An?lisis de los efectos de la certificaci?n como Operador Econ?mico Autorizado en las Micro y Peque?as Empresas en el marco del Derecho Aduanero y Comercio Exterior peruano

La certificaci?n como Operador Econ?mico Autorizado otorgado por la Divisi?n de OEA de la Superintendencia Nacional de Aduanas y de Administraci?n Tributaria (SUNAT) califica a los operadores de comercio exterior como seguros y confiables en sus operaciones de log?stica internacional, lo que les hace beneficiarios de una serie de facilidades de car?cter operativo, econ?mico y de control en sus procesos de comercio exterior, generando as?, una disminuci?n en sus costos y tiempos de atenci?n a la carga que ingresa o sale del pa?s. Sin embargo, esta certificaci?n puede generar un impacto negativo al sector privado (personas naturales o jur?dicas), esencialmente a las Micro y Peque?as Empresas, si es que se detecta que la Administraci?n Aduanera como parte de su potestad normativa de liderar proyectos relacionados con la cadena log?stica del comercio exterior, est? ejerciendo una obligatoriedad impl?cita de implementar la certificaci?n para que las compa??as inicien o contin?en desarrollando sus operaciones aduaneras

Androgen-dependent stimulation of brain dopaminergic systems in the female European eel (Anguilla anguilla).

Dopamine (DA), a neurotransmitter present in all vertebrates, is involved in processes such as motor function, learning and behavior, sensory activities, and neuroendocrine control of pituitary hormone release. In the female eel, we analyzed how gonadal steroids regulate brain expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of DA. TH mRNA levels were assayed by quantitative real-time RT-PCR. TH-positive nuclei were also localized by in situ hybridization (ISH) and immunohistochemistry, and the location of TH nuclei that project to the pituitary was determined using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindicarbocyanine perchlorate retrograde tracing. Chronic in vivo treatment with testosterone increased TH mRNA specifically in the periglomerular area of the olfactory bulbs and in the nucleus preopticus anteroventralis (NPOav). NPOav was labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindicarbocyanine perchlorate, showing that this nucleus is hypophysiotropic in the eel. The nonaromatizable 5alpha-dihydrotestosterone gave identical results in both areas, whereas 17beta-estradiol had no stimulatory effect, showing that the observed stimulatory effects of testosterone were androgen dependent. In teleosts, DA neurons originating from the NPOav directly inhibit gonadotropic function, and our results indicate an androgen-dependent, positive feedback on this neuroendocrine control in the eel. In mammals, DA interneurons in the olfactory bulbs are involved in the enhancement of olfactory sensitivity and discrimination. Our results in the European eel suggest an androgen-dependent stimulation of olfactory processing, a sensory function believed to be important in eel navigation during its reproductive migration toward the oceanic spawning grounds. To our knowledge, this is the first evidence from any vertebrate of an androgen-dependent effect on DAergic activity in the olfactory bulbs, providing a new basis for understanding the regulation by gonadal steroids of central DAergic systems in vertebrates

Rapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg

The POKEMON Speckle Survey of Nearby M dwarfs. I. New Discoveries

M dwarfs are favorable targets for exoplanet detection with current instrumentation, but stellar companions can induce false positives and inhibit planet characterization. Knowledge of stellar companions is also critical to our understanding of how binary stars form and evolve. We have therefore conducted a survey of stellar companions around nearby M dwarfs, and here we present our new discoveries. Using the DSSI speckle imager at the 4.3-meter Lowell Discovery Telescope, and the similar NESSI instrument at the 3.5-meter WIYN telescope, we carried out a volume-limited survey of M-dwarf multiplicity to 15 parsecs, with a special emphasis on including the later M dwarfs that were overlooked in previous surveys. Additional brighter targets at larger distances were included for a total sample size of 1070 M dwarfs. Observations of these 1070 targets revealed 26 new companions; 22 of these systems were previously thought to be single. If all new discoveries are confirmed, then the number of known multiples in the sample will increase by 7.6%. Using our observed properties, as well as the parallaxes and 2MASS K magnitudes for these objects, we calculate the projected separation, and estimate the mass ratio and component spectral types, for these systems. We report the discovery of a new M-dwarf companion to the white dwarf Wolf 672 A, which hosts a known M-dwarf companion as well, making the system trinary. We also examine the possibility that the new companion to 2MASS J13092185-2330350 is a brown dwarf. Finally, we discuss initial insights from the POKEMON survey.Comment: 23 pages, 6 figures, 5 table

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C

Deconstructing interventions: approaches to studying behavior change techniques across obesity interventions

Deconstructing interventions into the specific techniques that are used to change behavior represents a new frontier in behavioral intervention research. This paper considers opportunities and challenges in employing the Behavior Change Techniques Taxonomy (BCTTv1) developed by Michie and colleagues, to code the behavior change techniques (BCTs) across multiple interventions addressing obesity and capture dose received at the technique level. Numerous advantages were recognized for using a shared framework for intervention description. Coding interventions at levels of the social ecological framework beyond the individual level, separate coding for behavior change initiation vs. maintenance, fidelity of BCT delivery, accounting for BCTs mode of delivery, and tailoring BCTs, present both challenges and opportunities. Deconstructing interventions and identifying the dose required to positively impact health-related outcomes could enable important gains in intervention science

TFAW survey II: six newly validated planets and 13 planet candidates from K2

Searching for Earth-sized planets in data from Kepler's extended mission (K2) is a niche that still remains to be fully exploited. The TFAW survey is an ongoing project that aims to re-analyse all light curves in K2 C1-C8 and C12-C18 campaigns with a wavelet-based detrending and denoising method, and the period search algorithm TLS to search for new transit candidates not detected in previous works. We have analysed a first subset of 24 candidate planetary systems around relatively faint host stars (10.9 < Kp < 15.4) to allow for follow-up speckle imaging observations. Using vespa and TRICERATOPS, we statistically validate six candidates orbiting four unique host stars by obtaining false-positive probabilities smaller than 1 per cent with both methods. We also present 13 vetted planet candidates that might benefit from other, more precise follow-up observations. All of these planets are sub-Neptune-sized with two validated planets and three candidates with sub-Earth sizes, and have orbital periods between 0.81 and 23.98 d. Some interesting systems include two ultra-short-period planets, three multiplanetary systems, three sub-Neptunes that appear to be within the small planet Radius Gap, and two validated and one candidate sub-Earths (EPIC 210706310.01, K2-411 b, and K2-413 b) orbiting metal-poor stars

Observations with the Differential Speckle Survey Instrument. X. Preliminary Orbits of K Dwarf Binaries and Other Stars

This paper details speckle observations of binary stars taken at the Lowell Discovery Telescope, the WIYN Telescope, and the Gemini telescopes between 2016 January and 2019 September. The observations taken at Gemini and Lowell were done with the Differential Speckle Survey Instrument (DSSI), and those done at WIYN were taken with the successor instrument to DSSI at that site, the NN-EXPLORE Exoplanet Star and Speckle Imager (NESSI). In total, we present 378 observations of 178 systems and we show that the uncertainty in the measurement precision for the combined data set is ~2 mas in separation, ~1-2 degrees in position angle depending on the separation, and $\sim$0.1 magnitudes in magnitude difference. Together with data already in the literature, these new results permit 25 visual orbits and one spectroscopic-visual orbit to be calculated for the first time. In the case of the spectroscopic-visual analysis, which is done on the trinary star HD 173093, we calculate masses with precision of better than 1% for all three stars in that system. Twenty-one of the visual orbits calculated have a K dwarf as the primary star; we add these to the known orbits of K dwarf primary stars and discuss the basic orbital properties of these stars at this stage. Although incomplete, the data that exist so far indicate that binaries with K dwarf primaries tend not to have low-eccentricity orbits at separations of one to a few tens of AU, that is, on solar-system scales

Observations of Binary Stars with the Differential Speckle Survey Instrument. IX. Observations of Known and Suspected Binaries, and a Partial Survey of Be Stars

We report 370 measures of 170 components of binary and multiple star systems, obtained from speckle imaging observations made with the Differential Speckle Survey Instrument at Lowell Observatory's Discovery Channel Telescope in 2015 through 2017. Of the systems studied, 147 are binary stars, 10 are seen as triple systems, and 1 quadruple system is measured. Seventy-six high-quality non-detections and fifteen newly resolved components are presented in our observations. The uncertainty in relative astrometry appears to be similar to our previous work at Lowell, namely linear measurement uncertainties of approximately 2 mas, and the relative photometry appears to be uncertain at the 0.1 to 0.15 magnitude level. Using these measures and those in the literature, we calculate six new visual orbits, including one for the Be star 66 Oph, and two combined spectroscopic-visual orbits. The latter two orbits, which are for HD 22451 (YSC 127) and HD 185501 (YSC 135), yield individual masses of the components at the level of 2 percent or better, and independent distance measures that in one case agrees with the value found in the Gaia DR2, and in the other disagrees at the 2-$\sigma$ level. We find that HD 22451 consists of an F6V+F7V pair with orbital period of $2401.1 \pm 3.2$ days and masses of $1.342 \pm 0.029$ and $1.236 \pm 0.026$ $M_{\odot}$. For HD 185501, both stars are G5 dwarfs that orbit one another with a period of $433.94 \pm 0.15$ days, and the masses are $0.898 \pm 0.012$ and $0.876 \pm 0.012$ $M_{\odot}$. We discuss the details of both the new discoveries and the orbit objects

The EARLY trials: a consortium of studies targeting weight control in young adults

Young adulthood has been identified as a high-risk period for the development of obesity but few interventions have been tested in this population. One way to escalate our learning about effective interventions is to test a number of interventions simultaneously as a consortium of research trials. This paper describes the Early Adult Reduction of weight through LifestYle intervention (EARLY) trials. Seven research sites were funded to conduct intervention trials, agreeing to test similar primary outcomes and cooperating to use a set of common measurement tools. The EARLY consortium was able to work cooperatively using an executive committee, a steering committee, workgroups and subcommittees to help direct the common work and implement a set of common protocol and measurement tools for seven independent but coordinated weight-related intervention trials. Using a consortium of studies to help young adults reach or maintain a healthy weight will result in increased efficiency and speed in understanding the most effective intervention strategies