History and Diagnostic Significance of C-Peptide

Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its bearings on understanding protein biosynthesis; the pioneering role of insulin, proinsulin, C-peptide, and mini-C-peptides in the development of recombinant DNA technology; and the discovery of the enzymes for the endoproteolytic processing of proinsulin into insulin and C-peptide, completing the pathway of biosynthesis. Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions

Novel hepatoselective insulin analog

Cel pracy. Zbadanie, czy tyroksylowy analog insuliny z ograniczonym dostępem do receptora w tkankach obwodowych wykazuje względnie wybiórcze powinowactwo do wątroby u ludzi. MATERIAŁ i metody. Pięć zdrowych osób otrzymywało podskórnie Na B1L-thyroksyl-insulinę (B1-T4-Ins) lub insulinę NPH w przypadkowej kolejności. Posługując się metodą klamry euglikemicznej i rozcieńczania znacznika izotopowego([D-6,6-2H2] glukozy), badano kinetykę insuliny oraz jej względny wpływ na wątrobową produkcję i obwodowy wychwyt glukozy. Pobierano próbki krwi w celu oznaczenia całkowitego stężenia insuliny immunoreaktywnej (bądź jej analogu) oraz w celu określenia stopnia wiązania analogu insuliny z białkami krwi, który badano metodą chromatografii cieczowej. Wyniki. Po podskórnym podaniu B1-T4-Ins była dobrze tolerowana i szybko wchłaniana. Analog cechował się długim czasem półtrwania w surowicy oraz wysokim stopniem wiązania (ok. 86%) z białkami. Jego czas działania, mierzony czasem wlewu glukozy niezbędnym do utrzymania euglikemii, był podobny do czasu działania insuliny NPH. Wpływ analogu na wątrobową produkcję glukozy był podobny do wpływu insuliny NPH, co wskazuje na podobny stopień oddziaływania. Analog w mniejszym stopniu działał na obwodowy wychwyt insuliny w porównaniu z insuliną NPH (p = 0,025), nie wpływał na szybkość przemian metabolicznych glukozy oraz wykazywał zmniejszoną zdolność do hamowania lipolizy (p < 0,05). Wnioski. U osób zdrowych B1-T4-Ins po podaniu podskórnym jest dobrze tolerowana, szybko się wchłania i ma wysoki stopień związania z białkami krwi, co odpowiada za długi czas połowicznego zaniku w surowicy. Analog ten wydaje się bardziej wybiórczy w oddziaływaniu na komórki wątroby, a zatem potencjalnie ma bardziej fizjologiczny profil działania w porównaniu z dotychczas stosowanymi preparatami insuliny.OBJECTIVE. To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. RESEARCH DESIGN AND METHODS. Five normal human subjects received a subcutaneous bolus injection of either N B1 L-thyroxyl-insulin (B1-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-2H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. RESULTS. After subcutaneous administration, B1-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (~86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0,025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P < 0,05). CONCLUSIONS. When injected subcutaneously into normal human subjects, B1-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma half-life. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used

Система управления тягового электропривода подземного рудничного электровоза

РЕФЕРАТ Выпускная квалификационная работа содержит 156 страниц, 39 рисунков, 12 таблиц, 45 источников, 3 приложения. Ключевые слова: рудничный электровоз; тяговый асинхронный электродвигатель; частотно-регулируемый электропривод; динамические характеристики; система управления движением, люфт, буксование, многомассовая модель подвижного состава Цель работы: Разработать критерии выбора оптимальной конструкции тягового асинхронного двигателя и преобразователя частоты для рудничного электровоза, учитывающие ограничение скорости движения по условиям торможения в режиме номинальной нагрузки, независимое охлаждение двигателей и исполнение корпуса. Разработать математическую модель электромеханической части подвижного состава рудничного электровоза в среде Matlab Simulink с учетом динамического перераспределения нагрузок между осями, при реализации тяги, люфты, и упругости сцепок состава. Разработка научно обоснованные технических решений проблем предотвращения буксования и юза применительно к асинхронному тяговому приводу на шахтных электровозах. Выпускная квалификационная работа выполнена в текстовом редакторе Microsoft Office Word 2010 с использованием пакетов: Microsoft Visio 2010, Matlab Simulink и представлена на диске (в конверте на обороте обложки).ESSAY Final qualifying work contains 156 pages, 39 figures, 12 tables, 45 sources, 3 annexes. Keywords: mine electric locomotives; traction induction motor; VFD; dynamic characteristics; traffic control system, backlash, slippage, multibody model of rolling stock Objective: To develop criteria for selection of the optimal design of traction induction motor and frequency converter for mine electric locomotives, taking into account the speed limit by braking conditions in the mode of the nominal load, independent engine cooling and performance of the body. The mathematical model of electromechanical part of a rolling stock of electric mine in Matlab Simulink environment, taking into account the dynamic load transfer between the axles, the implementation of thrust clearances and elastic coup

Thermal production of ultrarelativistic right-handed neutrinos: Complete leading-order results

The thermal production of relativistic right-handed Majorana neutrinos is of importance for models of thermal leptogenesis in the early Universe. Right-handed neutrinos can be produced both by 1 2 decay or inverse decay and by 2 -> 2 scattering processes. In a previous publication, we have studied the production via 1 2 (inverse) decay processes. There we have shown that multiple scattering mediated by soft gauge boson exchange also contributes to the production rate at leading order, and gives a strong enhancement. Here we complete the leading order calculation by adding 2 -> 2 scattering processes involving either electroweak gauge bosons or third-generation quarks. We find that processes with gauge interactions give the most important contributions. We also obtain a new sum rule for the Hard Thermal Loop resummed fermion propagator.Comment: 27 pages, 7 figures. Error in the matrix element for the (subdominant) subprocess with s-channel fermion exchange corrected. This changes the corresponding phase space integral and the constant c_V. Numerically it increases the total 2 -> 2 rate by about 2 percent and the complete rate by about 1 percent. The main results and conclusions are unaffecte

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of s√=7TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

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

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

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter