Organoplatinum: Some Reaction Modes

The thermal decomposition of organoplatinum(ll) complexes of the type cis-L2PtAr2 and (biL)PtAr2 [Ar =C6H5, 4-Me-C6H4; L = Ph3P, (4-Me-C6H4)3P, Ph2MeP; biL = Ph2PCH2PPh2 (dpm), Ph2PC2H4PPh2 (dpe), Me2PC2H4PMe2 (dmpe)] has been studied. In the condensed phase, the thermolyses have been examined by thermal analytical techniques (DSC and simultaneous TGA/DTA) and by product analysis (GLC). The results indicate that the complexes undergo thermal disruption via a predominant primary route which involves concerted reductive elimination of the platinum-bound aryl ligands as biaryl. This process is intramolecular, and no intermolecular exchange of aryls occurs prior to, or during, decomposition. Secondary reactions which produce quantities of arene and biaryl originating from the arylphosphine ligands, and whose operation is concurrent with, but essentially independent of, the primary reductive elimination, are also observed. These data are interpreted in terms of slower reactions (subsequent to the primary process) of the species L2Pto or (biL)Pto , involving aryl- or hydride-transfer to platinum, by oxidative insertion into P-C or C-H bonds, and ultimate reductive eliminations. Although their identities remain uncertain,analysis of the glassy, red-brown decomposition residues provides more evidence for these propositions. In the presence of an added equimolar amount of the appropriate phosphine, primary concerted reductive elimination of biaryl is facilitated. The effect is most marked for complexes of dpm in presence of free ligand. This general observation is in qualitative agreement with previous predictions and is discussed in terms of nucleophilic attack at Pt(ll) by a phosphorus donor. Secondary reactions are largely, if not altogether suppressed, and this is attributable to the diminished tendency of Pt(0) to undergo the oxidative insertion sequences in higher coordination number phospbine complexes. An exception is (dpm)2Pt(0) which appears to decompose under the conditions of its formation. In this case, an additional secondary process involves rupture of the P-C-P bridge, presumably again by oxidative insertion of Pt(0) into P-C (the first such example with P-alkyl). When a phosphine different to that already present is added, there is some evidence that exchange may occur prior to the Pt-C scission processes. The thermal decomposition of these systems was, additionally, followed in toluene solution. Product analyses served to corroborate the mechanistic conclusions drawn from the condensed-phase data. Primary, concerted, intramolecular reductive elimination is followed by the same slower secondary processes. Kinetic studies showed that the primary elimination is first-order in platinum complex and that, again, reductive elimination is facilitated by the presence of free phosphine. Only the complexes cis-(Ph3P)2PtAr2 displayed sufficient lability to be extensively studied under these conditions. Such activation parameters as were determined for these systems suggested that the enhanced lability of the 4-tolylplatinum species compared with its phenyl-analogue, and that of either system in the presence of Ph3P (relative to the complex alone) may be largely due to entropy effects, interpretations of which are discussed

Exploring the Technical Expression of Academic Knowledge: The Science-in-CTE Pilot Study

The Science-in-CTE pilot study tested a curriculum integration model that enhanced the science that occurs in CTE curricula. The study replicated the National Research Center for Career and Technical Education's (NRCCTE) Math-in-CTE experimental research design (Stone, Alfeld, & Pearson, 2008

Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts

Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain

cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 m coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphereforming cells detected in individual 400 m sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 276) or colonies (4275 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU/Ki-67) or competent to divide (BrdU/Mcm-2), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery