New antithrombotic agents

The wide range of compounds currently being developed is the result of the continuing need for validated new antithrombotic agents. The prevention and treatment of venous thrombosis is predominated by anticoagulants: low molecular weight heparins, and potentially new antithrombin agents including hirudin. The effectiveness of new antiplatelet agents, and particularly c7E3 and integrelin, confirms the hypothesis concerning the role played by platelets in thrombogenesis in coronary arteries. But, due to the proaggregating effect of thrombin, anticoagulants could also have an important role in preventing arterial clots, either when given alone or in combination. Finally, the development of antithrombin and anti-platelet-glycoprotein IIb IIIa given orally is one of the major objectives of current research. Until the ideal antithrombotic agent is discovered, multiple-drug regimens combining anticoagulants and/or antiplatelet agents could be proposed in patients with a very high risk of thrombosis. Such regimens must taken into account the increased risk of bleeding and be adapted on the basis of careful laboratory surveillance.     

Modeling the positive-feedback regenerative process of CMOS latchupby a positive transient pole method. I. theoretical derivation

A novel method to characterize the mechanism of positive-feedback regeneration in a p-n-p-n structure during CMOS latchup transition is developed. It is based on the derived time-varying transient poles in large-signal base-emitter voltages of the lumped equivalent circuit of a p-n-p-n structure. Through calculating the time-varying transient poles during CMOS latchup transition, if is found that there exists a transient pole to change from negative to positive and then this pole changes to negative again. A p-n-p-n structure, which has a stronger positive-feedback regeneration during turn-on transition, will lead to a larger positive transient pole. The time when the positive transient pole occurs during CMOS latchup transition is the time when the positive-feedback regeneration starts. By this positive transient pole, the positive-feedback regenerative process of CMOS latchup can be quantitatively characterized     

Sterically inhomogenous viscoelastic behavior of human saccular cerebral aneurysms

To clarify the mechanism leading to the development and rupture of intracranial aneurysms, tensile strength and viscoelastic parameters of 22 human saccular aneurysms were investigated. Meridional and circumferential strips from the thin and the thick part of the aneurysm sack and 18 control strips from the basilar artery of 8 patients with pathologies not affecting the cerebral arterial system were studied. The length of the strips was increased in 200- microm steps, while distending force was recorded. Tensile strength and viscoelastic parameters were computed. In both directions, tensile strength of thick strips was significantly lower than that of controls. In the meridional direction, tensile strength of thin strips was significantly larger than that of thick ones (14.5 +/- 4.1 x 10(6) vs. 7.5 +/- 2.0 x 10(6) dyn/cm2, p < 0.05). In the circumferential direction, thin strips tore at lower strain values than thick ones (29 +/- 4 vs. 55 +/- 16%, p < 0.05). Viscoelastic parameters changed in parallel. In circumferential direction, values of thick and thin strips were significantly lower than those of controls. In the meridional direction, values of thin strips were significantly higher than those of the thick ones. These observations show that characteristic mechanical deterioration and steric inhomogeneities accompany the loss of smooth muscle cells and the derangement of connective tissue elements in the wall of intracranial aneurysms, which may explain certain steps in their initiation, enlargement and rupture.     

Computerized continuous monitoring and analysis of ozone in solution

This paper presents a method for continuous monitoring of ozone in water by using the Indigo colorimetric technique. The details of an instrument developed and used for this purpose are explained. Data obtained using the continuous ozone reading equipment in monitoring the ozone levels are presented. The instrument also can be used to measure the decay of ozone in ozonated waters, continuously giving a very accurate measure of ozone decay coefficients.     

Functionally Graded,Bone‐ and Tendon‐Like Polyurethane for Rotator Cuff Repair

Critical considerations in engineering biomaterials for rotator cuff repair include bone‐tendon‐like mechanical properties to support physiological loading and biophysicochemical attributes that stabilize the repair site over the long‐term. In this study, UV‐crosslinkable polyurethane based on quadrol (Q), hexamethylene diisocyante (H), and methacrylic anhydride (M; QHM polymers), which are free of solvent, catalyst, and photoinitiator, is developed. Mechanical characterization studies demonstrate that QHM polymers possesses phototunable bone‐ and tendon‐like tensile and compressive properties (12–74 MPa tensile strength, 0.6–2.7 GPa tensile modulus, 58–121 MPa compressive strength, and 1.5–3.0 GPa compressive modulus), including the capability to withstand 10 000 cycles of physiological tensile loading and reduce stress concentrations via stiffness gradients. Biophysicochemical studies demonstrate that QHM polymers have clinically favorable attributes vital to rotator cuff repair stability, including slow degradation profiles (5–30% mass loss after 8 weeks) with little‐to‐no cytotoxicity in vitro, exceptional suture retention ex vivo (2.79–3.56‐fold less suture migration relative to a clinically available graft), and competent tensile properties (similar ultimate load but higher normalized tensile stiffness relative to a clinically available graft) as well as good biocompatibility for augmenting rat supraspinatus tendon repair in vivo. This work demonstrates functionally graded, bone‐tendon‐like biomaterials for interfacial tissue engineering.     

The interprocess NIR sampling as an alternative approach to multivariate statistical process control for identifying sources of product-quality variability

We are presenting a new approach of identifying sources of variability within a manufacturing process by NIR measurements of samples of intermediate material after each consecutive unit operation (interprocess NIR sampling technique). In addition, we summarize the development of a multivariate statistical process control (MSPC) model for the production of enteric-coated pellet product of the proton-pump inhibitor class. By developing provisional NIR calibration models, the identification of critical process points yields comparable results to the established MSPC modeling procedure. Both approaches are shown to lead to the same conclusion, identifying parameters of extrusion/spheronization and characteristics of lactose that have the greatest influence on the end-product’s enteric coating performance. The proposed approach enables quicker and easier identification of variability sources during manufacturing process, especially in cases when historical process data is not straightforwardly available. In the presented case the changes of lactose characteristics are influencing the performance of the extrusion/spheronization process step. The pellet cores produced by using one (considered as less suitable) lactose source were on average larger and more fragile, leading to consequent breakage of the cores during subsequent fluid bed operations. These results were confirmed by additional experimental analyses illuminating the underlying mechanism of fracture of oblong pellets during the pellet coating process leading to compromised film coating.     

Investigation on seal-ring rules for IC product reliability in 0.25-μm CMOS technology

The distance between active region and the seal-ring location has been investigated in a 0.25-μm CMOS process. From the experimental results, this distance can be shrunk to only 5 μm without increasing leakage current and decreasing ESD robustness of the ESD protection devices after reliability tests of High-Accelerated Stress Test (HAST) and Temperature Cycling Test (TCT).     

Active ESD protection circuit design against charged-device-model ESD event in CMOS integrated circuits

CDM ESD event has become the main ESD reliability concern for integrated-circuits products using nanoscale CMOS technology. A novel CDM ESD protection design, using self-biased current trigger (SBCT) and source pumping, has been proposed and successfully verified in 0.13-μm CMOS technology to achieve 1-kV CDM ESD robustness.     

New Layout Arrangement to Improve ESD Robustness of Large-Array High-Voltage nLDMOS

In high-voltage applications, large-array n-channel lateral DMOS (LA-nLDMOS) is usually required to provide high driving capability. However, without following the foundry-suggested electrostatic discharge (ESD) design guidelines in order to reduce total layout area, LA-nLDMOS is easily damaged once the parasitic bipolar junction transistor is triggered under ESD stresses. Accordingly, the bipolar triggering of LA-nLDMOS usually limits the ESD robustness of LA-nLDMOS, particularly in the open-drain structure. In this letter, a new layout arrangement for LA-nLDMOS has been proposed to suppress the bipolar triggering under ESD stresses. Measurement results in a 0.5- ${rm mu}hbox{m}$ 16-V bipolar CMOS DMOS process have confirmed that the new proposed layout arrangement can successfully increase the human-body-model ESD level of the LA-nLDMOS with effective width of 3000 ${rm mu}hbox{m}$ from the original 0.75 kV up to 2.75 kV.      

Optimization on MOS-Triggered SCR Structures for On-Chip ESD Protection

MOS-triggered silicon-controlled rectifier (SCR) devices have been reported to achieve efficient on-chip electrostatic discharge (ESD) protection in deep-submicrometer CMOS technology. The channel length of the embedded MOS transistor in the MOS-triggered SCR device dominates the trigger mechanism and current distribution to govern the trigger voltage, holding voltage, on resistance, second breakdown current, and ESD robustness of the MOS-triggered SCR device. The embedded MOS transistor in the MOS-triggered SCR device should be optimized to achieve the most efficient ESD protection in advanced CMOS technology. In addition, the layout style of the embedded MOS transistor can be adjusted to improve the MOS-triggered SCR device for ESD protection.