Cosmic ray records in Antarctic meteorites

The cosmogenic radionuclides Be(10), Al(26), and Mn(53) and noble gases were determined in more than 28 meteorites from Antarctica by nuclear analytical techniques and static mass spectrometry, respectively. The summarized results are listed. The concentrations of Al(26) and Mn(53) are normalized to the repective main target elements and given in dpm/kg Si sub eq and dpm/kg Fe. The errors stated include statistical as well as systematical errors. For noble gas concentrations estimated errors are 5% and for isotopic ratios 1.5%. Cosmic ray exposure ages T sub 21 were calculated by the noble gas concentrations and the terrestrial residence time (T) on the basis of the spallogenic nuclide Al(26). The suggested pairing of the LL6 chondrite RKPA 80238 and RKPA 80248 and the eucrites ALHA 76005 and ALHA 79017 is confirmed not only by the noble gas data but also by the concentrations of the spallation produced radionuclides. Futhermore, ALHA 80122, clasified as an H6 chondrite, has a noble gas pattern which suggest that this meteorite belongs to the ALHA 80111 shower

Cosmogenic rare gases and 10-Be in a cross section of Knyahinya

The concentrations of cosmogenic nuclides were studied as a function of shielding on samples from a cross section of the 293 kg main fragment of the L5 chondrite Knyahinya. The stone broke into two nearly symmetrical parts upon its fall in 1866. The planar cross section has diameters between 40 and 55 cm. He, Ne, and Ar were measured on about 20 samples by mass spectrometry and the 10-Be activities on aliquots of 10 selected samples were determined by AMS. The 10-Be data are presented and the abundances of spallogenic nuclides are compared with the model calculations reported by Reedy for spherical L chondrites. The 10-Be production rates in Knyahinya are shown versus the shielding parameter 22-Ne/21-Ne

From the HINDAS Project : Excitation Functions for Residual Nuclide Production by Proton-Induced Reactions

peer reviewe

Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy

Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.Toxicolog

Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia

Surface-enhanced Raman spectroscopy of the endothelial cell membrane

We applied surface-enhanced Raman spectroscopy (SERS) to cationic gold-labeled endothelial cells to derive SERS-enhanced spectra of the bimolecular makeup of the plasma membrane. A two-step protocol with cationic charged gold nanoparticles followed by silver-intensification to generate silver nanoparticles on the cell surface was employed. This protocol of post-labelling silver-intensification facilitates the collection of SERS-enhanced spectra from the cell membrane without contribution from conjugated antibodies or other molecules. This approach generated a 100-fold SERS-enhancement of the spectral signal. The SERS spectra exhibited many vibrational peaks that can be assigned to components of the cell membrane. We were able to carry out spectral mapping using some of the enhanced wavenumbers. Significantly, the spectral maps suggest the distribution of some membrane components are was not evenly distributed over the cells plasma membrane. These results provide some possible evidence for the existence of lipid rafts in the plasma membrane and show that SERS has great potential for the study and characterization of cell surfaces

Examination of the Cytotoxic and Embryotoxic Potential and Underlying Mechanisms of Next-Generation Synthetic Trioxolane and Tetraoxane Antimalarials

Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria

Polarized Secretion of Drosophila EGFR Ligand from Photoreceptor Neurons Is Controlled by ER Localization of the Ligand-Processing Machinery

Trafficking within the endoplasmic reticulum and specialized localization of the intra-membrane protease Rhomboid regulate EGF ligand-dependent signaling in Drosophila photoreceptor axon termini

Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect