Infrared 8-13µ Spectroscopy of the Moon and Some Cold Silicate Powders

Laboratory investigations were made of the spectral emission properties of a limited number of silicate powders in vacuum and surface temperatures of 180-240°K. The effect on the emission spectrum of mineral composition, powder grain-size, surface contamination and thermal gradient was studied. The low sample surface temperature enhanced the spectral contrast of quartz but had little effect on spectra of rock materials. In general, there was a decrease in spectral contrast with decreasing sample grain-size. However, this effect was more pronounced for individual mineral samples than for rock samples. When the particle size was reduced to less than 38μ individual rock types could not be identified. However, quartz bearing or generally acidic rocks could be differentiated from quartz free or generally basic rock types. A quartz sample which had been contaminated by iron oxide did not lose its spectral features in spite of being visibly colored. The effect of a thermal gradient in the sample on its emission spectrum was shown to be negligible. Differential 8-13μ spectroscopy of 22 lunar points, spanning the major types of lunar features, was undertaken to determine if compositional differences or age are evidenced in the 8-13μ emission spectra of the features. A method was devised to remove precisely the atmospheric absorption and allow the integration of many spectra in order to reduce uncertainties caused by atmospheric absorption fluctuations and detector noise. Twenty of the 22 points showed no spectral differences greater than 1%. Two points, Plato and Mare Humorum, showed definite, consistent spectral differences from the rest of the points measured, at the short wavelength end of the spectrum. The interpretation made here of these results is that these two points have significantly fresher surfaces exposed which still show some spectral contrast or they are compositionally different from their surroundings. In the former case the anomalous areas must be partially covered with a non-silicate material in order to be consistent with the data obtained. If the points are compositionally different and the uniform areas show spectral contrast, the uniform areas must contain quartz and the anomalous areas are then more basic in composition than the uniform areas. The alternative to these two possibilities is that some process, perhaps an effect of the solar wind, is operating in such a way as to produce spectra which are unknown and hence can be falsely interpreted.</p

Becoming a general practitioner - Which factors have most impact on career choice of medical students?

<p>Abstract</p> <p>Background</p> <p>In Germany, there is a shortage of young physicians in several specialties, the situation of general practitioners (GP) being especially precarious. The factors influencing the career choice of German medical students are poorly understood. This study aims to identify factors influencing medical students' specialty choice laying a special focus on general practice.</p> <p>Methods</p> <p>The study was designed as a cross-sectional survey. In 2010, students at the five medical schools in the federal state of Baden-Wuerttemberg (Germany) filled out an online-questionnaire. On 27 items with 5-point Likert scales, the students rated the importance of specified individual and occupational aspects. Furthermore, students were asked to assign their intended medical specialty.</p> <p>Results</p> <p>1,299 students participated in the survey. Thereof, 1,114 students stated a current choice for a specialty, with 708 students choosing a career in one of the following 6 specialties: internal medicine, surgery, gynaecology and obstetrics, paediatrics, anaesthetics and general practice. Overall, individual aspects ('Personal ambition', 'Future perspective', 'Work-life balance') were rated as more important than occupational aspects (i.e. 'Variety in job', 'Job-related ambition') for career choice. For students favouring a career as a GP individual aspects and the factor 'Patient orientation' among the occupational aspects were significantly more important and 'Job-related ambition' less important compared to students with other specialty choices.</p> <p>Conclusions</p> <p>This study confirms that future GPs differ from students intending to choose other specialties particularly in terms of patient-orientation and individual aspects such as personal ambition, future perspective and work-life balance. Improving job-conditions in terms of family compatibility and work-life balance could help to increase the attractiveness of general practice. Due to the shortage of GPs those factors should be made explicit at an early stage at medical school to increase the number of aspirants for general practice.</p

A Nonsense Mutation in TMEM95 Encoding a Nondescript Transmembrane Protein Causes Idiopathic Male Subfertility in Cattle

Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e.,idiopathic subfertility). Artificial insemination (AI) in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS). Imputed genotypes of 652, 856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV) population. Male reproductive ability (MRA) was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08x10(-59)). Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35, 671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome resequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c. 483C>A, p.Cys161X) in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic variation in TMEM95

Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer

Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to the tumor where they promote tumor growth and proliferation. Cancer stem cells (CSCs) are a population of tumor cells that are responsible for tumor initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, and its activity has been correlated with poor overall prognosis in human PC. Myeloid cells have been shown to impact tumor stemness, but the impact of immunosuppressive tumor-infiltrating granulocytic and monocytic myeloid-derived suppressor cells (Mo-MDSC) on ALDH1(Bright) CSCs and epithelial to mesenchymal transition is not well understood. In this study, we demonstrate that Mo-MDSC (CD11b(+)/Gr1(+)/Ly6G(−)/Ly6C(hi)) significantly increase the frequency of ALDH1(Bright) CSCs in a mouse model of PC. Additionally, there was significant upregulation of genes associated with epithelial to mesenchymal transition. We also found that human PC converts CD14(+) peripheral blood monocytes into Mo-MDSC (CD14(+)/HLA-DR(low/−)) in vitro, and this transformation is dependent on the activation of the STAT3 pathway. In turn, these Mo-MDSC increase the frequency of ALDH1(Bright) CSCs and promote mesenchymal features of tumor cells. Finally, blockade of STAT3 activation reversed the increase in ALDH1(Bright) CSCs. These data suggest that the PC tumor microenvironment transforms monocytes to Mo-MDSC by STAT3 activation, and these cells increase the frequency of ALDH1(Bright) CSCs. Therefore, targeting STAT3 activation may be an effective therapeutic strategy in targeting CSCs in PC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1527-x) contains supplementary material, which is available to authorized users

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.</p

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.</p