Preliminary optical design of PANIC, a wide-field infrared camera for CAHA

In this paper, we present the preliminary optical design of PANIC (PAnoramic Near Infrared camera for Calar Alto), a wide-field infrared imager for the Calar Alto 2.2 m telescope. The camera optical design is a folded single optical train that images the sky onto the focal plane with a plate scale of 0.45 arcsec per 18 micron pixel. A mosaic of four Hawaii 2RG of 2k x 2k made by Teledyne is used as detector and will give a field of view of 31.9 arcmin x 31.9 arcmin. This cryogenic instrument has been optimized for the Y, J, H and K bands. Special care has been taken in the selection of the standard IR materials used for the optics in order to maximize the instrument throughput and to include the z band. The main challenges of this design are: to produce a well defined internal pupil which allows reducing the thermal background by a cryogenic pupil stop; the correction of off-axis aberrations due to the large field available; the correction of chromatic aberration because of the wide spectral coverage; and the capability of introduction of narrow band filters (~1%) in the system minimizing the degradation in the filter passband without a collimated stage in the camera. We show the optomechanical error budget and compensation strategy that allows our as built design to met the performances from an optical point of view. Finally, we demonstrate the flexibility of the design showing the performances of PANIC at the CAHA 3.5m telescope.Comment: This paper has been presented in the SPIE of Astronomical Telescopes and Instrumentation 2008 in Marseille (France

Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)

Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Texas; Estados UnidosFil: Benavides, Fernando. University of Texas; Estados UnidosFil: Blando, Jorge. University of Texas; Estados UnidosFil: Pérez, Carlos. University of Texas; Estados UnidosFil: Cardenas, Kim. University of Texas; Estados UnidosFil: Richie, Ellen. University of Texas; Estados UnidosFil: Knudsen, Erik S.. Thomas Jefferson University; Estados UnidosFil: Johnson, David G.. University of Texas; Estados UnidosFil: Senderowicz, Adrian M.. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research; Estados UnidosFil: Rodriguez Puebla, Marcelo L.. University of North Carolina; Estados UnidosFil: Conti, Claudio. University of Texas; Estados Unido

Amplification curve analysis: Data-driven multiplexing using real-time digital PCR

Information about the kinetics of PCR reactions are encoded in the amplification curve. However, in digital PCR (dPCR), this information is typically neglected by collapsing each amplification curve into a binary output (positive/negative). Here, we demonstrate that the large volume of raw data obtained from realtime dPCR instruments can be exploited to perform data-driven multiplexing in a single fluorescent channel using machine learning methods, by virtue of the information in the amplification curve. This new approach, referred to as amplification curve analysis (ACA), was shown using an intercalating dye (EvaGreen), reducing the cost and complexity of the assay and enabling the use of melting curve analysis for validation. As a case study, we multiplexed 3 carbapenem-resistant genes to show the impact of this approach on global challenges such as antimicrobial resistance. In the presence of single targets, we report a classification accuracy of 99.1% (N = 16188) which represents a 19.7% increase compared to multiplexing based on the final fluorescent intensity. Considering all combinations of amplification events (including coamplifications), the accuracy was shown to be 92.9% (N = 10383). To support the analysis, we derived a formula to estimate the occurrence of co-amplification in dPCR based on multivariate Poisson statistics, and suggest reducing the digital occupancy in the case of multiple targets in the same digital panel. The ACA approach takes a step towards maximizing the capabilities of existing real-time dPCR instruments and chemistries, by extracting more information from data to enable data-driven multiplexing with high accuracy. Furthermore, we expect that combining this method with existing probe-based assays will increase multiplexing capabilities significantly. We envision that once emerging point-of-care technologies can reliably capture real-time data from isothermal chemistries, the ACA method will facilitate the implementation of dPCR outside of the lab

Typological analysis of slidequakes emitted from landslides : experiments on an expander body pile and Sobradinho landslide (Brasilia, Brazil)

Reactivation of a landslide is usually accompanied by microseismic signals emitted from the deforming soil mass. The reproduction of similar signals in a physical model test conducted under control conditions can allow researchers to explore and test such complicated signals to improve the prediction of full-scale failure. The present study investigates the similarity between the slidequakes (microseismicity) naturally emitted from an existing colluvial landslide (Sobradinho, Brazil) in response to rainfalls and the emissions generated by a pullout test of an expander body (EB) pile in tropical soil under controlled conditions. The microseismic signals emitted from both experimental sites (i.e. the landslide and the EB pile test) were recorded and compared. Data were acquired by mini-arrays of four short-period seismometers. For the signal nomenclature, a typological scheme was adopted, in which sonograms/spectral contents of the signals were used. As a result, short duration microseismic signals were observed during the pullout test. In contrast, at the Sobradinho landslide, the testing detected signals of different characteristics whose source mechanisms have remained ambiguous, mainly because of the short duration of the data campaigns. However, at the landslide, propagating events were observed that might be attributed to the energies generated by the river bedload during the heavy rains. The present study offers some insight into the pre-collapse dynamic behavior of unstable slopes in clayey formations

Identification of viral infections in the prostate and evaluation of their association with cancer

<p>Abstract</p> <p>Background</p> <p>Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls.</p> <p>Methods</p> <p>130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method.</p> <p>Results</p> <p>R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined.</p> <p>Conclusions</p> <p>We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.</p

Coffee consumption and prostate cancer risk: further evidence for inverse relationship

<p>Abstract</p> <p>Background</p> <p>Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.</p> <p>Results</p> <p>Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.</p> <p>Conclusion</p> <p>Coffee consumption reduces the risk of aggressive PC but not the overall risk.</p

A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

Breast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients’ blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management