MMP-15 Is Upregulated in Preeclampsia, but Does Not Cleave Endoglin to Produce Soluble Endoglin

Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15–phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity–also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin

Associations between genetic variations in the FURIN gene and hypertension

<p>Abstract</p> <p>Background</p> <p>Hypertension is a complex disease influenced by multiple genetic and environmental factors. The Kazakh ethnic group is characterized by a relatively high prevalence of hypertension. Previous research indicates that the FURIN gene may play a pivotal role in the renin-angiotensin system and maintaining the sodium-electrolyte balance. Because these systems influence blood pressure regulation, we considered FURIN as a candidate gene for hypertension. The purpose of this study was to systematically investigate the association between genetic variations in the FURIN gene and essential hypertension in a Xinjiang Kazakh population.</p> <p>Methods</p> <p>We sequenced all exons and the promoter regions of the FURIN gene in 94 hypertensive individuals to identify genetic variations associated with the disorder. Genotyping was performed using the TaqMan polymerase chain reaction method for four representative common single nucleotide polymorphisms (SNPs, -7315C > T, 1970C > G, 5604C > G, 6262C > T) in 934 Kazakh Chinese people. One SNP (1970C > G) was replicated in 1,219 Uygur Chinese people.</p> <p>Results</p> <p>Nine novel and seven known single nucleotide polymorphisms were identified in the FURIN gene. The results suggest that 1970C > G was associated with a hypertension phenotype in Kazakh Chinese (additive model, <it>P </it>= 0.091; dominant model, <it>P = </it>0.031, allele model, <it>P </it>= 0.030), and after adjustment with logistic regression analysis, ORs were 1.451 (95%CI 1.106-1.905, <it>P </it>= 0.008) and 1.496 (95% 1.103-2.028, <it>P </it>= 0.01) in additive and dominant models, respectively. In addition, the association between 1970C > G and hypertension was replicated in Uygur subjects (additive model, <it>P </it>= 0.042; dominant model, <it>P </it>= 0.102; allele model, <it>P </it>= 0.027) after adjustment in additive and dominant models, ORs were 1.327 (95% 1.07-1.646), <it>P </it>= 0.01 and 1.307 (95%CI 1.015-1.681, <it>P </it>= 0.038), respectively. G allele carriers exhibited significant lower urinary Na⁺excretion rate than non-carriers in the Kazakh Chinese population (152.45 ± 76.04 uM/min vs 173.33 ± 90.02 uM/min, <it>P </it>= 0.007).</p> <p>Conclusion</p> <p>Our results suggest that the FURIN gene may be a candidate gene involved in human hypertension, and that the G allele of 1970C > G may be a modest risk factor for hypertension in Xinjiang Kazakh and Uygur populations.</p

Kombinasi Format Factory, U-lead dan Microsoft Office Powerpoint dalam Upaya Meningkatkan Kualitas Media Pembelajaran

Peserta didik mempunyai gaya belajar yang berbeda-beda. Gaya belajar tersebut meliputi auditori, visual dan kinestetik (VAK). Seorang guru harus mampu memenuhi kebutuhan masing-masing gaya belajar peserta didik tersebut. Salah satu cara yang dapat dilakukan adalah dengan menggunakan media pembelajaran berbasis VAK. Media pembelajaran berbasis VAK dapat dipenuhi dengan menyisipkan file video di dalamnya. Selain itu, penggunaan file video sebagai media pembelajaran mendukung implementasi pembelajaran saintifik pada kurikulum 2013. Namun, belum semua guru memiliki kemampuan untuk mengemas file video tersebut dalam bentuk media pembelajaran. Tujuan penelitian ini adalah untuk meningkatkan kemampuan guru-guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran berbasis VAK dengan kombinasi software Format Factory, U-Lead dan PowerPoint. Hasil penelitian menunjukkan bahwa terjadi peningkatan kemampuan para guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran. Peningkatan kemampuan guru-guru tersebut berada di atas target yang direncanakan. Rerata peningkatan kemampuan guru-guru di SMA Negeri 1 Teras 7,87% di atas target, sedangkan di SMA Negeri 1 Boyolali 9,58% di atas target. Kata kunci: Media Pembelajaran, Format Factory, U-Lead, PowerPoint Students have different learning styles. Learning styles include visual learners, auditory learners, and kinesthetic learners. A teacher must be able to fulfill the needs of individual students\u27 learning styles. One way that can be applied is using Visual, Audio and Kinesthetic (VAK) learning media based. VAK-learning media based can be created by inserting video files on it. In addition, using video file as a learning media can support the implementation of scientific learning on the 2013 curriculum. However, not all teachers have the ability to use video files into a learning media. The purpose of this study is to improve the teachers\u27 ability at SMA Negeri 1 Teras and SMAN 1 Boyolali on making VAK-learning media based with a combination of Format Factory, U-Lead and PowerPoint software. The results showed that the teachers\u27 ability on making VAK-learning media based was increased. Increased the teachers\u27 ability was above planned target score. The mean score of the teachers\u27 ability at SMA Negeri 1 Teras 7.87% above the target, while at SMAN 1 Boyolali 9.58% above the target

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30