gebhart/patrepeval huggingface dataset:
Practical Problems With Aerosol Therapy in COPD (2006)

Inhaled aerosol drugs commonly used by patients with chronic obstructive pulmonary disease include short-acting and long-acting bronchodilators, as well as corticosteroids. These agents are available in a variety of inhaler devices, which include metered-dose inhalers (MDI), breath-actuated MDIs, nebulizers, and, currently, 5 different models of dry powder inhaler (DPI). There is evidence to suggest that multiple inhaler types cause confusion among patients and increase errors in patient use. Problems with MDIs include failure to coordinate inhalation with actuation of the MDI, inadequate breath-hold, and inappropriately fast inspiratory flow. Lack of a dose counter makes determining the number of remaining doses in an MDI problematic. Patient misuse of MDIs is compounded by lack of knowledge of correct use among health-care professionals. Several factors often seen with elderly patients have been identified as predictive of incorrect use of MDIs. These include mental-state scores, hand strength, and ideomotor dyspraxia. Holding chambers and spacers are partially intended to reduce the need for inhalation-actuation coordination with MDI use. However, such add-on devices can be subject to incorrect assembly. Possible delays between MDI actuation and inhalation, rapid inspiration, chamber electrostatic charge, and firing multiple puffs into the chamber can all reduce the availability of inhaled drug. Because they are breath-actuated, DPIs remove the need for inhalation-actuation synchrony, but there is evidence that patient errors in use of DPIs may be similar to those with MDIs. One of the biggest problems is loading and priming the DPI for use, and this may be due to the fact that every DPI model in current use is different. Medical personnel's knowledge of correct DPI use has also been shown to be lacking. The optimum inhalation profiles are different for the various DPIs, but, generally, chronic obstructive pulmonary disease patients have been shown to achieve a minimum therapeutic dose, although the inhaled amount may be suboptimal. A limitation of DPIs that have multidose powder reservoirs (eg, the Turbuhaler) is ambient humidity, which can reduce the released dose. Small-volume nebulizers are limited by bulk, treatment time, and variable performance, but are easy for patients to use. Important features identified by patients for an ideal inhaler are ease of use during an attack, dose counter, and general ease of use and learning. A breath-actuated-pMDI, such as the Autohaler, ranked at the top of inhaler preference in a study of 100 patients with airflow obstruction, compared to DPIs and MDIs. Short of a universal simple inhaler, patient and caregiver education remains the best solution to correct patient errors in use.
Flecainide-induced Torsades de Pointes: Case Report and Review of Literature (2015)

Several antiarrhythmic drugs are prone to cause QT interval prolongation and torsades de pointes (TDP). Predisposing risk factors include congenital channelopathies, severe bradycardia, drugs, and hypokalemia. Individual genetic variation and drug metabolism exaggerate susceptibility to adverse reactions. These proarrhythmic effects create a deficit in the repolarization reserve and prolong action potential duration, resulting in early afterdepolarizations, which promote a reentry circuit. Flecainide, a class IC drug, also exhibits inhibitory actions on the K(+) channels, causing QT interval prolongation. We identified six cases of flecainide-induced TDP in the literature. Most patients had other predisposing factors. Bradycardia was present in all cases. Our case demonstrates two arrhythmias caused by flecainide: atrial flutter with 1:1 atrioventricular conduction and TDP. Both arrhythmias developed in the absence of hypokalemia, with the use of other drugs that prolong QT interval, or genetic predisposition. Therefore, this is purely a drug effect. This case report illustrates a rare but serious proarrhythmic property of flecainide observed particularly in women.
Construction, properties and specific fluorescent labeling of a bovine prothrombin mutant engineered with a free C-terminal cysteine (1996)

To define the role of phosphatidylserine-induced conformational changes in prothrombin activation during blood coagulation, a recombinant bovine prothrombin was constructed, characterized and shown to have a globally native-like conformation. We introduced a cysteine to replace the penultimate residue (Gly581) of a previously constructed active site mutant, and expressed the double mutant in Chinese hamster ovary cells at the level of 0.6 microgram/ml of cell culture medium. Specific labeling with fluorescein maleimide was accomplished by limited reduction with dithiothreitol to free the engineered cysteine while maintaining the native-like functional properties of the molecule. The average stoichiometry of labeling was 0.84 probe/protein. The location of the probe at the C-terminus was confirmed by proteolysis by native thrombin, by Taipan venom, and by carboxypeptidase Y. Both the double mutant and labeled prothrombin could be activated by snake venoms and the prothrombinase but, as expected, the double mutant meizothrombin did not autolyze as does native meizothrombin. Thus, for the first time, a native-like but specifically labeled prothrombin has been constructed. This molecule will be an essential tool for elucidating the structural role of membranes during prothrombin activation. In addition, the methods described might be usefully applied to labeling of an odd, engineered cysteine in other disulfide bond-containing proteins.
A DC-DC charge pump design based on voltage doublers (2001)

A novel organization of switched capacitor charge pump circuits based on voltage doubler structures is presented in this paper. Each voltage doubler takes a dc input and outputs a doubled dc voltage. By cascading n voltage doublers the output voltage increases up to 2/sup n/ times. A two-phase voltage doubler and a multiphase voltage doubler (MPVD) structures are discussed and design considerations are presented. A simulator working in the Q-V realm was used for simplified circuit level simulation. In order to evaluate the power delivered by a charge pump, a resistive load is attached to the output of the charge pump and an equivalent capacitance is evaluated. A comparison of the voltage doubler circuits with Dickson charge pump and Makowski's voltage multiplier is presented in terms of the area requirements, the voltage gain, and the power level. This paper also identifies optimum loading conditions for different configurations of the charge pumps. Design guidelines for the desired voltage and power levels are discussed. A two-stage MPVD was fabricated using MOSIS 2.0-/spl mu/m CMOS technology. It was designed with internal frequency regulation to reduce power consumption under no load condition.
An Immunotherapeutic Program for the Treatment of Nicotine Addiction:  Hapten Design and Synthesis (2001)

People continue to smoke and use tobacco products despite well-established hazardous consequences. The most contributing factor is the addictive nature of nicotine. There is no highly effective treatment for the problem of nicotine dependence. Immunotherapy offers an alternative to conventional approaches. The chemistry necessary for a comprehensive immunopharmacological program is presented. Haptens for the generation of antibodies specific for naturally occurring (S)-nicotine, (S)- and (R)-nornicotine, and the metabolite (S)-cotinine were prepared with high optical purity. Preliminary data for antinicotine antibodies are reported.
Experimental Support for Planar Pseudopericyclic Transition States in Thermal Cheletropic Decarbonylations (2004)

Low-temperature crystal structures of three pyrrolediones (3-5) and a furandione (9) were obtained and compared to structurally related compounds that cannot undergo decarbonylation. Systematic trends in bond lengths and angles are consistent with distortions along the reaction coordinate, in accord with the structure correlation principle of Dunitz. Since the pyrroledione and furandione rings in 3-5 and 9 are planar, these ground-state geometries prefigure the calculated planar, pseudopericyclic transition states.
A general high-efficiency procedure for production of microcell hybrids. (1981)

The relative efficiency of microcell-mediated chromosome transfer vs. somatic cell hybridization has been determined. The prolonged mitotic arrest generally used to micronucleate donor cells also reduced the fusion efficiency to 1/10th-1/5th of that in whole cell hybridizations. Here we report an alternative micronucleation protocol, involving sequential treatment of the donor cells with Colcemid and cytochalasin B, which yielded micronucleated cells that hybridized with the same efficiency as whole cells. The enucleation, purification, and fusion steps of the microcell procedure have also been refined. By using these modifications the practical yield of microcell hybrid clones can be increased 50- to 100-fold.
Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs (2006)

Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs. None of the markers in CRHR2 was associated with obesity-type traits in cattle, which is consistent with findings in human. Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.
Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy (2005)

Age-related maculopathy (ARM) is a leading cause of visual impairment in elderly Americans and is a complex genetic disorder. Hypothesized pathways for the etiology of ARM include cholesterol and lipoprotein metabolism and transport, extracellular matrix integrity, oxidative stress and inflammatory/immunologic processes. This study investigates 21 polymorphisms within 15 candidate genes whose products function within these pathways by performing family and case-control genetic association studies using clearly affected familial cases (n=338 families, 796 individuals), clearly affected, unrelated sporadic cases (n=196) and clearly unaffected, unrelated controls (n=120). Two genes demonstrated significant association with ARM status. A Met299Val variant in the elongation of very long chain fatty acids-like 4 (ELOVL4) gene was significantly associated with ARM in the case-control allele (P=0.001), case-control genotype (P=0.001) and case-control family (P<0.0001) tests. A Tyr402His variant in exon 9 in the complement factor H (CFH) gene was also significantly associated with ARM in the case-control allele (P<0.0001), case-control genotype (P<0.0001) and case-control family (P<0.0001) tests. All of these results remain significant after adjusting for false discovery rates to control for the impact of multiple testing. In addition, the CFH variant appears to play a role in exudative and atrophic disease, whereas the ELOVL4 variant may play a greater role in exudative disease in our population. These results support a potential role for multiple pathways in the etiology of ARM, including pathways involved with fatty acid biosynthesis and the complement system.
Autonomous navigation of mobile agents using RFID-enabled space partitions (2008)

Existing techniques for autonomous indoor navigation are often environment-specific and thus limited in terms of their applicability. In this paper, we take a fundamentally different approach to indoor navigation and propose an active environment based navigation system. We argue that for a versatile navigation system the environment itself should provide spatial information. In our proposed approach, navigation is based on the concept of space partitions where the location of an agent is approximated by the closest partition. We show that Radio Frequency Identification (RFID) technology is a viable option for generating space partitions. We present a cost effective deployment strategy for passive RFID tags to construct a complete partitioning of the environment. A sparse deployment of tags leads to coarse partitioning, which in turn allows an agent to only approximate its position. We introduce a path planning algorithm that enables an agent reach its destination with a small overhead compared to the shortest path algorithm assuming precise information. Our experiments show that the deployment allows efficient path planning even under a large degree of imprecision.
Superimposed AC- and DC electric field guided deposition of a single DNA molecule along a microfabricated gap (2004)

A single DNA molecule was deposited along a two-electrode microfabricated gap, using the Composite Electric-field Guided Assembly (CEGA) method. The suggested nano-assembly technique based on a superimposed ac- and dc electric field enabled attraction of a single DNA molecule out of an extremely diluted aqueous solution (/spl sim/10 aM), subsequent stretching and deposition of the molecule along a gap formed by a pair of electrodes. The stretching of the single DNA is attributed to an electrohydrodynamic flow generated by the electric field.
Inherited Thyroxine-Binding Globulin Abnormalities in Man* (1989)

IN 1959, Beierwaltes and Robbins (1) reported a family with T4-binding globulin (TBG) excess thus recognizing for the first time the existence of inherited TBG abnormalities in man. Subsequently, the occurrence of inherited complete (2–4) and partial (5–7) TBG deficiencies were described. These three forms of TBG abnormalities (complete deficiency, partial deficiency, and excess) followed, in general, an X-chromosome-linked inheritance pattern (7–9). Because earlier studies of these subjects failed to show physical or chemical changes of their TBG (7, 10), nor circulating substances interfering with hormone binding to the molecule (4, 11), and because labeled normal TBG tracer had normal survival time when given to the affected subjects (12), it was postulated that inherited TBG defects represent either mutations of a gene controlling TBG synthesis (12) or mutations at the promoter site of the TBG gene proper (13). In the 1980s, two new inherited TBG types were described, both involving distinct ethnic groups. In 1980/1981, Dick and Watson (14, 15) reported that the low serum total T4 (TT4) concentration found in approximately 40% of Australian Aborigines was due to a TBG variant with low affinity for T4. In 1981, Daiger et al. (16, 17) reported a TBG with slow electrophoretic mobility and with isoelectric focusing (IEF) pattern exhibiting a cathodal shift in 5–16% of subjects from African and Oceanian origin. Inheritance of these two variant TBGs was shown also to be X-chromosome-linked (16, 18), suggesting that the structural gene of the molecule is located on the X-chromosome. Over the past 3 yr, five additional TBG variants were detected (19–22). Four were associated with partial TBG deficiency (19–21), and three of these were found to have high serum levels of denatured TBG (19, 20), which was measured using an antibody directed against the primary structure of the molecule. Another TBG variant had, as a sole abnormality, resistance to denaturation at high temperatures and in acid conditions (22).
Detection of explosives on skin using ambient ionization mass spectrometry (2007)

Single nanogram amounts of the explosives TNT, RDX, HMX, PETN and their mixtures were detected and identified in a few seconds on the surface of human skin without any sample preparation by desorption electrospray ionization (DESI) using a spray solution of methanol-water doped with sodium chloride to form the chloride adducts with RDX, HMX, and PETN while TNT was examined as the radical anion and tandem mass spectrometry was used to confirm the identifications.
Comparison between the surface electromyogram of the quadriceps surrounding the knees of healthy women and the knees of women with osteoarthrosis. (1994)

The purpose of this study was to compare the electromyographic (EMG) activity of the quadriceps femoris (QF) muscles of women with osteoarthrosis (OA) of the knee with the EMG activity of the QF muscles of healthy women. To this end, a total of 14 subjects attended a single test session during which full-wave rectified surface electromyograms were recorded from the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) muscles during maximum voluntary isometric quadriceps contractions performed at knee angles of 30 degrees and 60 degrees flexion. A comparison of the resultant normalized peak EMG ratios using independent t-tests demonstrated significantly higher composite QF muscle activation for the osteoarthrotic subjects (p < 0.05). A higher RF activation also differentiated the two groups. The findings raise the possibility of a direct correlation between abnormal activation of the QF and joint status. They also suggest that patients with knee OA may benefit functionally from rehabilitation designed to improve QF coordination and endurance, and not merely strength.
Tryptase‐like activity in crevicular fluid from gingivitis and periodontitis patients (1989)

Crevicular fluid was collected from gingivitis and periodontitis patients on filter paper strips and then eluted into buffer. The eluates hydrolyzed ZAlaArgArgAFC at alkaline pH and the effector response at pH 8.5 indicated serine proteinase activity. The results, particularly the substantial increase in activity produced by heparin, were suggestive of mast cell tryptase. They were also consistent with the properties of the tryptase-like enzyme identified in extracts of inflamed human gingiva (Cox and Eley, Arch Oral Biol, in press). Partial inhibition of crevicular fluid eluate activity by soybean trypsin inhibitor suggested the additional presence of a second trypsin-like enzyme which might be of host or bacterial origin.
Construction and evaluation of a robust multifeature speech/music discriminator (2002)

We report on the construction of a real-time computer system capable of distinguishing speech signals from music signals over a wide range of digital audio input. We have examined 13 features intended to measure conceptually distinct properties of speech and/or music signals, and combined them in several multidimensional classification frameworks. We provide extensive data on system performance and the cross-validated training/test setup used to evaluate the system. For the datasets currently in use, the best classifier classifies with 5.8% error on a frame-by-frame basis, and 1.4% error when integrating long (2.4 second) segments of sound.
beta-Galactosidase containing a human immunodeficiency virus protease cleavage site is cleaved and inactivated by human immunodeficiency virus protease. (1990)

A "cleavage cassette" specifying a decapeptide human immunodeficiency virus (HIV) protease cleavage site was introduced into six different locations of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in Escherichia coli. Four of these constructs retained beta-galactosidase activity despite the insertion of the cleavage cassette. Of these four constructs, one was cleaved by HIV protease, resulting in the inactivation of beta-galactosidase both in vivo and in vitro. This cleavage was inhibited by pepstatin A, a known inhibitor of HIV protease. Thus, beta-galactosidase has been converted into an easily assayed substrate for HIV protease. An analogous construct of beta-galactosidase containing a polio protease cleavage site was cleaved likewise by polio protease, suggesting that this system may be generic for monitoring cleavage by a variety of proteases.
Treatment of Allergic Rhinitis. (2010)

Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.
Compact Method for Modeling and Simulation of Memristor Devices (2011)

Abstract : A compact model and simulation methodology for chalcogenide based memristor devices is proposed. From a microprocessor design view point, it is important to be able to simulate large numbers of devices within the integrated circuit architecture in order to speed up reliably the development process. Ideally, device models would accurately describe the characteristic device behavior and would be represented by single-valued equations without requiring the need for recursive or numerically intensive solutions. With this in mind, we have developed an empirical chalcogenide compact memristor model that accurately describes all regions of operations of memristor devices employing single-valued equations.
Self‐Assembling Polyethylenimine Derivatives Mediate Efficient siRNA Delivery in Mammalian Cells (2008)

Simple and efficient: In this study, we examined the relationships between siRNA delivery efficacy and aggregating properties for different amino acid-modified polyethylenimines (PEIs). Full modification of the primary amines of PEI with tyrosine enables the polymer to self-assemble into cationic particles and to convey siRNA into mammalian cells very efficiently, even in the presence of serum.
An architecture for a multimedia teleconferencing system (1986)

We present an object-oriented architecture for a computer-based, real-time, multimedia conferencing system. This architecture divides the system into five functional areas: a multimedia shared workspace, a user interface, conference management, communications, and an information base. The structure and operation of the first four areas are modeled with object-based concepts that address design requirements identified during the development of a proof-of-concept prototype, that preceded the architecture specification. The shared workspace, the most important component, is thoroughly discussed; the other components support its realization. The modeling of workspace entities emphasizes their aggregation into composed entities and the homogeneous handling of several data media. The user interface manages uniformly the man-machine interaction for both local and remote user actions. Conference management deals with session establishment, participation, and control of multiple media floors. The communication functions replicate user actions over workspace objects in all hosts participating in a conference, matching traffic types with transmission services in the process.