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In mild-to-moderate inflammatory bowel disease, particularly ulcerative colitis, 5-aminosalicylic acid (5-ASA) remains a cornerstone of therapy. Sulfasalazine, originally synthesized in 1940 as an arthritis treatment for Sweden's King Gustaf V, is an azo-linked compound between 5-ASA and sulfapyridine. This medication was soon discovered to be effective in treating ulcerative colitis. However, dose-related side effects of the sulfapyridine moiety led to considerable effort in developing medications to deliver 5-ASA to the desired parts of the intestine. The newest generation of 5-ASA medications allows high-dose medication delivery with decreased pill burden, thereby improving patient compliance. This review will describe the pharmacokinetics of various 5-ASA preparations, particularly focusing on high-dose formulations and their role in therapy; will examine current scientific literature; and will review clinical outcomes and safety profiles.

A low-IF fully integrated tuner for DBS satellite TV applications has been realized in 0.13-mum CMOS. A wideband ring oscillator-based frequency synthesizer having a large frequency step was used to downconvert a cluster of channels to a sliding low-IF frequency, while the second downconversion to baseband was performed in the digital domain. Eliminating the inductors and using a small-area oscillator has reduced both the parasitic magnetic and substrate coupling, allowing single-chip integration of the sensitive tuner and the noisy digital demodulator. A significant reduction in die area was achieved by using a single oscillator to cover the entire satellite TV spectrum, while a noise attenuator was cascaded with the PLL passive loop filter to reduce the equivalent VCO tuning gain. This improves PLL noise and spur performance and allows the on-chip integration of the loop filter. The digital low-IF tuner allows the use of a discrete step AGC loop that results in lower noise figure and higher linearity. Automatic signal path gain and bandwidth digital calibration was realized using replica ring oscillators. Tuner specifications include: 90 dB gain range, 10 dB noise figure at max gain, +25dBm IIP3 at min gain, 1.3deg rms integrated phase noise

This paper presents the first low-IF fully integrated receiver for DBS satellite TV applications realized in 0.13 mum CMOS. A wideband ring oscillator based frequency synthesizer having a large frequency step was used to downconvert a cluster of channels to a coarsely defined low-IF frequency, while the second downconversion to baseband was performed in the digital domain. Eliminating the oscillator inductors reduced the parasitic magnetic coupling from the digital core, allowing a single-chip integration of the sensitive tuner and the noisy digital demodulator. A significant die area reduction was achieved by using a single oscillator to cover the entire satellite TV spectrum, while a noise attenuator was cascaded with the PLL loop filter to reduce the equivalent tuning gain. The low-IF architecture allowed a discrete-step AGC that improves both tuner noise and linearity performance. Tuner gain and IF corner frequency were calibrated using replica ring oscillators that are tuned up to the onset of oscillations. The tuner specifications include: 90 dB gain range, 9 dB noise figure at max gain, +25 dBm IIP3 at min gain, 1.3degrms integrated phase noise, les50 dBc spurs, 0.7 W power consumption from dual 1.8/3.3-V supplies, and 1.8times1.2 mm 2 die area

This paper describes the development of a technology designed for social connectedness. The goal was to design and develop a technology that allows older adults to be more connected with family and/or close ones. Bridging Unmet Modes of Participation (BUMP) respond to the needs of designing technology products for inclusion and integration of older adults and addressing issues of isolation and social disconnected experienced with the aging population.

In order to minimize total active power consumption in digital circuits, one must take into account subthreshold leakage currents that grow exponentially as technology scales. This research develops a theoretical model to predict how dynamic power and subthreshold power must be balanced to give an optimal V/sub DD//V/sub t/ operating point that minimizes total active power consumption for different workload and operating conditions. A 175-mV multiply-accumulate test chip using a triple-well technology with tunable supply and body bias values is measured to experimentally verify the tradeoffs between the various sources of power. The test chip shows that there is an optimum V/sub DD//V/sub t/ operating point, although it differs from the theoretical limit because of excessive forward bias currents. Finally, we propose a preliminary automatic supply and body biasing architecture (ASB) that automatically configures a circuit to operate with the lowest possible active power consumption.

The purpose of the present investigation was to determine whether the sensitivity to systemic toxic effects of cocaine is altered in genetically epilepsy-prone rats (GEPRs). Moderate seizure (GEPR-3) and severe seizure (GEPR-9) rats, and the control strain, Sprague-Dawley rats, 10 weeks of age, were lightly anesthetized with halothane and nitrous oxide. Following surgical preparation and stabilization, the animals were given a constant intravenous infusion of cocaine (4 mg/kg per min) until death. Blood pressure, ECG, and EEG were monitored continuously throughout the experiment. Cocaine doses required to produce seizures (i.e., epileptiform activity on the EEG) were not significantly different between GEPRs and control rats (16.8+/-0.6 mg/kg in GEPR-3, 18.7+/-0.7 mg/kg in GEPR-9, and 14.7+/-1.3 mg/kg in Sprague-Dawley). Seizure duration, amplitude and the number of epileptiform bursts were also similar among the three strains. Additionally, there was no significant difference in cocaine doses that produced arrhythmias and cardiac asystole between GEPRs and control. The results indicate that genetically epilepsy-prone rats do not exhibit altered sensitivity to cocaine-induced seizures despite the marked susceptibility to sound-evoked seizures. Local anesthetic-induced seizures and acoustically-evoked seizures apparently have different underlying mechanisms.

To establish and standardize a nociceptive response in anesthetized rats, the hypertensive responses to defined electrical and mechanical stimuli were studied. Rats (n = 7) were given etomidate, 3.8 mg/kg/hr intravenously (i.v.) 2 hr following carotid artery and jugular vein cannulation. At 15 min after beginning the infusion, four types of noxious stimuli were administered sequentially at 1-min intervals (14 stimuli total): Type 1: Square electrical waves, 125 cps, 1.6 msec, 2-sec train duration, varying current from 0.4 to 12 mA (11 stimuli); Type 2: A single 10-mA electrical stimulus, 5-sec train duration; Type 3: Tail clamping; and, Type 4: Skin incision. After each stimulus, maximum change in systolic blood pressure (delta SBP) was measured. delta SBP after the most intense stimuli was as follows: Type 1 (12 mA, 2 sec), 32.1 +/- 2.14 mmHg; Type 2 (10 mA 5 sec), 42.9 +/- 2.4 mmHg; Type 3 (tail-clamping), 34.3 +/- 3.3 mmHg; Type 4 (skin incision), 14.2 +/- 2.8 mmHg. For the multiple Type-2 stimuli, a relationship between current and delta SBP was present. The authors believe that characterized graded electrical stimulation will allow a more quantitative evaluation of the hypertensive response to noxious stimuli in etomidate anesthetized rats, as compared to observing a single response to a single stimulus. The characterization of the electrical stimulation by amplitude, frequency, and wave form makes research work on nociception under anesthesia easily reproducible.

The successful management of a cesarean section in a parturient with a single ventricle and pulmonary atresia using general anesthesia is discussed. After cyanosis at birth, the patient underwent cardiac catheterization, which showed an apparent severe tetralogy of Fallot, atresia of the main pulmonary artery (PA), and a large patent ductus arteriosus. When she was 7 months of age, a Blalock-Taussig shunt (right subclavian artery to right PA) was done. She remained stable until age 11, when cyanosis increased and exercise tolerance decreased. Recatheterization more clearly defined the lesion: closed shunt, pulmonary valvular atresia, severe ductal stenosis, reduced pulmonary flow, double-outlet right ventricle, and severe hypoplasia of the left atrium, mitral valve, and left ventricle. A Potts shunt (left descending aorta to left PA) was done. Compliance with therapy was poor and follow-up difficult. Exercise tolerance was poor, but the patient remained otherwise stable. At 28 weeks' gestation, this 23-year-old parturient presented with severe congestive heart failure (CHF). After initial therapy with oxygen, bed rest, digoxin, and diuretics, she improved and remained stable for a month. At that time (32 weeks' gestation), CHF worsened. Because the cervix was unfavorable for a vaginal delivery, a cesarean section was planned. The patient was then taken to the operating room electively, and an opioid-based general anesthetic was administered. Both mother and infant did well. This case is presented because the physiology of the patient's lesion and her unusual social history presented challenges for her anesthetic management.

The proposed DDFS-driven mixing-DAC consists of several parallel-connected Gilbert cells driven directly by the binary and thermometer DDFS data compromise between power-dissipation and harmonic-rejection performance is achieved with 5b binary LSBs and 5b thermometer MSBs segmented mixing-DAC. The 2.8-to-3.2 GHz DDFS sampling frequency is selected such that it provides in excess of two samples per cycle up to 1 GHz, while the LO sampling spurs (fsplusmnfL0) are always outside the receiver desired frequency band. It is dynamically adjusted for each received channel to minimize in-band DDFS induced spurs.

A digital low-IF receiver for satellite TV applications was realized in 110 nm CMOS taking advantage of high speed and moderate resolution ADCs and high digital processing power available in nanometer CMOS. A discrete gain step signal path and a digital power level measurement together with a digital AGC loop implementation resulted in lower receiver area and power and a smaller noise figure penalty. Image rejection in excess of 50 dB was achieved by using a continuous digital I/Q mismatch correction engine that relaxes the matching requirements on the analog front-end and thus reduces the occupied die area. A dynamic digital clock frequency management algorithm was implemented to avoid receiver de-sensitization due to digitally coupled in-band spurs. SoC specifications include: 0.2 dB implementation loss

A fully-integrated 0.13 μm CMOS ring oscillator based PLL for digital low-IF DVB-S/S2 satellite TV tuner is presented. An attenuator loop filter reduces the oscillator gain, helping both front-end noise and spur rejection, while a noiseless resistor multiplication feed-forward architecture allows the on-chip integration of the loop filter capacitance. Eliminating oscillator inductors lead to a significant die area reduction and a low sensitivity to magnetic coupling, allowing the integration of a large digital core on the same die with the sensitive RF front-end. A multi-regulator biasing architecture was used to minimize the supply spur injection. PLL specifications include

A fully-integrated digital low-IF DVB-S/DVB-S2 satellite TV tuner was realized in 0.13 μm CMOS. It uses a first analog down-conversion to a sliding low-IF, followed by digitization, a second digital mixing to baseband and digital channel selection. Performing more signal processing in the digital domain lead to a relaxation of the RF front-end specifications, allowing its CMOS implementation. The digital low-IF architecture provides a digital power estimation and allows the use of a discrete-step AGC loop that results in a lower noise and linearity degradation in comparison with continuous AGC loops. Digital calibration is used throughout the DVB tuner, minimizing the gain variation over corners and relaxing the noise and linearity constraints. Partitioning the DVB-S2 receiver into a front-end tuner IC built in a mixed-signal CMOS process and a back-end demodulator and MPEG processor IC implemented in a straight digital CMOS process minimizes the receiver cost

A first low-IF fully-integrated tuner for DBS satellite TV applications was realized in 0.13 mum CMOS. A wide bandwidth, ring oscillator integer-N frequency synthesizer having a large frequency step was used to down-convert a cluster of channels to a coarsely defined low-IF frequency, while the second down-conversion to base band was performed in the digital domain. Eliminating the oscillator inductors has reduced the parasitic magnetic coupling from the digital circuitry, allowing single-chip tuner-demodulator integration

A digital low-IF fully-integrated dual tuner for DVB-S2 satellite TV applications was realized in 0.11 μm CMOS. It provides baseband digital I/Q outputs for a demodulator-on-host back-end processor. A wide bandwidth ring oscillator based frequency synthesizer having a large frequency step was used to down-convert a cluster of channels to a sliding low-IF frequency, while the second down-conversion to baseband was performed in the digital domain. The low-IF architecture allows a discrete AGC loop, while avoiding 1/f noise and DC offset issues. Eliminating the VCO tank inductors minimizes frequency pulling and parasitic coupling to front-end LNA, allowing the integration of a large digital core on the same die with the sensitive RF front-end.

The first low-IF fully-integrated tuner for DBS satellite TV applications was realized in 0.13 /spl mu/m CMOS. A wideband ring oscillator based frequency synthesizer having a large frequency step was used to down-convert a cluster of channels to a coarsely defined low-IF frequency, while the second down-conversion to baseband was performed in the digital domain. Eliminating the oscillator inductors has reduced the parasitic magnetic coupling, allowing a single-chip integration of the sensitive tuner and the noisy digital demodulator. A significant die area reduction was achieved by using a single oscillator to cover the entire satellite TV spectrum, while a noise attenuator was cascaded with the PLL loop filter to reduce the equivalent tuning gain.

A fully integrated 0.13mum CMOS ring-oscillator-based PLL for low-IF single-chip DBS satellite tuner-demodulator IC is presented. A noise-attenuating loop filter reduces the oscillator gain, helping both front-end noise and spur rejection and allowing the on-chip integration of the filter capacitance. The PLL shows

Bidirectional adaptive body bias (ABB) is used to compensate for die-to-die parameter variations by applying an optimum pMOS and nMOS body bias voltage to each die which maximizes the die frequency subject to a power constraint. Measurements on a 150 nm CMOS test chip which incorporates on-chip ABB, show that ABB reduces variation in die frequency by a factor of seven, while improving the die acceptance rate. An enhancement of this technique, that compensates for within-die parameter variations as well, increases the number of dies accepted in the highest frequency bin. ABB is therefore shown to provide bin split improvement in the presence of increasing process parameter variations.

As technology scales, subthreshold leakage currents grow exponentially and become an increasingly large component of total power dissipation. CAD tools to help model and manage subthreshold leakage currents will be needed for developing ultra low power and high performance integrated circuits. This paper gives an overview of current research to control leakage currents, with an emphasis on areas where CAD improvements will be needed. The first part of the paper explores techniques to model subthreshold leakage currents at the device, circuit, and system levels. Next, circuit techniques such as source biasing, dual V/sub t/ partitioning, MTCMOS, and VTCMOS are described. These techniques reduce leakage currents during standby states and minimize power consumption. This paper also explores ways to reduce total active power by limiting leakage currents and optimally trading off between dynamic and leakage power components.

As technology scales, subthreshold leakage currents grow exponentially and become an increasingly large component of total power dissipation. CAD tools to help model and manage subthreshold leakage currents will be needed for developing ultra low power and high performance integrated circuits. This paper gives an overview of current research to control leakage currents, with an emphasis on areas where CAD improvements will be needed. The first part of the paper explores techniques to model subthreshold leakage currents at the device, circuit, and system levels. Next, circuit techniques such as source biasing, dual Vt partitioning, MTCMOS, and VTCMOS are described. These techniques reduce leakage currents during standby states and minimize power consumption. This paper also explores ways to reduce total active power by limiting leakage currents and optimally trading off between dynamic and leakage power components.

Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3), an isoform of the intracellular Ca2+pump that has been shown to mediate endothelium-dependent relaxation of vascular smooth muscle, is also expressed in tracheal epithelium. To determine its possible role in regulation of airway mechanical function, we compared tracheal contractility in gene-targeted mice deficient in SERCA3 (SERCA3−) with that in wild-type tracheae. Cumulative addition of ACh elicited concentration-dependent increases in isometric force (ED50= 2 μM, maximum force = 8 mN/mm2) that were identical in SERCA3−and wild-type tracheae. After ACh stimulation, substance P (SP) elicited a transient relaxation (42.6 ± 3.2%, n = 28) in both tracheae. However, the rate of relaxation was significantly ( P < 0.04, n = 9) more rapid in the wild-type [half-time ( t½) = 34.3 s] than in the SERCA3−( t½= 61.6 s) trachea. The SP relaxation was reduced by rubbing the trachea, indicative of epithelial cell involvement. This was verified using a perfused trachea preparation. SP in the outside medium had no effect, whereas SP in the perfusate bathing the epithelial side elicited a relaxation. Nitric oxide synthase inhibition (0.2 mM Nω-nitro-l-arginine) reduced the SP relaxation by 36.5 ± 12.5%, whereas the SP effect was abolished by eicosanoid inhibition (10 μM indomethacin). ATP also elicited an epithelium-dependent relaxation similar to SP but with a more rapid relaxation in the SERCA3−trachea than in the wild-type trachea. Our results indicate that SERCA3 gene ablation does not directly affect smooth muscle, which is consistent with the distribution of the isoform, but suggest that SERCA3 plays a role in epithelial cell modulation of airway smooth muscle function.

Multi-threshold CMOS is a popular circuit style that will provide high performance and low power operation. Optimally sizing the gating sleep transistor to provide adequate performance is difficult because the overall delay characteristics are strongly dependent on the discharge patterns of internal gates. This paper proposes a methodology for sizing the sleep transistor for a large module based on mutual exclusive discharge patterns of internal blocks. This algorithm can be applied at all levels of a circuit hierarchy, where the internal blocks can represent transistors, cells within an array, or entire modules. This methodology will give an upper bound for the sleep transistor size required to meet any performance constraint.

Multi-threshold CMOS is an increasingly popular circuitapproach that enables high performance and low power operation.However, no methodologies have been developed to size the highV{t} sleep transistor in an intelligent manner that trades off area andperformance. In fact, many attempts at sizing the sleep transistorwithout close consideration of input vector patterns or internalstructures can lead to large overestimates or large underestimatesin sleep transistor sizing. This paper describes some of the issuesinvolved in sizing transistors for MTCMOS and also introduces avariable breakpoint switch level simulator that can rapidly calculatedelay in MTCMOS circuits as functions of design variablessuch as V{dd}, V{t}, and sleep transistor sizing.

The MIT remote microscope is a telemicroscopy system that allows users to remotely control and view a microscope over the internet with a graphical interface that runs on an ordinary workstation computer. The microscope server consists of an automated Zeiss microscope that is controlled by a personal computer, while the client interface is implemented with custom software developed at MIT. The system was designed primarily to provide remote inspection capabilities for semiconductor researchers during the remote fabrication of integrated circuits, but can also be used as a general purpose instrument for remote inspections. The remote microscope also allows any number of clients to simultaneously view the microscope in a conference inspection mode, enabling collaboration opportunities among distant viewers. Because clients require no special hardware, the internet remote microscope is extremely accessible and easy to use, yet provides powerful remote inspection capabilities, collaboration opportunities, and easy access to hard to reach locations such as clean room environments for semiconductor processing.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Mivacurium is metabolized by plasma cholinesterase catalyzed ester hydrolysis. Acetylcholinesterase antagonists used in the reversal of muscle relaxation may also inhibit plasma cholinesterase and, therefore, delay the hydrolysis of mivacurium. The clinical interaction between acetylcholinesterase antagonists and mivacurium induced neuromuscular blockade was studied.Intraoperative muscle relaxation was maintained with a mivacurium infusion to achieve a constant intense block (first twitch, T1, 2-3% of control). Patients were randomly divided into three groups. Patients in Group 1 received no anticholinesterase, in Group 2 neostigmine 0.07 mg.kg-1, and in Group 3 edrophonium 1 mg.kg-1. The times between termination of the mivacurium infusion (Group 1) or the administration of the anticholinesterase (Groups 2 and 3) to 25%, 50%, 75% and 95% T1 recovery, and to 50%, 70% and 90% recovery in the ratio, T4/T1 (TR) were recorded.In the neostigmine Group, T1 recovery to 25%, 50% and 75% (2.32 +/- 1.41, 3.90 +/- 1.85 and 6.88 +/- 2.66 min) was accelerated compared with control (3.36 +/- 1.34, 5.78 +/- 2.22, and 8.58 +/- 3.60, and), but recovery to 95% (18.53 +/- 9.09 vs 13.29 +/- 5.24 min) was delayed. Also, TR recovery to 50%, 70%, and 90% was slower (14.47 +/- 8.73, 21.25 +/- 11.06 and 31.37 +/- 12.11 min vs 11.75 +/- 3.74, 13.78 +/- 4.39 and 17.86 +/- 6.44 min). However, all T1 and TR recovery times were decreased in the edrophonium group (0.88 +/- 0.51, 2.00 +/- 1.50, 4.97 +/- 2.96, and 9.35 +/- 5.24 min for T1 and 6.86 +/- 3.93, 9.05 +/- 4.51 and 12.24 +/- 6.66 min for TR).Neostigmine reversal of intense mivacurium neuromuscular block should be avoided, as this may result in prolongation of the block.

BACKGROUND Previous studies have shown that pulse oximeters whose sensors are positioned improperly may yield erroneously low saturation (SpO2) values on normoxemic subjects. The behavior of oximeters with malpositioned sensors during hypoxemia has not been studied. The current study is aimed at determining the behavior of several different pulse oximeters over a wide range of arterial oxygen saturation (SaO2). METHODS In each of 12 healthy volunteers, a radial artery cannula was inserted, and eight different pulse oximeters, five of which had malpositioned sensors, were applied. Subjects breathed controlled mixtures of nitrogen and oxygen to slowly vary their SaO2 from 100% to 70%. Arterial blood samples were analyzed and pulse oximeter data were recorded at five stable SaO2 values for each subject. RESULTS The oximeters with malpositioned sensors vary greatly in their behavior, depending on both the actual SaO2 and the manufacturer and model. One oximeter underestimated saturation at all SaO2 values, while three others underestimated at high SaO2 and overestimated at low SaO2. Linear regression analysis shows a decrease in the slope of SpO2 versus SaO2 in most cases, indicating a loss of sensitivity to SaO2 changes. Between-subject variation in response curves was significant. CONCLUSIONS The calibration curves of the pulse oximeters studied were changed greatly by sensor malpositioning. At low SaO2 values, these changes could cause the oximeter to indicate that a patient was only mildly hypoxemic when, in fact, hypoxemia was profound. It is recommended that sensor position be checked frequently and that inaccessible sensor locations be avoided whenever possible.

Rotational functions of thirty-five compounds have been extensively and systematically studied by employing the molecular-orbital-based molecular mechanics (MOMM) approach. Various pathways have been examined and transition states identified. Comparisons were made between experimental and theoretical values for structures and rotational barriers. Hindered rotational transition-state geometries were calculated to be nonplanar, with significantly distorted aryl rings.

The structures of S 4 2+ and S 4 2− have been investigated by ab initio calculations using the GAUSSIAN 70 system of programs and the 44-31G basis set. Electronic singlet states of the square form and three possible conformations of the chain structure were examined for both ions, and the singlet rectangle form of S 4 2− was also investigated. The anti chain form of S 4 2+ was found to be 78.3 kJ mol − more stable than the square form, in contrast to previous experimental data. S 4 2− is predicted to adopt the chain structure with the anti conformation.

The conformational characteristics of allyl alcohol were fully investigated by the ab initio method using various basis sets. The results indicate that, in the gas phase, the molecule exists in a number of conformations through rotations about the CCOH and the CCCO bond. The GE ′ ( gauche -CCOH and eclipsed′-CCCH) and GC ( gauche -CCOH and cis -CCCO) forms are the predominant species while the other three conformations ( G′E′ : gauche ′-CCOH and eclipsed′-CCCH; TE ′: trans -CCOH and eclipsed′-CCCH; and TC : trans -CCOH and cis -CCCO) are slightly less stable. Comparisons with previous experimental and theoretical results are made and rationale for the conformational characteristics is explored. Structural analysis does not support the view that intramolecular hydrogen bonding is the important factor in determining the stable conformations.

The influence of electronegative substituents on the N ′-methyl group of nicotine upon the conformation of the pyrrolidine ring has been evaluated by the exact analysis of the high field 1 H NMR spectra of nicotine ( 1 ), N ′-ethylnornicotine ( 2 ), N ′-(2,2-difluoroethyl)-nornicotine ( 3 ) and N ′-(2,2,2-trifluoroethyl) nornicotine ( 4 ). The vicinal coupling constants for the pyrrolidine ring of 1–4 remain nearly constant, suggesting that as the electronegativity of the N ′-methyl substituent increases, only very small changes are seen for the C 3′ —C 4′ —C 5′ —N′ and the C 2′ —C 3′ —C 4′ —C 5′ dihedral angles. Substitution on the N ′-methyl group appears to have little effect on the orientation of the pyridyl ring with respect to the pyrrolidine ring. Ab initio calculations have been performed on the analogous 2-substituted diethylamines (diethylamine, N -ethyl-2-fluoroethylamine, N -ethyl-2,2-difluoroamine, and N -ehtyl-2,2,2-trifluoroethylamine) which constitute substructure models of 1–4 . These calculations confirm the NMR results in that they both indicate little, if any, effects on the rotational barriers and conformational energy profiles as a function of number of fluorine atoms.