Analysis of intracellular transport and functionality of human kidney anion exchanger 1 (kAE1) in yeast and mammalian cells

Anion exchanger proteins facilitate chloride-bicarbonate movement across the plasma membrane and play an important role in maintaining acid-base homeostasis in the human body. Kidney anion exchanger 1 (kAE1) is one of the major bicarbonate transporters among this group and helps to reabsorb bicarbonate for chloride in distal nephrons. Defects of this protein result in functional impairment of the anion exchange process that eventually leads to the development of a clinical condition known as distal renal tubular acidosis (dRTA). Although the genetic basis of kAE1 mutants leading to disease is largely known, the precise molecular processes of dRTA pathophysiology are still inadequately understood. Here, the potential of baker’s yeast was evaluated to address various cellular aspects of kAE1 physiology. For the first time, unmodified and tagged full-length versions of kAE1 were successfully expressed in yeast. Moreover, partial localization of the anion exchanger at the plasma membrane was validated by accomplishing several light and confocal microscopy techniques and biochemical assays. Subsequently, biological activity of the protein was demonstrated by performing intracellular pH measurements and chloride uptake assays. Additionally, a set of novel dRTA mutants was characterized in mIMCD3 cells, resembling the closest cellular model to α-intercalated cells. In sum, this study highlights novel possibilities to investigate kAE1-related physiology and pathology in more detail.Anionenaustauscherproteine erleichtern die Bewegung von Chlorid-Bicarbonat durch die Plasmamembran und spielen eine wichtige Rolle bei der Aufrechterhaltung der Säure-Base-Homöostase im menschlichen Körper. Der Anionenaustauscher 1 (kAE1) der Niere ist einer der wichtigsten Bicarbonat-Transporter, der die Resorption von Bicarbonat für Chlorid im distalen Nephron unterstützt. Defekte dieses Proteins führen zu einer Beeinträchtigung des Anionen-Austauschprozesses und zur Entwicklung der distalen renalen tubulären Azidose (dRTA). Obwohl der genetische Hintergrund der krankmachenden kAE1-Mutanten weitgehend bekannt ist, sind die molekularen Prozesse der dRTA-Pathophysiologie nur unzureichend verstanden. In dieser Studie wurde die Bäckerhefe zur Untersuchung zellulärer Aspekte der kAE1-Physiologie eingesetzt. Erstmalig wurden eine unmodifizierte und getaggte kAE1-Volllängenversion erfolgreich in Hefe exprimiert. Darüber hinaus wurde die partielle Lokalisierung des Anionenaustauschers in der Plasmamembran durch Mikroskopietechniken und biochemische Assays validiert. Anschließend wurde die biologische Proteinaktivität durch intrazelluläre pH-Messungen und Chlorid-Aufnahmestudien nachgewiesen. Zusätzlich wurde eine Reihe von neuen dRTA-Mutanten in mIMCD3-Zellen charakterisiert, die als zelluläres Modell den α-interkalierten Zellen am nächsten kommen. Damit eröffnet die vorliegende Dissertation neue Möglichkeiten, die kAE1-Physiologie und -Pathologie genauer untersuchen zu können

Analisis Komponen Volatil Dan Laju Alir Lava Pada Erupsi Gunung Semeru, Jawa Timur

Gunung Semeru merupakan salah satu gunung aktif di Indonesia dan telah mengalami Perubahan tipe erupsi sejak tahun 1967. Sehingga penting untuk dilakukan penelitian mengenai analisis erupsi berdasarkan komponen volatil dan penentuan laju alir lava Gunung Semeru dengan tujuan untuk memperkirakan mekanisme sifat erupsi pada masa sekarang dan untuk mengetahui potensi daerah berbahaya aliran lava G. Semeru bila terjadi letusan eksplosif.Analisis erupsi didasarkan pada parameter fisika terhadap analisis geokimia batuan sedangkan laju alir lava didasarkan pada kemiringan topografi yang dilaluinya. Hasil penelitian menunjukkan berkurangnya tekanan akan mengakibatkan lepasnya gas dari magma dengan cepat, Hal ini memicu terjadinya sifat hembusan. Daerah yang memiliki laju alir lava G. Semeru paling cepat adalah Desa Oro oro Ombo, Kecamatan Pronojiwo, Kabupaten Lumajang

Isolation, synthesis and optimization of cyclopropanation process of 4-allyl-2-methoxyphenol

The synthesis of 4-((2,2-dichlorocyclopropyl)methyl)-2-methoxyphenol 2 have been accomplished by using cyclopropanation process and Reponse Surface Methodology [1,2]. This methodology was used to determine the optimal conditions for the cyclopropanation reaction of eugenol 1. The reaction time (X1) and the ratio of the reaction mixture’s solvent (X2) were the two investigated factors. The statistical analysis of this study indicates that both of these factors had significant effects on the cyclopropanation yield. The central composite design showed that polynomial regression models were in good agreement with the experimental results of the coefficient determination (0.95) of product 2 yield. The optimal conditions were 17.44 and 5.78 hours. In such condition, the predicted yield of the product 2 was 43.96%. Keywords: Eugenol; 4-((2,2-dichlorocyclopropyl)methyl)-2-methoxyphenol; Central composite design; Optimization experiment

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

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

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino