nanofibers morphology, structure, oxygen vacancy contents and the gas sensing performances. X-ray photoelectron spectroscopy analysis revealed that the granular hollow SnO2nanofibers, which show the highest responses, contain a significant number of oxygen vacancies, which are favorable for gas sensor operating at low temperatures.

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase–like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell–activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74–MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.

BACKGROUND AND OBJECTIVE:Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of age-related macular degeneration (AMD). Because increased flavoprotein fluorescence (FPF) is indicative of mitochondrial dysfunction, the authors attempted to detect mitochondrial dysfunction in eyes with AMD using FPF.PATIENTS AND METHODS:Six nonexudative eyes with AMD, including three with geographic atrophy (GA), and age-matched control eyes were imaged with a FPF device. Qualitative and quantitative analyses were conducted on the FPF images.RESULTS:Five eyes with AMD, including all three eyes with GA, showed qualitative and/or quantitative FPF heterogeneity that was not present in control eyes. Mean FPF average intensities of eyes with AMD with (Five eyes with AMD, including all three eyes with GA, showed qualitative and/or quantitative FPF heterogeneity that was not present in control eyes. Mean FPF average intensities of eyes with AMD with (P= .044) and without (P= .00060) GA were significantly greater than those of control eyes. The standard deviations of FPF images were greater in eyes with AMD (P= .020).CONCLUSION:In this small cluster of patients with AMD, retinal FPF is increased, suggesting elevated mitochondrial dysfunction. FPF heterogeneity indicates that an increased variability in mitochondrial dysfunction seems to be present in eyes with advanced disease.

Here, we demonstrate that niobium pentoxide (Nb2O5) is an ideal candidate for increasing the efficiencies of dye-sensitized solar cells (DSSCs). The key lies in developing a Nb2O5crisscross nanoporous network, using our unique elevated temperature anodization process. For the same thicknesses of ∼4 μm, the DSSC based on the Nb2O5layer has a significantly higher efficiency (∼4.1%) when compared to that which incorporates a titanium dioxide nanotubular layer (∼2.7%). This is the highest efficiency among all of the reported photoanodes for such a thickness when utilizing back-side illumination. We ascribe this to a combination of reduced electron scattering, greater surface area, wider band gap, and higher conduction band edge, as well as longer effective electron lifetimes.

Minocycline is a semi-synthetic tetracycline that inhibits bacterial protein synthesis and hence is used for the treatment of many infectious diseases. Over the years, many other interesting properties of minocycline have been identified and been used to make patents which include anti-inflammatory, anti-apoptotic, matrix metalloproteinase inhibitor and free oxygen radical scavenger activity. Ischemia-reperfusion injury is a concern for almost every clinical specialty and minocycline seems to be an attractive cytoprotective agent that can ameliorate the damage due to these properties. Ischemia-reperfusion injury is a complex process and involves various pathways that lead to cell death. This review focuses on the body of evidence describing various proposed mechanisms of action of minocycline and its current experimental use in various animal models of ischemia-reperfusion injury.

The article discusses Swedish magician Johan Stahl's efforts in introducing a course in magic at the Stockholm University of Dance and Circus in Sweden while also discussing some of his famous magic tricks, his ideas on teaching magic , and the structure of the magicians community.

We identify an intronic deletion in VANGL1that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.1,2We identify a large deletion in intron 7 of Van Gogh Like 1(VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1+/−mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE.

High-performance anion-exchange chromatography (HPAEC) with pulsed-amperometric detection was used to monitor the consistency of the oligosaccharides released from several partially purified preparations of a tissue-type plasminogen activator mutant (TNK-tPA). Differences in the oligosaccharide map were observed, primarily in the neutral carbohydrate region of the separation. Subsequent investigations using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF/MS) identified the neutral oligosaccharides to be primarily asialo-diantennary complex-type glycans with 2, 1, or 0 galactose residues. Additional asialo-triantennary and asialo-tetrantennary structures were also observed with varying amounts of galactose. Hydrolysis of the chromogenic substrate 4-methyl umbelliferyl-β-galactoside confirmed that host-cell lysosomal β-galactosidase is present at the first step in the purification process and is the cause of the observed glycan degradation. Subsequent steps in the purification process quantitatively remove this enzyme. Comparison of HPAEC and MALDI/TOF/MS analysis of time-course samples revealed quite similar rates of degradation and demonstrates the quantitative utility of these methods. HPAEC did not reveal significant changes in the sialylated structures as evidenced by nearly identical profiles for the sialic acid-containing structures.

Caine remembers it was on this premise that Kennedy Martin first pitched him the movie: "He said, 'Let us destroy all these symbols of wealth, like cars. From the Lamborghini Miura in the title sequence to Michael Caine zipping around London in an Aston Martin DB4 Convertible, the film also takes in Fiat Dinos and two Jaguar E-types along the way. Kennedy Martin was savvy enough to understand how the film could benefit the marketing and publicity departments at British Motor Corporation. [Extracted from the article]

This paper reports a high-level python package for selecting machine learning algorithms and ensembles of machine learning algorithms parameters by using the particle swarm optimization (PSO) algorithm named PSPSO. The first version of PSPSO supports four algorithms: Support Vector Machine (SVM), Multi-Layer Perceptron (MLP), Extreme Gradient Boosting (XGBoost) and Gradient Boosting Decision Trees (GBDT). PSPSO provides an easy framework for building machine learning algorithms using PSO and a new platform for researchers to investigate their selection methods. In addition, it provides a basis for establishing new selection ideas and can be easily extended to support other algorithms.

The article profiles Colin Rose, craftsman and magician. Colin who is working under the name Five of Hearts Magic has been creating extraordinary pieces and many of them in turned wood that have found their way onto the shelves of collectors and into the repertoires of working magicians. Prior for being a performer, Collin was trained to become a Masonic Jeweller but preferred to pursue his magic career. He is also a fine metal worker and has produced faithful re-creations of Coin Wands.

Several letters to the editor are presented in response to articles in previous issues including a clarification to the HR X2 engine serial number prefixed with 186K, a description of fitting a fiberglass bonnet to a reader's BA XR6 Turbo, and an information on drag racing personality Wayne Jones.

The article discusses Association for Career and Technical Education (ACTE)'s convention in Las Vegas, Nevada from November 30-December 3 , 2016 featuring speakers businesswoman Debbi Fields, Kim Scott of Cirque du Soleil firm and Kimberly J. Mcwaters of Universal Technical Institute Inc.

The article analyzes the prospect of student housing shortages with the end of the cap on undergraduate numbers in England taking effect in the 2015-2016 academic year. It reports the difficulties facing universities in meeting student accommodation with the sudden increases in student enrollment. Also discussed are the opportunity for universities and developers to improve and expand accommodation and facilities and the problem with the lack of purpose-built student accommodation.

The article presents a discussion between CMJ NMM editor-in-chief Kenny Herzog and contributing writer Matthew Field on the comeback album of the punk rock group Bad Brains titled "Build a Nation." Herzog says that the delay in the vocals of H. R. was used to cover the lost quality in his voice and to make it appear with more depth and vigor. Field claims that it was refreshing to hear a punk recording in 2007 that does not sound like ProTools production.

Reviews the motion picture "The Art of Card Splitting" starring Marty Grams.