C-H Bond Addition across a Transient Uranium-Nitrido Moiety and Formation of a Parent Uranium Imido Complex

Mullane, Kimberly C.,Ryu, Ho,Cheisson, Thibault,Grant, Lauren N.,Park, Ji Young,Manor, Brian C.,Carroll, Patrick J.,Baik, Mu-Hyun,Mindiola, Daniel J.,Schelter, Eric J. American Chemical Society 2018 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.140 No.36

<P>Uranium complexes in the +3 and +4 oxidation states were prepared using the anionic PN<SUP>-</SUP> (PN<SUP>-</SUP> = (<I>N</I>-(2-(diisopropylphosphino)-4-methylphenyl)-2,4,6-trimethylanilide) ligand framework. New complexes include the halide starting materials, (PN)<SUB>2</SUB>U<SUP>III</SUP>I (<B>1</B>) and (PN)<SUB>2</SUB>U<SUP>IV</SUP>Cl<SUB>2</SUB> (<B>2</B>), which both yield (PN)<SUB>2</SUB>U<SUP>IV</SUP>(N<SUB>3</SUB>)<SUB>2</SUB> (<B>3</B>) by reaction with NaN<SUB>3</SUB>. Compound <B>3</B> was reduced with potassium graphite to produce a putative, transient uranium-nitrido moiety that underwent an intramolecular C-H activation to form a rare example of a parent imido complex, [K(THF)<SUB>3</SUB>][(PN)U<SUP>IV</SUP>(═NH)[<SUP><I>i</I></SUP>Pr<SUB>2</SUB>P(C<SUB>6</SUB>H<SUB>3</SUB>Me)N(C<SUB>6</SUB>H<SUB>2</SUB>Me<SUB>2</SUB>CH<SUB>2</SUB>)]] (<B>4</B>). Calculated reaction energy profiles strongly suggest that a C-H insertion becomes unfavorable when a reductant is present, offering a distinctively different reaction pathway than previously observed for other uranium nitride complexes.</P> [FIG OMISSION]</BR>

Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences

Walsh, Patrick S.,Dean, Jacob C.,McBurney, Carl,Kang, Hyuk,Gellman, Samuel H.,Zwier, Timothy S. The Royal Society of Chemistry 2016 Physical chemistry chemical physics Vol.18 No.16

<P>The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse gamma-turn in the peptide backbone by forming a pair of H-bonds that bridge the gamma-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I beta-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the beta-turn not otherwise involved in a hydrogen bond. This beta-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y beta-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.</P>

Fyn promotes proliferation, differentiation, survival and function of osteoclast lineage cells

Kim, Hyun‐,Ju,Warren, Julia T.,Kim, Shin‐,Yoon,Chappel, Jean C.,DeSelm, Carl J.,Ross, F. Patrick,Zou, Wei,Teitelbaum, Steven L. Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.111 No.5

<P><B>Abstract</B></P><P>c‐Src and Lyn are the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). c‐Src promotes function via cytoskeletal organization of the mature resorptive cell while Lyn is a negative regulator of osteoclastogenesis. We establish that Fyn, another SFK, also impacts the OC, but in a manner distinctly different than c‐Src and Lyn. Fyn deficiency principally alters cells throughout the osteoclastogenic process, resulting in diminished numbers of resorptive polykaryons. Arrested OC formation in the face of insufficient Fyn reflects reduced proliferation of precursors, in response to M‐CSF and retarded RANK ligand (RANKL)‐induced differentiation, attended by suppressed activation of the osteoclastogenic signaling molecules, c‐Jun, and NF‐κB. The anti‐apoptotic properties of RANKL are also compromised in cells deleted of Fyn, an event mediated by increased Bim expression and failed activation of Akt. The defective osteoclastogenesis of Fyn−/− OCs dampens bone resorption, in vitro. Finally, while Fyn deficiency does not regulate basal osteoclastogenesis, in vivo, it reduces that stimulated by RANKL by ∼2/3. Thus, Fyn is a pro‐resorptive SFK, which exerts its effects by prompting proliferation and differentiation while attenuating apoptosis of OC lineage cells. J. Cell. Biochem. 111: 1107–1113, 2010. © 2010 Wiley‐Liss, Inc.</P>

A new and selective cycle for dehydrogenation of linear and cyclic alkanes under mild conditions using a base metal

Solowey, Douglas P.,Mane, Manoj V.,Kurogi, Takashi,Carroll, Patrick J.,Manor, Brian C.,Baik, Mu-Hyun,Mindiola, Daniel J. Nature Publishing Group 2017 Nature chemistry Vol.9 No.11

Selectively converting linear alkanes to α-olefins under mild conditions is a highly desirable transformation given the abundance of alkanes as well as the use of olefins as building blocks in the chemical community. Until now, this reaction has been primarily the remit of noble-metal catalysts, despite extensive work showing that base-metal alkylidenes can mediate the reaction in a stoichiometric fashion. Here, we show how the presence of a hydrogen acceptor, such as the phosphorus ylide, when combined with the alkylidene complex (PNP)Ti=CH<SUP>t</SUP>Bu(CH<SUB>3</SUB>) (PNP=N[2-P(CHMe<SUB>2</SUB>)<SUB>2</SUB>-4-methylphenyl]<SUB>2</SUB><SUP>−</SUP>), catalyses the dehydrogenation of cycloalkanes to cyclic alkenes, and linear alkanes with chain lengths of C<SUB>4</SUB> to C<SUB>8</SUB> to terminal olefins under mild conditions. This Article represents the first example of a homogeneous and selective alkane dehydrogenation reaction using a base-metal titanium catalyst. We also propose a unique mechanism for the transfer dehydrogenation of hydrocarbons to olefins and discuss a complete cycle based on a combined experimental and computational study.

Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire

Chang, S.,Yang, L.,Moon, Y.M.,Cho, Y.G.,Min, S.Y.,Kim, T.J.,Kim, Y.J.,Patrick, W.,Kim, H.Y.,Mohan, C. Pergamon Press 2009 Molecular immunology Vol.46 No.16

When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited three sequence motifs in their immunoglobulin heavy chains, including increased cationicity in CDR3 (''motif A''), reduced anionicity in CDR2 (''motif B'') and increased aspartate at H50 (''motif C''). The present study was designed to elucidate the extent to which these ANA-associated sequence motifs might be hard-wired into the primary B-cell repertoire in lupus. The immunoglobulin heavy chain sequence of total splenic B-cells, follicular B-cells and marginal zone B-cells from B6.Sle1 congenic mice and C57BL/6 controls were amplified by single-cell PCR and compared. Analysis of the primary immunoglobulin heavy chain repertoire indicated that the first two sequence motifs ''A'' and ''B'' were already encoded in the naive repertoire of B6.Sle1<SUP>z</SUP> mice, whereas the third motif ''C'' was introduced in part by somatic mutation. Site-directed mutagenesis confirmed that non-anionic CDR2 and cationic CDR3 residues in the immunoglobulin heavy chain facilitated nuclear antigen binding in concert, whereas aspartate at H50 strongly vetoed DNA-binding, while preserving nucleosome reactivity. Hence, anti-nuclear antibodies appear to arise as a consequence of two distinct processes-genetically programmed selection of specific CDR charge motifs into the primary immunoglobulin repertoire, with secondary contribution from somatic mutation. Polymorphisms in the lupus susceptibility gene Ly108 that impair central B-cell tolerance may be mechanistically responsible for these early repertoire differences in lupus.

4-1BB functions as a survival factor in dendritic cells.

Choi, Beom K,Kim, Young H,Kwon, Patrick M,Lee, Sang C,Kang, Sang W,Kim, Moon S,Lee, Myoung J,Kwon, Byoung S Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.7

<P>4-1BB (CD137) is expressed on dendritic cells (DCs) and its biological function has remained largely unresolved. By comparing 4-1BB-intact (4-1BB(+/+)) and 4-1BB-deficient (4-1BB(-/-)) DCs, we found that 4-1BB was strongly induced on DCs during the maturation and that DC maturation was normal in the absence of 4-1BB. However, DC survival rate was low in the absence of 4-1BB, which was due to the decreased Bcl-2 and Bcl-x(L) in 4-1BB(-/-) DCs compared with 4-1BB(+/+) DCs after DC maturation. Consistent with these results, 4-1BB(-/-) DCs showed an increased turnover rate in steady state and more severely decreased in spleen by injecting LPS compared with 4-1BB(+/+) DCs. When OVA-pulsed DCs were adoptively transferred to recipient mice along with OVA-specific CD4(+) T cells, 4-1BB(-/-) DCs did not properly migrate to the T cell zone in lymph nodes and poorly induced proliferation of CD4(+) T cells, although both DCs comparably expressed functional CCR7. Eventually, 4-1BB(-/-) DCs generated a reduced number of OVA-specific memory CD4(+) T cells compared with 4-1BB(+/+) DCs. To further assess the role of 4-1BB on DC longevity in vivo, 4-1BB(+/+) and 4-1BB(-/-) C57BL/6 were administrated with Propionibacterium acnes that develop liver granuloma by recruiting DCs. Number and size of granuloma were reduced in the absence of 4-1BB, but the inflammatory cytokine level was comparable between the mice, which implied that the granuloma might be reduced due to the decreased longevity of DCs. These results demonstrate that 4-1BB on DCs controls the duration, DC-T interaction, and, therefore, immunogenicity.</P>

Stress Urinary Incontinence in Women With Multiple Sclerosis

Caroline Massot,Hichem Khenioui,Olivier Agnani,Marc-Alexandre Guyot,Patrick Hautecoeur,Cécile Donze 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.3

Purpose: To report the prevalence and risk factors of stress urinary incontinence (SUI) and the prevalence of intrinsic sphincter deficiency in women with multiple sclerosis (MS). Methods: We conducted a retrospective study. Female patients with MS, followed for lower urinary tract symptoms (LUTS) during a 15-year period were included. Demographic data, MS history, expanded disability status scale (EDSS) score at the urodynamic visit, obstetrical past, birth weight, LUTS, and urodynamic findings were collected. SUI was defined as incontinence during cough, or any effort. A maximum urethral closure pressure less than 30 cm H2O defined intrinsic sphincter deficiency. Results: We included 363 women with a mean age of 46.7±10.8 years and a mean disease duration of 12.9±8.7 years. The incidence of relapsing remitting MS, a secondary progressive form, and a primary progressive form was 60.6%, 32.8%, and 6.6%, respectively. The prevalence of SUI was 31.4%. The prevalence of intrinsic sphincter deficiency was 1.4% and 0.8% of these patients had a SUI (P=0.300). In a multivariate analysis, women with a SUI had significantly higher birth weight (P=0.030), a pelvic organ prolapse (P=0.021), urgent urinary incontinence (P=0.006), a lower EDSS score (P=0.019), and a weaker containing effort (P<0.001). Conclusions: The prevalence of SUI in women with MS was 31.4%. This symptom could affect the quality of life of women with MS.

Particle tracking acceleration via signed distance fields in direct-accelerated geometry Monte Carlo

Patrick C. Shriwise,Andrew Davis,Lucas J. Jacobson,Paul P.H. Wilson 한국원자력학회 2017 Nuclear Engineering and Technology Vol.49 No.6

Computer-aided design (CAD)-based Monte Carlo radiation transport is of value to the nuclear engineering community for its ability to conduct transport on high-fidelity models of nuclear systems, but it is more computationally expensive than native geometry representations. This work describes the adaptation of a rendering data structure, the signed distance field, as a geometric query tool for accelerating CAD-based transport in the direct-accelerated geometry Monte Carlo toolkit. Demonstrations of its effectiveness are shown for several problems. The beginnings of a predictive model for the data structure's utilization based on various problem parameters is also introduced.

A multi-targeting bionanomatrix coating to reduce capsular contracture development on silicone implants

Patrick Hwang,Chung Min Shin,Jennifer A. Sherwood,김동호,Vineeth M. Vijayan,Krishna C. Josyula,Reid C. Millican,Donald Ho,Brigitta C. Brott,Vinoy Thomas,Chul Hee Choi,Sang‑Ha Oh,김동운,Ho‑Wook Jun 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Capsular contracture is a critical complication of silicone implantation caused by fibrotic tissue formation from excessive foreign body responses. Various approaches have been applied, but targeting the mechanisms of capsule formation has not been completely solved. Myofibroblast differentiation through the transforming growth factor beta (TGF-β)/p-SMADs signaling is one of the key factors for capsular contracture development. In addition, biofilm formation on implants may result chronic inflammation promoting capsular fibrosis formation with subsequent contraction. To date, there have been no approaches targeting multi-facted mechanisms of capsular contracture development. Methods In this study, we developed a multi-targeting nitric oxide (NO) releasing bionanomatrix coating to reduce capsular contracture formation by targeting myofibroblast differentiation, inflammatory responses, and infections. First, we characterized the bionanomatrix coating on silicon implants by conducting rheology test, scanning electron microcsopy analysis, nanoindentation analysis, and NO release kinetics evaluation. In addition, differentiated monocyte adhesion and S. epidermidis biofilm formation on bionanomatrix coated silicone implants were evaluated in vitro. Bionanomatrix coated silicone and uncoated silicone groups were subcutaneously implanted into a mouse model for evaluation of capsular contracture development for a month. Fibrosis formation, capsule thickness, TGF-β/SMAD 2/3 signaling cascade, NO production, and inflammatory cytokine production were evaluated using histology, immunofluorescent imaging analysis, and gene and protein expression assays. Results The bionanomatrix coating maintained a uniform and smooth surface on the silicone even after mechanical stress conditions. In addition, the bionanomatrix coating showed sustained NO release for at least one month and reduction of differentiated monocyte adhesion and S. epidermidis biofilm formation on the silicone implants in vitro. In in vivo implantation studies, the bionanomatrix coated groups demonstrated significant reduction of capsule thickness surrounding the implants. This result was due to a decrease of myofibroblast differentiation and fibrous extracellular matrix production through inhibition of the TGF-β/p-SMADs signaling. Also, the bionanomatrix coated groups reduced gene expression of M1 macrophage markers and promoted M2 macrophage markers which indicated the bionanomatrix could reduce inflammation but promote healing process. Conclusions In conclusion, the bionanomatrix coating significantly reduced capsular contracture formation and promoted healing process on silicone implants by reducing myfibroblast differentiation, fibrotic tissue formation, and inflammation. Graphical Abstract A multi-targeting nitric oxide releasing bionanomatrix coating for silicone implant can reduce capsular contracture and improve healing process. The bionanomatrix coating reduces capsule thickness, α-smooth muscle actin and collagen synthesis, and myofibroblast differentiation through inhibition of TGF-β/SMADs signaling cascades in the subcutaneous mouse models for a month.

Simulating and evaluating regolith propagation effects during drilling in low gravity environments

Suermann, Patrick C.,Patel, Hriday H.,Sauter, Luke D. Techno-Press 2019 Advances in computational design Vol.4 No.2

This research is comprised of virtually simulating behavior while experiencing low gravity effects in advance of real world testing in low gravity aboard Zero Gravity Corporation's (Zero-G) research aircraft (727-200F). The experiment simulated a drill rig penetrating a regolith simulant. Regolith is a layer of loose, heterogeneous superficial deposits covering solid rock on surfaces of the Earth' moon, asteroids and Mars. The behavior and propagation of space debris when drilled in low gravity was tested through simulations and visualization in a leading dynamic simulation software as well as discrete element modeling software and in preparation for comparing to real world results from flying the experiment aboard Zero-G. The study of outer space regolith could lead to deeper scientific knowledge of extra-terrestrial surfaces, which could lead us to breakthroughs with respect to space mining or in-situ resource utilization (ISRU). These studies aimed to test and evaluate the drilling process in low to zero gravity environments and to determine static stress analysis on the drill when tested in low gravity environments. These tests and simulations were conducted by a team from Texas A&M University's Department of Construction Science, the United States Air Force Academy's Department of Astronautical Engineering, and Crow Industries