Peripherally-metallated porphyrins: meso-n1-porphyrinyl-platinum(II) complexes of 5,15-diaryl- and 5,10,15-triarylporphyrins

Attempted metathesis reactions of peripherally-metallated meso-η1-porphyrinylplatinum(II) complexes such as trans-[PtBr(NiDPP)(PPh3)2] (H2DPP = 5,15-diphenylporphyrin) with organolithium reagents fail due to competitive addition at the porphyrin ring carbon opposite to the metal substituent. This reaction can be prevented by using 5,10,15-triarylporphyrins, e.g. 5,10,15-triphenylporphyrin (H2TrPP) and 5-phenyl-10,20-bis(3’,5’-di-t-butylphenyl)porphyrin (H2DAPP) as substrates. These triarylporphyrins are readily prepared using the method of Senge and co-workers by addition of phenyllithium to the appropriate 5,15-diarylporphyrins, followed by aqueous protolysis and oxidation. They are convenient, soluble building blocks for selective substitutions and subsequent transformations at the remaining free meso carbon. The sequence of bromination, optional central metallation and oxidative addition of Pt(0) tris(phosphine) complexes generates the organoplatinum porphyrins in high overall yields. The bromo ligand on the Pt(II) centre can be substituted by alkynyl nucleophiles, including 5-ethynylNiDPP, to form the first examples of meso-η1-porphyrinylplatinum(II) complexes with a second Pt-C bond. The range of porphyrinylplatinum(II) bis(tertiary phosphine) complexes was extended to the triethylphosphine analogues, by oxidative addition of H2TrPPBr to Pt(PEt3)3, and the initially-formed cis adduct is only slowly thermally transformed to trans-[PtBr(H2TrPP)(PEt3)2] 16. The molecular structures of NiDAPP 9b, trans-[Pt(NiDPP)(C2NiDPP)(PPh3)2] 14 and 16 were determined by X-ray crystallography

Everyday Occupations: Traffic, Hazards, And Mobility In The West Bank

Mobility in the West Bank is inherently tied to the Israeli military occupation. Each new stage of the decades old conflict comes with new implications for the way Palestinians move around the West Bank. The past years have seen a transition during which the severe mobility restrictions that constituted the closure policy of the second intifada eased and intercity travel has increased. In this study I examine day-to-day experiences of mobility in the West Bank in the post-closure period. In doing so I highlight the ways in which routine experiences of mobility, those with traffic, road hazards, and infrastructure, bring elements on the Israeli occupation to the forefront of Palestinian experiences and conscience. I suggest that some of the static boundaries and binaries that have formed the lens though which scholars have viewed Palestinian experiences miss complexities and dynamics that become hyper visible through an examination of the everyda

Medium-evolved fragmentation functions

Medium-induced gluon radiation is usually identified as the dominant dynamical mechanism underling the {\it jet quenching} phenomenon observed in heavy-ion collisions. In its actual implementation, multiple medium-induced gluon emissions are assumed to be independent, leading, in the eikonal approximation, to a Poisson distribution. Here, we introduce a medium term in the splitting probabilities so that both medium and vacuum contributions are included on the same footing in a DGLAP approach. The improvements include energy-momentum conservation at each individual splitting, medium-modified virtuality evolution and a coherent implementation of vacuum and medium splitting probabilities. Noticeably, the usual formalism is recovered when the virtuality and the energy of the parton are very large. This leads to a similar description of the suppression observed in heavy-ion collisions with values of the transport coefficient of the same order as those obtained using the {\it quenching weights}.Comment: LaTeX, 18 pages, 13 figures included using epsfig, uses JHEP3; v2: enlarged discussions, one figure replaced, some references added, final versio

First-time, mild diverticulitis: Antibiotics or watchful waiting?

Review of: Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.First-time, mild diverticulitis: antibiotics or watchful waiting? Don't jump to antibiotic Tx for mild, uncomplicated diverticulitis, a recent RCT says. Observation may be just as effective. Practice changer: For mild, computed tomography-proven acute diverticulitis, consider observation only instead of antibiotic therapy. Stength of recommendation: B: Based on a single randomized controlled trial.Bob Marshall, MD, MPH, MISM, FAAFP; Shailendra Prasad, MBBS, MPH; Mary Alice Noel, MD; Jeffrey Burket, MD, FAAFP; Michael Arnold, DO, FAAFP; Benjamin Arthur, MD; Nick Bennett, DO; Ashley Smith, MD ; Madigan Family Medicine Residency, Gig Harbor, Wash (Drs. Marshall, Noel, Burket, Arnold, Arthur, Bennett, Smith); University of Minnesota Family Medicine and Community Health, Minneapolis (Dr. Prasad

Evolution of mechanism of parton energy loss with transverse momentum at RHIC and LHC in relativistic collision of heavy nuclei

We analyze the suppression of particle production at large transverse momenta in ($0-5$ most) central collisions of gold nuclei at $\sqrt{s_\textrm{NN}}=$ 200 GeV and lead nuclei at $\sqrt{s_{\textrm{NN}}}=$ 2.76 TeV. Full next-to-leading order radiative corrections at ${\cal{O}}(\alpha_s^3)$, and nuclear effects like shadowing and parton energy loss are included. The parton energy loss is implemented in a simple multiple scattering model, where the partons lose an energy $\epsilon=\lambda \times dE/dx$ per collision, where $\lambda$ is their mean free path. We take $\epsilon=\kappa E$ for a treatment which is suggestive of the Bethe Heitler (BH) mechanism of incoherent scatterings, $\epsilon = \sqrt{\alpha E}$ for LPM mechanism, and $\epsilon=$ constant for a mechanism which suggests that the rate of energy loss ($dE/dx$) of the partons is proportional to total path length ($L$) of the parton in the plasma, as the formation time of the radiated gluon becomes much larger than $L$. We find that while the BH mechanism describes the nuclear modification factor $R_{\textrm{AA}}$ for $p_T \leq$ 5 GeV/$c$ (especially at RHIC energy), the LPM and more so the constant $dE/dx$ mechanism provides a good description at larger $p_T$. This confirms the earlier expectation that the energy loss mechanism for partons changes from BH to LPM for $p_T \ge \lambda$, where $\lambda \approx$ 1 fm and $\approx$ 1 GeV$^2$ is the average transverse kick-squared received by the parton per collision. The energy loss per collision at the $\sqrt{s_\textrm{NN}}$ =2.76 TeV is found to be about twice of that at 0.2 TeV.Comment: Discussion expanded, additional references added, 14 pages, 6 figures, To appear in Journal of Physics

Jet coherence in QCD media: the antenna radiation spectrum

We study the radiation of a highly energetic partonic antenna in a colored state traversing a dense QCD medium. Resumming multiple scatterings of all involved constituents with the medium we derive the general gluon spectrum which encompasses both longitudinal color coherence between scattering centers in the medium, responsible for the well known Landau-Pomeranchuk-Migdal (LPM) effect, and transverse color coherence between partons inside a jet, leading, in vacuum, to angular ordering of the parton shower. We discuss shortly the onset of transverse decoherence which is reached in opaque media. In this regime, the spectrum consists of independent radiation off the antenna constituents.Comment: 15 pages, 2 figures, paper shortened and partly rewritten, references added, results unchange

Corrigendum: Cathepsin D Variants Associated With Neurodegenerative Diseases Show Dysregulated Functionality and Modified α-Synuclein Degradation Properties

Cathepsin D (CTSD) is a lysosomal protease important for the degradation of various substrates, including disease-associated proteins like α-synuclein (a-syn), amyloid precursor protein (APP) and tau, all of which tend to aggregate if not efficiently degraded. Hence, it is not surprising that genetic variants within the CTSD gene have been linked to neurodegenerative diseases, like Parkinson's and Alzheimer's disease (PD, AD), as well as the lysosomal storage disorder neuronal ceroid lipofuscinosis type-10 (NCL10). Although recent studies have shown the molecular dependence of substrate degradation via CTSD within autophagic pathways, only little is known about the precise role of lysosomal CTSD function in disease development. We here performed biochemical, cellular and structural analyses of eleven disease-causing CTSD point mutations found in genomic sequencing data of patients to understand their role in neurodegeneration. These CTSD variants were analyzed for cellular localization, maturation and enzymatic activity in overexpression analyses. Moreover, for PD-associated mutants, intracellular degradation of a-syn was monitored. In summary, our results suggest that NCL10-associated CTSD variants are significantly impaired in lysosomal maturation and enzymatic activity, whereas the AD- and PD-associated variants seemed rather unaffected, indicating normal maturation, and lysosomal presence. Interestingly, a PD-associated CTSD variant (A239V) exhibited increased enzymatic activity accompanied by enhanced a-syn degradation. By structural analyses of this mutant utilizing molecular dynamics simulation (MDS), we identified a structural change within a loop adjacent to the catalytic center leading to a higher flexibility and potentially accelerated substrate exchange rates. Our data sheds light onto the role of CTSD in disease development and helps to understand the structural regulation of enzymatic function, which could be utilized for targeted CTSD activation. Because of the degradative function of CTSD, this enzyme is especially interesting for therapeutic strategies tackling protein aggregates in neurodegenerative disorders

A Feynman-Kac Formula for Anticommuting Brownian Motion

Motivated by application to quantum physics, anticommuting analogues of Wiener measure and Brownian motion are constructed. The corresponding Ito integrals are defined and the existence and uniqueness of solutions to a class of stochastic differential equations is established. This machinery is used to provide a Feynman-Kac formula for a class of Hamiltonians. Several specific examples are considered.Comment: 21 page

Error‐related brain activity in adolescents with obsessive‐compulsive disorder and major depressive disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145307/1/da22767_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145307/2/da22767.pd

Parkes Weber syndrome associated with two somatic pathogenic variants in RASA1

Parkes Weber syndrome is associated with autosomal dominant inheritance, caused by germline heterozygous inactivating changes in th