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In this paper we present a silicon tunnel FET based on line-tunneling to achieve better subthreshold performance. The fabricated device shows an on-current of I on  = 2.55 × 10 −7  A/µm at V ds  = V on  = V gs  − V off  = −0.5 V for an I off  = 1 nA/µm and an average SS of 55 mV/dec over two orders of magnitude of I d . Furthermore, the analog figures of merit have been calculated and show that the transconductance efficiency g m /I d beats the MOSFET performance at low currents. [ABSTRACT FROM AUTHOR]

The benefits of a gate-normal tunneling architecture in enhancing the on-current and average subthreshold swing of tunneling field-effect transistors were scrutinized in experiment through careful physical analysis of a Si0.50Ge0.50/Si heterostructure. In accordance with theoretical predictions, it is confirmed that the on-current is governed by line tunneling scaling with the source-gate overlap area of our devices. Our analysis identifies the early onset of parasitic diagonal tunneling paths as most detrimental for a low average subthreshold swing. By counter doping the channel, this onset can be shifted favorably, permitting low average subthreshold swings down to 87 mV/dec over four decades of drain current and high on-off current ratios exceeding 106. [ABSTRACT FROM AUTHOR]

This paper systematically studies GeSn n-FETs, from individual process modules to a complete device. High-k gate stacks and NiGeSn metallic contacts for source and drain are characterized in independent experiments. To study both direct and indirect bandgap semiconductors, a range of 0–14.5 at.% Sn-content GeSn alloys are investigated. Special emphasis is placed on capacitance-voltage (C-V) characteristics and Schottky-barrier optimization. GeSn n-FET devices are presented including temperature dependent I-V characteristics. Finally, as an important step towards implementing GeSn in tunnel-FETs, negative differential resistance in Ge 0.87 Sn 0.13 tunnel-diodes is demonstrated at cryogenic temperatures. The present work provides a base for further optimization of GeSn FETs and novel tunnel FET devices. [ABSTRACT FROM AUTHOR]

GS-9857, an inhibitor of the hepatitis C virus ( HCV) nonstructural protein ( NS) 3/4A, demonstrates potent activity against HCV genotypes 1-6 and improved coverage against commonly encountered NS3 resistance-associated variants ( RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1-4 infection. Patients with genotype 1-4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. GS-9857 was well tolerated; all reported adverse events (AEs) were mild or moderate in severity. Diarrhoea and headache were the most commonly reported AEs. Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated potent antiviral activity in patients with chronic HCV infection, achieving mean and median maximum reductions in HCV RNA of ≥3 log10 IU/mL following administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 infection. The antiviral activity of GS-9857 was unaffected by the presence of pretreatment NS3 RAVs. In patients with genotype 1-4 infection, GS-9857 exhibited linear PK and was associated with a median half-life of 29-42 h, supporting once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile of GS-9857 support its further evaluation for treatment of patients with chronic HCV infection. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) atom lattices provide model setups with Coulomb correlations that induce competing ground states. Here, SiC emerges as a wide-gap substrate with reduced screening. We report the first artificial high-Z atom lattice on SiC(0001) by Sn adatoms, based on experimental realization and theoretical modeling. Density-functional theory of our triangular structure model closely reproduces the scanning tunneling microscopy. Photoemission data show a deeply gapped state (∼2 eV gap), and, based on our calculations including dynamic mean-field theory, we argue that this reflects a pronounced Mottinsulating scenario. We also find indications that the system is susceptible to antiferromagnetic superstructures. Such artificial lattices on SiC(0001) thus offer a novel platform for coexisting Coulomb correlations and spin-orbit coupling, with bearing for unusual magnetic phases and proposed topological quantum states of matter. [ABSTRACT FROM AUTHOR]

Residual stress profiles are introduced in an alumino-silicate glass using ion-exchange. Due to a high central tension in these glasses, fracture is often followed by fragmentation. Fracture was initiated by loading the glasses with a Vicker's indenter, either monotonically to fracture, or loading to a fixed load, and then unloading. Fracture loads in the load–unload method were ½–⅓ of that during monotonic loading. A qualitative explanation of this phenomenon is proposed by extending an analysis of stresses at the indentation site. The process of fragmentation under indentation, crack propagation and repeated multiple branching, is described. The fragmentation behavior when fracture is initiated in biaxial loading is different: a single crack creates numerous branches, which then propagate without further branching. This process is explained in terms of the stress distribution in the sample prior to fracture initiation. The implications for practical instances where fragmentation is important are discussed. [ABSTRACT FROM AUTHOR]

Abstract: When Mg surfaces are oxidized the released chemical energy is partly dissipated non-adiabatically by exciting hot charge carriers in the metal surface. Different types of Mg/p-Si(111) Schottky diodes with homogeneous barrier heights of 0.7 and 0.8eV are used to detect chemicurrents during exposure of the devices to oxygen. The detected chemicurrent transients represent the kinetics of the chemical reaction which is attributed to an oxide nucleation and growth mode. The current strength is related to the homogeneous Schottky barrier height of the diode. Together with exoelectron emission data the energy distribution of the chemically induced hot charge carriers is deduced and may be described by a Boltzmann type function with an effective temperature of 1730K. Consequently, the chemicurrent method is found to be almost four orders of magnitude more effective to detect hot charge carriers than exoelectron emission. [Copyright &y& Elsevier]

A chip‐based biosensor system for marker‐free detection of affinity and molecular interaction kinetics was developed. It applies surface‐acoustic‐waves. Combined with a novel double‐frequency measurement‐mode, which assures reliable reference measurements, it allows a precise real‐time detection of mass loading and viscosity alteration. The system is equipped with five independently working channels, which enable it to simultaneously perform different, e.g., reference measurements. Exemplarily performed investigations of the association of thrombin and antithrombin antibodies demonstrated the applicability of the system to affinity and kinetic analyses. The system yielded a mean value for the equilibrium dissociation constant of K D =116±9 nM, which compares well with the supplier specification. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tobramycin, used to treat respiratory exacerbations in cystic fibrosis (CF), is also a renal tubular toxin. Tubular dysfunction leads to increased urinary levels of the proximal tubular lysosomal enzyme, N-acetyl-beta-d-glucosaminidase (NAG) and the proximal tubular protein, retinol-binding protein (RBP). Hypermagnesuria and resulting hypomagnesaemia are indicative of more severe tubular damage, occasionally seen following repeated courses of intravenous tobramycin. Using these biochemical markers we studied the effect of a 2-week course of this agent on tubular function. Methods: Twenty-two children (11 boys) with CF were studied. Median age=10.9 years, range 3.1–16.4 years. All had a normal predicted glomerular filtration rate (pGFR). They received tobramycin 3 mg/kg/dose tds. Urinary NAG, RBP, creatinine and plasma magnesium and creatinine were assayed: [a)] immediately before commencing tobramycin [b)] immediately following the course [c)] 4 weeks after the end of the course. Results: Mean log UrNAG and UrRBP rose significantly between time points a) and b) before falling to almost pre-treatment levels by time c). Using two way ANOVA analysis the results for UrNAG and UrRBP were both highly statistically significant (p <0.0001). Paired t-tests on the logged values revealed highly significant differences between all time points for UrNAG and in the case of UrRBP for all other than a) compared to c). In all patients plasma magnesium and pGFR remained within normal limits. Conclusions: Intravenous tobramycin produces acute tubular injury, which showed evidence of almost complete recovery after 4 weeks. The insult to the tubules was not sufficient to produce hypomagnesaemia in our study group. To assess cumulative tubular damage in more detail it would be necessary to repeat this study after further courses of tobramycin. We recommend monitoring plasma magnesium during courses of intravenous tobramycin. [Copyright &y& Elsevier]

Abstract: Specific binding of the anticoagulants heparin and antithrombin III to the blood clotting cascade factor human thrombin was recorded as a function of time with a Love-wave biosensor array consisting of five sensor elements. Two of the sensor elements were used as references. Three sensor elements were coated with RNA or DNA aptamers for specific binding of human thrombin. The affinity between the aptamers and thrombin, measured using the biosensor, was within the same range as the value of KD measured by filter binding experiments. Consecutive binding of the thrombin inhibitors heparin, antithrombin III or the heparin–antithrombin III complex to the immobilized thrombin molecules, and binding of a ternary complex of heparin, anithrombin III, and thrombin to aptamers was evaluated. The experiments showed attenuation of binding to thrombin due to heparin–antithrombin III complex formation. Binding of heparin activated the formation of the inhibitory complex of antithrombin III with thrombin about 2.7-fold. Binding of the DNA aptamer to exosite II appeared to inhibit heparin binding to exosite I. [Copyright &y& Elsevier]

This paper discusses tensile testing techniques and results derived as part of a broader microstructure-properties investigation of structural materials used in surface micromachined (SMM), and LIGA MEMS technologies. SMM techniques produce devices on the surface of a silicon wafer, with critical dimensions as small as 1–2 μm, using a subtractive multilayer film deposition process. Two structural materials have been investigated: SUMMiT™ polysilicon and amorphous Diamond (a-D). Mechanical properties presented in this paper on these SMM structural materials were obtained from a direct tensile testing method using the lateral force measurement capability of a nanoindentation system. LIGA, a German acronym extracted from the words “Lithographie, Galvanoformung, Abformung,” is an additive process in which structural material is electrodeposited into a polymethyl-methacrylate (PMMA) molds realized by deep x-ray lithography. LIGA tensile specimens of several different materials have been evaluated using a mini-servohydraulic load frame, designed to test specimens of sizes similar to structural components. In this paper, tensile test results from LIGA fabricated Ni and Ni-alloys and examples of their correlation to processing and microstructure will be presented. [ABSTRACT FROM AUTHOR]

The low-temperature (180 K) interaction of NO molecules with thin Ag films deposited on hydrogen terminated Si(1 1 1) is investigated by X-ray photoelectron spectroscopy, scanning electron microscopy and chemicurrent measurements. The chemicurrent transients recorded from the thin film Ag/Si Schottky diodes demonstrate two maxima according to NO molecular adsorption and intermolecular reactions of (NO)2 dimer decomposition. Below a critical film thickness of 8 nm the original smooth Ag films are disrupted by the NO exposure leading to a nano-patterned network of coalescing Ag islands. Thicker films are stable upon NO exposure. Warming of NO-exposed diodes to room temperature changes the Ag/Si interface properties drastically by reducing the effective Schottky barrier height and increasing the diode’s sensitivity to detect electrons excited in the metal. This is observed by enhanced maximum chemicurrents after annealing. [Copyright &y& Elsevier]

Examines the magnitudes of residual stresses in polycrystalline alumina using experimentally-determined crystal orientation and finite element analysis. Stress distribution; Crack initiation and propagation; Ratio between grain boundary energy and surface energy.

This article presents the results of nuclear magnetic resonance imaging (MRI) studies of gas adsorption/desorption in nanoporous solids. MR images obtained as a function of the equilibrium pressure, at constant temperature, form a pixel-by-pixel map of adsorption isotherms. Analysis of these isotherms using Brunauer-Emmett-Teller (BET) theory results in spatial maps of the specific surface area, the net energy of adsorption, and the pore morphology. Results obtained using MRI for γ-Al[SUB2]O[SUB3] and ZnO powders and partially sintered ceramics of these materials, as well as Vycor® porous glass, compare well to results for bulk samples obtained using conventional N[SUB2] BET adsorption. MRI studies of gas adsorption are shown to provide statistical averages of the pore microstructure parameters, resolved on a macroscopic scale. [ABSTRACT FROM AUTHOR]

The gate–source overlap length (${L}_{{\text {OV}}}$) in the line tunneling FET (L-TFET) can be used as a design parameter to improve the analog circuit performance. In this paper, we investigate the drain current (${I}_{D}$) dependence on ${L}_{{\text {OV}}}$ , considering the electrostatics of the gate–source overlap region. It is observed that ${I}_{D}$ increases with ${L}_{{\text {OV}}}$ exhibiting a nonlinear behavior. This happens as the impact of the lateral electric field at the far end of the tunnel junction reduces, thereby reducing the tunneling rate. Based on our semiempirical physical ${I}_{D}$ – ${L}_{{\text {OV}}}$ model, a novel ${L}_{{\text {OV}}}$ variation-aware small signal model for L-TFET is also proposed. The output resistance and the gate–drain capacitance remain almost independent of ${L}_{{\text {OV}}}$ in the saturation regime. The gate–source capacitance and the transconductance linearly increase with ${L}_{{\text {OV}}}$. A common source amplifier is demonstrated with ~2.4 times increase in the voltage gain when ${L}_{{\text {OV}}}$ is increased from 20 to 50 nm, with a penalty of ~10% in the bandwidth. We observe that it is not possible to achieve the gain similar to one obtained using 2.5 times increase in ${L}_{{\text {OV}}}$ even after increasing the device width five times. However, the bandwidth reduces 30% at such width owing to an increase in the gate capacitances. [ABSTRACT FROM AUTHOR]

The efficiency of photoconductive (PC) devices, including terahertz detectors, is constrained by the bulk optical constants of PC materials. Here, we show that optical absorption in a PC layer can be modified substantially within a hybrid cavity containing nanoantennas and a Distributed Bragg Reflector. We find that a hybrid cavity, consisting of a GaAs PC layer of just 50 nm, can be used to absorb >75% of incident photons by trapping the light within the cavity. We provide an intuitive model, which describes the dependence of the optimum operation wavelength on the cavity thickness. We also find that the nanoantenna size is a critical parameter, small variations of which lead to both wavelength shifting and reduced absorption in the cavity, suggesting that impedance matching is key for achieving efficient absorption in the optically thin hybrid cavities. [ABSTRACT FROM AUTHOR]

Introduction: One factor of opioid attractiveness with recreational abuse is the rate of drug absorption and corollary pharmacodynamic experience. In this study, the relationship between abuse potential and the pharmacokinetic profile (maximum plasma concentration [Cmax] and time to maximum plasma concentration [Tmax]) of differing formulations of hydromorphone and placebo was explored in recreational drug users. Method: This post-hoc analysis of a double-blind, placebo-controlled, randomized, 2-phase, crossover study of subjects with histories of recreational opioid use who received single oral doses of placebo and of 2 formulations of hydromorphone: immediate-release (IR) hydromorphone 8mg (Dilaudid®) and once-daily hydromorphone extended-release (ER) (EXALGOtm) at doses of 16, 32, and 64mg intact and 8mg milled to disrupt the extended-release properties of EXALGO tablets. Results: When adjusted for dose, Cmax for all intact once-daily hydromorphone ER treatments, yielded significantly lower Cmax compared with 8-mg IR hydromorphone (P <0.001). Tmax was delayed and AQ (Cmax/Tmax) was lower with all intact once-daily hydromorphone ER doses compared with 8mg IR hydromorphone. In the 28 subjects completing all treatments and included in the final analyses, the intact once-daily hydromorphone ER formulations had significantly lower liking and euphoria effects for the first 4 hours (P <0.05) compared with the 8mg IR and 8mg milled hydromorphone ER tablets. Conclusions: If liking and euphoria effects drives opioid use, then once-daily hydromorphone ER intact may be less attractive than IR hydromorphone or hydromorphone ER milled. Delaying the peak in plasma concentrations may be associated with reduced abuse liability. [ABSTRACT FROM AUTHOR]

This paper discusses the design and use of low-temperature (850 °C to 950 °C) cofired ceramic (LTCC) planar magnetic flyback transformers for applications that require conversion of a low-voltage to high-voltage (>100-V) with significant volumetric constraints. Measured performance and modeling results for multiple designs show that the LTCC flyback transformer design and construction imposes serious limitations on the achievable coupling, and significantly impacts the transformer performance and output voltage. This paper discusses the impact of various design factors that can provide improved performance by increasing transformer coupling and output voltage. The experiments performed on prototype units demonstrate LTCC transformer designs capable of greater than 2-kV output. Finally, the paper investigates the effect of the LTCC microstructure on transformer insulation. Although this paper focuses on generating voltages in the kV range, the experimental characterization and discussion presented in this paper applies to designs requiring lower voltage. [ABSTRACT FROM AUTHOR]

Heart rate (HR) and ratings of perceived exertion (RPE) are common exercise intensity regulatory strategies, however, some individuals are unable to use these strategies effectively. Alternative or conjunctive strategies may aid in the transition to self-guided programs. The purpose of the present study was to examine the value of a brief, field-based exercise intensity learning trial on self-regulation of intensity during a weeklong exercise program. Forty-two males were randomly assigned to either a paced learning trial (P) or non-paced control (NP), and then one of three intensity feedback groups: HR, HR+RPE, or no feedback (CONT). The paced trial consisted of an 800-m trial at 75% of maximal heart rate reserve (MHRR) on day one. Subjects then completed four 800-m trials each day for four days and received feedback on deviation from target HR (THR) after each 800-m trial. Four-way MANOVA (pacing × feedback × trials × days) was used to assess the influence of the learning trial on THR deviation scores across the week. The pacing × feedback × trials interaction was significant (Pillai's Trace = 0.36, - F (6,70)=2.56, p=0.03) and thus, the influence of the learning trial was assessed within feedback group. There were no significant differences in THR deviation scores for P vs. NP within the HR or HR + RPE feedback groups. However, P was significantly more accurate then NP (p < 0.05) within the CONT feedback groups during each trial averaged across the week (T1 = - 2.6 vs. 5.3; T2=2.6 vs. 14.2; T3=4.6 vs. 16.2; T4=5.3 vs. 20.5 beats·min-1). These results demonstrate that a brief intensity learning trial, in the absence of HR or HR+RPE feedback, provided for accurate self-regulation of vigorous exercise training. These results would support the efficacy of a brief intensity learning trial within the context of transitioning an individual to a self-guided exercise program. [ABSTRACT FROM AUTHOR]

Multi-step ion-exchange processing can produce complex stress profiles in glass surfaces, which can result in increased fracture strength, reduced strength dispersion, flaw tolerance and multiple cracking behavior. Glass displaying this set of properties is termed engineered stress profile (ESP) glass. Treatments at 400–450 °C in molten KNO3 and NaNO3 salt baths were used to create residual stresses in the surface of soda lime silicate float glass. Stress profiles were measured using optical stress birefringence, allowing derivation of apparent fracture toughness curves and prediction of crack stability over a range of flaw sizes. Specimens were tested in the four-point bend configuration to determine fracture strength and to study the multiple cracking which results from crack growth stabilization. The results were compared to predictions from the fracture toughness curves, in terms of the strength dispersion and crack stability criteria. Indented specimens were tested to determine the response of the glass to contact damage. [Copyright &y& Elsevier]

Doped HfO2 has become a promising candidate for non-volatile memory devices since it can be easily integrated into existing CMOS technology. Many dopants like Y, Gd, and Sr have been investigated for the stabilization of ferroelectric HfO2. Here, we report the fabrication of capacitors comprising ferroelectric HfO2 metal-insulator-metal structures with TiN bottom and top electrodes using the dopant Lu. Amorphous 5% Lu doped HfO2 was deposited by pulsed laser deposition and afterwards annealed to achieve the ferroelectric, orthorhombic phase (space group Pbc21). The polarization of the layers was confirmed by capacitance-voltage, polarization-voltage, and currentvoltage measurements. Depending on the anneal temperature, the remanent polarization changes and the initial state of the oxide varies. The layer exhibits initially a pinched hysteresis up to an annealing temperature of 600 °C and an unpinched hysteresis at 700 °C. The maximum polarization is about 11 μC/cm2 which is measured after 104 cycles and stable up to 106 cycles. The influence of the layer thickness on the oxide properties is investigated for 10–40 nm thick HfLuO; however, a thickness dependence of the ferroelectric properties is not observed. [ABSTRACT FROM AUTHOR]

Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high–atomic number element and is experimentally realized as a bismuth honeycomb lattice on top of the insulating silicon carbide substrate SiC(0001). Using scanning tunneling spectroscopy, we detect a gap of ~0.8 electron volt and conductive edge states consistent with theory. Our combined theoretical and experimental results demonstrate a concept for a quantum spin Hall wide-gap scenario, where the chemical potential resides in the global system gap, ensuring robust edge conductance. [ABSTRACT FROM AUTHOR]

Objective: Little is known about how best to target cardiovascular health promotion messages to minorities. This study describes key lessons that emerged from a community and culture-centered approach to developing a multimedia, coronary heart disease (CHD) patient education program (PEP) for medically underserved South Asian immigrants.Methods: The prototype PEP integrated the surface structures (e.g. language) and deeper structures (e.g. explanatory models (EMs), values) of South Asians' socio-cultural context. Seven focus groups and 13 individual interviews were used to investigate South Asians' reactions and obtain qualitative feedback after viewing the culturally targeted PEP. Qualitative data were organized into emergent thematic constructs.Results: Participants (n=56) mean age was 51 years and 48 % were Hindi speakers. Community members had a strong, negative reaction to some of the targeted messages, "This statement is a bold attack. You are pin-pointing one community." Other important themes emerged from focus groups and interviews about the PEP: 1) it did not capture the community's heterogeneity; 2) did not sufficiently incorporate South Asians' EMs of CHD; and 3) did not address economic barriers to CHD prevention. Feedback was used to revise the PEP.Conclusion: A community and culture-centered approach to developing cardiovascular health promotion messages revealed tensions between the researcher's vantage point of "cultural targeting" and the community's perceptions and reactions to these messages. Engaging communities in every phase of message design, incorporating their EMs, recognizing community heterogeneity, and addressing economic and structural barriers, are critical steps to ensuring that health promotion messages reach their intended audience and achieve true cultural appropriateness. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Multimedia diabetes education programs (MDEP) have the potential to improve communication and education of those with low health literacy. We examined the effect of a MDEP targeted to patients with low literacy on knowledge and assessed the association between literacy and knowledge improvement. METHODS: We showed the MDEP to 190 patients recruited from clinics at a federally qualified health center and an academic health center. We measured diabetes knowledge before and after viewing the MDEP. RESULTS: Seventy-nine percent of patients had adequate literacy, 13% marginal, and 8% inadequate literacy. Patients across all literacy levels had significant increases in knowledge scores after viewing the MDEP (p-value<0.001). Patients with inadequate literacy learned significantly less after the MDEP (adjusted beta-coefficient=-2.3, SE=0.70) compared to those with adequate literacy. CONCLUSIONS: A MDEP designed for those with low literacy significantly increased diabetes knowledge across literacy levels. However, the MDEP did not overcome the learning gap between patients with low and high literacy. PRACTICE IMPLICATIONS: A literacy appropriate MDEP may be an effective way to teach patients about diabetes. Combining the MDEP with other education methods may improve comprehension and learning among those with low literacy. Research is needed to identify which characteristics of low-literate patients influence the ability to learn health information. Identifying these factors and incorporating solutions into a diabetes education intervention may help bridge the learning gap related to literacy status. [ABSTRACT FROM AUTHOR]

The strength of sintered low-temperature co-fired ceramic (LTCC) disks was measured under dry (<2% relative humidity [RH]) and wet (98% RH) conditions, using ring-on-ring, biaxial-flexure testing in the stressing rate range of 0.002–2 MPa/s. The empirical sub-critical crack growth parameters, n and A, were calculated. The values of the parameters in the wet environment were higher than in the dry environment. It is argued that the high RH n value is more representative of material behavior. Results of fractographic examination are reported and expected lifetime and safe design stresses for LTCC are calculated. [ABSTRACT FROM AUTHOR]

Incorporation into a 20-crown-6 of a bulky substituent capable of impeding cation/anion access to one face of the crown ether cavity is shown to afford compounds exhibiting good extraction selectivity for potassium ion over both alkaline earth cations (Ca2+, Sr2+) and other alkali metal ions (Na+, Cs+), an apparent result of diminished flexibility of the crown ether cavity, inhibition of the formation of extractable “sandwich' complexes with large cations, and the destabilizing effect of forcing charge-neutralizing counter anions to approach from one face of the crown cavity. [ABSTRACT FROM AUTHOR]

A liquid chromatographic–tandem mass spectrometric (LC–MS–MS) assay was developed and validated to quantitatively determine olanzapine (OLZ) concentrations in human blood. Liquid–liquid extraction, using n-butanol:cyclohexane (3:47, v/v), was used to isolate OLZ and its internal standard, LY170158, from the biological matrix. Chromatographic resolution of OLZ from endogenous interferences and known metabolites was accomplished with a MetaChem Monochrom HPLC column (4.6×150 mm, dp 5 μm). Detection occurred using a Perkin-Elmer Sciex API III Plus triple quadrupole mass spectrometer using positive ion APCI and multiple reaction monitoring (MRM). The linear dynamic range was from 5 to 500 ng ml−1 based on a 0.25-ml aliquot of human blood. The inter-day precision (%RSD) and accuracy (%RE) ranged from 3.65 to 10.64 and from −2.14 to 3.07, respectively. Modifications to an existing assay for the determination of OLZ in human plasma were necessary. A different structural analog was used as the internal standard due to instability observed for the original analog when using human blood as the matrix. A second modification was the addition of the anti-oxidant sodium ascorbate to inhibit degradation of OLZ in human blood, as has been noted by other investigators. Upon fortification of human blood with sodium ascorbate (final concentration, 0.33 mM), OLZ was found to be stable for at least 1 week at −70°C as well as through two freeze–thaw cycles. This assay, which will be used to investigate the distribution of OLZ in human blood, grants insight into the proper sample handling conditions needed to perform valid determinations of OLZ in human blood. [Copyright &y& Elsevier]

NFκB is an important transcriptional regulator of multiple pro-inflammatory genes. In non-stimulated cells NFκB is anchored in the cytoplasm via the inhibitory protein IκBα. Following exposure to diverse pro-inflammatory signals (e.g. TNFα, IL1, LPS) various signal transduction cascades are initiated converging on the IκB kinase (IKK). IKK phosphorylates IκBα on serines 32 and 36 signaling the inhibitory protein for ubiquitin-mediated degradation. The SCFβ-TRCP complex is the ubiquitin ligase responsible for mediating phosphorylation dependent ubiquitination of IκBα. Here we reconstitute phosphorylation dependent ubiquitination of IκBα using recombinant components. Our results suggest that the cullin specificity of the SCF complex may reflect its ability to associate with Rbx1. We demonstrate specific ubiquitination of IκBα by Ubc3 and Ubc4 in a phosphorylation and SCFβ-TRCP dependent manner and that both are capable of associating with the SCFβ-TRCP complex isolated from human cells. Finally, we show that Ubc4 is in excess to Ubc3 in THP.1 cells and 19 times more efficient in catalyzing the reaction, suggesting that Ubc4 is the preferentially used Ubc in this reaction in vivo. Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho-IκBα in a SCFβ-TRCP dependent reaction. Oncogene (2000) 19, 3529–3536 [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether portable chest radiography (CXR) scores are associated with coronavirus disease 2019 (COVID-19) status and various clinical outcomes.Materials and Methods: This retrospective study included 500 initial CXR from COVID-19-suspected patients. Each CXR was scored based on geographic extent and degree of opacity as indicators of disease severity. COVID-19 status and clinical outcomes including intensive care unit (ICU) admission, mechanical ventilation, mortality, length of hospitalisation, and duration on ventilator were collected. Multivariable logistic regression analysis was performed to evaluate the relationship between CXR scores and COVID-19 status, CXR scores and clinical outcomes, adjusted for code status, age, gender and co-morbidities.Results: The interclass correlation coefficients amongst raters were 0.94 and 0.90 for the extent score and opacity score, respectively. CXR scores were significantly (p < 0.01) associated with COVID-19 positivity (odd ratio [OR] = 1.49; 95% confidence interval [CI]: 1.27 - 1.75 for extent score and OR = 1.75; 95% CI: 1.42 - 2.15 for opacity score), ICU admission (OR = 1.19; 95% CI: 1.09 - 1.31 for extent score and OR = 1.26; 95% CI: 1.10 - 1.44 for opacity score), and invasive mechanical ventilation (OR = 1.22; 95% CI: 1.11 - 1.35 for geographic score and OR = 1.21; 95% CI: 1.05 - 1.38 for opacity score). CXR scores were not significantly different between survivors and non-survivors after adjusting for code status (p>0.05). CXR scores were not associated with length of hospitalisation or duration on ventilation (p>0.05).Conclusions: Initial CXR scores have prognostic value and are associated with COVID-19 positivity, ICU admission, and mechanical ventilation. [ABSTRACT FROM AUTHOR]