Simultaneous Continuation of Infinitely Many Sinks Near a Quadratic Homoclinic Tangency

We prove that the $C^3$ diffeomorphisms on surfaces, exhibiting infinitely many sinksnear the generic unfolding of a quadratic homoclinic tangency of a dissipative saddle, can be perturbed along an infinite dimensional manifold of $C^3$ diffeomorphisms such that infinitely many sinks persist simultaneously. On the other hand, if they are perturbed along one-parameter families that unfold generically the quadratic tangencies, then at most a finite number of those sinks have continuation

Graphene-based mid-infrared room-temperature pyroelectric bolometers with ultrahigh temperature coefficient of resistance.

There is a growing number of applications demanding highly sensitive photodetectors in the mid-infrared. Thermal photodetectors, such as bolometers, have emerged as the technology of choice, because they do not need cooling. The performance of a bolometer is linked to its temperature coefficient of resistance (TCR, ∼2-4% K-1 for state-of-the-art materials). Graphene is ideally suited for optoelectronic applications, with a variety of reported photodetectors ranging from visible to THz frequencies. For the mid-infrared, graphene-based detectors with TCRs ∼4-11% K-1 have been demonstrated. Here we present an uncooled, mid-infrared photodetector, where the pyroelectric response of a LiNbO3 crystal is transduced with high gain (up to 200) into resistivity modulation for graphene. This is achieved by fabricating a floating metallic structure that concentrates the pyroelectric charge on the top-gate capacitor of the graphene channel, leading to TCRs up to 900% K-1, and the ability to resolve temperature variations down to 15 μK

Taxonomic Review of South American Butter Frogs: Phylogeny, Geographic Patterns, and Species Delimitation in the Leptodactylus latrans Species Group (Anura: Leptodactylidae)

The Leptodactylus latrans species group currently comprises eight medium- to large-sized frog species with a convoluted taxonomic history, particularly related to the specific limits of the L. latrans complex, and the species pair Leptodactylus chaquensis–Leptodactylus macrosternum. Their homogeneous external morphology and continental geographic distribution in South America have posed severe limitations to a comprehensive review, such that taxonomic consensus and species limits remain uncertain. This is further worsened by the presence of chromatic polymorphism among coexisting species that can hardly be distinguished by external morphology. Based on a large-scale geographic sampling including multilocus DNA analyses, and acoustic and morphological data, we provide a comprehensive evaluation of the taxonomic status and species limits of the L. latrans group, focusing on the resolution of the L. latranscomplex and the species pair L. chaquensis–L. macrosternum. We gathered 728 mitochondrial sequences from 429 localities, encompassing the entire geographic distribution of the group. Both generalized mixed Yule coalescent and automatic barcode gap discovery species delimitation methods recovered four major mitochondrial evolutionary lineages within the L. latrans complex, also supported by distribution patterns, multilocus molecular, morphological and/or bioacoustic data. One lineage is linked to nominal L. latrans,one revalidated as Leptodactylus luctator, and the other two are formally named and described. Another lineage encompasses all specimens previously assigned to the species pair L. chaquensis–L. macrosternum, clustered as a single evolutionary entity and is now regarded as L. macrosternum. We provide a revised diagnosis for these species based on acoustic data, morphological/chromatic variation, and phylogenetic relationships of all species currently included in the L. latrans group. Our findings reinforce the view that Neotropical diversity is highly underestimated and stress that appropriate geographic sampling in an integrative framework is crucial for the establishment of specific limits among broadly distributed and morphologically cryptic Neotropical frogs

Graphene-based mid-infrared room-temperature pyroelectric bolometers with ultrahigh temperature coefficient of resistance

There is a growing number of applications demanding highly sensitive photodetectors in the mid-infrared. Thermal photodetectors, such as bolometers, have emerged as the technology of choice, because they do not need cooling. The performance of a bolometer is linked to its temperature coefficient of resistance (TCR 2–4%K^(-1) for state-of-the-art materials). Graphene is ideally suited for optoelectronic applications, with a variety of reported photodetectors ranging from visible to THz frequencies. For the mid-infrared, graphene-based detectors with TCRs 4–11%K^(-1) have been demonstrated. Here we present an uncooled, mid-infrared photodetector, where the pyroelectric response of a LiNbO3 crystal is transduced with high gain (up to 200) into resistivity modulation for graphene. This is achieved by fabricating a floating metallic structure that concentrates the pyroelectric charge on the top-gate capacitor of the graphene channel, leading to TCRs up to 900%K^(-1), and the ability to resolve temperature variations down to 15mK

A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis

Exposure of human pancreatic beta cells to pro-inflammatory cytokines or metabolic stressors is used to model events related to type 1 and type 2 diabetes, respectively. Quantitative real-time PCR is commonly used to quantify changes in gene expression. The selection of the most adequate reference gene(s) for gene expression normalization is an important pre-requisite to obtain accurate and reliable results. There are no universally applicable reference genes, and the human beta cell expression of commonly used reference genes can be altered by different stressors. Here we aimed to identify the most stably expressed genes in human beta cells to normalize quantitative real-time PCR gene expression. We used comprehensive RNA-sequencing data from the human pancreatic beta cell line EndoC-βH1, human islets exposed to cytokines or the free fatty acid palmitate in order to identify the most stably expressed genes. Genes were filtered based on their level of significance (adjusted P-value >0.05), fold-change (|fold-change| <1.5) and a coefficient of variation <10%. Candidate reference genes were validated by quantitative real-time PCR in independent samples. We identified a total of 264 genes stably expressed in EndoC-βH1 cells and human islets following cytokines–or palmitate-induced stress, displaying a low coefficient of variation. Validation by quantitative real-time PCR of the top five genes ARF1, CWC15, RAB7A, SIAH1 and VAPA corroborated their expression stability under most of the tested conditions. Further validation in independent samples indicated that the geometric mean of ACTB and VAPA expression can be used as a reliable normalizing factor in human beta cells

Use of transgenic Aedes aegypti in Brazil: risk perception and assessment.

The OX513A strain of Aedes aegypti, which was developed by the British company Oxitec, expresses a self-limiting transgene that prevents larvae from developing to adulthood. In April 2014, the Brazilian National Technical Commission on Biosafety completed a risk assessment of OX513A and concluded that the strain did not present new biological risks to humans or the environment and could be released in Brazil. At that point, Brazil became the first country to approve the unconstrained release of a genetically modified mosquito. During the assessment, the commission produced a comprehensive list of ? and systematically analysed ? the perceived hazards. Such hazards included the potential survival to adulthood of immature stages carrying the transgene ? should the transgene fail to be expressed or be turned off by exposure to sufficient environmental tetracycline. Other perceived hazards included the potential allergenicity and/or toxicity of the proteins expressed by the gene, the potential for gene flow or increased transmission of human pathogens and the occupation of vacant breeding sites by other vector species. The Zika epidemic both elevated the perceived importance of Ae. aegypti as a vector ? among policy-makers and regulators as well as the general public ? and increased concerns over the release of males of the OX513A strain. We have therefore reassessed the potential hazards. We found that release of the transgenic mosquitoes would still be both safe and of great potential value in the control of diseases spread by Ae. aegypti, such as the chikungunya, dengue and Zika virus disease

Nitric Oxide-mediated cytotoxic effect induced by zoledronic acid treatment on Human Gingival Fibroblasts

Zoledronic acid (ZA) belongs to bisphosphonates (BPs), drugs administered to treat resorptive bone diseases. Although ZA is largely used in the clinical practice, significant adverse effects of ZA, such as osteonecrosis of the jaw (ONJ), were recorded. The aim of this work was to evaluate the role of Nitric Oxide (NO) in the in vitro response of Human Gingival Fibroblasts (HGFs) to 1, 5, 10 and 100μM ZA. HGFs morphology was evaluated through phase contrast microscopy and live/ dead staining; MTT and ELISA assays were applied to measure cell viability, Collagen Type I and IL6 secretion. ROS production and mitochondrial membrane potential were evaluated by flow cytometry; NO production and NOS activity by spectrophotometric analysis; eNOS and nNOS expression by fluorescence microscopy. Viable fibroblasts are evidenced in control sample while floating dead cells and cells close to detachment phase in ZA treated sample along with decreased level of Collagen Type I. Control sample shows higher number of viable cells respect to ZA treated one and ROS production increases when ZA is added. Released NO in ZA treated sample appears higher and NO overproduction is related to increased nNOS activity. IL 6 secretion level is higher in ZA treated sample than in control one. Our results suggest ROS involvement in NO overproduction, due to nNOS recruitment, both at low and high doses. In turn, NO release seems to be able to trigger the inflammatory response only when high doses are administered

Resistência ao octreotide LAR em pacientes acromegálicos com alta expressão do SSTR2: avaliação da expressão do AIP

We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6Apresentamos os dados clínicos e moleculares de dois pacientes com acromegalia tratados com octreotide LAR após cirurgia não curativa, com diferentes respostas a essa terapia medicamentosa. As expressões do receptor de somatostatina tipo 2 e 5 (SSTR2 e SSTR5) e da proteína de interação com o receptor aril hidrocarbono (AIP) foram analisadas por qPCR. Em ambos os casos, foi encontrada uma expressão elevada de SSTR2 e baixa do SSTR5. No entanto, o controle da doença foi obtido após tratamento com octreotide LAR em apenas um dos pacientes. Quando analisamos a expressão do AIP em ambos os casos, o paciente cuja doença foi controlada após a terapia medicamentosa apresentou uma expressão duas vezes maior do que a do paciente não controlado com o tratamento. Conclui-se que esses dois casos ilustram que, embora os análogos de somatostatina atualmente disponíveis se liguem preferencialmente ao SSTR2, alguns pacientes não respondem ao tratamento, apesar de uma elevada expressão desse receptor. Isso poderia ser explicado por alterações nas vias de sinalização pós-receptor, incluindo o envolvimento recentemente descrito da AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)PfizerPfizerNovartis BiocienciasNovartis BiocienciasIpsenIpse

Cardiac anisotropy in boundary-element models for the electrocardiogram

The boundary-element method (BEM) is widely used for electrocardiogram (ECG) simulation. Its major disadvantage is its perceived inability to deal with the anisotropic electric conductivity of the myocardial interstitium, which led researchers to represent only intracellular anisotropy or neglect anisotropy altogether. We computed ECGs with a BEM model based on dipole sources that accounted for a “compound” anisotropy ratio. The ECGs were compared with those computed by a finite-difference model, in which intracellular and interstitial anisotropy could be represented without compromise. For a given set of conductivities, we always found a compound anisotropy value that led to acceptable differences between BEM and finite-difference results. In contrast, a fully isotropic model produced unacceptably large differences. A model that accounted only for intracellular anisotropy showed intermediate performance. We conclude that using a compound anisotropy ratio allows BEM-based ECG models to more accurately represent both anisotropies