Theory and simulations of a gyrotron backward wave oscillator using a helical interaction waveguide

A gyrotron backward wave oscillator (gyro-BWO) with a helically corrugated interaction waveguide demonstrated its potential as a powerful microwave source with high efficiency and a wide frequency tuning range. This letter presents the theory describing the dispersion properties of such a waveguide and the linear beam-wave interaction. Numerical simulation results using the PIC code MAGIC were found to be in excellent agreement with the output measured from a gyro-BWO experiment

Breeding systems of floral colour forms in the Drosera cistiflora species complex

The study was supported by the National Research Foundation of South Africa (Grant 46372 to SDJ).Variation in plant breeding systems has implications for pollinator‐mediated selection on floral traits and the ecology of populations. Here we evaluate pollinator contribution to seed production, self‐compatibility and pollen limitation in different floral colour forms of Drosera cistiflora sensu lato (Droseraceae). These insectivorous perennial plants are endemic to fynbos and renosterveld vegetation in the Cape Floristic Region of South Africa, and the species complex includes five floral colour forms (pink, purple, red, white and yellow), some of which are known to be pollinated by beetles. Controlled hand‐pollination experiments were conducted in 15 populations of D. cistiflora s.l. (two to four populations per floral colour form) to test whether the colour forms vary in their degree of self‐compatibility and their ability to produce seeds through autonomous self‐fertilization. Yellow‐flowered forms were highly self‐incompatible, while other floral colour forms exhibited partial self‐compatibility. Seed set resulting from autonomous selfing was very low, and pollinator dependence indices were high in all populations. Since hand cross‐pollination resulted in greater seed set than open pollination in 13 of the 15 populations, we inferred that seed production is generally pollen‐limited.Drosera cistiflora s.l. typically exhibits high levels of pollinator dependence and pollen limitation. This is unusual among Drosera species worldwide and suggests that pollinators are likely to mediate strong selection on attractive traits such as floral colour and size in D. cistiflora s.l. These results also suggest that the floral colour forms of D. cistiflora s.l. which are rare and threatened are likely to be vulnerable to local extinction if mutualisms were to collapse indefinitely.PostprintPeer reviewe

Revival of the spin-Peierls transition in Cu_xZn_(1-x)GeO_3 under pressure

Pressure and temperature dependent susceptibility and Raman scattering experiments on single crystalline Cu_xZn_(1-x)GeO_3 have shown an unusually strong increase of the spin-Peierls phase transition temperature upon applying hydrostatic pressure. The large positive pressure coefficient (7.5 K/GPa) - almost twice as large as for the pure compound (4.5 K/GPa) - is interpreted as arising due to an increasing magnetic frustration which decreases the spin-spin correlation length, and thereby weakens the influence of the non-magnetic Zn-substitution.Comment: LaTeX, 15 pages, 5 eps figures, Phys. Rev. B, to appea

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Colossal dielectric constants in transition-metal oxides

Many transition-metal oxides show very large ("colossal") magnitudes of the dielectric constant and thus have immense potential for applications in modern microelectronics and for the development of new capacitance-based energy-storage devices. In the present work, we thoroughly discuss the mechanisms that can lead to colossal values of the dielectric constant, especially emphasising effects generated by external and internal interfaces, including electronic phase separation. In addition, we provide a detailed overview and discussion of the dielectric properties of CaCu3Ti4O12 and related systems, which is today's most investigated material with colossal dielectric constant. Also a variety of further transition-metal oxides with large dielectric constants are treated in detail, among them the system La2-xSrxNiO4 where electronic phase separation may play a role in the generation of a colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom

Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3 /g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.Hannah R. Wardill, Ana Rita Da Silva Ferreira, Himanshu Kumar, Emma H. Bateman, Courtney B. Cross, Joanne M. Bowen, Rick Havinga, Hermie J. M. Harmsen, Jan Knol, Bram Dorresteijn, Miriam van Dijk, Jeroen van Bergenhenegouwen, and Wim J. E. Tissin

SEDIGISM-ATLASGAL: Dense Gas Fraction and Star Formation Efficiency Across the Galactic Disk

By combining two surveys covering a large fraction of the molecular material in the Galactic disk we investigate the role the spiral arms play in the star formation process. We have matched clumps identified by ATLASGAL with their parental GMCs as identified by SEDIGISM, and use these giant molecular cloud (GMC) masses, the bolometric luminosities, and integrated clump masses obtained in a concurrent paper to estimate the dense gas fractions ($DGF_{gmc} = ∑M_{clump}/M_{gmc}$) and the instantaneous star forming efficiencies (i.e., $SFE_{gmc} = ∑L_{clump}/M_{gmc}$). We find that the molecular material associated with ATLASGAL clumps is concentrated in the spiral arms (∼60 per cent found within ±10 km s$^{−1}$ of an arm). We have searched for variations in the values of these physical parameters with respect to their proximity to the spiral arms, but find no evidence for any enhancement that might be attributable to the spiral arms. The combined results from a number of similar studies based on different surveys indicate that, while spiral-arm location plays a role in cloud formation and HI to H$_2$ conversion, the subsequent star formation processes appear to depend more on local environment effects. This leads us to conclude that the enhanced star formation activity seen towards the spiral arms is the result of source crowding rather than the consequence of a any physical process

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input

Nutrient regulation of the islet epigenome controls adaptive insulin secretion

Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme Lysine-specific demethylase 1 (Lsd1) in islets. β-cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome

Electromagnetic wave propagation in rain and polarization effects

This paper summarizes our study on microwave and millimeter-wave propagation in rain with special emphasis on the effects of polarization. Starting from a recount of our past findings, we will discuss developments with these and how they are connected with subsequent research