Siyasi komiserler yeni başbakanı ayaklarına kadar getirttiler:Ali Rıza Paşa İngiliz yardımını talep etti

Taha Toros Arşivi, Dosya Adı: Milli Mücadele İstiklal Harbi GazetesiUnutma İstanbul projesi İstanbul Kalkınma Ajansı'nın 2016 yılı "Yenilikçi ve Yaratıcı İstanbul Mali Destek Programı" kapsamında desteklenmiştir. Proje No: TR10/16/YNY/010

Additional file 1: of An investigation of mainland china high school biology teachers’ attitudes toward and ethical reasoning of three controversial bioethics issues

Appendix A. A survey of teachers’ opinions on three bioethical issues (DOC 32 kb

Structural and Energetic Effects in the Molecular Recognition of Amino Acids by 18-Crown-6

Absolute 18-crown-6 (18C6) affinities of five amino acids (AAs) are determined using guided ion beam tandem mass spectrometry techniques. The AAs examined in this work include glycine (Gly), alanine (Ala), lysine (Lys), histidine (His), and arginine (Arg). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the AAs as well as the proton bound complexes comprised of these species, (AA)­H⁺(18C6). The proton affinities (PAs) of Gly and Ala are lower than the PA of 18C6, whereas the PAs of Lys, His, and Arg exceed that of 18C6. Therefore, the collision-induced dissociation (CID) behavior of the (AA)­H⁺(18C6) complexes differs markedly across these systems. CID of the complexes to Gly and Ala produces H⁺(18C6) as the dominant and lowest energy pathway. At elevated energies, H⁺(AA) was produced in competition with H⁺(18C6) as a result of the relatively favorable entropy change in the formation of H⁺(AA). In contrast, CID of the complexes to the protonated basic AAs results in the formation of H⁺(AA) as the only direct CID product. H⁺(18C6) was not observed, even at elevated energies, as a result of unfavorable enthalpy and entropy change associated with its formation. Excellent agreement between the measured and calculated (AA)­H⁺–18C6 bond dissociation energies (BDEs) is found with M06 theory for all complexes except (His)­H⁺(18C6), where theory overestimates the strength of binding. In contrast, B3LYP theory significantly underestimates the (AA)­H⁺–18C6 BDEs in all cases. Among the basic AAs, Lys exhibits the highest binding affinity for 18C6, suggesting that the side chains of Lys residues are the preferred binding site for 18C6 complexation in peptides and proteins. Gly and Ala exhibit greater 18C6 binding affinities than Lys, suggesting that the N-terminal amino group provides another favorable binding site for 18C6. Trends in the 18C6 binding affinities among the five AAs examined here exhibit an inverse correlation with the polarizability and proton affinity of the AA. Therefore, the ability of the N-terminal amino group to compete for 18C6 complexation is best for Gly and should become increasing less favorable as the size of the side chain substituent increases

Re-Evaluation of the Proton Affinity of 18-Crown‑6 Using Competitive Threshold Collision-Induced Dissociation Techniques

The proton affinity (PA) of 18-crown-6 (18C6) is determined using competitive threshold collision-induced dissociation (TCID) techniques. The PA of 18C6 is derived from four thermochemical cycles involving the relative thresholds for production of the protonated bases, H⁺(B), and protonated crown, H⁺(18C6), from the collision-induced dissociation (CID) of four proton bound heterodimers, (B)­H⁺(18C6). The bases examined include glycine (Gly), alanine (Ala), imidazole (Imid), and 4-methylimidazole (4MeImid). In all cases, CID pathways for the loss of intact B and 18C6 are observed in competition. Loss of intact 18C6 is observed as the lowest-energy CID pathway for the (Imid)­H⁺(18C6) and (4MeImid)­H⁺(18C6) complexes. In contrast, loss of intact Gly and Ala is observed as the lowest-energy CID pathway for the (Gly)­H⁺(18C6) and (Ala)­H⁺(18C6) complexes, respectively. Excellent agreement between the measured and calculated (B)­H⁺–18C6 and (18C6)­H⁺–B bond dissociation energies (BDEs) is found with M06 theory, whereas B3LYP theory systematically underestimates these BDEs. On the basis of the relative TCID thresholds for the primary and competitive CID pathways, as well as the literature PAs of the bases, the PA of 18C6 is evaluated. The PA determined here for 18C6 exhibits excellent agreement with M06 and B3LYP theories, and very good agreement with the value reported by Meot-Ner determined using high pressure mass spectrometry (HPMS) techniques, suggesting that the PA of 18C6 reported in the NIST Webbook based on HPMS measurements by Kebarle and co-workers is overestimated

Structural and Energetic Effects in the Molecular Recognition of Protonated Peptidomimetic Bases by 18-Crown-6

Absolute 18-crown-6 (18C6) affinities of nine protonated peptidomimetic bases are determined using guided ion beam tandem mass spectrometry techniques. The bases (B) included in this work are mimics for the n-terminal amino group and the side chains of the basic amino acids, i.e., the favorable sites for binding of 18C6 to peptides and proteins. Isopropylamine is chosen as a mimic for the n-terminal amino group, imidazole and 4-methylimidazole are chosen as mimics for the side chain of histidine (His), 1-methylguanidine is chosen as a mimic for the side chain of arginine (Arg), and several primary amines including methylamine, ethylamine, n-propylamine, n-butylamine, and 1,5-diamino pentane as mimics for the side chain of lysine (Lys). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the peptidomimetic bases, as well as the proton bound complexes comprised of these species, (B)­H⁺(18C6). The measured 18C6 binding affinities of the Lys side chain mimics are larger than the measured binding affinities of the mimics for Arg and His. These results suggest that the Lys side chains should be the preferred binding sites for 18C6 complexation to peptides and proteins. Present results also suggest that competition between Arg or His and Lys for 18C6 is not significant. The mimic for the n-terminal amino group exhibits a measured binding affinity for 18C6 that is similar to or greater than that of the Lys side chain mimics. However, theory suggests that binding to n-terminal amino group mimic is weaker than that to all of the Lys mimics. These results suggest that the n-terminal amino group may compete with the Lys side chains for 18C6 complexation

Precursor-Directed Biosynthesis of Phenylbenzoisoquinolindione Alkaloids and the Discovery of a Phenylphenalenone-Based Plant Defense Mechanism

Phenylbenzoisochromenone glucosides (oxa-phenylphenalenone glucosides) occurring in some phenylphenalenone-producing plants of the Haemodoraceae undergo conversion to phenylbenzoisoquinolindiones (aza-phenylphenalenones) in extracts of <i>Xiphidium caeruleum</i>. Precursor-directed biosynthetic experiments were used to generate a series of new phenylbenzoisoquinolindiones from native phenylbenzoisochromenone glucosides and external amines, amino acids, and peptides. Intermediates of the conversion were isolated, incubated with cell-free extracts, and exposed to reactions under oxidative or inert conditions, respectively, to elucidate the entire pathway from phenylbenzoisochromenones to phenylbenzoisoquinolindiones. An intermediate in this pathway, a reactive hydroxylactone/aldehyde, readily binds not only to amines in vitro but may also bind to the <i>N</i>-terminus of biogenic peptides and proteins of herbivores and pathogens in vivo. The deactivation of biogenic amino compounds by <i>N</i>-terminal modification is discussed as the key reaction of a novel phenylphenalenone-based plant defense mechanism. According to these data, the ecological function of phenylphenalenone-type compounds in the Haemodoraceae, subfamily Haemodoroideae, has been substantiated

Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation

Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nanomedicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnO_<i>x</i> component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnO_<i>x</i> component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H₂O₂) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonstrated to facilitate SDT-induced reactive oxygen species production and enhance SDT efficacy subsequently. The targeted accumulation of these composite nanosonosensitizers efficiently suppressed the growth of U87 tumor xenograft on nude mice after US-triggered SDT treatment. The high <i>in vivo</i> biocompatibility and easy excretion of these multifunctional nanosonosensitizers from the body have also been evaluated and demonstrated to guarantee their future clinical translation, and their TME-responsive <i>T</i>₁-weighted magnetic resonance imaging capability provides the potential for therapeutic guidance and monitoring during SDT

Molecular Basis of Substrate Recognition and Product Release by the <i>Klebsiella pneumoniae</i> Carbapenemase (KPC-2)

Carbapenem-resistant <i>Enterobacteriaceae</i> are resistant to most β-lactam antibiotics due to the production of the <i>Klebsiella pneumoniae</i> carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general

A New Scalable Route to 4‑(2-Hydroxyethyl)-1,3-dihydro‑2<i>H</i>‑indol-2-one: A Key Intermediate for Ropinirole Hydrochloride

A new and efficient manufacturing technology is disclosed in the present work for the preparation of 4-(2-hydroxyethyl)-1,3-dihydro-2<i>H</i>-indol-2-one, which is a key intermediate for ropinirole hydrochloride. The whole process gives the target molecule in 71% overall yield with 99% purity. In the final step, a novel nitro reduction/ring-closing/debenzylation takes place in one pot. All the intermediates can be used directly for the next step without purification in this process

NMR Study of Thermoresponsive Hyperbranched Polymer in Aqueous Solution with Implication on the Phase Transition

High-resolution ¹H NMR has been used on the thermoresponsive hyperbranched polyethylenimines (HPEIs) modified with isobutyramide (IBAm) groups (HPEI-IBAm), to study the structure and dynamics of the macromolecules in aqueous solution before and after the phase transition. It shows that the HPEI-IBAm macromolecule having a high IBAm substitution degree has a clear phase transition in aqueous solution, whereas the HPEI-IBAm macromolecule having a low IBAm substitution degree does not. The different phase transition behaviors have been attributed to the content as well as the distribution of the IBAm groups in the macromolecules. In order to deepen the understanding of the phase transition, the hydrophobic–hydrophobic interaction inside the HPEI-IBAm macromolecules was investigated by monitoring the ¹H–¹H NOEs between the different hydrophobic groups. An enhanced hydrophobic–hydrophobic interaction was observed in the HPEI-IBAm macromolecule having a high IBAm substitution degree after the phase transition, which provides a new perspective for our understanding of the phase transition of the macromolecules in aqueous solution. By using PFG diffusion NMR, the weight distributions of the moving particles in the solution were monitored. The β parameter used in the PFG diffusion NMR, which reflects the change of the weight distributions of the moving particles in solution, has proved to be a good way to monitor the aggregation process of the moving particles in the solution