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Salting is one of the oldest methods of preserving food. The main limitation of salting is its extended processing time due to slow salt diffusion. A moderate electric field (MEF) can improve the mass transfer rate through electroporation. Regularly, mass transfer processes are modeled with Fick’s second law. However, due to the anisotropic nature of food microstructures, it might be more appropriate to use an anomalous model. The main objective of this study was to search for a phenomenological explanation for salt and water diffusion in the salmon brining process coupled with MEF. Salmon fillets were cut into finite cylinders (0.025 × 0.025 m) and brined in two salt concentrations (6 and 24% w/w NaCl) at 6 °C for 20 h. MEFs were applied in the range of 0 to 2 V/cm. The salt and water contents of the salmon were measured during the process. Fick’s second law and anomalous model based on fractional calculus were used to describe the diffusion phenomena. The results showed that an MEF tended to reduce the brining processing time and increase the salt content of salmon. This effect is predominantly due to an increase in the equilibrium salt concentration in the salmon tissue. Mathematical analysis shows that the anomalous diffusion model is more suitable for representing the brining process, exhibiting superdiffusion behavior (α > 1). An MEF accelerates the salt mass transfer into salmon tissue even at lower temperatures, significantly reducing the processing time. In addition, the diffusion process can be characterized with an anomalous model.

JAK3-activating mutations are commonly seen in chronic or acute hematologic malignancies affecting the myeloid, megakaryocytic, lymphoid, and natural killer (NK) cell compartment. Overexpression models of mutant JAK3 or pharmacologic inhibition of its kinase activity have highlighted the role that these constitutively activated mutants play in the T-cell, NK cell, and megakaryocytic lineages, but to date, the functional impact of JAK3 mutations at an endogenous level remains unknown. Here, we report a JAK3A572V knockin mouse model and demonstrate that activated JAK3 leads to a progressive and dose-dependent expansion of CD8+ T cells in the periphery before colonization of the bone marrow. This phenotype is dependent on the γc chain of cytokine receptors and presents several features of the human leukemic form of cutaneous T-cell lymphoma (L-CTCL), including skin involvements. We also showed that the JAK3A572V-positive malignant cells are transplantable and phenotypically heterogeneous in bone marrow transplantation assays. Interestingly, we revealed that activated JAK3 functionally cooperates with partial trisomy 21 in vivo to enhance the L-CTCL phenotype, ultimately leading to a lethal and fully penetrant disorder. Finally, we assessed the efficacy of JAK3 inhibition and showed that CTCL JAK3A572V-positive T cells are sensitive to tofacitinib, which provides additional preclinical insights into the use of JAK3 inhibitors in these disorders. Altogether, this JAK3A572V knockin model is a relevant new tool for testing the efficacy of JAK inhibitors in JAK3-related hematopoietic malignancies.

The National Aeronautics and Space Administration (NASA)’s Arctic Radiation-IceBridge Sea and Ice Experiment (ARISE) acquired unique aircraft data on atmospheric radiation and sea ice properties during the critical late summer to autumn sea ice minimum and commencement of refreezing. The C-130 aircraft flew 15 missions over the Beaufort Sea between 4 and 24 September 2014. ARISE deployed a shortwave and longwave broadband radiometer (BBR) system from the Naval Research Laboratory; a Solar Spectral Flux Radiometer (SSFR) from the University of Colorado Boulder; the Spectrometer for Sky-Scanning, Sun-Tracking Atmospheric Research (4STAR) from the NASA Ames Research Center; cloud microprobes from the NASA Langley Research Center; and the Land, Vegetation and Ice Sensor (LVIS) laser altimeter system from the NASA Goddard Space Flight Center. These instruments sampled the radiant energy exchange between clouds and a variety of sea ice scenarios, including prior to and after refreezing began. The most critical and unique aspect of ARISE mission planning was to coordinate the flight tracks with NASA Cloud and the Earth’s Radiant Energy System (CERES) satellite sensor observations in such a way that satellite sensor angular dependence models and derived top-of-atmosphere fluxes could be validated against the aircraft data over large gridbox domains of order 100–200 km. This was accomplished over open ocean, over the marginal ice zone (MIZ), and over a region of heavy sea ice concentration, in cloudy and clear skies. ARISE data will be valuable to the community for providing better interpretation of satellite energy budget measurements in the Arctic and for process studies involving ice–cloud–atmosphere energy exchange during the sea ice transition period.

The aim of this study was to develop a semi automatic image processing algorithm (AIPA) based on the simultaneous information provided by X-ray and radioisotopic images to determine the biokinetic models of Tc-99m radiopharmaceuticals from quantification of image radiation activity in murine models. These radioisotopic images were obtained by a CCD (charge couple device) camera coupled to an ultrathin phosphorous screen in a preclinical multimodal imaging system (Xtreme, Bruker). The AIPA consisted of different image processing methods for background, scattering and attenuation correction on the activity quantification. A set of parametric identification algorithms was used to obtain the biokinetic models that characterize the interaction between different tissues and the radiopharmaceuticals considered in the study. The set of biokinetic models corresponded to the Tc-99m biodistribution observed in different ex vivo studies. This fact confirmed the contribution of the semi-automatic image processing technique developed in this study.

Because the quality and shelf life of a frozen food greatly depend on the freezing processing time, its accurate estimation is highly relevant. In addition, the estimation of the freezing time is an enormous task due to the difficulty in developing a robust and accurate mathematical model and the need for appropriate thermophysical properties for an immense variety of foods. The objective of this study was to explore, via simulation, the capability of an inverse method to simultaneously determine the thermal conductivity ( k(T) ) and apparent volumetric specific heat ( C(T) ) of foods in the freezing temperature range (i.e., initial freezing point to −40 °C). Experiments and validation experiments were designed with the purpose of a systematic analysis and assessment of the potential capability of an inverse procedure for simultaneously determining the thermophysical properties of foods in the freezing temperature range. Assuming a one-dimensional freezing process and known thermophysical properties of the food material, temperatures were generated at different locations of the food sample by numerically solving the partial differential equation for heat conduction. The inverse method was designed to obtain the unknown parameters for the equations of the thermophysical properties C(T) and k(T) . The ability of the inverse method to simultaneously determine C(T) and k(T) in the freezing temperature range was investigated, and it was determined that the technique is accurate, rapid and robust to typical measurement errors. This fact was supported by a sensitivity coefficient analysis, which compared the direct-adjustment to the inverse method.

El efecto del ayuno ante-mortem en la calidad de carne de conejo ha sido poco estudiado. Se utilizaron 180 conejos machos de la raza Nueva Zelanda Blanca de 2,0 kg ± 0,04 de peso vivo (PV), los cuales fueron distribuidos en cuatro tratamientos (0, 4, 8 y 12 h de ayuno). Se utilizó un diseño completamente al azar, con el peso vivo al sacrificio como covariable. Se evaluaron las pérdidas de peso vivo (PV), el rendimiento de la canal, el pH inicial de la canal y final (24 h) de la carne. En el músculo Longissimus dorsi se evaluó el color, la capacidad de retención de agua (CRA), las pérdidas de cocción y la fuerza de corte. El PV disminuyó 0, 31, 54 y 76 g respecto al peso inicial, según el orden de los tratamientos. El rendimiento de la canal con 12 h de ayuno aumentó con respecto al testigo. El pH inicial fue mayor con 8 h respecto al resto de los tratamientos; sin embargo, el pH final fue menor con 12 h de ayuno con respecto al testigo. El color no se modificó por efecto de los tratamientos. La CRA disminuyó con 4 y 8 h de ayuno y la fuerza de corte se redujo con 8 h de ayuno, ambas respecto al testigo. Cuando se incrementó el tiempo de ayuno se reduce el peso de la víscera digestiva y urinaria e incrementa el rendimiento de la canal.

Aim Tropical forests store 25% of global carbon and harbour 96% of the world's tree species, but it is not clear whether this high biodiversity matters for carbon storage. Few studies have teased apart the relative importance of forest attributes and environmental drivers for ecosystem functioning, and no such study exists for the tropics. Location Neotropics. Methods We relate aboveground biomass (AGB) to forest attributes (diversity and structure) and environmental drivers (annual rainfall and soil fertility) using data from 144,000 trees, 2050 forest plots and 59 forest sites. The sites span the complete latitudinal and climatic gradients in the lowland Neotropics, with rainfall ranging from 750 to 4350 mm year−1. Relationships were analysed within forest sites at scales of 0.1 and 1 ha and across forest sites along large-scale environmental gradients. We used a structural equation model to test the hypothesis that species richness, forest structural attributes and environmental drivers have independent, positive effects on AGB. Results Across sites, AGB was most strongly driven by rainfall, followed by average tree stem diameter and rarefied species richness, which all had positive effects on AGB. Our indicator of soil fertility (cation exchange capacity) had a negligible effect on AGB, perhaps because we used a global soil database. Taxonomic forest attributes (i.e. species richness, rarefied richness and Shannon diversity) had the strongest relationships with AGB at small spatial scales, where an additional species can still make a difference in terms of niche complementarity, while structural forest attributes (i.e. tree density and tree size) had strong relationships with AGB at all spatial scales. Main conclusions Biodiversity has an independent, positive effect on AGB and ecosystem functioning, not only in relatively simple temperate systems but also in structurally complex hyperdiverse tropical forests. Biodiversity conservation should therefore be a key component of the UN Reducing Emissions from Deforestation and Degradation strategy.

From its inception, Universidad de Ingenieria y Tecnologia (UTEC) has had the vision of causing a disruptive change in society by educating a new generation of holistic engineers. The university has recently embarked on a radical transformation of its educational model, in order to deliver its promise. A flexible curriculum provides students not only with a strong STHEAM backbone imparted in a student-centered, active-learning format, but also exposes them to real engineering challenges and promotes the acquisition of professional skills from the onset. For this radical change to be implemented successfully, UTEC has decided to design and launch a Laboratory for Educational Innovation, called Moray. Moray has been conceived as an open platform, consisting of a common space and a set of protocols through which faculty, students, staff, and experts from top universities worldwide can work interdisciplinarily and collaboratively, towards the enhancement of learning experiences in higher education.

Chagas disease vector control campaigns are being conducted in Latin America, but little is known about medium-term or long-term effectiveness of these efforts, especially in urban areas. After analyzing entomologic data for 56,491 households during the treatment phase of a Triatoma infestans bug control campaign in Arequipa, Peru, during 2003–2011, we estimated that 97.1% of residual infestations are attributable to untreated households. Multivariate models for the surveillance phase of the campaign obtained during 2009–2012 confirm that nonparticipation in the initial treatment phase is a major risk factor (odds ratio [OR] 21.5, 95% CI 3.35–138). Infestation during surveillance also increased over time (OR 1.55, 95% CI 1.15–2.09 per year). In addition, we observed a negative interaction between nonparticipation and time (OR 0.73, 95% CI 0.53–0.99), suggesting that recolonization by vectors progressively dilutes risk associated with nonparticipation. Although the treatment phase was effective, recolonization in untreated households threatens the long-term success of vector control.

We calculated Antarctic sea-ice freeboard and thickness for ICESat and ATM campaigns. A Gridded ATM freeboard map of nine IceBridge campaigns in October 2009, 2010, and 2011 is shown in Figure 1.

We derive mass changes of the Greenland ice sheet (GIS) for 2003–07 from ICESat laser altimetry and compare them with results for 1992–2002 from ERS radar and airborne laser altimetry. The GIS continued to grow inland and thin at the margins during 2003–07, but surface melting and accelerated flow significantly increased the marginal thinning compared with the 1990s. The net balance changed from a small loss of 7 ± 3 Gt a−1 in the 1990s to 171 ± 4 Gt a−1 for 2003–07, contributing 0.5 mm a−1 to recent global sea-level rise. We divide the derived mass changes into two components: (1) from changes in melting and ice dynamics and (2) from changes in precipitation and accumulation rate. We use our firn compaction model to calculate the elevation changes driven by changes in both temperature and accumulation rate and to calculate the appropriate density to convert the accumulation-driven changes to mass changes. Increased losses from melting and ice dynamics (17–206 Gt a−1) are over seven times larger than increased gains from precipitation (10–35 Gt a−1) during a warming period of ∼2 K (10 a)−1 over the GIS. Above 2000 m elevation, the rate of gain decreased from 44 to 28 Gt a−1, while below 2000 m the rate of loss increased from 51 to 198 Gt a−1. Enhanced thinning below the equilibrium line on outlet glaciers indicates that increased melting has a significant impact on outlet glaciers, as well as accelerating ice flow. Increased thinning at higher elevations appears to be induced by dynamic coupling to thinning at the margins on decadal timescales.

IFN-γ plays a central role in antitumor immunity. T cell Ig and mucin domain (Tim-3) is expressed on IFN-γ–producing Th1 cells; on interaction with its ligand, galectin-9, Th1 immunity is terminated. In this study, we show that transgenic overexpression of Tim-3 on T cells results in an increase in CD11b+Ly-6G+ cells and inhibition of immune responses. Molecular characterization of CD11b+Ly-6G+ cells reveals a phenotype consistent with granulocytic myeloid-derived suppressor cells. Accordingly, we find that modulation of the Tim-3/galectin-9 (Gal-9) pathway impacts on tumor growth. Similarly, overexpression of Tim-3 ligand, Gal-9, results in an increase in CD11b+Ly-6G+ cells and inhibition of immune responses. Loss of Tim-3 restores normal levels of CD11b+Ly-6G+ cells and normal immune responses in Gal-9 transgenic mice. Our data uncover a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses and identifies this pathway as a therapeutic target in diseases where myeloid-derived suppressor cells are disadvantageous.

From its inception, Universidad de Ingeniería y Tecnología (UTEC) has functioned under the mandate of causing a disruptive effect in society by educating a new generation of holistic engineers bound to become empowered change agents. The university has recently embarked on a radical transformation of its educational model, in order to deliver this promise. A flexible curriculum provides students not only with a strong STHEAM backbone imparted in a student-centered active-learning format, but also exposes them to real engineering challenges and promotes the acquisition of professional skills from the onset. For this change to be implemented successfully, UTEC has decided to design and launch a Laboratory for Educational Innovation, called Moray. Conceived as an open platform, Moray sits at the intersection of physical and virtual spaces and is organized around flexible protocols that allow faculty, students, staff, and experts from top universities worldwide to work interdisciplinarily and collaboratively, towards the enhancement of teaching and learning dynamics in higher education.

There are between 8 and 11 million cases of America Human Trypanosomiasis, commonly known as Chagas disease, in Latin America. Chagas is endemic in southern Peru, especially the Arequipa region, where it has expanded from poor, rural areas to periurban communities. This paper summarizes the findings of four studies in periurban Arequipa: on determinants of disease-vector infestation; on prevalence, spatial patterns, and risk factors of Chagas; on links between migration, settlement patterns, and disease-vector infestation; and on the relationship between discordant test results and spatially clustered transmission hotspots. These studies identified two risk factors associated with the disease: population dynamics and the urbanization of poverty. Understanding the disease within this new urban context will allow for improved public health prevention efforts and policy initiatives. Discovered in 1909 by Brazilian physician Carlos Chagas, American Human Trypanosomiasis is a chronic and potentially life-threatening illness found throughout Latin America (Moncayo, 2003). Indeed, it is estimated that there are between 8 and 11 million cases in Mexico and Central and South America (Centers for Disease Control [CDC], 2009). Chagas disease, as it is most commonly known, is endemic in southern Peru, especially in the region of Arequipa. Once thought to be limited to poor, rural areas, the disease is now appearing in the periurban communities that surround Arequipa City, the capital of the region (Cornejo del Carpio, 2003). Understanding the urbanization of Chagas disease will allow public health and medical professionals to better combat the further transmission of the disease. After providing an overview of Chagas and introducing the scope of the disease in Latin America, this paper will summarize the findings of four recent studies conducted in periurban districts in Arequipa. Ultimately, this paper seeks to identify the risk factors associated with Chagas infection in Arequipa’s periurban communities.

The article “Preclinical Biokinetic Modelling of Tc-99m Radiophamaceuticals Obtained from Semi-Automatic Image Processing”, written by Luz G. Cornejo-Aragon, Clara L. Santos-Cuevas, Blanca E. Ocampo-Garcia, Isaac Chairez-Oria, Lorenza Diaz-Nieto, Janice Garcia-Quiroz was originally published Online First without open access. After publication in volume [37], issue [6], page [887–898] the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) [2018] and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made

JAK3 is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells and that has been implicated in the signal transduction of the common gamma chain subfamily of cytokine receptors. As a result, JAK3 plays an essential role in hematopoieisis during T cell development. JAK3 inactivating mutations result in immunodeficiency syndromes (SCID) in both humans and mice. Recent data indicate that abnormal activation of JAK3 due to activating mutations is also found in human hematological malignancies, including acute megakaryoblastic leukemia (AMKL) and cutaneous T celI lymphoma (CTCL). After a brief summary of the JAK3 structure and function, we will review the evidence on the emerging role of JAK3 activation in hematological malignancies that warrant further studies to test the relevance of specific inhibition of JAK3 as a therapeutic approach to these challenging clinical entities.

The tyrosine kinase JAK3 plays a well-established role during normal lymphocyte development and is constitutively phosphorylated in several lymphoid malignancies. However, its contribution to lymphomagenesis remains elusive. In this study, we used the newly identified activating JAK3A572V mutation to elucidate the effect of constitutive JAK3 signaling on murine lymphopoiesis. In a bone marrow transplantation model, JAK3A572V induces an aggressive, fatal, and transplantable lymphoproliferative disorder characterized by the expansion of CD8+TCRαβ+CD44+CD122+Ly-6C+ T cellsthat closely resemble an effector/memory T-cell subtype. Compared with wild-type counterparts, these cells show increased proliferative capacities in response to polyclonal stimulation, enhanced survival rates with elevated expression of Bcl-2, and increased production of interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), correlating with enhanced cytotoxic abilities against allogeneic target cells. Of interest, the JAK3A572V disease is epidermotropic and produces intraepidermal microabscesses. Taken together, these clinical features are reminiscent of those observed in an uncommon but aggressive subset of CD8+ human cutaneous T-cell lymphomas (CTCLs). However, we also observed a CD4+ CTCL-like phenotype when cells are transplanted in an MHC-I–deficient background. These data demonstrate that constitutive JAK3 activation disrupts T-cell homeostasis and induces lymphoproliferative diseases in mice.

To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-RasG12D murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to γ-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways.

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

Activated tyrosine kinases have been frequently implicated in the pathogenesis of cancer, including acute myeloid leukemia (AML), and are validated targets for therapeutic intervention with small-molecule kinase inhibitors. To identify novel activated tyrosine kinases in AML, we used a discovery platform consisting of immunoaffinity profiling coupled to mass spectrometry that identifies large numbers of tyrosine-phosphorylated proteins, including active kinases. This method revealed the presence of an activated colony-stimulating factor 1 receptor (CSF1R) kinase in the acute megakaryoblastic leukemia (AMKL) cell line MKPL-1. Further studies using siRNA and a small-molecule inhibitor showed that CSF1R is essential for the growth and survival of MKPL-1 cells. DNA sequence analysis of cDNA generated by 5′RACE from CSF1R coding sequences identified a novel fusion of the RNA binding motif 6 (RBM6) gene to CSF1R gene generated presumably by a t(3;5)(p21;q33) translocation. Expression of the RBM6-CSF1R fusion protein conferred interleukin-3 (IL-3)–independent growth in BaF3 cells, and induces a myeloid proliferative disease (MPD) with features of megakaryoblastic leukemia in a murine transplant model. These findings identify a novel potential therapeutic target in leukemogenesis, and demonstrate the utility of phosphoproteomic strategies for discovery of tyrosine kinase alleles.

This investigation describes the development of a MATLAB algorithm to quantify automatically the radiation activity and kinetics from images acquired with the preclinical imaging system XTREME (Bruker) using 99mTc-Bombesin/99mTc-RGD2 radiopharmaceuticals in murine models.

Simple interventions may facilitate vector control and prevent periurban transmission of Chagas disease., In Arequipa, Peru, vectorborne transmission of Chagas disease by Triatoma infestans has become an urban problem. We conducted an entomologic survey in a periurban community of Arequipa to identify risk factors for triatomine infestation and determinants of vector population densities. Of 374 households surveyed, triatomines were collected from 194 (52%), and Trypanosoma cruzi–carrying triatomines were collected from 72 (19.3%). Guinea pig pens were more likely than other animal enclosures to be infested and harbored 2.38× as many triatomines. Stacked brick and adobe enclosures were more likely to have triatomines, while wire mesh enclosures were protected against infestation. In human dwellings, only fully stuccoed rooms were protected against infestation. Spatially, households with triatomines were scattered, while households with T. cruzi–infected triatomines were clustered. Keeping small animals in wire mesh cages could facilitate control of T. infestans in this densely populated urban environment.

Changes in ice mass are estimated from elevation changes derived from 10.5 years (Greenland) and 9 years (Antarctica) of satellite radar altimetry data from the European Remote-sensing Satellites ERS-1 and -2. For the first time, the dH/dt values are adjusted for changes in surface elevation resulting from temperature-driven variations in the rate of firn compaction. The Greenland ice sheet is thinning at the margins (–42 ± 2Gta¯1 below the equilibrium-line altitude (ELA)) and growing inland (+53 ± 2Gta-1 above the ELA) with a small overall mass gain (+11 ± 3Gta–1; –0.03 mma–1 SLE (sea-level equivalent)). The ice sheet in West Antarctica (WA) is losing mass (–47 ± 4Gta–1) and the ice sheet in East Antarctica (EA) shows a small mass gain (+16 ± 11 Gta–1) for a combined net change of –31 ± 12 Gta–1 (+0.08mma–1 SLE). The contribution of the three ice sheets to sea level is +0.05±0.03mma–1. The Antarctic ice shelves show corresponding mass changes of –95 ± 11 Gta–1 in WA and +142 ± 10Gta–1 in EA. Thinning at the margins of the Greenland ice sheet and growth at higher elevations is an expected response to increasing temperatures and precipitation in a warming climate. The marked thinnings in the Pine Island and Thwaites Glacier basins of WA and the Totten Glacier basin in EA are probably ice- dynamic responses to long-term climate change and perhaps past removal of their adjacent ice shelves. The ice growth in the southern Antarctic Peninsula and parts of EA may be due to increasing precipitation during the last century.

Comparison of the distribution of seasonal variations in surface elevation derived from a firn-densification–elevation model with observed variations derived from ERS-1/-2 satellite radar altimetry shows close similarity in the patterns of the amplitude of the variations over the North Greenland ice sheet. The amplitudes of the seasonal variations decrease from west to east and from south to north, determined by the accumulation rate and the surface-temperature distribution pattern. Several methods of estimating the amplitude of the seasonal variation in the observations are compared, including the use of a three-frequency sinusoidal function derived from the modeled seasonal variation that is asymmetric. The resulting correlation coefficient between the observed amplitude, estimated with the three-frequency function, and the modeled amplitude is 0.66 and the slope is 0.7. Residual differences may be caused by interannual variability in accumulation and temperature and other approximations in the model.

The multi-element analysis of aerosol samples collected on polycarbonate filters and the wet digestion procedure in open vessel were investigated. The concentrations of Na, K, Ca, Mg and Zn were determined by flame atomic absorption spectrometry with a micro injection system while Cd, Pb, Cu, Ni and V were determined by graphite furnace atomic absorption spectrometry (AAS). NIES N[ddot] 8 “Vehicle Exhaust Particulate” Certified Reference Material from the Japan Environment Agency was used to study the decomposition of the samples. Different treatments were applied in order to completely dissolve the aerosol samples. It was found that, from all the methods tested, attack with micro-quantities of HNO3 and HCIO4 in an air pressure digestion system was the best procedure for the determination of the elements by AAS. The recommended method was appropriate for all elements and it was applied to real samples. Two nondestructive analytical techniques for the determination of Na, K, Ca, Mg, Zn and Pb have...

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1, Author Summary Chagas disease has become an urban problem in the city of Arequipa, Peru, yet there are very few people exhibiting severe symptoms of the disease. Severe symptoms often do not appear until decades after infection. To determine why so few people were exhibiting severe symptoms, we used a new method, epicenter regression, to trace the history of Chagas disease transmission in a community of Arequipa, Peru. Our findings suggest that transmission in Arequipa occurred through a series of small epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before the insect that carries Chagas disease, Triatoma infestans, was eliminated by insecticide application. Most human infections in the study community arose over a brief period of time immediately prior to the insecticide application. According to our findings, the severe symptoms of Chagas disease are expected to be absent from the community because of the short duration of infection with the parasite, even among older individuals with Chagas disease.

The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.

Background The history of Chagas disease control in Peru and many other nations is marked by scattered and poorly documented vector control campaigns. The complexities of human migration and sporadic control campaigns complicate evaluation of the burden of Chagas disease and dynamics of Trypanosoma cruzi transmission. Methodology/Principal Findings We conducted a cross-sectional serological and entomological study to evaluate temporal and spatial patterns of T. cruzi transmission in a peri-rural region of La Joya, Peru. We use a multivariate catalytic model and Bayesian methods to estimate incidence of infection over time and thereby elucidate the complex history of transmission in the area. Of 1,333 study participants, 101 (7.6%; 95% CI: 6.2–9.0%) were confirmed T. cruzi seropositive. Spatial clustering of parasitic infection was found in vector insects, but not in human cases. Expanded catalytic models suggest that transmission was interrupted in the study area in 1996 (95% credible interval: 1991–2000), with a resultant decline in the average annual incidence of infection from 0.9% (95% credible interval: 0.6–1.3%) to 0.1% (95% credible interval: 0.005–0.3%). Through a search of archival newspaper reports, we uncovered documentation of a 1995 vector control campaign, and thereby independently validated the model estimates. Conclusions/Significance High levels of T. cruzi transmission had been ongoing in peri-rural La Joya prior to interruption of parasite transmission through a little-documented vector control campaign in 1995. Despite the efficacy of the 1995 control campaign, T. cruzi was rapidly reemerging in vector populations in La Joya, emphasizing the need for continuing surveillance and control at the rural-urban interface., Author Summary The historically rural problem of Chagas disease is increasing in urban areas in Latin America. Peri-rural development may play a critical role in the urbanization of Chagas disease and other parasitic infections. We conducted a cross-sectional study in an urbanizing rural area in southern Peru, and we encountered a complex history of Chagas disease in this peri-rural environment. Specifically, we discovered: (1) long-standing parasite transmission leading to substantial burden of infection; (2) interruption in parasite transmission resulting from an undocumented insecticide application campaign; (3) relatively rapid re-emergence of parasite-infected vector insects resulting from an unsustained control campaign; (4) extensive migration among peri-rural inhabitants. Long-standing parasite infection in peri-rural areas with highly mobile populations provides a plausible mechanism for the expansion of parasite transmission to nearby urban centers. Lack of commitment to control campaigns in peri-rural areas may have unforeseen and undesired consequences for nearby urban centers. Novel methods and perspectives are needed to address the complexities of human migration and erratic interventions.

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20–30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections.

The rational design of interventions is critical to controlling communicable diseases, especially in urban environments. In the case of the Chagas disease vector Triatoma infestans , successful control is stymied by the return of the insect after the effectiveness of the insecticide wanes. Here, we adapt a genetic algorithm, originally developed for the travelling salesman problem, to improve the spatio-temporal design of insecticide campaigns against T. infestans , in a complex urban environment. We find a strategy that reduces the expected instances of vector return 34-fold compared with the current strategy of sequential insecticide application to spatially contiguous communities. The relative success of alternative control strategies depends upon the duration of the effectiveness of the insecticide, and it shows chaotic fluctuations in response to unforeseen delays in a control campaign. We use simplified models to analyse the outcomes of qualitatively different spatio-temporal strategies. Our results provide a detailed procedure to improve control efforts for an urban Chagas disease vector, as well as general guidelines for improving the design of interventions against other disease agents in complex environments.

Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting.

Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two-megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus oncogene (MPL) efficiently induced a short-latency AMKL that recapitulated all the features of human AMKL, including megakaryoblast hyperproliferation and maturation block, thrombocytopenia, organomegaly, and extensive fibrosis. Our results establish that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL.

Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized α-helical peptides that target a critical protein–protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL. The NOTCH complex is of tremendous interest because of its role as a master developmental regulator of gene transcription, a substrate for γ-secretase and an oncogene inappropriately activated in many cancers including T-cell leukaemias. Like the majority of transcription factors, NOTCH was thought to be untargetable by synthetic cell-permeable molecules. But now a promising NOTCH antagonist has been designed, and found to be effective in reducing leukaemia growth in a mouse model. The hydrocarbon-stapled peptide SAHM1 acts by preventing assembly of the active transcriptional complex, providing a potentially valuable tool for studies of the role of NOTCH and a starting point for therapeutic agents. In addition, the direct targeting of transactivation complexes may be applicable to several other transcription factor complexes previously considered untargetable. It is notoriously difficult to target transcription factors with aberrant activity in cancer. Inappropriate activation of the NOTCH complex of transcription factors is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia. The design of synthetic, cell-permeable, stabilized α-helical peptides that disrupt protein–protein interactions in NOTCH is now described.

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13–0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

Background. Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones. Methods. We conducted a serosurvey of 1615 children