Hydrogenase biomimetics with redox-active ligands: Electrocatalytic proton reduction by [Fe2(CO)4(κ2-diamine)(μ-edt)] (diamine = 2,2′-bipy, 1,10-phen)

Diiron complexes bearing redox active diamine ligands have been studied as models of the active site of [FeFe]-hydrogenases. Heating [Fe2(CO)6(μ-edt)] (edt = 1,2-ethanedithiolate) with 2,2′-bipyridine (2,2′-bipy) or 1,10-phenanthroline (1,10-phen) in MeCN in the presence of Me3NO leads to the formation of [Fe2(CO)4(κ2-2,2′-bipy)(μ-edt)] (1-edt) and [Fe2(CO)4(κ2-1,10-phen)(μ-edt)] (2-edt), respectively, in moderate yields. In the solid state the diamine resides in dibasal sites, while both dibasal and apical–basal isomers are present in solution. Both stereoisomers protonate readily upon addition of strong acids. Cyclic voltammetry in MeCN shows that both complexes undergo irreversible oxidation and reduction, proposed to be a one- and two-electron process, respectively. The structures of neutral 2-edt and its corresponding one- and two-electron reduced species have been investigated by DFT calculations. In 2-edt− the added electron occupies a predominantly ligand-based orbital, and the iron–iron bond is maintained, being only slightly elongated. Addition of the second electron affords an open-shell triplet dianion where the second electron populates an Fe–Fe σ* antibonding orbital, resulting in effective scission of the iron–iron bond. The triplet state lies 4.2 kcal mol−1 lower in energy than the closed-shell singlet dianion whose HOMO correlates nicely with the LUMO of the neutral species 2-edt. Electrocatalytic proton reduction by both complexes has been studied in MeCN using CF3CO2H as the proton source. These catalysis studies reveal that while at high acid concentrations the active catalytic species is [Fe2(CO)4(μ-H)(κ2-diamine)(μ-edt)]+, at low acid concentrations the two complexes follow different catalytic mechanisms being associated with differences in their relative rates of protonation

Cell-Derived Microparticles in the Pathogenesis of Cardiovascular Disease Friend or Foe?

Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease. (Arterioscler Thromb Vasc Biol. 2011;31:4-9.

स्मार्ट सिरी र कोसिड–१९ः तथमाांक पमाररस्थिसतकीय प्रणमाली सिरमा्टणको लमासि िमारतबमार सिसकएको रुख्य पमाठ

This brief distils best data practice recommendations through consideration of key issues involved in the use of technology for surveillance, fact-checking and coordinated control during crisis or emergency response in resource constrained urban contexts. We draw lessons from how data enabled technologies were used in urban COVID-19 response, as well as how standard implementation procedures were affected by the pandemic. Disease control is a long-standing consideration in building smart city architecture, while humanitarian actions are increasingly digitised. However, there are competing city visions being employed in COVID-19 response. This is symptomatic of a broader range of tech-based responses in other humanitarian contexts. These visions range from aspirations for technology driven, centralised and surveillance oriented urban regimes, to ‘frugal innovations’ by firms, consumers and city governments. Data ecosystems are not immune from gendered- and socio-political discrimination, and technology-based interventions can worsen existing inequalities, particularly in emergencies. Technology driven public health (PH) interventions thus raise concerns about 1) what types of technologies are appropriate, 2) whether they produce inclusive outcomes for economically and socially disadvantaged urban residents and 3) the balance between surveillance and control on one hand, and privacy and citizen autonomy on the other.يستعرض هذا الموجز التوصيات المثلى بشأن الممارسات المتعلقة بالبيانات من خلال النظر في القضايا الرئيسية المرتبطة باستخدام التكنولوجيا لأغراض المراقبة وتقصي الحقائق والضوابط المُنسقة أثناء الأزمات أو الاستجابة للطوارئ في في السياقات الحضرية المحدودة الموارد. من الضروري أن نستخلص الدروس من كيفية استخدام تقنيات تمكين البيانات في استجابة المدن الحضرية لكوفيد -19 ، وكذلك كيفية تأثر إجراءات التنفيذ الموحدة بالوباء. لقد باتت مكافحة الأمراض من الممارسات التي تلعب دوراً واضحاً في تصميم و بناء المدن الذكية منذ أمد طويل، ويبدو أن هناك توجه متزايد نحو استخدام الرقمنة في الأعمال الإنسانية. ومع ذلك، هناك رؤى متنافسة للمدينة يتم توظيفها في الاستجابة لـكوفيد-19. وتأتي هذه الاستجابة ضمن مجموعة أوسع من الاستجابات القائمة على التكنولوجيا في سياقات إنسانية أخرى. تتراوح هذه الرؤى من التطلعات إلى الأنظمة الحضرية القائمة على التكنولوجيا و التي تتسم بدرجة من المركزية وموجهة نحو المراقبة، إلى "الابتكارات المقتصدة" من قبل الشركات والمستهلكين وحكومات المدن. النظم الإيكولوجية للبيانات ليست بمنأى عن التمييز الجنساني والاجتماعي والسياسي، وقد تؤدي التدخلات القائمة على التكنولوجيا إلى تفاقم أوجه عدم المساواة القائمة، ولا سيما في حالات الطوارئ. وفي هذا السياق، فإن تدخلات الصحة العامة القائمة على التكنولوجيا تثير مخاوف بشأن ( 1) ما هي أنواع التكنولوجيا المناسبة ،( 2) ما إذا كانت تحقق نتائج شاملة لسكان المناطق الحضرية المحرومين اقتصاديًا واجتماعيًا و (3) هل هناك توازن بين المراقبة والتحكم من جهة ، وهل تراعي الخصوصية والاستقلالية للمواطن من جهة أخرى.सीमित स्रोत भएका सहरी सन्दर्भमा विपद् वा आपत्काल िन् अवस्थाम ा नि गरानी, तथ्य जाँच र व्यवस्थि त नियन् त्रणको लागि प्रविधि प्रयोग गर्दा संलग्न गर्नुपर्न प्रमुख सवालहरु ध्या नमा राखेर यो सारांशले डेटाका उत्कृ ष्ट अभ्या सबारे सझु ाव प्रदान गर्छ।शहरी क्षेत्रमा कोभि ड–१९ को प्रति कार्यको लागि डेटामा आधारित प्रविधिहरु कसरी प्रयोग भए भन्ने सि काईंहरु यसमा समावेश छन् साथै महामारीका कारण कसरी कार्या न्वय न प्रक्रियाका मानकहरु प्रभावित भए भन्ने सि काईंसमेत समेटि एको छ।स्मार्ट सि टी योजना निर्मा णको लागि महामारी नियन् त्रण प्रमुख बि षय हो भने यस्ता मानवीय कार्यहरु डिजि टल माध्यमबाट हुने क्रम बढ्दो छ।यद्यपि , कोभि ड–१९ को प्रति कार्यको लागि भिन्न –भिन्न खालका योजनाहरु कार्या न्वय न भइरहेका छन्।यो अन्य मानवीय सन्दर्भहरुमा प्रविधिमा आधारित बृहत् प्रति कार्यको सूचक हो।यहाँ समावेश गरिएका अवध ारणा फरक फरक खालका छन्।प्रविधिमा आधारित भएर प्रति कार्य गर्ने लक्ष्य राखेकादेखि केन्द् रिकृत तथा नि गरानीमा आधारित भएका सहरी शासन, सरकार तथा उपभोक्ता र विभिन्न कम्पनीले आविष्का र गरेका मितव्ययी खालका अवध ारणा समेत यसमा पर्छन्।डेटाको पारिस्थिति कीय प्रणाली लैङ्गिक तथा सामाजि क–राजनीति क विभेदबाट अछुतो छैनन् भने विशेषगरी आपत्काल ीन परिस्थितिम ा प्रविधिमा आधारित हस्तक्षेपले विद्यमान असमानतालाई थप बढाउन सक्छ।यसकारण, सार्वजनि क स्वा स्थ्यमा प्रविधिमा आधारित हस्तक्षेपले केही चासो उठान गर्छ १) कस्तो खालको प्रविधि उपयुक्त हुन्छ ?, २) के यीनले आर्थिक तथा सामाजि क रुपमा असहज अवस्थाम ा रहेका सहरी जनसंख्या को लागि समावेशी नति जा दिन सक्छ ?, र ३) एकतर्फ नि गरानी र नियन् त्रणबीचको सन्तुल न र अर्कोतर्फ गोपनिय ता तथा नागरिकको स्वतन्त्रता।Wellcome TrustFCDOEuropean Commissio

Comparison of seven methods for producing Affymetrix expression scores based on False Discovery Rates in disease profiling data

BACKGROUND: A critical step in processing oligonucleotide microarray data is combining the information in multiple probes to produce a single number that best captures the expression level of a RNA transcript. Several systematic studies comparing multiple methods for array processing have used tightly controlled calibration data sets as the basis for comparison. Here we compare performances for seven processing methods using two data sets originally collected for disease profiling studies. An emphasis is placed on understanding sensitivity for detecting differentially expressed genes in terms of two key statistical determinants: test statistic variability for non-differentially expressed genes, and test statistic size for truly differentially expressed genes. RESULTS: In the two data sets considered here, up to seven-fold variation across the processing methods was found in the number of genes detected at a given false discovery rate (FDR). The best performing methods called up to 90% of the same genes differentially expressed, had less variable test statistics under randomization, and had a greater number of large test statistics in the experimental data. Poor performance of one method was directly tied to a tendency to produce highly variable test statistic values under randomization. Based on an overall measure of performance, two of the seven methods (Dchip and a trimmed mean approach) are superior in the two data sets considered here. Two other methods (MAS5 and GCRMA-EB) are inferior, while results for the other three methods are mixed. CONCLUSIONS: Choice of processing method has a major impact on differential expression analysis of microarray data. Previously reported performance analyses using tightly controlled calibration data sets are not highly consistent with results reported here using data from human tissue samples. Performance of array processing methods in disease profiling and other realistic biological studies should be given greater consideration when comparing Affymetrix processing methods

Search for electromagnetic properties of the neutrinos at the LHC

Exclusive production of neutrinos via photon-photon fusion provides an excellent opportunity to probe electromagnetic properties of the neutrinos at the LHC. We explore the potential of processes pp-> p gamma gamma p -> p nu anti-nu p and pp -> p gamma gamma p -> p nu anti-nu Z p to probe neutrino-photon and neutrino-two photon couplings. We show that these reactions provide more than seven orders of magnitude improvement in neutrino-two photon couplings compared to LEP limits.Comment: 11 pages, 4 tables, New backgrounds have been adde

Reversible C-H bond activation at a triosmium centre: A comparative study of the reactivity of unsaturated triosmium clusters Os3(CO)8(μ-dppm)(μ-H)2 and Os3(CO)8(μ-dppf)(μ-H)2 with activated alkynes

Heating a benzene solution of the unsaturated cluster Os3(CO)8(μ-dppm)(μ-H)2 (1) [dppm = bis(diphenylphosphino)methane] with MeO2CCtriple bond; length of mdashCCO2Me (DMAD) or EtO2CCtriple bond; length of mdashCCO2Et (DEAD) at 80 °C furnished the dinuclear compounds Os2(CO)4(μ-dppm)(μ-η2;η1;к1-RO2CCCHCO2R)(μ-H) (3a, R = Me, 3b, R = Et) and the saturated trinuclear complexes Os3(CO)7(μ-dppm)(μ3-η2;η1;η1-RO2CCCCO2R)(μ-H)2 (4a, R = Me, 4b, R = Et). In contrast, similar reactions using unsaturated Os3(CO)8(μ-dppf)(μ-H)2 (2) [dppf = bis(diphenylphosphino)ferrocene] afforded only the trinuclear complexes Os3(CO)8(μ-dppf)(μ-η2;η1-RO2CCHCCO2R)(μ-H) (5a, R = Me; 5b, R = Et) and Os3(CO)7(μ-dppf)(μ3-η2;η1;η1-RO2CCCCO2R)(μ-H)2 (6a, R = Me; 6b, R = Et). Control experiments confirm that 5a and 5b decarbonylate at 80 °C to give 6a and 6b, respectively. Both 5a and 5b exist as a pair of isomers in solution, as demonstrated by 1H NMR and 31P{1H} NMR spectroscopy. DFT calculations on cluster 5a (as the dppf-Me4 derivative) indicate that the isomeric mixture derives from a torsional motion that promotes the conformational flipping of the cyclopentadienyl groups of the dppf-Me4 ligand relative to the metallic plane. VT NMR measurements on clusters 6a and 6b indicate that while the hydride ligand associated with the dppf-bridged Os-Os bond is nonfluxional at room temperature, the second hydride rapidly oscillates between the two non-dppf-bridged Os-Os edges. DFT examination of this hydride fluxionality confirms a “windshield wiper” motion for the labile hydride that gives rise to a time-average coupling of this hydride to both phosphorus centers of the dppf ligand. Thermolysis of 6a and 6b in refluxing toluene yielded Os3(CO)7(μ-dppf)(μ-η2;η1;к1-CCHCO2R) (7a, R=Me; 7b, R=Et). The vinylidene moieties in 7a and 7b derive from the carbon-carbon bond cleavage of coordinated alkyne ligands, and these two products exhibit high thermal stability in refluxing toluene

Shaping bursting by electrical coupling and noise

Gap-junctional coupling is an important way of communication between neurons and other excitable cells. Strong electrical coupling synchronizes activity across cell ensembles. Surprisingly, in the presence of noise synchronous oscillations generated by an electrically coupled network may differ qualitatively from the oscillations produced by uncoupled individual cells forming the network. A prominent example of such behavior is the synchronized bursting in islets of Langerhans formed by pancreatic \beta-cells, which in isolation are known to exhibit irregular spiking. At the heart of this intriguing phenomenon lies denoising, a remarkable ability of electrical coupling to diminish the effects of noise acting on individual cells. In this paper, we derive quantitative estimates characterizing denoising in electrically coupled networks of conductance-based models of square wave bursting cells. Our analysis reveals the interplay of the intrinsic properties of the individual cells and network topology and their respective contributions to this important effect. In particular, we show that networks on graphs with large algebraic connectivity or small total effective resistance are better equipped for implementing denoising. As a by-product of the analysis of denoising, we analytically estimate the rate with which trajectories converge to the synchronization subspace and the stability of the latter to random perturbations. These estimates reveal the role of the network topology in synchronization. The analysis is complemented by numerical simulations of electrically coupled conductance-based networks. Taken together, these results explain the mechanisms underlying synchronization and denoising in an important class of biological models

Iron carbonyl complexes bearing phenazine and acridine ligands: X-ray structures of Fe(CO)(3)(eta(4)-C12H8N2), Fe(CO)(2){P(OMe)(3)}(eta(4)-C12H8N2), Fe(CO)(2)(PPh3) (eta(4)-C13H9N), and Fe(CO)(2)(kappa(1)-dppm) (eta(4)-C12H8N2)

Reactions of Fe3(CO)12 with the heterocycles phenazine and acridine in refluxing benzene afforded the mononuclear complexes Fe(CO)3(η4-C12H8N2) (1a) and Fe(CO)3(η4-C13H9N) (1b), respectively. Treatment of 1a with P(OMe)3 and PPh3 in the presence of Me3NO at room temperature yielded the carbonyl substitution products Fe(CO)2{P(OMe)3}(η4-C12H8N2) (2a) and Fe(CO)2(PPh3) (η4-C12H8N2) (3a), respectively. Similar reactions of 1b yielded Fe(CO)2{P(OMe)3}(η4-C13H9N) (2b) and Fe(CO)2(PPh3) (η4-C13H9N) (3b). Treatment of 1a with the diphosphines dppm and dppf under similar conditions afforded the mononuclear compounds Fe(CO)2(κ1-dppm) (η4-C12H8N2) (4a) and Fe(CO)2(κ1-dppf) (η4-C12H8N2) (4b). Compounds 1a, 2a, 3b, and 4a have been structurally characterized by X-ray crystallography. The ancillary phenazine and acridine ligands in these products adopt an η4-coordination mode by using only the peripheral carbon atoms in one of the carbocyclic rings. Given the rarity of this coordination mode in metal carbonyl complexes, we have performed electronic structure calculations on 1a, and these data are discussed relative to the solid-state structur