1,330 research outputs found

    Widely-tunable mid-IR frequency comb source based on difference frequency generation

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    We report on a mid-infrared frequency comb source of unprecedented tunability covering the entire 3-10 {\mu}m molecular fingerprint region. The system is based on difference frequency generation in a GaSe crystal pumped by a 151 MHz Yb:fiber frequency comb. The process was seeded with Raman shifted solitons generated in a highly nonlinear suspended-core fiber with the same source. Average powers up to 1.5 mW were achieved at 4.7 {\mu}m wavelength.Comment: 3 pages, 3 figure

    A Computational Approach to the Functional Screening of Genomes

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    Comparative genomics usually involves managing the functional aspects of genomes, by simply comparing gene-by-gene functions. Following this approach, Mushegian and Koonin proposed a hypothetical minimal genome, Minimal Gene Set (MGS), aiming for a possible oldest ancestor genome. They obtained MGS by comparing the genomes of two simple bacteria and eliminating duplicated or functionally identical genes. The authors raised the fundamental question of whether a hypothetical organism possessing MGS is able to live or not. We attacked this viability problem specifying in silico the metabolic pathways of the MGS-based prokaryote. We then performed a dynamic simulation of cellular metabolic activities in order to check whether the MGS-prokaryote reaches some equilibrium state and produces the necessary biomass. We assumed these two conditions to be necessary for a living organism. Our simulations clearly show that the MGS does not express an organism that is able to live. We then iteratively proceeded with functional replacements in order to obtain a genome composition that gives rise to equilibrium. We ruled out 76 of the original 254 genes in the MGS, because they resulted in duplication from a functional point of view. We also added seven genes not present in the MGS. These genes encode for enzymes involved in critical nodes of the metabolic network. These modifications led to a genome composed of 187 elements expressing a virtually living organism, Virtual Cell (ViCe), that exhibits homeostatic capabilities and produces biomass. Moreover, the steady-state distribution of the concentrations of virtual metabolites that resulted was similar to that experimentally measured in bacteria. We conclude then that ViCe is able to “live in silico.

    Alleviating inequality in climate policy costs: An integrated perspective on mitigation, damage and adaptation

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    Equity considerations play an important role in international climate negotiations. While policy analysis has often focused on equity as it relates to mitigation costs, there are large regional differences in adaptation costs and the level of residual damage. This paper illustrates the relevance of including adaptation and residual damage in equity considerations by determining how the allocation of emission allowances would change to counteract regional differences in total climate costs, defined as the costs of mitigation, adaptation, and residual damage. We compare emission levels resulting from a global carbon tax with two allocations of emission allowances under a global cap-and-trade system: one equating mitigation costs and one equating total climate costs as share of GDP. To account for uncertainties in both mitigation and adaptation, we use a model-comparison approach employing two alternative modeling frameworks with different damage, adaptation cost, and mitigation cost estimates, and look at two different climate goals. Despite the identified model uncertainties, we derive unambiguous results on the change in emission allowance allocation that could lessen the unequal distribution of adaptation costs and residual damages through the financial transfers associated with emission trading

    YAP and β-catenin co-operate to drive oncogenesis in basal breast cancer

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    Targeting cancer stem cells (CSCs) can serve as an effective approach toward limiting resistance to therapies and the development of metastases in many forms of cancer. While basal breast cancers encompass cells with CSC features, rational therapies remain poorly established. Here, we show that receptor tyrosine kinase Met signalling promotes the activity of the Hippo component YAP in basal breast cancer. Further analysis revealed enhanced YAP activity within the CSC population. Using both genetic and pharmaceutical approaches, we show that interfering with YAP activity delays basal cancer formation, prevents luminal to basal trans-differentiation and reduces CSC survival. Gene expression analysis of YAP knock-out mammary glands revealed a strong decrease in β-catenin target genes in basal breast cancer, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, we find that nuclear YAP interacts and overlaps with β-catenin and TEAD4 at common gene regulatory elements. Analysis of proteomic data from primary breast cancer patients identified a significant upregulation of the YAP activity signature in basal compared to other breast cancers, suggesting that YAP activity is limited to basal types. Our findings demonstrate that in basal breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal (triple-negative) breast cancers

    Influence of the Location of the Internal Temperature Control Loop on the Performance of the Dual Temperature Control for Feed Temperature Disturbance

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    A control strategy with distributed corrective action for distillation has been proposed and consists of a conventional dual temperature control combined with an additional column tray. In this work, we evaluated the influence of the location of this internal loop as part of the new proposal, compared to a conventional system. Tests were carried out in a 13-column tray distillation equipment and feed temperature was disturbed. Two different column trays from the stripping section were used (11 and 12) for internal decentralized temperature control, each one separately, plus the dual control of top and bottom temperatures. The results demonstrated that this proposed control approach with distributed corrective action is faster than the conventional one, regardless of the column tray in use. It was also determined that the internal loop close to the feed (disturbance) is more interesting as a way to minimize transients

    ACP-TX-I and ACP-TX-II, two novel phospholipases A(2) isolated from trans-pecos copperhead agkistrodon contortrix pictigaster venom: biochemical and functional characterization

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    This work reports the purification and biochemical and functional characterization of ACP-TX-I and ACP-TX-II, two phospholipases A(2) (PLA(2)) from Agkistrodon contortrix pictigaster venom. Both PLA(2)s were highly purified by a single chromatographic step on a C-18 reverse phase HPLC column. Various peptide sequences from these two toxins showed similarity to those of other PLA(2) toxins from viperid snake venoms. ACP-TX-I belongs to the catalytically inactive K49 PLA(2) class, while ACP-TX-II is a D49 PLA(2), and is enzymatically active. ACP-TX-I PLA(2) is monomeric, which results in markedly diminished myotoxic and inflammatory activities when compared with dimeric K49 PLA(2)s, confirming the hypothesis that dimeric structure contributes heavily to the profound myotoxicity of the most active viperid K49 PLA(2)s. ACP-TX-II exhibits the main pharmacological actions reported for this protein family, including in vivo local myotoxicity, edema-forming activity, and in vitro cytotoxicity. ACP-TX-I PLA(2) is cytotoxic to A549 lung carcinoma cells, indicating that cytotoxicity to these tumor cells does not require enzymatic activity11CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂŤFICO E TECNOLĂ“GICO - CNPQ163536/2013-

    Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells

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    Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis. Western blot analysis indicated that Tyrphostin AG 1024-induced apoptosis was associated with a downregulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression, especially when combined with irradiation. To our knowledge, this is the first report showing that an IGF-1 inhibitor was able to markedly increase the response of tumour cells to ionizing radiation. These results suggest that Tyrphostin AG 1024 could be used as a potential therapeutic agent in combination with irradiation.   http://www.bjcancer.com © 2001 Cancer Research Campaig

    Antenatal syphilis serology in pregnant women and follow-up of their infants in northern Italy

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    ABSTRACTPositive syphilis serology was noted in 119 (0.49%) of the 24 053 pregnant women delivering at St Orsola Hospital in Bologna, Italy, from November 2000 through July 2007. Six presumptive cases of congenital syphilis with IgM western blot positive results were found. Two infants had a positive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory test result (one also had a positive CSF PCR result), another presented long-bone lesions, and the remaining three were preterm. These observations confirmed that antenatal syphilis screening facilitates treatment during pregnancy and offsets vertical transmission; moreover, the use of IgM western blot and careful CSF examination allowed the identification and treatment of high-risk newborns
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