Spectral distortions from promising single and multifield inflationary models

Forthcoming missions probing the absolute intensity of the CMB are expected to be able to measure spectral distortions, which are deviations from its blackbody distribution. As cosmic inflation can induce spectral distortions, these experiments offer a possibility to further test the various promising inflationary proposals, whose predictions need to be carefully determined. After numerically fitting all inflationary observables to match current observations, we compute the predicted spectral distortions of various promising single and multifield inflationary models. The predictions of single-field inflationary models display deviations between 1% and 20% with respect to the standard cosmological model in the observable window, where multi-natural and axion-monodromy inflation stand out in this respect. In the case of multifield inflation, we observe a richer structure of the power spectrum, which, in the case of so-called hybrid attractors, yields spectral distortions about 100 times more intense than the standard signal. These observations open up questions about the relation among our results and other cosmological observables that are also to be probed soon.Comment: 30 pages + references, 17 figures, 6 table

Peak Power Estimation: A Case Study on CPU Cores

International audienceHigh peak power consumption during test may lead to yield loss. On the other hand, reducing too much test power may lead to test escape. In order to overcome this problem, test power has to mimic the power consumed during functional mode, being as high as possible but not crossing the frontier of over-consumption. Measuring power consumption is a very time consuming activity, therefore many works in the literature focused on the indirect ways to provide power consumption estimation in a fast manner. In this paper we concentrate on a similar issue, concentrating our effort on devising a fast method for the identification and estimation of the peak power produced by test patterns. In particular we provide a detailed discussion on case studies related to peak power estimation of CPU cores when executing functional patterns, the proposed method uses the gate-level description of the CPU to identify a subset of time points over the entire test pattern that are showing the most significant peak power values. The proposed methodology has been validated on two case studies synthesized in a 65nm industrial technology

FastIC: a fast integrated circuit for the readout of high performance detectors

This work presents the 8-channel FastIC ASIC developed in CMOS 65 nm technology suitable for the readout of positive and negative polarity sensors in high energy physics experiments, Cherenkov detectors and time-of-flight systems. The front-end can be configured to perform analog summation of up to 4 single-ended channels before discrimination in view of improving time resolution when segmenting a SiPM. The outputs encode the time-of-arrival information and linear energy measurement which captures the peak amplitude of the input signal in the 5 µA–25 mA input peak current range. Power consumption of the ASIC is 12 mW/ch with default settings. Measurements of single photon time resolution with a red-light laser source and a HPK SiPM S13360-3050CS are ≈140 ps FWHM

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy

Role of KLHL3 and dietary K⁺ in regulating KS-WNK1 expression

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordThe physiological role of the shorter isoform of WNK1 that is exclusively expressed in the kidney (KS-WNK1), with particular abundance in the distal convoluted tubule, remains elusive. KS-WNK1 despite lacking the kinase domain, is nevertheless capable of stimulating the NaCl cotransporter (NCC), apparently through activation of WNK4. It has recently been shown that a less severe form of the Familial Hyperkalemic Hypertension featuring only hyperkalemia is caused by missense mutations in the WNK1 acidic domain that preferentially affect CUL3-KLHL3 E3-induced degradation of KS-WNK1, rather than that of the full-length WNK1 (L-WNK1). Here we show that L-WNK1 is indeed less impacted by the CUL3-KLHL3 E3 ligase complex compared to KS-WNK1. We demonstrate that the unique 30 amino acid amino N-terminal fragment of KS-WNK1 is essential for its activating effect on NCC and recognition by KLHL3. We identify specific amino acid residues in this region critical for the functional effect of KS-WNK1 and KLHL3 sensitivity. To further explore this, we generated KLHL3-R528H knock-in mice that mimic human mutations causing Familial Hyperkalemic Hypertension. These mice revealed that the KLHL3 mutation specifically increased expression of KS-WNK1 in the kidney. We also observed that in wild type mice, expression of KS-WNK1 is only detectable after exposure to low potassium diet. These findings provide new insights into the regulation and function of KS-WNK1 by the CUL3-KLHL3 complex in DCT and indicate that this pathway is regulated by dietary K+ levels.National Institutes of Health (NIH)Conacyt MexicoPAPIIT UNAML'OréalMedical Research Council (MRC

First measurement of the CP-violating phase in B0s→J/ψ( → e+e−)ϕ decays

A flavour-tagged time-dependent angular analysis of B0 s → J/ψφ decays is presented where the J/ψ meson is reconstructed through its decay to an e +e − pair. The analysis uses a sample of pp collision data recorded with the LHCb experiment at centre-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb−1 . The CP-violating phase and lifetime parameters of the B0 s system are measured to be φs = 0.00 ± 0.28 ± 0.05 rad, ∆Γs = 0.115 ± 0.045 ± 0.011 ps−1 and Γs = 0.608 ± 0.018 ± 0.011 ps−1 where the first uncertainty is statistical and the second systematic. This is the first time that CP-violating parameters are measured in the B0 s → J/ψφ decay with an e +e − pair in the final state. The results are consistent with previous measurements in other channels and with the Standard Model predictions

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil.

BACKGROUND: In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. OBJECTIVES: 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. METHODS: We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. RESULTS AND CONCLUSIONS: The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course

Comparative Microsatellite Typing of New World Leishmania infantum Reveals Low Heterogeneity among Populations and Its Recent Old World Origin

Leishmania infantum (syn. L. chagasi) is the causative agent of visceral leishmaniasis (VL) in the New World (NW) with endemic regions extending from southern USA to northern Argentina. The two hypotheses about the origin of VL in the NW suggest (1) recent importation of L. infantum from the Old World (OW), or (2) an indigenous origin and a distinct taxonomic rank for the NW parasite. Multilocus microsatellite typing was applied in a survey of 98 L. infantum isolates from different NW foci. The microsatellite profiles obtained were compared to those of 308 L. infantum and 20 L. donovani strains from OW countries previously assigned to well-defined populations. Two main populations were identified for both NW and OW L. infantum. Most of the NW strains belonged to population 1, which corresponded to the OW MON-1 population. However, the NW population was much more homogeneous. A second, more heterogeneous, population comprised most Caribbean strains and corresponded to the OW non-MON-1 population. All Brazilian L. infantum strains belonged to population 1, although they represented 61% of the sample and originated from 9 states. Population analysis including the OW L. infantum populations indicated that the NW strains were more similar to MON-1 and non-MON-1 sub-populations of L. infantum from southwest Europe, than to any other OW sub-population. Moreover, similarity between NW and Southwest European L. infantum was higher than between OW L. infantum from distinct parts of the Mediterranean region, Middle East and Central Asia. No correlation was found between NW L. infantum genotypes and clinical picture or host background. This study represents the first continent-wide analysis of NW L. infantum population structure. It confirmed that the agent of VL in the NW is L. infantum and that the parasite has been recently imported multiple times to the NW from southwest Europe

Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer

BACKGROUND: Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. CC progression shows a continuum of neoplastic transitions until invasion. Matrix metalloproteinases (MMPs) and cathepsins play a central role on the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. MMPs -2 and -9 expression has been widely studied in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have been yet related with the progression and/or invasion of this type of cancer. METHODS: Three HPV18 CC cell lines, two HPV16 CC cell lines and three HPV16 tumor CC tissues were compared with three morphologically normal, HPV negative, cervical specimens by cDNA arrays. Overexpression of selected genes was confirmed by end point semiquantitative reverse transcription-PCR with densitometry. In situ hybridization and protein expression of selected genes was further studied by means of two tissue microarrays, one consisting of 10 HSIL and 15 CC and the other one of 15 normal cervical and 10 LSIL tissues. RESULTS: TIMP1, Integrins alpha 1 and 4, cadherin 2 and 11, Cathepsins F, B L2, MMP 9, 10 11 and 12 were upregulated and Cathepsin S, L, H and C, Cadherins 3 and 4, TIMP3, MMP 13, Elastase 2 and Integrin beta 8 were found to be downregulated by cDNA arrays. Endpoint RT-PCR with densitometry gave consistent results with the cDNA array findings for all three genes selected for study (CTSF, MMP11 and MMP12). In situ hybridization of all three genes confirmed overexpression in all the HSIL and CC. Two of the selected proteins were detected in LSIL, HSIL and CC by immunohistochemistry. CONCLUSION: Novel undetected CC promoting genes have been identified. Increased transcription of these genes may result in overexpression of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the pathogenesis of CC