Advanced experimental applications for x-ray transmission gratings Spectroscopy using a novel grating fabrication method

A novel fabrication method for soft x-ray transmission grating and other optical elements is presented. The method uses Focused-Ion-Beam (FIB) technology to fabricate high-quality free standing grating bars on Transmission Electron Microscopy grids (TEM-grid). High quality transmission gratings are obtained with superb accuracy and versatility. Using these gratings and back-illuminated CCD camera, absolutely calibrated x-ray spectra can be acquired for soft x-ray source diagnostics in the 100-3000 eV spectral range. Double grating combinations of identical or different parameters are easily fabricated, allowing advanced one-shot application of transmission grating spectroscopy. These applications include spectroscopy with different spectral resolutions, bandwidths, dynamic ranges, and may serve for identification of high-order contribution, and spectral calibrations of various x-ray optical elements

The Impact of Data Characteristics on the Selection of Data Mining Methods for Predictive Classification

This research-in-process is exploring a contingency approach to the construction and selection of data mining models for predictive classification. This approach considers the structure of the data set and the relationships between and among the various attributes characterizing the data set, with the goal of selecting a model that provides greater insight into the data – and therefore predicts most accurately -- given a particular data structure. Preliminary results obtained from analysis of hospital patient records indicate that concentration indices, commonly used to measure firm concentration within an industry, are useful in characterizing data set structures and therefore in guiding the model selection process. The eventual goal of this research is the construction of a decision support system that can aid decision makers in the model selection task

UV-curable glassy material for the manufacture of bulk and nano-structured elements

An ultra violet (UV) -cured glassy material with less than 30% organic residues was fabricated by the fast sol-gel method. The material presents high thermal stability, good optical quality and high adhesive strength. It is suitable for optical bonding and, for manufacture of optical elements and micro-structured optical devices. Either soft-lithography or photo-lithography may be used for manufacture of the material while its curing can be thermal (few hours) or UV (few seconds). In this work we present the technology to fabricate optical elements at scales spanning the sub-micron to centimeter range. This technology enables mass-production of optical elements at low cost

Optical bonding with fast sol-gel

We investigate here the properties of fast sol-gel for optical bonding. The precursors of the fast sol-gel material are organically modified alkoxides generating a transparent hybrid (organic-inorganic) substance with silica glass-like properties whose index of refraction can be modified by the addition of various metal-oxides. The fast sol-gel method consists of rapid fabrication of a viscous resin and its subsequent dilution for long shelf life use. This material, when used as an adhesive offers the option of either a thermal or UV curing procedure. We demonstrate a bonding strength of ~ 10 MPa when a 15 µm layer is applied between two glass elements. The bonding remained stable after an extensive -40ºC – 120ºC temperature cycling with minimal residual solvent evaporation at 150ºC. The fast sol-gel material was tested for optical bonding between silica bulks, between silica bulk and silicon wafers and as an adhesive in silica fibre couplers

Maternal Condition Does Not Influence Birth Sex Ratios in Anubis Baboons (Papio anubis)

Trivers and Willard predicted that when parental condition has differential effects on the fitness of male and female offspring, parents who are in good condition will bias investment toward the sex that benefits most from additional investment. Efforts to test predictions derived from Trivers and Willard's model have had mixed results, perhaps because most studies have relied on proxy measures of parental condition, such as dominance rank. Here, we examine the effects of female baboons condition on birth sex ratios and post-natal investment, based on visual assessments of maternal body condition. We find that local environmental conditions have significant effects on female condition, but maternal condition at conception has no consistent relationship with birth sex ratios. Mothers who are in poorer condition at the time of conception resume cycling significantly later than females who are in better condition, but the sex of their infants has no effect on the time to resumption of cycling. Thus, our findings provide strong evidence that maternal condition influences females' ability to reproduce, but females do not facultatively adjust the sex ratio of their offspring in relation to their dominance rank or current condition

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion

Conventional cytotoxic chemotherapy is highly effective in certain cancers, but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise (‘exhaustion’), which limits the use of chemotherapy and success of cancer therapy. Here, we show that the co-administration of G1T28 (trilaciclib), a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil (5FU) treatment model. Consistent with a cell intrinsic effect, we show directly preserved HSC function resulting in a more rapid recovery of peripheral blood counts, enhanced serial transplantation capacity and reduced myeloid skewing. When administered to healthy human volunteers, G1T28 demonstrated excellent in vivo pharmacology and transiently inhibited bone marrow (BM) HSPC proliferation. These findings suggest that the combination of CDK4/6 inhibitors (CDK4/6i) with cytotoxic chemotherapy should provide a means to attenuate therapy-induced BM exhaustion in patients with cancer

Isolated Splenic Metastasis from Renal Cell Carcinoma: Case Report and Review

This report presents the case of a 70-year-old woman with a previous history of a left nephrectomy for renal cell carcinoma (RCC), who developed general malaise and fatigue. Abdominal computed tomography demonstrated an enhancing 6 × 7 cm necrotic lesion in the lower pole of the spleen suggestive of a metastasis. Given the highly suspicious nature of the lesion we proceeded to splenectomy. The tumour did not breach the splenic capsule, and there was no local diaphragmatic involvement. The mass was concluded to be a true metastasis of the original RCC rather than local recurrence of the disease. The causes of isolated solid splenic lesions are wide and varied, however a past or present history of malignancy should lead to a high index of suspicion for a splenic metastasis. We report an extremely unusual case of spread from a RCC