W-CMP for sub-micron inverse metallisation

Chemical Mechanical Polishing (CMP) of tungsten for an inverse metallisation scheme is investigated. The influence of CMP parameters on removal rate and uniformity is studied. The main effects on the removal rate are the applied pressure and the rotation rate of the polishing pad. To the first order Preston's equation is obeyed. The uniformity is best with equal rpm of pad and wafer and with perforated pads. Also, pattern density effects of CMP of W/PETEOS are investigated. Dishing increased at larger W-linewidth. Oxide erosion increased at larger pattern density and smaller W-linewidth. Electrical measurements on submicron (0.4 and 0.5 ¿m) test structures yielded good CMP results

A Nonword Repetition Task for Speakers with Misarticulations: The Syllable Repetition Task (SRT)

Purpose. Conceptual and methodological confounds occur when non(sense) repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. We describe a nonword repetition task, the Syllable Repetiton Task (SRT) that eliminates this confound and report findings from three validity studies. Method. Ninety-five preschool children with Speech Delay and 63 with Typical Speech, completed an assessment battery that included the Nonword Repetition Task (NRT: Dollaghan & Campbell, 1998) and the SRT. SRT stimuli include only four of the earliest occurring consonants and one early occurring vowel. Results. Study 1 findings indicated that the SRT eliminated the speech confound in nonword testing with speakers who misarticulate. Study 2 findings indicated that the accuracy of the SRT to identify expressive language impairment was comparable to findings for the NRT. Study 3 findings illustrated the SRT’s potential to interrogate speech processing constraints underlying poor nonword repetition accuracy. Results supported both memorial and auditory-perceptual encoding constraints underlying nonword repetition errors in children with speech-language impairment. Conclusion. The SRT appears to be a psychometrically stable and substantively informative nonword repetition task for emerging genetic and other research with speakers who misarticulate

Renal Denervation Update From the International Sympathetic Nervous System Summit:JACC State-of-the-Art Review

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications

Bacterial Toxicity of Potassium Tellurite: Unveiling an Ancient Enigma

Biochemical, genetic, enzymatic and molecular approaches were used to demonstrate, for the first time, that tellurite (TeO(3) (2−)) toxicity in E. coli involves superoxide formation. This radical is derived, at least in part, from enzymatic TeO(3) (2−) reduction. This conclusion is supported by the following observations made in K(2)TeO(3)-treated E. coli BW25113: i) induction of the ibpA gene encoding for the small heat shock protein IbpA, which has been associated with resistance to superoxide, ii) increase of cytoplasmic reactive oxygen species (ROS) as determined with ROS-specific probe 2′7′-dichlorodihydrofluorescein diacetate (H(2)DCFDA), iii) increase of carbonyl content in cellular proteins, iv) increase in the generation of thiobarbituric acid-reactive substances (TBARs), v) inactivation of oxidative stress-sensitive [Fe-S] enzymes such as aconitase, vi) increase of superoxide dismutase (SOD) activity, vii) increase of sodA, sodB and soxS mRNA transcription, and viii) generation of superoxide radical during in vitro enzymatic reduction of potassium tellurite

Catalases Are NAD(P)H-Dependent Tellurite Reductases

Reactive oxygen species damage intracellular targets and are implicated in cancer, genetic disease, mutagenesis, and aging. Catalases are among the key enzymatic defenses against one of the most physiologically abundant reactive oxygen species, hydrogen peroxide. The well-studied, heme-dependent catalases accelerate the rate of the dismutation of peroxide to molecular oxygen and water with near kinetic perfection. Many catalases also bind the cofactors NADPH and NADH tenaciously, but, surprisingly, NAD(P)H is not required for their dismutase activity. Although NAD(P)H protects bovine catalase against oxidative damage by its peroxide substrate, the catalytic role of the nicotinamide cofactor in the function of this enzyme has remained a biochemical mystery to date. Anions formed by heavy metal oxides are among the most highly reactive, natural oxidizing agents. Here, we show that a natural isolate of Staphylococcus epidermidis resistant to tellurite detoxifies this anion thanks to a novel activity of its catalase, and that a subset of both bacterial and mammalian catalases carry out the NAD(P)H-dependent reduction of soluble tellurite ion (TeO(3) (2−)) to the less toxic, insoluble metal, tellurium (Te°), in vitro. An Escherichia coli mutant defective in the KatG catalase/peroxidase is sensitive to tellurite, and expression of the S. epidermidis catalase gene in a heterologous E. coli host confers increased resistance to tellurite as well as to hydrogen peroxide in vivo, arguing that S. epidermidis catalase provides a physiological line of defense against both of these strong oxidizing agents. Kinetic studies reveal that bovine catalase reduces tellurite with a low Michaelis-Menten constant, a result suggesting that tellurite is among the natural substrates of this enzyme. The reduction of tellurite by bovine catalase occurs at the expense of producing the highly reactive superoxide radical

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Deep Eutectic Solvents (DESs) and their applications [forthcoming]

Deep Eutectic Solvents (DESs) and Their Application

Revelations About Carotid Body Function Through its Pathological Role in Resistant Hypertension

Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension. We predict that carotid glomectomy will be a powerful way to temper excessive sympathetic discharge in diseases such as hypertension. We propose a model to explain that signalling from the ‘hypertensive’ carotid body is tonic, and hypothesise that there will be a sub-population of glomus cells that channel separately into reflex pathways controlling sympathetic motor outflows