Di- and Trinuclear Mixed-Valence Copper Amidinate Complexes from Reduction of Iodine

Molecular examples of mixed-valence copper complexes through chemical oxidation are rare but invoked in the mechanism of substrate activation, especially oxygen, in copper-containing enzymes. To examine the cooperative chemistry between two metals in close proximity to each other we began studying the reactivity of a dinuclear Cu(I) amidinate complex. The reaction of [(2,6-Me2C6H3N)2C(H)]2Cu2, 1, with I2 in tetrahydrofuran (THF), CH3CN, and toluene affords three new mixed-valence copper complexes [(2,6-Me2C6H3N)2C(H)]2Cu2(μ2-I3)(THF)2, 2, [(2,6-Me2C6H3N)2C(H)]2Cu2(μ2-I) (NCMe)2, 3, and [(2,6-Me2C6H3N)2C(H)]3Cu3(μ3-I)2, 4, respectively. The first two compounds were characterized by UV-vis and electron paramagnetic resonance spectroscopies, and their molecular structure was determined by X-ray crystallography. Both di- and trinuclear mixed-valence intermediates were characterized for the reaction of compound 1 to compound 4, and the molecular structure of 4 was determined by X-ray crystallography. The electronic structure of each of these complexes was also investigated using density functional theory

The Effect of Oral Leucine on Protein Metabolism in Adolescents with Type 1 Diabetes Mellitus

Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-13C] Leucine was used to assess whole-body protein metabolism in six adolescent females (16–18 yrs) with type 1 diabetes during consumption of a basal diet (containing 58 μmoles leucine/kg/h) and the basal diet with supplemental leucine (232 μmoles leucine/kg/h). Net leucine balance was significantly higher with supplemental leucine (56.33 ± 12.13 μmoles leucine/kg body weight/hr) than with the basal diet (−11.7 ± −5.91, P < .001) due to reduced protein degradation (49.54 ± 18.80 μmoles leucine/kg body weight/hr) compared to the basal diet (109 ± 13.05, P < .001)

Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy:a narrative review

Introduction: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. Areas covered: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF, including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. Expert opinion: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.</p

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

Exfoliated Nanocomposites Based on Polyaniline and Tungsten Disulfide

Nanocomposite materials consisting of polyaniline (PANI) and exfoliated WS2 were synthesized. The WS2 was prepared by reacting tungstic acid with thiourea at 500°C under nitrogen flow. Samples were prepared with a WS2 content of 1, 5, 7.5, 10, 12.5, 15, 20, 37, and 64% by mass. An improvement in the electronic conductivity value of the PANI was observed through the incorporation of exfoliated WS2. The electronic conductivity of PANI-15%WS2 was 24.5 S/cm, an eightfold increase when compared to pure PANI. Powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron paramagnetic resonance (EPR) provided evidence that the nanocomposites are in an exfoliated state. XRD and TEM showed that the nanocomposites were completely amorphous, suggesting lack of structural order in these materials, while their EPR signals were considerably narrower compared to pure PANI, indicating the formation of genuine exfoliated systems. Furthermore, our research showed that WS2 can be used as a filler to improve activation energy of decomposition of the polymer. By using the Ozawa method, we studied the decomposition kinetics for the nanocomposites, as well as for the pure polymer. The activation energy for the decomposition of pure PANI was found to be 131.2 kJ/mol. Increasing the amount of WS2 to 12.5% in the PANI increases the activation energy of decomposition to 165.4 kJ/mol, an enhancement of 34.2 kJ/mol over the pure polymer

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial.

Lessons learnedThe addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation.BackgroundThis randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer.MethodsPatients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS).ResultsOne hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen.ConclusionAddition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup

Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

Chemoselective Detection and Discrimination of Carbonyl-Containing Compounds in Metabolite Mixtures by \u3csup\u3e1\u3c/sup\u3eH-Detected \u3csup\u3e15\u3c/sup\u3eN Nuclear Magnetic Resonance

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl-selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating 15N in the aminooxy functional group, 15N-edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. Here, we demonstrate that the chemical shifts of the aminooxy adducts of ketones and aldehydes are very different, which can be used to discriminate between aldoses and ketoses, for example. Utilizing the 2-bond or 3-bond 15N-1H couplings, the 15N-edited NMR analysis was optimized first with authentic standards and then applied to an extract of the lung adenocarcinoma cell line A549. More than 30 carbonyl-containing compounds at NMR-detectable levels, six of which we have assigned by reference to our database. As the aminooxy probe contains a permanently charged quaternary ammonium group, the adducts are also optimized for detection by mass spectrometry. Thus, this sample preparation technique provides a better link between the two structural determination tools, thereby paving the way to faster and more reliable identification of both known and unknown metabolites directly in crude biological extracts

Mesophilic mineral-weathering bacteria inhabit the critical-zone of a perennially cold basaltic environment

The weathering of silicate in the world’s critical-zone (rock-soil interface) is a natural mechanism providing a feedback on atmospheric CO2 concentrations through the carbonate-silicate cycle. We examined culturable bacterial communities from a critical-zone in western Iceland to determine the optimum growth temperature, ability to solubilise phosphate-containing minerals, which are abundant within the critical-zone area examined here. The majority of isolated bacteria were able to solubilize mineral-state phosphate. Almost all bacterial isolates were mesophilic (growth optima of 20-45°C), despite critical-zone temperatures that were continuously below 15°C, although all isolates could grow at temperatures associated with the critical-zone (-2.8 – 13.1°C). Only three isolates were shown to have thermal optima for growth that were within temperatures experienced at the critical-zone. These findings show that the bacteria that inhabit the western Icelandic critical-zone have temperature growth optima suboptimally adapted to their environment, implying that other adaptations may be more important for their long-term persistence in this environment. Moreover, our study showed that the cold basaltic critical-zone is a region of active phosphate mineral-weathering

Proton Differential Elliptic Flow and the Isospin-Dependence of the Nuclear Equation of State

Within an isospin-dependent transport model for nuclear reactions involving neutron-rich nuclei, we study the first-order direct transverse flow of protons and their second-order differential elliptic flow as a function of transverse momentum. It is found that the differential elliptic flow of mid-rapidity protons, especially at high transverse momenta, is much more sensitive to the isospin dependence of the nuclear equation of state than the direct flow. Origins of these different sensitivities and their implications to the experimental determination of the isospin dependence of the nuclear equation of state by using neutron-rich heavy-ion collisions at intermediate energies are discussed.Comment: 15 pages, 6 figures. Phys. Rev. C (2001) in pres