A portable lab‐on‐a‐chip instrument based on MCE with dual top–bottom capacitive coupled contactless conductivity detector in replaceable cell cartridge

A new design for a compact portable lab‐on‐a‐chip instrument based on MCE and dual capacitively coupled contactless conductivity detection (dC⁴D) is described. The instrument is battery powered with total dimension of 14 × 25 × 8 cm³ (w × l × h), and weighs 1.2 kg. The device consists of a front electrophoresis compartment which has the chip holder and the chip, the associated high‐voltage electrodes for electrophoresis injection and separation and the detector. The detection cell is integrated into the device housing with an exchangeable plug‐and‐play cartridge format. The design of the dC⁴D cell has been optimized for maximum performance. The cartridge includes the top–bottom excitation and pick up electrodes incorporated into the cell and connected to push‐pull self‐latching pins that are insulated with plastic. The metal frame of the cartridge is grounded completely to eliminate electronic interferences. The cartridge is designed to clamp a thin fluidic chip at the detection point. The cartridges are replaceable whereby different cartridges have different detection electrode configurations to employ according to the sensitivity or resolution needed in the specific analytical application. The second compartment consists of all the electronics, data acquisition card, high‐voltage modules of up to ±5 kV both polarity, and batteries for 10 h of operation. The improved detector performance is illustrated by the electrophoresis analysis of six cations (NH₄⁺, K⁺, Ca²⁺, Na⁺, Mg²⁺, Li⁺) with a detection limit of approximately 5 μM and the analysis of the anions (Br^?, Cl^?, NO₂^?, NO₃^?, SO₄^2?, F^?) with a detection limit of about 3 μM. Analytical capabilities of the instrument for food and medical applications were evaluated by simultaneous detection of organic and inorganic acids in fruit juice and inorganic cations and anions in rabbit blood samples and human urine samples are also demonstrated.     

Silica‐Grafted Tris(neopentyl)aluminum: A Monomeric Aluminum Solid Co‐catalyst for Efficient Nickel‐Catalyzed Ethene Dimerization

A silica‐supported monomeric alkylaluminum co‐catalyst was prepared via surface organometallic chemistry by contacting tris(neopentyl)aluminum and partially dehydroxylated silica. This system, fully characterized by solid‐state ²⁷Al NMR spectroscopy augmented by computational studies, efficiently activates (ⁿBu₃P)₂NiCl₂ towards dimerization of ethene, demonstrating comparable activity to previously reported dimeric diethylaluminum chloride supported on silica. Three types of aluminum surface species have been identified: monografted tetracoordinated Al species as well as two types of bisgrafted Al species—tetra‐ and pentacoordinated. Of them, only the monografted Al species is proposed to be able to activate the (ⁿBu₃P)₂NiCl₂ complex and generate the active cationic species.     

Thiol–Anhydride Dynamic Reversible Networks

The reaction of thiols and anhydrides to form ring opened thioester/acids is shown to be highly reversible and it is accordingly employed in the fabrication of covalent adaptable networks (CANs) that possess tunable dynamic covalent chemistry. Maleic, succinic, and phthalic anhydride derivatives were used as bifunctional reactants in systems with varied stoichiometries, catalyst, and loadings. Dynamic characteristics such as temperature‐dependent stress relaxation, direct reprocessing and recycling abilities of a range of thiol–anhydride elastomers, glasses, composites and photopolymers are discussed. Depending on the catalyst strength, 100 % of externally imposed stresses were relaxed in the order of minutes to 2 hours at mild temperatures (80–120 °C). Pristine properties of the original materials were recovered following up to five cycles of a hot‐press reprocessing technique (1 h/100 °C).     

Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone’s antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB₁ receptor), SR144528 (CB₂ receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB₁, PPARα and PPARγ in zerumbone’s action against mechanical allodynia, whereas only CB₁ and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.     

Catalytic Regio- and Stereoselective Alkene Sulfenoamination for 1,4-Benzothiazine Synthesis

An alkene sulfenoamination reaction with 2-aminothiophenol is developed using iodide catalysis. This reaction renders access to useful 1,4-benzothiazines with good functional group compatibility including both electron-donating and electron-withdrawing substituents. The reaction is proposed to proceed through an inversion of the polarity of the thiol functionality. Our mechanistic studies reveal that both thiiranium and thiyl radical pathways are plausible and that the disulfide reagent can also function as a viable substrate in this reaction.     

Gluino reach and mass extraction at the LHC in radiatively-driven natural SUSY

Radiatively-driven natural SUSY (RNS) models enjoy electroweak naturalness at the 10% level while respecting LHC sparticle and Higgs mass constraints. Gluino and top-squark masses can range up to several TeV (with other squarks even heavier) but a set of light Higgsinos are required with mass not too far above \(m_h\sim 125\) GeV. Within the RNS framework, gluinos dominantly decay via \(\tilde{g}\rightarrow t\tilde{t}_1^{*},\ \bar{t}\tilde{t}_1 \rightarrow t\bar{t}\widetilde{Z}_{1,2}\) or \(t\bar{b}\widetilde{W}_1^-+c.c.\), where the decay products of the higgsino-like \(\widetilde{W}_1\) and \(\widetilde{Z}_2\) are very soft. Gluino pair production is, therefore, signaled by events with up to four hard b-jets and large \(\not \!\!{E_T}\). We devise a set of cuts to isolate a relatively pure gluino sample at the (high-luminosity) LHC and show that in the RNS model with very heavy squarks, the gluino signal will be accessible for \(m_{\tilde{g}} < 2400 \ (2800)\) GeV for an integrated luminosity of 300 (3000) fb\(^{-1}\). We also show that the measurement of the rate of gluino events in the clean sample mentioned above allows for a determination of \(m_{\tilde{g}}\) with a statistical precision of 2–5% (depending on the integrated luminosity and the gluino mass) over the range of gluino masses where a 5\(\sigma \) discovery is possible at the LHC.     

Synthesis and Antibacterial Activity of Novel (4‐Fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone Derivatives

A novel series of (4‐fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone derivatives were synthesized from reaction of 6‐(naphthalen‐2‐yl)‐4‐aryl‐3,4‐dihydropyrimidine‐2(1H)‐thiones with 4‐fluorobenzoylchloride in dichloromethane in the presence of triethylamine. The synthesized compounds were screened for antibacterial activity against Gram positive bacteria, namely, Staphylococcus aureus ATCC25923 and Listeria monocytogenes MTCC657, and Gram negative bacteria, namely, Escherichia coli ATCC25922 and Klebsiella pneumoniae ATCC700603, respectively. Some of the tested compounds showed significant antimicrobial activity.     

Pharmacokinetics of gadoversetamide injection, a gadolinium-based contrast agent, in pediatric patients

Objective

The pharmacokinetics of gadoversetamide were examined in pediatric patients scheduled to undergo contrast-enhanced MRI of the central nervous system.

Materials and Methods

One hundred patients received an intravenous injection of gadoversetamide at a dose of 0.1 mmol/kg for a contrast-enhanced MRI procedure. A subpopulation of 30 patients were enrolled to evaluate the pharmacokinetics of gadoversetamide in patients 2–11 and 12–18 years of age. Serial blood and urine samples were collected before and after the administration of gadoversetamide.

Results

The terminal half-life, initial concentration and area under the curve assessments for gadoversetamide showed no significant (P>.05) differences between the age groups or the sexes. Although no sex-related differences occurred in the volume of distribution or clearance, significant (P<.05) age-related differences were found, but once corrected for body mass or surface area the differences were no longer significant.

Conclusions

The pharmacokinetic behavior of gadoversetamide was not significantly altered by differences in age or sex in pediatric patients from 2 to 18 years of age. Although significant differences in volumes of distribution, and clearance occurred between the age groups, these differences appeared to depend on body size rather than on age in pediatric patients between 2 and 18 years of age.     

Heavy-flavor tagging and the supersymmetry reach of the CERN Large Hadron Collider

The branching fraction for the decays of gluinos to third generation quarks is expected to be enhanced in classes of supersymmetric models where either third generation squarks are lighter than other squarks, or in mixed-higgsino dark matter models constructed so as to be in concordance with the measured density of cold dark matter. In such scenarios, gluino production events at the CERN Large Hadron Collider should be rich in top and bottom quark jets. Requiring b jets in addition to E _T ^miss should, therefore, enhance the supersymmetry signal relative to Standard Model backgrounds from V + jet, VV and QCD backgrounds (V=W,Z). We quantify the increase in the supersymmetry reach of the LHC from b-tagging in a variety of well-motivated models of supersymmetry. We also explore “top tagging” at the LHC. We find that while the efficiency for this turns out to be too low to give an increase in reach beyond that obtained via b-tagging, top tagging can indeed provide a confirmatory signal if gluinos are not too heavy. We also examine c jet tagging but find that it is not useful at the LHC. Finally, we explore the prospects for detecting the direct production of third generation squarks in models with an inverted squark mass hierarchy. This is signaled by b jets + E _T ^miss events being harder than in the Standard Model, but softer than those from the production of gluinos and heavier squarks. We find that while these events can be readily separated from the SM background (for third generation squark masses ∼300–500 GeV), the contamination from the much heavier gluinos and squarks remains formidable if these are also accessible.