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The application of NMR spectroscopy to complex mixture analysis and, in particular, to metabolomics is limited by the low sensitivity of NMR. We recently showed that dissolution dynamic nuclear polarization (d-DNP) could enhance the sensitivity of 13C NMR for complex metabolite mixtures, leading to the detection of highly sensitive 13C NMR fingerprints of complex samples such as plant extracts or urine. While such experiments provide heteronuclear spectra, which are complementary to conventional NMR, hyperpolarized 1H NMR spectra would also be highly useful, with improved limits of detection and compatibility with the existing metabolomics workflow and databases. In this technical note, we introduce an approach capable of recording both 1H and 13C hyperpolarized spectra of metabolite mixtures in a single experiment and on the same hyperpolarized sample. We investigate the analytical performance of this method in terms of sensitivity and repeatability, and then we show that it can be efficiently applied to a plant extract. Significant sensitivity enhancements in 1H NMR are reported with a repeatability suitable for metabolomics studies without compromising on the performance of hyperpolarized 13C NMR. This approach provides a way to perform both 1H and 13C hyperpolarized NMR metabolomics with unprecedented sensitivity and throughput.

Social networks have become an important aspect of our modern times and are gradually becoming an integral means of communication worldwide. Overwhelming amounts of data are being transferred over social networks every day. Hence ensuring security becomes a necessity. Suspicious users or spammers may pose a threat to the information and data shared by users over the network. With this in mind, outliers detection is a crucial aspect of network communication. In our paper, a new technique is proposed to identify the anomalies in a network from a global perspective by using the network community structure. In general, state-of-the-art outliers detection algorithms mainly focus on the individual nodes and their direct neighborhood. But our technique considers only those nodes which tend to belong to multiple communities or whose neighbors belong to the same community or do not belong to any community. Results after experiments on synthetic and real-world networks show an improvement of 7-10% and 29% in F-Score and Jaccard similarity, respectively, compared to the state-of-the-art algorithms. Furthermore, we achieve almost 1.83 times speedup compared to the state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Hyperpolarized 13C NMR at natural abundance, based on dissolution dynamic nuclear polarization (d-DNP), provides rich, sensitive and repeatable 13C NMR fingerprints of complex mixtures. However, the sensitivity enhancement is associated with challenges such as peak overlap and the difficulty to assign hyperpolarized 13C signals. Ultrafast (UF) 2D NMR spectroscopy makes it possible to record heteronuclear 2D maps of d-DNP hyperpolarized samples. Heteronuclear UF 2D NMR can provide correlation peaks that link quaternary carbons and protons through long-range scalar couplings. Here, we report the analytical assessment of an optimized UF long-range HETCOR pulse sequence, applied to the detection of metabolic mixtures at natural abundance and hyperpolarized by d-DNP, based on repeatability and sensitivity considerations. We show that metabolite-dependent limits of quantification in the range of 1–50 mM (in the sample before dissolution) can be achieved, with a repeatability close to 10% and a very good linearity. We provide a detailed comparison of such analytical performance in two different dissolution solvents, D2O and MeOD. The reported pulse sequence appears as an useful analytical tool to facilitate the assignment and integration of metabolite signals in hyperpolarized complex mixtures.

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The development of a rational strategy for achieving site-selective C4–H halogenation of indoles is an appealing yet challenging task. Herein, we disclose a Pd(II)-catalyzed transient directing group (TDG)-assisted methodology for realizing C4 chlorination/bromination of indoles employing glycine as the TDG and NFSI as a bystanding oxidant. The use of inexpensive and commercially available CuX2as the halide source is the key highlight of this protocol. Furthermore, the TDG methodology was also extended to accessing C4 acetoxylated indoles employing acetic acid as the acetate source and 1-fluoro-2,4,6-trimethylpyridinium triflate as the oxidant.

Dolerite dyke swarms are widespread within the Singhbhum Craton (eastern India) that emplaced from the Neoarchean to Paleoproterozoic era just after the stabilization of crust before c.3 Ga. These dyke swarms are oriented in NE–SW to NNE–SSW, NW–SE to WNW–ESE, east–west and north–south directions. The WNW–ESE-trending c.1.77 Ga Pipilia dyke swarm is sampled from the Satkosia area of Orissa state. The dyke shows a noticeable disparity in terms of the modal proportion and grain size of pyroxenes, plagioclase, Fe–Ti oxide minerals and texture across the trend. In places the primary silicates are altered to secondary hydrated mineral assemblages of amphibole, chlorite and sericite. The primary silicates are clinopyroxene (augite – Mg# = 65.7–82.6; En37–48Fs11–17Wo36–41), orthopyroxene (clinoenstatite – Mg# = 68.5–78; En63–70Fs20–29Wo4–5) and plagioclase (An11–39Ab44–82Or1–7) and the Fe–Ti oxides are titanomagnetite (FeO, 34.38–39.50 wt%; Fe2O3, 48.26–56.21 wt%; TiO2, 5.05–9.60 wt%) and ilmenite (FeO, 40.75–43.79 wt%; Fe2O3, 3.54–10.03 wt%; TiO2, 47.82–50.87 wt%). Application of two-pyroxene thermometry yields an equilibration temperature range of 1065–978°C, and coexisting titanomagnetite–ilmenite pairs reveal 731.39–573.37°C under the oxygen fugacity (fO2) condition NNO + 0.3 to FMQ − 1.03. The dyke contains disseminated sulfides at the interstices of Fe–Ti oxides and silicates. Major sulfide minerals are pyrite, chalcopyrite and vaesite; pyrite–vaesite assemblages occur in association with secondary silicate minerals. Pyrite grains contain variable concentrations of Co (0.01–5.70 wt%) and Ni (0.02–1.95 wt%). Coexisting vaesite contains Co (2.42–10.44 wt%), Ni (26.40–47.88 wt%) and Fe (7.32–26.55 wt%). Texture, sulfide–silicate assemblage and the presence of low metal/S sulfides such as the pyrite–vaesite assemblage indicate that primary Fe–Ni sulfides (pyrrhotite–pentlandite) that segregated from immiscible sulfide liquid at high temperature are modified by late magmatic/hydrothermal fluid activities. Numerous sulfide-bearing deposits hosted in ultramafic–mafic intrusions of Paleoproterozoic age have been recorded globally and the occurrence of Fe–Ni sulfides in the c.1.77 Ga Pipilia dyke swarm in the Singhbhum Craton enhances the exploration potential of this craton in eastern India.

Platooning is one of the efficient methods for preventing traffic congestion and achieving improved performance efficiency. It is the process by which vehicles follow their preceding vehicles by maintaining a specified pattern, and distance. If the same process is carried out using autonomous vehicles, then an autonomous platooning is obtained. Due to different vehicle dynamics, terrains, and environmental conditions, the autonomous platooning requires a robust control strategy. In this paper, an observer based sliding mode control with power rate exponential reaching law (PREL) is designed to attain desired pattern of vehicles while keeping a desired safe distance between them. The derived control input is suitable for practical implementation as it is continuous in nature. The proposed approach is compared with the conventional sliding mode control (CSMC) approach with constant reaching law. The convergence of states is derived and the performance of the proposed approach is shown using numerical simulations.

In this article, we propose a systematic approach for fire station location planning. We develop machine learning models, based on Random Forest and Extreme Gradient Boosting, for demand prediction and utilize the models further to define a generalized index to measure quality of fire service in urban settings. Our model is built upon spatial data collected from multiple different sources. Efficacy of proper facility planning depends on choice of candidates where fire stations can be located along with existing stations, if any. Also, the travel time from these candidates to demand locations need to be taken care of to maintain fire safety standard. Here, we propose a travel time-based clustering technique to identify suitable candidates. Finally, we develop an optimization problem to select best locations to install new fire stations. Our optimization problem is built upon maximum coverage problem, based on integer programming. We further develop a two-stage stochastic optimization model to characterize the confidence in our decision outcome. We present a detailed experimental study of our proposed approach in collaboration with city of Victoria Fire Department, MN, USA. Our demand prediction model achieves true positive rate of 80% and false positive rate of 20% approximately. We aid Victoria Fire Department to select a location for a new fire station using our approach. We present detailed results on improvement statistics by locating a new facility, as suggested by our methodology, in the city of Victoria.

An unprecedented bidentate directing-group-assisted cobalt-catalyzed oxidative C–H activation of aryl hydrazones followed by a syn-diastereoselective [3 + 2] annulation reaction has been achieved, employing allenes as the annulation partners. The selective 2,3-migratory insertion of allenes with arylcobalt(III) species and the subsequent intramolecular diastereoselective nucleophilic addition of η1-allylcobalt onto the imine resulted in [3 + 2] annulation over the alternative [4 + 2] annulation. Furthermore, the oxidative annulation obviates the need for stoichiometric metal oxidants and proceeds under aerobic conditions.

Metabolomics plays a pivotal role in systems biology, and NMR is a central tool with high precision and exceptional resolution of chemical information. Most NMR metabolomic studies are based on 1H 1D spectroscopy, severely limited by peak overlap. 13C NMR benefits from a larger signal dispersion but is barely used in metabolomics due to ca. 6000-fold lower sensitivity. We introduce a new approach, based on hyperpolarized 13C NMR at natural abundance, that circumvents this limitation. A new untargeted NMR-based metabolomic workflow based on dissolution dynamic nuclear polarization (d-DNP) for the first time enabled hyperpolarized natural abundance 13C metabolomics. Statistical analysis of resulting hyperpolarized 13C data distinguishes two groups of plant (tomato) extracts and highlights biomarkers, in full agreement with previous results on the same biological model. We also optimize parameters of the semiautomated d-DNP system suitable for high-throughput studies.

An efficient cobalt-catalyzed [4 + 2] annulation of hydrazones and 1,3-diynes has been developed for the synthesis of 3-alkynylated isoquinolines engaging 2-aminopyridine as a traceless bidentate directing group. The strategy has been successfully extended for the synthesis of 3,3′-biisoquinoline moieties via both one-pot as well as sequential approaches. The utilization of a traceless bidentate directing group with an inexpensive and earth-abundant cobalt-catalyst under operationally simple reaction conditions makes the present transformation more valuable and appealing.

2,2,2-Trifluoroethanol (TFE) is one of the fluoroalcohols that have been known to induce and stabilize an open helical structure in many proteins and peptides. The current study has benchmarked low-field 19F NMR relaxation and 19F Overhauser dynamic nuclear polarization (ODNP) by providing a brief account of TFE solvent dynamics in a model melittin (MLT, an antimicrobial peptide) solution with a TFE–D2O cosolvent mixture at pH 7.4. Further, this approach has been employed to reveal the solvation of MLT by TFE in a nonbuffered solution with pH 2.8 for the first time. The structural transition of MLT has been elucidated viasolvent dynamics by measuring the 19F TFE relaxation rates at 0.34 T for various TFE–D2O compositions in the absence (bulk TFE) and in the presence of MLT at both the pH values. A complementary initial record of circular dichroism experiments on these aqueous MLT solutions with TFE as the cosolvent at two different pH conditions demonstrated the structural transition from a random coil to a helical or from a folded helical to an open helical structure. The molecular correlation time derived from the corresponding relaxation rates shows that TFE resides on the MLT surface in both pH conditions. However, the trends in the variation of molecular correlation time ratio as a function of TFE concentration represent that the mechanism and the extent to which TFE affects the MLT structural integrity are different at different pH values. The extraction of the DNP coupling parameter from steady-state 19F ODNP experiments performed in the presence of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl at 0.34 T revealed changes in the solvation dynamics of TFE concomitant with the MLT structural transition. In summary, 19F relaxation and ODNP measurements made at a low field have allowed direct monitoring of TFE dynamics during the MLT structural transition in terms of preferential solvation. The choice of experiments performed at a moderately low field (0.34 T) enabled us to exploit on the one hand almost 1200-fold mitigation of the strong contribution of 19F chemical shift anisotropy at 11.76 T, whereas on the other hand, the ODNP experiment offered a window for probing molecular dynamics on timescales of the order of 10–1000 ps.

In this note, constant reference tracking using integral control for negative-imaginary (NI) systems preceded by hysteresis nonlinearity is addressed. The hysteresis nonlinearity is considered to be slope-restricted, though no specific modeling framework is exploited. It is effectively shown that integral tracking controllers are guaranteed to exist when a stable NI system with sign-definite dc-gain is preceded by such hysteresis nonlinearities. When the dc-gain is negative-definite, under positive feedback configuration with positive slope-restricted hysteresis, it is established that the integral controller gain can be any positive diagonal matrix. The development of the proposed model-independent inversion-free scheme is carried out in general state-space setting and is applicable for multiple-input multiple-output systems with decoupled hysteresis nonlinearities. Effectiveness of the results is illustrated with examples. [ABSTRACT FROM AUTHOR]

Highly efficient visible-light-assisted photocatalytic reduction of Cr(vi) to Cr(iii) from water using multifunctional Zr(iv)-porphyrin MOFs, Zr6(μ3-OH)8(OH)8(MTCPP)2, (PCN-222(M)) (M = H2, ZnII, CuII, NiII, CoII, FeIIICl, and MnIIICl) is presented. The remarkable chemical stability of these Zr-MOFs in water and the visible-light harvesting property of the porphyrin-linker promoted efficient photocatalytic activity for the reduction of Cr(vi) to Cr(iii) in the aqueous phase. Interestingly, the pristine MOF, PCN-222, showed an unprecedentedly high photocatalytic activity with 100% reduction of Cr(vi) to Cr(iii) within 25 min with the highest rate (0.1289 min−1) amongst the MOFs reported so far. The superior photocatalytic activity of PCN-222 (no metal) over PCN-222(M) MOFs has been attributed to its lower band gap and efficient transfer of photo-excited electrons to the catalytic site, supported by combined experimental and theoretical studies. Remarkably, the PCN-222 MOF catalyst could be reused for up to 10 cycles without significant loss of catalytic activity. Further, a detailed mechanistic investigation of the visible light-assisted photoreduction of Cr(vi) by combined experimental and theoretical studies is presented. Overall, this work represents a unique demonstration of the influence of band gap engineering of porphyrin MOFs for efficient aqueous-phase photoreduction of Cr(vi) from water under visible light irradiation.

The structure of fluorinated alcohols is a matter of considerable interest in view of wide-ranging biomolecular applications. The microheterogeneity of fluorinated alcohols in the liquid state, in particular, has been a matter of debate and discussion in recent years using experimental and theoretical methods, including neutron or X-ray diffraction, as well as density functional theory (DFT) and molecular dynamics (MD) simulations. Here, we show that 1H and 19F Overhauser dynamic nuclear polarization (ODNP) buildup curves in solution state at room temperature show unusual behavior that could offer a novel approach to investigate the structural heterogeneity and dynamics of such homogeneous liquids with improved sensitivity. A detailed analysis of multiexponential ODNP buildup curves as a function of microwave irradiation time is shown to evidence microheterogeneity in such systems. Experimental ODNP buildup rates are interpreted using simple motional models that yield the motional correlation times of the relevant species in solution. It may be emphasized that this information is not available from standard approaches of high-resolution nuclear magnetic resonance (NMR) spectroscopy. While the present study focuses on fluorinated alcohols, it is to be anticipated that this approach would be valuable in the study of molecular assemblies in the solution state, including peptides, surfactant systems, etc.

Restrictive gender norms and gender inequalities are replicated and reinforced in health systems, contributing to gender inequalities in health. In this Series paper, we explore how to address all three through recognition and then with disruptive solutions. We used intersectional feminist theory to guide our systematic reviews, qualitative case studies based on lived experiences, and quantitative analyses based on cross-sectional and evaluation research. We found that health systems reinforce patients' traditional gender roles and neglect gender inequalities in health, health system models and clinic-based programmes are rarely gender responsive, and women have less authority as health workers than men and are often devalued and abused. With regard to potential for disruption, we found that gender equality policies are associated with greater representation of female physicians, which in turn is associated with better health outcomes, but that gender parity is insufficient to achieve gender equality. We found that institutional support and respect of nurses improves quality of care, and that women's empowerment collectives can increase health-care access and provider responsiveness. We see promise from social movements in supporting women's reproductive rights and policies. Our findings suggest we must view gender as a fundamental factor that predetermines and shapes health systems and outcomes. Without addressing the role of restrictive gender norms and gender inequalities within and outside health systems, we will not reach our collective ambitions of universal health coverage and the Sustainable Development Goals. We propose action to systematically identify and address restrictive gender norms and gender inequalities in health systems.

A bidentate chelation-assisted cobalt-catalyzed C(sp2)–H activation and annulation of benzamides and alkylidenecyclopropanes (ACPs) has been realized. The unique reactivity of organocobalt species led to selective migratory insertion across the more electron-rich C═C bond of the ACP followed by faster reductive elimination from the seven-membered cobaltacycle leading to spiro-dihydroisoquinoline derivatives with conservation of the cyclopropyl ring. The operationally simple reaction conditions allowed the C–H activation of both aryl and heteroaryl amides at room temperature.

An efficient and convenient cobalt(III)‐catalyzed highly diastereoselective strategy was demonstrated for the synthesis of epoxybenzophenanthridinone derivatives. The sp2C−H activation of N‐methoxybenzamides and their annulation reaction with 7‐oxa/aza benzonorbornadienes proceeds under mild conditions and exhibits excellent functional group tolerance. In addition, the products were transformed to biologically relevant phenanthridinones by an acid‐catalyzed ring opening/aromatization sequence. A bicycle made for 4+2: A highly diastereoselective redox‐neutral [4+2] annulation of N‐methoxybenzamides and strained 7‐oxa/azabenzonorbornadienes for the synthesis of epoxybenzo[b]phenanthridinones using earth‐abundant and cost‐effective Co‐salts was demonstrated.

Intra-uterine devices (IUDs) are a safe and effective method to delay or space pregnancies and are available for free or at low cost in the Indian public health system; yet, IUD uptake in India remains low. Limited quantitative research using national data has explored factors that may affect IUD use. Machine Learning (ML) techniques allow us to explore determinants of low prevalence behaviors in survey research, such as IUD use. We applied ML to explore the determinants of IUD use in India among married women in the 4th National Family Health Survey (NFHS-4; N = 499,627), which collects data on demographic and health indicators among women of childbearing age. We conducted ML logistic regression (lasso and ridge) and neural network approaches to assess significant determinants and used iterative thematic analysis (ITA) to offer insight into related variable constructs generated from a series of regularized models. We found that couples’ shared family planning (FP) goals were the strongest determinants of IUD use, followed by receipt of FP services and desire for no more children, higher wealth and education, and receipt of maternal and child health services. Findings highlight the importance of male engagement and family planning services for IUD uptake and the need for more targeted efforts to support awareness of IUD as an option for spacing, especially for those of lower SES and with lower access to care.

Son preference, an ongoing concern in India, is a known driver of ideal family size preferences and contraceptive use among couples. These associations can vary substantially with parity and can influence men and women differently. This study assesses the association of sex composition of children by parity and a) men's higher ideal family size preference relative to women and b) use of modern contraceptives by couples.

Rh(III)-catalyzed redox-neutral chemodivergent coupling of N-phenoxyacetamides and alkylidenecyclopropanes (ACPs) has been documented. The reaction proceeds viaC–H activation, regioselective migratory insertion and stereoselective β-carbon elimination followed by β-hydride elimination, resulting in o-dienylation of phenols in nonpolar solvents, whereas [3 + 2]-annulation leading to dihydrobenzofurans was realized in polar fluorinated solvents. It was observed that the nucleophilic directing group controls the elimination of β-carbon and so plays a vital role for achieving high stereoselectivities. The synthetic utility of the dienylation and annulation was demonstrated by carrying out gram scale reactions and further derivatization.

ABSTRACTBackground: This paper explores the heterogeneities in antenatal care (ANC) utilization in India’s most populated state, Uttar Pradesh. Taking an intersectionality lens, multiple individual- and district-level factors are used to identify segments of any antenatal care usage in Uttar PradeshObjective: This paper seeks to understand the multilevel contexts of ANC utilization. The planning and programming challenge is that such knowledge of contextual specificity is rarely known upfront at the initial stages of planning or implementing an intervention. Exploratory data analysis might be needed to identify such contextual specificity.Methods: Tree-structured regression methods are used to identify segments and interactions between factors. The results from the tree-structured regression were complemented with multilevel models that controlled for the clustering of individuals within districts.Results: Heterogeneities in utilization of any ANC were observed. The multiple segments of ANC utilization that were developed went from a low utilization of 23.7% for respondents who were not literate and did not have home ownership to a high of 82.4% for respondents who were literate and at the highest level of wealth. Key variables that helped define the segments of ANC utilization include: woman’s literacy, ownership of home, wealth index, and district-level sex ratio. Based on the multilevel model of any ANC utilization, cross-level interactions also were obtained between sex ratio and ownership of home as well as between sex ratio and literacy. Increases in sex ratio increased the influence of ownership of home on any ANC, while increases in sex ratio reduced the impact of woman’s literacy on receiving any ANC.Conclusion: We argue that a focus on heterogeneous segments of utilization can help build knowledge of the mechanisms that underlie inequities in maternal health utilization. Such knowledge of heterogeneity needs to be incorporated in contextualizing interventions to meet a variety of recipients’ needs.

ABSTRACTBackground:This paper explores the multilevel factors associated with maternal health utilization in India’s most populous state, Uttar Pradesh. 3 key utilization practices: registration of pregnancy, receipt of antenatal care, and delivery at home are examined for district and individual level predictors. The data is based on 5666 household surveys conducted as part of a baseline evaluation of the Uttar Pradesh Technical Support Unit (UPTSU.) program.Objectives:This intervention aims to assist the Government of Uttar Pradesh in increasing the efficiency, effectiveness, and equity of service delivery across a continuum of reproductive, maternal, new-born, child, and adolescent health (RMNCH+A) outcomes.Methods:The paper employs multilevel models that control for individuals being nested within districts in order to understand the predictors of maternal health care utilization.Results:The study identifies several individual-level predictors of health care utilization, including: literacy of the woman, the husband’s schooling, age at marriage, and socio-economic factors. Key predictors of pregnancy registration include husband’s schooling (OR 1.49, 95% CI 1.26–1.76), having a bank account (OR 1.36, 95% CI 1.11–1.68), and owning a house (OR 2.28, 95% CI 1.85–2.80). Factors affecting antenatal care include the woman’s literacy (OR 1.49, 95% CI 1.28–1.73), the respondent having had a job in the last year (OR 1.39, 95% CI 1.10–1.77), and owning a house (OR 2.83, 95% CI 2.27–3.53). Home delivery tends to be associated with woman’s literacy (OR 0.62, 95% CI 0.54–0.72) and marriage age of 15 and younger (OR 1.48, 95% CI 1.26–1.73).Conclusions:Interventions having equity considerations need to disrupt existing patterns of the health gradient. Successful implementation of such interventions, necessitate understanding the mechanisms that can disrupt the unequal utilization patterns and target domains of disadvantage. Knowledge of key predictors of utilization can aid in the implementation of such complex interventions.