37,345 research outputs found
Antiatherosclerotic effect of the new Ca++ antagonist sim 6080: "In vitro" and "In vivo studies
No full textRadiolabeled Antibody Fragment for Preparation of (<sub>177</sub>Lu-DOTA)<sub>m</sub>-PAMAM G3.0-F(ab’)<sub>2</sub> trastuzumab as a Radiopharmaceutical for Cancer Therapy
No full textSeveral radiolabeled monoclonal antibodies (mAbs) have been used as radioimmunotherapy (RIT) agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α) particles, beta (β) particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of (177Lu-DOTA)m-PAMAM G3-F(ab')2-trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2). Due to its reduced molecular weight, the use of F(ab')2-trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH2 functional groups that are able to bind many DOTAs (£ 31) which in turn can bind a large number of 177Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab')2-trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab')2-trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) to produce SMCC-F(ab')2-trastuzumab. The next reaction was to conjugate SMCC-F(ab')2-trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab. Finally, the (DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab was radiolabelled with 177Lu to produce (177Lu-DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column.Received: 31 October 2015; Revised: 30 June 2016; Accepted: 25 September 2016</p
The Natural Human-igg Anti-f(ab')(2) Antibody Recognizes A Conformational Igg1 Hinge Epitope
No full textNatural IgG anti-F(ab')(2) Abs are part of the physiologic immune repertoire and have important immunoregulatory functions. Although previous work suggested that some of these Abs recognize epitopes located in the constant region of the F(ab')(2) molecule, an exact epitope mapping has not been performed. We found that the anti-F(ab')(2) Ab binds strongly to F(ab')(2) but only weakly to Fab fragments. Fab fragments are lacking the core and lower hinge region. In our experiments, we show that the IgG anti-F(ab')(2) Ab binds strongly to a synthetic double chain peptide (225-237/225'-237') comprising the core and lower hinge region of the human IgG1 molecule. In contrast, it binds only weakly to the same peptide in monomeric form (225-237) or to a short double chain hinge peptide (225-232/225'-232'). The double chain peptides comprise a cyclic region between the two cystine bridges and an exocyclic region. Previous nuclear magnetic resonance analyses showed that the cyclic portion of the short double chain hinge peptide adopts the same conformation as that found in the intact IgG1 molecule. The dichroic properties of the short and long double chain hinge peptides indicate that they have identical conformations in their cyclic regions, but have different conformations in their exocyclic regions. The conformational differences in the exocyclic regions explain the binding of the Ab to the long double chain hinge peptide and the lack of binding to the short one. The circular dichroism spectrum of the monomeric hinge peptide, which is not recognized by the Ab, is consistent with the absence of an ordered peptide structure. These findings lead us to conclude that the IgG anti-F(ab')(2) Ab recognizes a conformational IgG1 hinge epitope
Ab initio direct semiclassical molecular dynamics
No full textA multiple coherent states time-averaging [1] semiclassical initial value representation (MC-TA-SC-IVR) method for spectra calculations is presented.[2, 3] The method is implemented for ab initio semiclassical simulations, i.e. a direct dynamics approach, and it is shown to faithfully reproduce all kind of quantum effects, including ZPEs, anharmonicities, tunneling splittings, resonances [4] and vibrational eigenfunctions.[5] This on-the-fly approach is useful in particular for complex systems,[5, 6] where the elaboration of a pre-computed potential energy surface can turn into a formidable task. I will show that the method can deal with molecules with multiple wells and as complex as glycine.
[1] A. L. Kaledin and W. H. Miller, J. Chem. Phys. 118, 7174 (2003)
[2] M. Ceotto, S. Atahan, S. Shim, G. F. Tantardini, and A. Aspuru-Guzik, Phys. Chem. Chem. Phys. 11, 3861 (2009)
[3] M. Ceotto, S. Atahan, G. F. Tantardini, and A. Aspuru-Guzik, J. Chem. Phys. 130, 234113 (2009)
[4] M. Ceotto, D. Dell'Angelo, and G. F. Tantardini, J. Chem. Phys. 133, 054701 (2010)
[5] M. Ceotto, S. Valleau, G. F. Tantardini, and A. Aspuru-Guzik, J. Chem Phys. 134, 234103 (2011)
[6] M. Ceotto, G. F. Tantardini, and A. Aspuru-Guzik, J. Chem. Phys. 135, 214108 (2011)
[7] M. Ceotto, Y. Zhuang, and W.L. Hase, J. Chem. Phys. 138, 054116 (2013
Quantum Mechanical Methods for Spectroscopic Calculations of High Dimensional Molecular Systems
No full textI will present some novel semiclassical methods for spectroscopic calculations. These approaches can be employed for spectroscopic calculations of gas-phase molecular and supramolecular systems
up to hundreds of degrees of freedom, as well as to condensed phase systems. Some methods are based on a “divide-and-conquer” approach, where the full dimensional spectra are obtained as a
composition of several lower dimensional ones. Others exploit hierarchically the different levels of accuracy of different semiclassical propagators.
All methods are amenable to ab initio molecular dynamics simulations.
References
1. M. Micciarelli, R. Conte, J. Suarez, and M. Ceotto, JCP 149, 064115 (2018);
2. M. Buchholz, F. Grossmann, and M. Ceotto, JCP 148, 114107 (2018);
3. G. Di Liberto, R. Conte, and M. Ceotto, JCP 148, 104302 (2018);
4. G. Di Liberto, R. Conte, and M. Ceotto, JCP 148, 014307 (2018);
5. M. Buchholz, F. Grossmann, and M. Ceotto, JCP 147, 164110 (2017);
6. M. Ceotto, G. Di Liberto, and R. Conte, PRL 119, 010401 (2017);
7. F. Gabas, R. Conte, and M. Ceotto, JCTC 13, 2378-2388 (2017);
8. G. Di Liberto, M. Ceotto, JCP 145, 144107 (2016);
9. M. Buchholz, F. Grossmann, M. Ceotto, JCP 144, 094102 (2016)
Addition-fragmentation kinetics of fluorodithioformates (F-RAFT) in styrene, vinyl acetate, and ethylene polymerization: An Ab initio investigation
No full textThe kinetics and thermodynamics of the addition-fragmentation equilibrium in fluorodithioformate (S=C(F)SR; F-RAFT) mediated polymerization of styrene and vinyl acetate were investigated via high-level ab initio molecular orbital calculations. The fragmentation efficiencies of a wide range of leaving groups (R = C(CH3)2CN, CH2CN, C(CH3) 2Ph, CH(Ph)CH3, CH2Ph, CH(COOCH 3)CH3, CH2COOCH3, CH(OCOCH 3), CH2-OCOCH3, C(CH3)3, CH2CH3, CH3) were also investigated. The calculations confirm earlier predictions, on the basis of thermodynamic considerations alone, that these agents are likely to function as genuine multipurpose RAFT agents. Thus, stable propagating radicals (as in styrene polymerization) are capable of adding to the RAFT agent with high rate coefficients (1.8 × 106 L mol-1 s-1 at 333.15 K), comparable to those observed with normal dithioesters such as S=C(CH3)SR (3.8 × 106 L mol-1 s -1). Concurrently, unstable propagating radicals (as in vinyl acetate polymerization) are capable of undergoing fragmentation with significantly higher rate coefficients (1.7 × 104 s -1) than that for S=C(CH3)SR (8.4 s-1) and are not expected to be rate retarded. On the basis of an examination of leaving group abilities and known reinitiation rate coefficients, the agents S=C(F)SC(CH3)2CN or S=C(F)SC(CH3) 2Ph are identified as optimal F-RAFT agents for styrene polymerization, while S=C(F)SCH2-CN or S=C(F)SC(CH3) 3 are identified as optimal F-RAFT agents for vinyl acetate and ethylene polymerization. The potential suitability of employing F-RAFT to invoke living free radical polymerization of ethylene has been tested by a general kinetic screening exercise as well as specific simulations that employ quantum chemically predicted F-RAFT rate coefficients. These results indicate that F-RAFT is expected to control ethylene free radical polymerization. © 2006 American Chemical Society
Nilai ketakteraturan sisi Graf kembang api Fn,m dengan n,m>=2
No full textSuatu pelabelan-k titik f: V(G)→{1,2,3,…,k} disebut pelabelan-k tak teratur sisi pada sebuah graf jika untuk setiap dua sisi berbeda ab dan cd, berlaku w_f (ab)≠w_f (cd), dimana bobot dari sisi (ab)∈E(G) adalah w_f (ab)=f(a)+f(b). Nilai k minimum sehingga suatu graf G memiliki pelabelan-k tak teratur sisi disebut nilai ketakteraturan sisi dari G, dinotasikan dengan es(G). Pada skripsi ini, penulis menentukan nilai ketakteraturan sisi pada Graf Kembang Api F_(n,m). Nilai ketakteraturan sisi dari Graf Kembang Api F_(n,m) dengan n,m ≥2 adalah ⌈(nm+n)/2⌉.
A vertex k-labeling f: V(G)→{1,2,3,…,k} is called an edge irregular k-labeling of the graph G if for every two different edges ab and cd satisfy w_f (ab)≠w_f (cd), what w_f (ab)=f(a)+f(b) is the weight of an edge (ab)∈E(G). The minimum k for which the graph G has an edge irregular k-labeling is called the edge irregularity strength of G, denoted by es(G). In this research, the author determine edge irregularity strength of firecrackes graphs F_(n,m). On the edge irregularity strength of firecrackes graphs F_(n,m) for m,n≥2 is ⌈(nm+n)/2⌉
Rükkehr der Helvetiern in ihr Land Ao. M. 3914
No full textDie Helvetier kehren in ihr Gebiet zurück, Wiederaufbau der BurgenJ. M. F. f.Unten "Einer Kunst und Tugend l. Jugend ab der Burgerbücherey zu Zürich am NeüJ ahrs Tag Ao. 1727 verehrt
Ausszug der Helvetieren in Galliam Ao. M. 3914
No full textAuszug der Helvetier aus der Heimat nach dem Abbrennen ihrer DörferJ. M. F. fecitUnten "Einer Kunst und Tugend L. Jugend ab der Burger Bücherey zu Zürich am Neü Jahrs-tag Ao. 1722 verehrt
Ausszug der Helvetieren in Galliam Ao. M. 3914
No full textAuszug der Helvetier aus der Heimat nach dem Abbrennen ihrer DörferJ. M. F. fecitUnten "Einer Kunst und Tugend L. Jugend ab der Burger Bücherey zu Zürich am Neü Jahrs-tag Ao. 1722 verehrt
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