1,8-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-4,11-dibenzyl-1,4,8,11-tetraazacyclotetradecane

A cyclam (1,4,8,11-tetraazacyclotetradecane)-based macrocycle bearing two benzyl and two 2-hydroxy-3,5-di-tert-butylbenzyl pendent arms was synthesized and characterized using spectroscopic techniques and single crystal X-ray diffraction. The macrocycle crystallizes in the triclinic space group P-1, with the asymmetric unit containing one-half of the molecule. The structure is stabilized by hydrogen-bonding which exists between the phenolic protons and the nitrogen atoms of the macrocyclic ring. The presence of this hydrogen bonding is observed in the 1H-NMR due to the deshielded nature of the phenolic OH peak (δ 9.99). Cyclic voltammetry of the ligand revealed a single quasi-reversible peak at −0.58 V (Epc = −0.48 V and Epa = −0.68 V), which is due to the electrochemical oxidation of the phenol to the phenoxyl radical

Who Says That God Loves the World? A Historical Argument to Identify the Ambiguous Speakers in John 3

This dissertation examines and catalogues the history of interpretation of the ambiguous speakers in John 3:16-21 and 3:31-36. The history of interpretation leads to the conclusion that the passages are best understood as spoken by Jesus, not the Evangelist. Chapter 1 introduces the topic and the disagreement within modern scholarship regarding the speakers.Part one contains the history of interpretation proper. Chapter 2 investigates the early Christian era including the second through sixth centuries. Authors throughout this period tend to identify Jesus as speaking in 3:16-21 and Jesus or the Baptist as speaking in 3:31-36. Few identify the Evangelist as speaking in one or both passages. In addition to this common interpretation, authors also correlate the identity of the speaker to a christological focus: Jesus/the Baptist is speaking when the focus is on the incarnation and the Evangelist is speaking when the focus is on the crucifixion. Chapter 3 covers the medieval era and demonstrates a continuation of the findings from the previous period. Although slightly more authors identify the Evangelist as speaking, the correlation between speaker and christological focus remains in most cases. The exceptions are relegated to 3:31-36; no authors break the correlation with regard to 3:16-21. Chapter 4 discusses the Reformation era and the new focus on the role of the Evangelist. Although these authors stress the importance of the Evangelist’s hand at work, the vast majority still attribute the words of both passages to either Jesus or the Baptist. Again, those that attribute the words to the Evangelist himself do so while discussing the crucifixion. Even in the Reformation era, authors still interpret 3:31-36 as the words of Jesus, although this phenomenon has become far less frequent. At the end of chapter 4, the early modern era comes into focus and shatters the established correlation. Several authors within a small time period attribute the words of 3:16-21 to Jesus while discussing the crucifixion. Chapter 5 explores the modern discussion on these ambiguous speakers and demonstrates that scholars agree very little as to the identity of the speaker in either passage. Using various methods and coming from various ideological backgrounds, scholars arrive at similar conclusions. Conversely, scholars coming from the same backgrounds or applying the same methods might arrive at vastly different conclusions. For this reason, the connection between the theological focus and the identity of the speakers is of utmost importance. Part two argues that both passages in John 3 should be attributes to Jesus in order to make the best sense of the theological focus of the chapter. Chapter 6 places John 3 within the larger context of the Book of Signs and the Gospel of John as a whole. By examining John’s larger rhetorical strategy, it becomes clear that John 3 is best understood as focused on the incarnation of the Christ and the testimony regarding Jesus’ self-revelation. Chapter 7 offers a reinterpretation of John 3 with Jesus as the speaker. It examines both positive arguments for this reading as well as the negative arguments against it, and concludes that this reading best explains that God demonstrates his love for the world through giving his Son in the incarnation. Chapter 8 concludes the dissertation with a recapitulation of the arguments and a brief discussion on areas of further study

Net Toroidal Magnetic Moment in the Ground State of a {Dy-6}-Triethanolamine Ring

A toroidal magnetic moment in the absence of conventional total magnetic moment is observed {Dy-6} ring. The reason for the net toroidal arrangement of the local Magnetic moments is the high symmetry of the complex in combination with strong intra-molecular dipolar interactions between Dy ions. The description of single ion and inter ion anisotropic magnetic interactions is achieved here for the first time fully ab initio, Le, without use of phenomenological parameters.</p

Comparison of three methods for measuring psoriasis severity in clinical studies (Part 2 of 2): use of quality of life to assess construct validity of the Lattice System Physician's Global Assessment, Psoriasis Area and Severity Index and Static Physician's Global Assessment

BackgroundSystems for determining psoriasis severity in clinical trials have not been sufficiently validated against patients’ perceived quality of life.ObjectiveTo validate three systems of physician‐determined psoriasis severity (the Lattice System Physician's Global Assessment [LS‐PGA], Psoriasis Area and Severity Index [PASI] and static Physician's Global Assessment [sPGA]).MethodsData were from a 24‐week randomized, double‐blind, placebo‐controlled, multicenter trial of therapy with oral calcineurin inhibitors in 445 patients. Construct validity was measured by correlations of the three severity scores with patients’ self‐reported quality of life (QoL) from the Dermatology Life Quality Index (DLQI) and a DLQI item about psoriasis symptoms.ResultsAll severity systems were moderately and positively correlated with QoL, indicating construct validity. QoL was most consistently related to physicians’ assessments of body surface area involved with psoriasis (iBSA) followed by, in the order of consistency, plaque elevation, erythema and scale.ConclusionsThe LS‐PGA weights iBSA and aspects of plaque morphology in concert with their relative effects on QoL. The LS‐PGA, sPGA and PASI are validated by their relationship to QoL in a clinical trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111946/1/jdv12861.pd

New archaeological discoveries in north-central Timor-Leste indicate sociocultural adaptations to landscape change during the Holocene

During the Holocene, Wallacea saw dramatic sociocultural changes during the Pre-ceramic, Neolithic, Metal-age, and Colonial periods, as well as climatic and associated environmental changes that affected the landscapes and ecologies of islands. These environmental and cultural processes appear to have influenced human socioeconomic adaptations throughout the archipelago. Here, we present new anthropological and archaeological data demonstrating the effects of these processes. Excavations at the cave site of Hatu Saur on the north coast of Timor-Leste have revealed a deep archaeological sequence that dates from ca. 10,500 years until the present. The site contains extensive assemblages of faunal remains, as well as stone artifacts, revealing settlement patterns that were influenced by sea level change and estuarine infilling after 7 ka. The sequence encompasses the beginning of the Neolithic in Timor-Leste, some 3500 years ago, and the period from ca. 700 years ago when outside influences, including Chinese and Makassar traders and Dutch and Portuguese colonization, greatly affected the indigenous culture and economy on the island of Timor, reflected in the material culture remains from Hatu Saur. The archaeological findings complement related anthropological research in the region that highlights unique local mythologies of settlement origins and their contested histories

Understanding the Mechanism of Magnetic Relaxation in Pentanuclear {MnIVMnIII2LnIII2} Single-Molecule Magnets

A new family of heterometallic pentanuclear complexes of formulas [MnIVMnIII2LnIII2O2(benz)4(mdea)3(NO3)2(MeOH)] (Ln = Dy (1-Dy), Tb (2-Tb), Gd (3-Gd), Eu (4-Eu), Sm (5-Sm), Nd (6-Nd), Pr (7-Pr); benz(H) = benzoic acid; mdeaH2= N-methyldiethanolamine) and [MnIVMnIII2LnIII2O2(o-tol)4(mdea)3(NO3)2(MeOH)] (Ln = Gd (8-Gd), Eu (9-Eu); o-tol(H) = o-toluic acid) have been isolated and structurally, magnetically, and theoretically characterized. dc magnetic susceptibility measurements reveal dominant antiferromagnetic magnetic interactions for each complex, except for 2-Tb and 3-Gd, which reveal an upturn in the χMT product at low temperatures. The magnetic interactions between the spin centers in the Gd derivatives, 3-Gd and 8-Gd, which display markedly different χMT vs T profiles, were found to be due to the interactions of the GdIII-GdIII ions which change from ferromagnetic (3-Gd) to antiferromagnetic (8-Gd) due to structural differences. ac magnetic susceptibility measurements reveal a nonzero out-of-phase component for 1-Dy and 7-Pr, but no maxima were observed above 2 K (Hdc = 0 Oe), which suggests single-molecule magnet (SMM) behavior. Out-of-phase signals were observed for complexes 2-Tb, 4-Eu, 8-Gd, and 9-Eu, in the presence of a static dc field (Hdc = 2000, 3000 Oe). The anisotropic nature of the lanthanide ions in the benzoate series (1-Dy, 2-Tb, 5-Sm, 6-Nd, and 7-Pr) were thoroughly investigated using ab initio methods. CASSCF calculations predict that the origin of SMM behavior in 1-Dy and 7-Pr and the applied field SMM behavior in 2-Tb does not solely originate from the single-ion anisotropy of the lanthanide ions. To fully understand the relaxation mechanism, we have employed the Lines model to fit the susceptibility data using the POLY_ANISO program, which suggests that the zero-field SMM behavior observed in complexes 1-Dy and 7-Pr is due to weak MnIII/IV-LnIII and LnIII-LnIII couplings and an unfavorable LnIII/MnIII/MnIV anisotropy. In complexes 4-Eu, 8-Gd, and 9-Eu ab initio calculations indicate that the anisotropy of the MnIII ions solely gives rise to the possibility of SMM behavior. Complex 7-Pr is a Pr(III)-containing complex that displays zero-field SMM behavior, which is rare, and our study suggests the possibility of coupling weak SOC lanthanide metal ions to anisotropic transition-metal ions to derive SMM characteristics; however, enhancing the exchange coupling in {3d-4f} complexes is still a stubborn hurdle in harnessing new generation {3d-4f} SMMs

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio