Presence Of Me Research Articles

Data-driven root cause analysis via causal discovery using time-to-event data

Data-driven approaches to root cause analysis (RCA) have received at- tention recently due to their ability to exploit increasing data availability for more effective root cause identification in complex processes. Advancements in the field of causal inference enable unbiased causal investigations using observational data. This study proposes a data-driven RCA method and a time-to-event (TTE) data simulation procedure built on the structural causal model (SCM) framework. A novel causality-based method is introduced for learning a representation of root cause mechanisms, termed in this work as root cause graphs (RCGs), from observational TTE data. Three case scenar- ios are used to generate TTE datasets for evaluating the proposed method. Finally, the utility of the method is demonstrated by using recovered RCGs to guide the estimation of root cause treatment effects. In the presence of me- diation, RCG-guided models produce superior estimates of root cause total effects compared to models that adjust for all covariates.

Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO2.

The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction of tertiary chiral centers. The asymmetric generation of acyclic products containing all-carbon quaternary stereocenters from substituted 1,3-dienes represents a more challenging, but highly desirable, synthetic process for which there are very few examples. Herein, we report the highly selective copper-catalyzed generation of chiral all-carbon acyclic quaternary stereocenters via functionalization of 1,3-dienes with CO2. A variety of readily available 1,1-disubstituted 1,3-dienes, as well as a 1,3,5-triene, undergo reductive hydroxymethylation with high chemo-, regio-, E/Z-, and enantioselectivities. The reported method features good functional group tolerance, is readily scaled up to at least 5 mmol of starting diene, and generates chiral products that are useful building blocks for further derivatization. Systemic mechanistic investigations using density functional theory calculations were performed and provided the first theoretical investigation for an asymmetric transformation involving CO2. These computational results indicate that the 1,2-hydrocupration of 1,3-diene proceeds with high π-facial selectivity to generate an (S)-allylcopper intermediate, which further induces the chirality of the quaternary carbon center in the final product. The 1,4-addition of an internal allylcopper complex, which differs from previous reports involving terminal allylmetallic intermediates, to CO2 kinetically determines the E/Z- and regioselectivity. The rapid reduction of a copper carboxylate intermediate to the corresponding silyl-ether in the presence of Me(MeO)2SiH provides the exergonic impetus and leads to chemoselective hydroxymethylation rather than carboxylation. These results provide new insights for guiding further development of asymmetric C-C bond formations with CO2.

Tracking chemical interactions of folic acid on gold surface by SERS spectroscopy

Surface-enhanced Raman scattering (SERS) spectroscopy was used in the investigation of the adsorption of folic acid (FA) on the surface of gold nanoparticles (AuNPs) in the absence and presence of surface modifiers hydrochloride acid (HCl) and 1-mercaptoethanol (ME). The proposal for the chemical interactions of FA with the metallic surface was based on vibrational assignment supported by Density Functional Theory (DFT) calculations. In the absence of surface modifiers, FA interacts with the gold surface through the pteridine moiety in a tilted geometry. In the presence of ME, the molecule of FA is anchored through hydrogen bonds with the surface modifier. The presence of HCl induced ion-pair interactions involving chloride ions, adsorbed on gold surfaces, and both the nitrogen N1 of the pteridine ring and the γ-carboxylic acid of the glutamic acid moiety. In this condition, keto-enol equilibrium can be evidenced by a remarkable enhancement of marker bands in the SERS spectra.

FIGHT: A phase 3 randomized, double-blind, placebo controlled study evaluating (bemarituzumab) FPA144 and modified FOLFOX6 (mFOLFOX6) in patients with previously untreated advanced gastric and gastroesophageal cancer with a dose finding phase 1 lead-in.

TPS4135Background: FGFR2b overexpression and FGFR2 gene amplification occurs in approximately 10% of patients with gastric cancer (GC) and is associated with a poor prognosis and the presence of me...

Multicomponent self-assembly of Mn(I)-based thiolato-bridged ester functionalized rectangular and V-shaped tetranuclear metallacyclophanes

Abstract Manganese(I)-based thiolato-bridged ester functionalized tetranuclear metallasupramolecules have been achieved by the self-assembly of Mn 2 (CO) 10 , diaryl/ p- tolyl disulfides (RSSR) and linear/bent ester functionalized ditopic azine ligands (L) {L = phenyl-1,4-bis(isonicotinate) (pbin) and bis(4-(4-pyridylcarboxyl)phenyl)dimethylmethane (bpcpd)}. Oxidative addition of diaryl/ p- tolyl disulfides to manganese carbonyl with linear/bent azine ligands in the presence of Me 3 NO has resulted into the formation of metallacyclophanes of general formula [{(CO) 3 Mn( µ -SR) 2 Mn(CO) 3 } 2 ( µ -L) 2 ] ( 1 – 4 ) under one-pot reaction condition. Compounds 1 – 4 have been characterized using elemental analyses, IR, NMR, UV–Vis absorption spectroscopic techniques and the molecular structures of 1 – 3 were elucidated by single-crystal X-ray diffraction studies.

ChemInform Abstract: Low‐Valent Titanium‐Catalyzed Deprotection of Allyl‐ and Propargyl‐Carbamates to Amines.

Abstract In the presence of Me 3 SiCl, Ti(O- i -Pr) 4 /Mg and CpTiCl 3 /Mg reagents effectively catalyzed the deprotection of allyloxycarbonyl (alloc)- and propargyloxycarbonyl (poc)-protected amines in THF at around room temperature to produce parent amines in good yields. Alloc- and poc-protected secondary amines were smoothly deprotected to parent amines by a reaction catalyzed by a Ti(O- i -Pr) 4 /Me 3 SiCl/Mg reagent. The deprotection of alloc- and poc-protected primary amines was successfully catalyzed by a CpTiCl 3 /Me 3 SiCl/Mg reagent.

ChemInform Abstract: Synthetic Reactions Using Low‐Valent Titanium Reagents Derived from Ti(OR)4 or CpTiX3 (X: O‐iPr or Cl) in the Presence of Me3SiCl and Mg

AbstractReview: [34 refs.

Effects of virginiamycin and monensin administered alone or together with Megasphaera elsdenii strain NCIMB 41125 on in vitro production of lactate and VFA and the effects of monensin and M. elsdenii strain NCIMB 41125 on health and performance of feedlot steers

Virginiamycin (VIR) and monensin (MON) are included in high concentrate diets to mitigate digestive disturbances and to increase performance of ruminants in intensive systems. Megasphaera elsdenii strain NCIMB 41125 (Me) rapidly utilises lactate in the rumen, thereby controlling ruminal pH and digestive disturbances. Me promotes butyrate and valerate production whereas VIR and MON promote propionate that is gluconeogenic and perceived to be more favourable to performance. The objective of the present study was to determine whether the ratio between VFA proportions is more favourable when VIR or MON is administered together with Me and whether their respective effects on health and performance are additive. Two studies of factorial design were conducted, one in vitro fermentation trial where VIR or MON was incubated in the absence of Me (Me-) or in the presence of Me (Me+), and one in vivo trial with steers where MON or Me was administered alone or together. In the in vitro trial VIR and MON were administered to the fermentation vessels in two concentrations, a low dose (0.125µg/mL) and a high dose (0.375mg/mL). Me was administered at 100µL/40mL, supplying 2.5×105cfu/mL. In the in vivo trial 224 Bonsmara steers were allocated to a finishing diet with 80kg/ton roughage and 224 were allocated to a finishing diet with 20kg/ton roughage. Within each diet 112 steers received MON (MONY) and 112 not (MONN) and 112 steers within each diet were dosed with Me (MeY) and 112 not (MeN). In the in vitro trial VIRMe- and MONMe- decreased gas production, whereas VIRMe+ and MONMe+ increased fermentation. VIRMe- and to a lesser extent MONMe- increased total bacterial counts, a result which was apparently due to stimulation of M. elsdenii numbers as determined by 16R DNA sequencing, although other lactate utilising bacteria could have contributed. Me+ reduced lactate and the reduction was more in VIRMe+ and MONMe+. Fermentation end products in Me+ favoured butyrate and valerate and VIRMe- and especially MONMe-, propionate. VIRMe+ and MONMe+ displayed the median. In the steer trial MONY decreased intake and improved feed conversion efficiency. MONY increased carcass gain and dressing percentage on the 80kg/ton roughage diet but not the 20kg/ton roughage diet. Rumen score on both diets was improved by MONY and liver score by MONYMeY on the 20kg/ton roughage diet. Carcass weight was improved by MONNMeY on the 20kg/ton roughage diet. Morbidity and mortality were not affected by MONY but were improved in the presence of Me (MeY). In general, the results suggest synergy between MON and Me.

Competitive Effects of Calcium and Magnesium Ions on the Photochemical Transformation and Associated Cellular Uptake of Iron by the Freshwater Cyanobacterial Phytoplankton Microcystis aeruginosa.

Photochemical reduction of iron and iron uptake by Microcystis were investigated in a freshwater medium (pH 8) containing a range of calcium (Ca) and magnesium (Mg) ion concentrations (0.002-20 mM). In a medium containing the chelator ethylenediaminetetraacetic acid (EDTA), 50-fold increases in net photochemical formation rates of unchelated ferrous iron (Fe(II)') were observed as the concentration of calcium or magnesium metal (Me) was increased to exceed the concentration of EDTA. Kinetic modeling of iron transformation processes indicated that the facilitated Fe(II)' formation is attributed to Me-promoted photoreductive dissociation of the ferric iron-EDTA complex. In the medium containing Suwanee River fulvic acid, in contrast, the competitive effect of Me on photochemical Fe(II)' formation appears to be negligible due to the weak binding affinities of fulvic acid to Me. The cellular iron uptake rate in the EDTA-buffered system increased by ∼3-fold in the excess Me condition where the increased rate of photochemical Fe(II)' formation was observed, whereas the presence of Me resulted in a decrease in iron uptake rate in the fulvic acid system (by up to 5-fold). The decrease in iron uptake is likely caused by Me binding to iron transporters and other entities involved in intracellular iron transport. The findings of this study indicate a significant effect of Ca and Mg concentrations in natural waters on iron uptake by Microcystis, with the magnitude of effect depending strongly on ligand type.

ChemInform Abstract: Synthesis of Linearly Bonded 1,1′‐Bis[4‐(1,3‐diselenan‐2‐yl)pyrazoles] from 1,1′‐Bis(pyrazole‐4‐carbaldehydes) and Propane‐1,3‐diselenol.

The reaction of linearly bonded 1,1 ’ -bis(pyrazole-4-carbaldehydes) with propane-1,3-diselenol at room temperature in the presence of Me 3 SiCl followed by treatment with triethylamine affords the corresponding 1,1 ’ -bis[4-(1,3-diselenan-2-yl)pyrazoles].

Efficacy and mode of action of selected non-ionophore antibiotics and direct-fed microbials in relation to Megasphaera elsdenii NCIMB 41125 during in vitro fermentation of an acidosis-causing substrate

The efficacy of prominent in-feed antibiotics and direct-fed microbials (DFM) to prevent or mitigate ruminal acidosis and lactate accumulation, in addition to whether their presence will enhance or inhibit Megasphaera elsdenii strain NCIMB 41125 (Me) were studied in vitro. The antibiotics studied were aureomycin+sulfamethazine as AS-700 (AS), terramycin as TM-200 (TM), zinc bacitracin (ZB), flavomycin (FM) and tylosin (TS). The DFM were Bovamine (BM) which contains a propionic bacterium and a lactobacillus, Levucell (LC) which contains a strain of the yeast Saccharomyces cerevisiae and Progut (PG) which contains a hydrolysate of S. cerevisiae. The antibiotics and DFM were introduced alone or in the presence of Me to an in vitro system with fermentation vessels containing a medium that promoted rapid gas production and lactate development. Dose sizes of the antibiotics were chosen to inhibit fermentation by 10–20% or 30–40% and for DFM dose sizes were according to the manufacturers. For Me the dose size was 100µl/40ml containing 2.5×105 colony forming units per ml. Me on average reduced lactate from 20.0mM to 4.89mM, increased VFA production and shifted VFA proportions to more butyrate and valerate (respectively from 5.80 to 16.0mM/100mM and from 0.51 to 4.71mM/100mM). The antibiotics moderately reduced lactate (26.7–16.8mM), and AS, ZB and TS enhanced a VFA proportional shift towards propionate (from 22.6 to 28.7mM/100mM). In the presence of Me lactate was reduced to levels of Me alone and the ratio butyrate to propionate was reduced. None of the antibiotics inhibited the action of Me; on the contrary the interaction was additive. In contrast to the antibiotics and PG, the DFM BM and LC did not affect fermentation resulting in no response with respect to any of the variables measured. PG in the presence of Me apparently enhanced the action of Me, as noticed by an additional increase in butyrate and valerate proportions.

低原子価チタン反応剤Ti(OR)<sub>4</sub>/Me<sub>3</sub>SiCl/Mgの開発と反応

In the presence of Me 3 SiCl or MgCl 2 , Ti(OR) 4 was reduced by Mg powder in THF to gradually generate a specific low-valent titanium species, which mediated or catalyzed several synthetic reactions such as C-O bond-cleavage of allyl and propargyl ethers and esters, intra- and intermolecular cyclotrimerization of alkynes, reduction of epoxides and oxetanes via homolytic ring-opening, McMurry coupling reaction of aryl aldehydes, imino-pinacol coupling and reductive N-S or O-S bond-cleavage of sulfonamides or sulfonyl esters.

Synthesis of linearly bonded 1,1’ -bis[4-(1,3-diselenan-2-yl)pyrazoles] from 1,1’ -bis(pyrazole-4-carbaldehydes) and propane-1,3-diselenol

The reaction of linearly bonded 1,1 ’ -bis(pyrazole-4-carbaldehydes) with propane-1,3-diselenol at room temperature in the presence of Me 3 SiCl followed by treatment with triethylamine affords the corresponding 1,1 ’ -bis[4-(1,3-diselenan-2-yl)pyrazoles].

Unusual Spontaneous α→β Isomerization of Unsymmetrical Benzoins

The spontaneous thermal α→β benzoins isomerization of the some mixed aryl(furyl)benzoins takes place at the absence of bases. It is caused by two structure factors: the presence of halogen atom in para -site of the aryl moiety and the presence of Me 2 NN=CH-substituent in 5-site of the furane ring.

Combinatorial synthesis of chemical building blocks 1. Azomethines

128 Azomethines were synthesized through condensation of carbonyl compounds with various amines in pyridine in the presence of Me(3)SiCl as promoter and water scavenger in 58-98% yield. Et(3)N was added to reaction mixtures before precipitating the product with H(2)O to prevent acid catalyzed hydrolysis of the C=N bond. The scope and limitation of the method are discussed. High yields and simple setup/workup procedure make this method suitable for the combinatorial synthesis of azomethines, which are suitable as starting materials for high throughput synthesis of various combinatorial libraries. The azomethines synthesized were used as starting materials in a one-pot combinatorial synthesis of amines and amides.

Friction, nanowear and corrosion properties of electroplated nickel surfaces after dual implantation of Cr+ and N2+ ions. Influence of the implantation energy of the N2+ ions

In this work, dual implantation of Cr+ and N2+ ions on electroplated Ni substrates have been investigated for N2+ implantation energies of 140keV, 100keV and 60keV. The implanted specimens have been analyzed by glow discharge optical emission spectroscopy, X-ray diffraction, nano-indentation, coefficient of friction, nano-wear and potentiodynamic corrosion curves. The properties of the dual implanted samples have been compared to Cr+ or N2+ implanted specimens.The microstructural and mechanical properties of the Ni plates depend on the penetration ranges of the Cr and N atomic profiles obtained after the implantation process. The increase of hardness reduced the coefficient of friction of the samples and the wear rates. Preferential formation of Cr–N over Ni–N compounds has been observed when the Cr and N atomic profiles coexist within the Ni matrix.The potentiodynamic corrosion curves in acidic solutions revealed that the presence of Me–N species is detrimental for the chemical stability of the plates. Both nano-wear and corrosion properties are optimized when a Ni–N sublayer is formed underneath a top Cr–Ni implanted film. This is achieved by tuning the implantation energies of Cr+ and N2+ ions at 140keV. This bilayer structure could be a suitable treatment for micro-embossing dies for plastic texturing processes.

Oxidative DNA Cleavage by Zn(X-BDPA)(NO3)2Complexes (X=F, H, and Me): Effect of Different Ligand Substituents

Metal complexes have a large potential in biological and medicinal applications because of their cationic character, modularity, reactivity, redox chemistry, photoreactions and defined three dimensional structures. Particularly, the catalytic effects of various metal complexes on the nucleic acids cleavage has been a subject for an intensive study. As a recent example, oxidative DNA cleavage by [M(2,2'dipyridylamine)2(NO3)n] x+ (M = Cd, Cu, Ni and Zn, n = 1, 2, x = 0, 1) metal complexes has been reported. The cleavage has been shown to depend on the nature of the central metal: Zn performed the fastest and Ni the slowest in double stranded DNA cleavage. Another report showed that (N,N'ethylenediaminediacetato) M(II) complexes (M = Cu, Co, Ni, Zn) cleaved plasmid DNA in the presence of hydrogen peroxide. The Cu(II) complex was more efficient in DNA cleavage than the Zn and Ni complexes; the different amounts of OH radicals among the complexes were responsible for their different efficiencies. In this study, we report the cleavage of supercoiled pgem7zf-nisin DNA (referred to as pgem DNA) by Zn(X-BDPA) (NO3)2 complexes (Figure 1). 6 As shown in the structure, the ligand possesses Me or F at the position of X. The presence of Me or F represents an electron donating or withdrawing group, respectively, resulting in a different electron density on the complex in each case (see Supporting Information for the syntheses and characterizations of three ligands and their metal complexes). Figure 2 depicts the time-dependent appearance of nicked circular and linear pgem DNA with respect to the incubation time. The amount of super coiled pgem DNA decreased with incubation time for all three complexes. After 40 minutes of incubation, no super coiled DNA was left for the Zn(X-BDPA)(NO3)2 complexes, where X represents H or Me. The appearance of linear DNA was also noted for the X = Me complex after 35 minutes of incubation. The band corresponding to linear DNA appeared after 50 minutes incubation for the complex with X = H.

Preparation and physical properties of early-late heterobimetallic compounds featuring Ir–M bonds (M = Ti, Zr, Hf)

Treatment of Cp*Ir N(t)Bu (1) with the appropriate metallocene equivalent is an effective route for the preparation of the heterobimetallic complexes Cp*Ir(μ-N(t)Bu)MCp(2) (2-M, M = Ti, Zr, Hf). The electronic structures of the isostructural series of compounds, 2-M, are described with reference to single-crystal X-ray, Raman, UV-vis, and cyclic voltammetry data. Density functional theory (DFT) calculations were used to aid in the interpretation of this experimental work. Treatment of the zirconium or hafnium congeners with 2,6-lutidinium triflate leads to protonation of the Ir-M bond, to afford Cp*Ir(μ-N(t)Bu)(μ-H)MCp(2)OTf (3-M, M = Zr, Hf). Compound 3-Zr was characterized by single-crystal X-ray diffraction and independently prepared by the reaction of 1 and Cp(2)Zr(H)Cl in the presence of Me(3)SiOTf. In reactions analogous to those for 2-Zr, 2-Hf reacts with S(8) and aryl azides to insert an S-atom or aryl azide fragment into the metal-metal bond, yielding Cp*Ir(μ-N(t)Bu)(μ-S)HfCp(2) (6-Hf) and Cp*Ir(μ-N(t)Bu)(N(3)Ph)HfCp(2) (4-Hf), respectively. Heating 4-Hf results in N(2) extrusion to form Cp*Ir(μ-N(t)Bu)(NPh)HfCp(2) (5-Hf). The kinetics of the latter reaction were studied to obtain activation parameters and a Hammett trend; these data are compared to those for the analogous reaction involving Ir-Zr heterobimetallics.

Active Cobalt Catalyst for the Cleavage of Benzyl Ether

An improved method for the deprotection of benzyl ethers using a catalytic amount of Co(2)(CO)(8) in the presence of Me(2)PhSiH and CO (1 atm) is described. The deprotection reaction is compatible with double bond or sulfur-containing substrates. The method also tolerates other functional groups, such as Ac, Piv, and Bz, and shows potential selectivity in perbenzylated monosaccharides.

Molybdenum-Catalyzed Transformation of Molecular Dinitrogen into Silylamine: Experimental and DFT Study on the Remarkable Role of Ferrocenyldiphosphine Ligands

A molybdenum-dinitrogen complex bearing two ancillary ferrocenyldiphosphine ligands, trans-[Mo(N(2))(2)(depf)(2)] (depf = 1,1'-bis(diethylphosphino)ferrocene), catalyzes the conversion of molecular dinitrogen (N(2)) into silylamine (N(SiMe(3))(3)), which can be readily converted into NH(3) by acid treatment. The conversion has been achieved in the presence of Me(3)SiCl and Na at room temperature with a turnover number (TON) of 226 for the N(SiMe(3))(3) generation for 200 h. This TON is significantly improved relative to those ever reported by Hidai's group for mononuclear molybdenum complexes having monophosphine coligands [J. Am. Chem. Soc.1989, 111, 1939]. Density functional theory (DFT) calculations have been performed to figure out the mechanism of the catalytic N(2) conversion. On the basis of some pieces of experimental information, SiMe(3) radical is assumed to serve as an active species in the catalytic cycle. Calculated results also support that SiMe(3) radical is capable of working as an active species. The formation of five-coordinate intermediates, in which one of the N(2) ligands or one of the Mo-P bonds is dissociated, is essential in an early stage of the N(2) conversion. The SiMe(3) addition to a "hydrazido(2-)" intermediate having the NN(SiMe(3))(2) group will give a "hydrazido(1-)" intermediate having the (Me(3)Si)NN(SiMe(3))(2) group rather than a pair of a nitrido (≡N) intermediate and N(SiMe(3))(3). The N(SiMe(3))(3) generation would not occur at the Mo center but proceed after the (Me(3)Si)NN(SiMe(3))(2) group is released from the Mo center. The flexibility of the Mo-P bond between Mo and depf would play a vital role in the high catalysis of the Mo-Fe complex.