1,844 research outputs found
Spanning Properties of Theta-Theta Graphs
We study the spanning properties of Theta-Theta graphs. Similar in spirit
with the Yao-Yao graphs, Theta-Theta graphs partition the space around each
vertex into a set of k cones, for some fixed integer k > 1, and select at most
one edge per cone. The difference is in the way edges are selected. Yao-Yao
graphs select an edge of minimum length, whereas Theta-Theta graphs select an
edge of minimum orthogonal projection onto the cone bisector. It has been
established that the Yao-Yao graphs with parameter k = 6k' have spanning ratio
11.67, for k' >= 6. In this paper we establish a first spanning ratio of
for Theta-Theta graphs, for the same values of . We also extend the class of
Theta-Theta spanners with parameter 6k', and establish a spanning ratio of
for k' >= 5. We surmise that these stronger results are mainly due to a
tighter analysis in this paper, rather than Theta-Theta being superior to
Yao-Yao as a spanner. We also show that the spanning ratio of Theta-Theta
graphs decreases to 4.64 as k' increases to 8. These are the first results on
the spanning properties of Theta-Theta graphs.Comment: 20 pages, 6 figures, 3 table
Physical mapping of a powdery mildew resistance related gene Hv-S/TPK by FISH with a TAC clone in wheat
Dissertação de mestrado integrado em Medicina (Hematologia), apresentado á Faculdade de Medicina da Universidade de Coimbra.A Policitemia Vera (PV) é uma doença clonal de etiologia desconhecida, na maior parte dos casos, que envolve a célula estaminal progenitora hematopoiética multipotencial. É uma neoplasia mieloproliferativa crónica (NMP) que se caracteriza pela expansão das três linhas celulares hematopoiéticas: eritróide, granulocítica e megacariocítica, com predomínio da primeira, de modo independente dos mecanismos normais de regulação da eritropoiese. Além disso, as células têm aspecto morfológico normal, a fibrose medular é pouco significativa e os níveis de eritropoietina (Epo) são habitualmente normais a baixos. Além da hipercelularidade medular com sobreprodução de uma ou de todas as linhas celulares, a doença cursa com hematopoiese extramedular, hiperviscosidade, propensão para complicações como trombose ou hemorragia e risco de desenvolvimento de mielofibrose ou transformação em leucemia aguda.
A descrição relativamente recente da associação de uma mutação no gene JAK2, localizado no cromosoma 9p24, com as doenças mieloproliferativas clássicas negativas para BCR-ABL, como a PV, veio permitir avanços significativos na compreensão da patofisiologia deste grupo de doenças hematológicas. A mutação provoca uma alteração do aminoácido V (valina) para F (fenilalanina) na posição 617 (JAK2V617F). De acordo com os dados publicados, a frequência da detecção da mutação JAK2V617F em doentes com PV é de cerca de 95%.
A proteína JAK2 é uma tirosina cinase citoplasmática, que se encontra associada ao domínio intracelular dos receptores de citocinas (como a Epo e trombopoietina - Tpo), e de factores de crescimento, essenciais para a função destes receptores. A mutação da JAK2 conduz à activação constitutiva dos receptores, independente da ligação à respectiva citocina e/ou hipersensibilidade a factores de crescimento, com consequente activação de múltiplas vias de sinalização intracelulares como a JAK/STAT (Janus Kinase/Signal Transductor and activator of transcription), a PI3K (fosfatidilinositol 3 cinase) e a MAPK (proteína cinase activadora de mitose), envolvidas na transformação e proliferação dos progenitores hematopoiéticos. Por outro lado, as células evidenciam alteração na diferenciação terminal e resistência à apoptose in vitro que poderá estar relacionada com o aumento da expressão da proteína anti-apoptótica Bcl-XL.
Além dos avanços no diagnóstico, a detecção da mutação JAK2V617F tem contribuido para melhorar a classificação e a terapêutica dos doentes com PV. Deste modo, o conhecimento dos mecanismos moleculares envolvidos na PV tem levado os investigadores à descoberta de novos fármacos dirigidos ao defeito molecular, permitindo novas abordagem terapêuticas mais eficazes e provavelmente de menor toxicidade.
Este trabalho procura fazer uma revisão sobre o actual conhecimento da caracterização molecular e clínica da PV e quais as suas implicações no diagnóstico e abordagem terapêutica desta NMP.Polycythemia Vera (PV) is a clonal disease of unknown etiology, which often involves the pluripotential hematopoietic stem cell. This disease integrates the family of chronic myeloproliferative neoplasm (MPN) and is characterized by the growth of the three hematopoietic celular lineages: granulocytic, megakaryocytic and erythroid, with predominance of the last one and regardless the normal mechanisms of erythropoiesis regulation. Moreover, cells have normal morphological aspect, bone marrow shows slight fibrosis and the levels of erythropoietin (Epo) usually vary from normal to low. Besides marrow hypercellularity with overproduction of one or all the celular lineages, the disease courses with extramedullary hematopoiesis, hyperviscosity, leading to complications such as thrombosis or bleeding and risk of transformation to myelofibrosis or acute leukemia.
Recently it has been described the association between the mutation in the JAK2 gene, located on chromosome 9p24, with the classic myeloproliferative disorders BCR-ABL negative, such as PV, which has brought significant advances in the understanding of the pathophysiology of this group of hematologic malignancies. The mutation causes a change of amino acid V (valine) to F (phenylalanine) at position 617 (JAK2V617F). According to published data, the frequency of JAK2V617F mutation detected in patients with PV is about 95%.
JAK2 protein is a cytoplasmic tyrosine kinase, which is associated to the intracelular domain of cytokine receptors, such as Epo and thrombopoietin (Tpo), and growth factors which are essential to the function of these receptors. JAK2 mutation leads to the constitutive receptors activation, independent of connection to their cytokine and / or hypersensitivity to growth factors, with consequent activation of multiple intracellular signaling pathways such as JAK / STAT (Janus Kinase / Signal transducer and transcription activator), the PI3K (phosphatidylinositol 3 kinase) and MAPK (Mitogen-activated protein), involved in the transformation and proliferation of hematopoietic progenitors. Moreover, the cells show changes in terminal differentiation and resistance to in vitro apoptosis which is possibly related to the increasing expression of anti-apoptotic protein Bcl-XL.
In addition to the advances in diagnosis, detection of JAK2V617F mutation has contributed to the improvement of classification and treatment in patients with PV. Thus, knowledge of the molecular mechanisms involved in PV has led investigators to the discovery of new drugs targeting molecular defects, allowing new therapeutic approach more efficient and probably less toxic.
The aim of this article is to review the current knowledge of clinical and molecular characterization of PV, and its implications on the diagnosis and therapeutic approach of this myeloproliferative disorder
Physical mapping of a powdery mildew resistance related gene Hv-S/TPK by FISH with a TAC clone in wheat
Deciphering the past to inform the future: preparing for the next (“really big”) extreme event
Climate change will bring more extremes in temperature and precipitation that will impact productivity and ecosystem resilience throughout agroecosystems worldwide. Historical events can be used to identify drivers that impact future events. A catastrophic drought in the US in the 1930s resulted in an abrupt boundary between areas severely impacted by the Dust Bowl and areas that were less severely affected. Historical primary production data confirmed the location of this boundary at the border between two states (Nebraska and Iowa). Local drivers of weather and soils explained production responses across the boundary before and after the drought (1926–1948). During the drought, however, features at the landscape scale (soil properties and wind velocities) and regional scale (the Missouri River, its floodplain, and the nearby Loess Hills) explained most of the observed variance in primary production. The impact of future extreme events may be affected by land surface properties that either accentuate or ameliorate the effects of these events. Consideration of large-scale geomorphic processes may be necessary to interpret and manage for catastrophic events
Fully gapped topological surface states in BiSe films induced by a d-wave high-temperature superconductor
Topological insulators are a new class of materials, that exhibit robust
gapless surface states protected by time-reversal symmetry. The interplay
between such symmetry-protected topological surface states and symmetry-broken
states (e.g. superconductivity) provides a platform for exploring novel quantum
phenomena and new functionalities, such as 1D chiral or helical gapless
Majorana fermions, and Majorana zero modes which may find application in
fault-tolerant quantum computation. Inducing superconductivity on topological
surface states is a prerequisite for their experimental realization. Here by
growing high quality topological insulator BiSe films on a d-wave
superconductor BiSrCaCuO using molecular beam epitaxy,
we are able to induce high temperature superconductivity on the surface states
of BiSe films with a large pairing gap up to 15 meV. Interestingly,
distinct from the d-wave pairing of BiSrCaCuO, the
proximity-induced gap on the surface states is nearly isotropic and consistent
with predominant s-wave pairing as revealed by angle-resolved photoemission
spectroscopy. Our work could provide a critical step toward the realization of
the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274
Slepian functions and their use in signal estimation and spectral analysis
It is a well-known fact that mathematical functions that are timelimited (or
spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the
finite precision of measurement and computation unavoidably bandlimits our
observation and modeling scientific data, and we often only have access to, or
are only interested in, a study area that is temporally or spatially bounded.
In the geosciences we may be interested in spectrally modeling a time series
defined only on a certain interval, or we may want to characterize a specific
geographical area observed using an effectively bandlimited measurement device.
It is clear that analyzing and representing scientific data of this kind will
be facilitated if a basis of functions can be found that are "spatiospectrally"
concentrated, i.e. "localized" in both domains at the same time. Here, we give
a theoretical overview of one particular approach to this "concentration"
problem, as originally proposed for time series by Slepian and coworkers, in
the 1960s. We show how this framework leads to practical algorithms and
statistically performant methods for the analysis of signals and their power
spectra in one and two dimensions, and on the surface of a sphere.Comment: Submitted to the Handbook of Geomathematics, edited by Willi Freeden,
Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verla
Scalar and vector Slepian functions, spherical signal estimation and spectral analysis
It is a well-known fact that mathematical functions that are timelimited (or
spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the
finite precision of measurement and computation unavoidably bandlimits our
observation and modeling scientific data, and we often only have access to, or
are only interested in, a study area that is temporally or spatially bounded.
In the geosciences we may be interested in spectrally modeling a time series
defined only on a certain interval, or we may want to characterize a specific
geographical area observed using an effectively bandlimited measurement device.
It is clear that analyzing and representing scientific data of this kind will
be facilitated if a basis of functions can be found that are "spatiospectrally"
concentrated, i.e. "localized" in both domains at the same time. Here, we give
a theoretical overview of one particular approach to this "concentration"
problem, as originally proposed for time series by Slepian and coworkers, in
the 1960s. We show how this framework leads to practical algorithms and
statistically performant methods for the analysis of signals and their power
spectra in one and two dimensions, and, particularly for applications in the
geosciences, for scalar and vectorial signals defined on the surface of a unit
sphere.Comment: Submitted to the 2nd Edition of the Handbook of Geomathematics,
edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be
published by Springer Verlag. This is a slightly modified but expanded
version of the paper arxiv:0909.5368 that appeared in the 1st Edition of the
Handbook, when it was called: Slepian functions and their use in signal
estimation and spectral analysi
Cell-cycle-dependent transcriptional and translational DNA-damage response of 2 ribonucleotide reductase genes in S. cerevisiae
The ribonucleotide reductase (RNR) enzyme catalyzes an essential step in the production of deoxyribonucleotide triphosphates (dNTPs) in cells. Bulk biochemical measurements in synchronized Saccharomyces cerevisiae cells suggest that RNR mRNA production is maximal in late G1 and S phases; however, damaged DNA induces RNR transcription throughout the cell cycle. But such en masse measurements reveal neither cell-to-cell heterogeneity in responses nor direct correlations between transcript and protein expression or localization in single cells which may be central to function. We overcame these limitations by simultaneous detection of single RNR transcripts and also Rnr proteins in the same individual asynchronous S. cerevisiae cells, with and without DNA damage by methyl methanesulfonate (MMS). Surprisingly, RNR subunit mRNA levels were comparably low in both damaged and undamaged G1 cells and highly induced in damaged S/G2 cells. Transcript numbers became correlated with both protein levels and localization only upon DNA damage in a cell cycle-dependent manner. Further, we showed that the differential RNR response to DNA damage correlated with variable Mec1 kinase activity in the cell cycle in single cells. The transcription of RNR genes was found to be noisy and non-Poissonian in nature. Our results provide vital insight into cell cycle-dependent RNR regulation under conditions of genotoxic stress.Massachusetts Institute of Technology. Center for Environmental Health Sciences (deriving from NIH P30-ES002109)National Institutes of Health (U.S.) (grant R01-CA055042)National Institutes of Health (U.S.) (grant DP1-OD006422)Massachusetts Institute of Technology (CSBi Merck-MIT Fellowship
The Tyrosine Kinase c-Src Directly Mediates Growth Factor-Induced Notch-1 and Furin Interaction and Notch-1 Activation in Pancreatic Cancer Cells
The proteolytic activity of Furin responsible for processing full length Notch-1 (p300) plays a critical role in Notch signaling. The amplitude and duration of Notch activity can be regulated at various points in the pathway, but there has been no report regarding regulation of the Notch-1-Furin interaction, despite its importance. In the present study, we found that the Notch-1-Furin interaction is regulated by the non-receptor tyrosine kinase, c-Src. c-Src and Notch-1 are physically associated, and this association is responsible for Notch-1 processing and activation. We also found that growth factor TGF-α, an EGFR ligand, and PDGF-BB, a PDGFR ligand, induce the Notch-1-Furin interaction mediated by c-Src. Our results support three new and provocative conclusions: (1) The association between Notch-1 and Furin is a well-regulated process; (2) Extracellular growth factor signals regulate this interaction, which is mediated by c-Src; (3) There is cross-talk between the plasma growth factor receptor-c-Src and Notch pathways. Co-localization of Notch-1 and c-Src was confirmed in xenograft tumor tissues and in the tissues of pancreatic cancer patients. Our findings have implications for the mechanism by which the Notch and growth factor receptor-c-Src signaling pathways regulate carcinogenesis and cancer cell growth
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