cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of metabolic responses, genetic variations, and microsatellite instability in ammonia-stressed CHO cells grown in fed-batch cultures

As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10’s of milligrams to over 10’s of grams per liter. Most of these gains in productivity can be attributed to increasing cell densities within bioreactors. As such, strategies have been developed to minimize accumulation of metabolic wastes, such as lactate and ammonia. Unfortunately, neither cell growth nor biopharmaceutical production can occur without some waste metabolite accumulation. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a suboptimal culture environment, little is known about the genotoxic properties of these compounds that may lead to global genome instability. In this study, we examined the effects of high and moderate extracellular ammonia on the physiology and genomic integrity of Chinese hamster ovary (CHO) cells. Through whole genome sequencing, we discovered 2394 variant sites within functional genes comprised of both single nucleotide polymorphisms and insertion/deletion mutations as a result of ammonia stress with high or moderate impact on functional genes. Furthermore, several of these de novo mutations were found in genes whose functions are to maintain genome stability, such as Tp53, Tnfsf11, Brca1, as well as Nfkb1. Furthermore, we characterized microsatellite content of the cultures using the CriGri-PICR Chinese hamster genome assembly and discovered an abundance of microsatellite loci that are not replicated faithfully in the ammonia-stressed cultures. Unfaithful replication of these loci is a signature of microsatellite instability. With rigorous filtering, we found 124 candidate microsatellite loci that may be suitable for further investigation to determine whether these loci may be reliable biomarkers to predict genome instability in CHO cultures. This study advances our knowledge with regards to the effects of ammonia accumulation on CHO cell culture performance by identifying ammonia-sensitive genes linked to genome stability and lays the foundation for the development of a new diagnostic tool for assessing genome stability.
Graduate Education for a New Sustainable Urban Systems Science: Designing a New PhD Curriculum Integrating Sustainability Science and Urban Science

This is a report on the discussions held during an NSF SUS conference “Graduate Education for a New Sustainable Urban Systems Science: Designing a New PhD Curriculum Integrating Sustainability Science and Urban Science”. The conference was motivated by the call made by the NSF for “…developing the next generation of sustainable urban systems science.” (NSF 2018) The conference was premised on the assumption that such continued development will require the training of new generations of urban sustainability scientists, and that both the content and manner of training will be different from established degree programs.
Examining DIR/Floortime™ as a Treatment for Children With Autism Spectrum Disorders: A Review of Research and Theory

Purpose:To review and assess theory and research supporting DIR/Floortime™, a method proposed for treatment of young children with autism spectrum disorders (ASD).Methods:Published materials descri...
SN1987A: The Birth of a Supernova Remnant

This grant was intended to support the development of theoretical models needed to interpret and understand the observations by the Hubble Space Telescope and the Chandra X-ray telescope of the rapidly developing remnant of Supernova 1987A. In addition, we carried out a few investigations of related topics. The project was spectacularly successful. The models that we developed provide the definitive framework for predicting and interpreting this phenomenon. Following is a list of publications based on our work. Some of these papers include results of both theoretical modeling supported by this project and also analysis of data supported by the Space Telescope Science Institute and the Chandra X-ray Observatory. We first list papers published in refereed journals, then conference proceedings and book chapters, and also an educational web site.
Adding by Subtracting: How Limited Scope Agreements for Dispute Resolution Representation Can Increase Access to Attorney Services

Given the complexities of the legal system, pro se litigants understandably have difficulties navigating the legal labyrinth, and empirical evidence confirms that unrepresented parties rarely prevail in litigation. In other words, pro se litigants often do not have true “access to justice.” One effort to increase access to justice for those otherwise unable to afford legal services has been in the area of unbundled legal services, or limited scope representation. Traditionally, providers of unbundled services have focused on litigation activities, such as document drafting and hearing representation. These actions, however, simply move a pro se litigant along in the process without ever helping those parties resolve the real issues facing them. This Article brings a new suggestion to the literature dealing with limited scope representation by urging counsel and clients to use unbundled services to settle cases – not prolong them. Through the use of effective client counseling, attorneys and clients should spend funds for limited scope representation on alternative dispute resolution services, including negotiation counseling, negotiation representation, collaborative law, cooperative law, mediation counseling, mediation representation, and arbitration representation. These types of services have the means to truly achieve client interests and solve disputes, thus making them the most economical choice for clients. Attorneys, court systems, and pro bono groups also benefit from the proposal by giving increased work to attorneys, lightening court dockets, and offering manageable pro bono opportunities.
Lionel Fox and the International Penal and Penitentiary Commission

In August, 1946, the International Penal and Penitentiary Commission met in Berne. The war had interrupted its labor and this was the first time since 1938 that the Commission had been able to convene. In the meanwhile, its president, Giovanni Novelli, had died. Its vice-president Alexander Paterson was incapacitated by an illness which was to terminate in his death the following year. Mr. Lionel Fox, chairman of the Prison Commission of England and Wales, came to the meeting as one of the British delegates, the other being Miss Margery Fry, and when he was elected to chair the sessions, he noted that this was the first time that he had been chosen to preside over an international meeting.
Morphology of Photopolymerized End-Linked Poly(ethylene glycol) Hydrogels by Small-Angle X-ray Scattering

Because of the biocompatibility of poly(ethylene glycol) (PEG), PEG-based hydrogels have attracted considerable interest for use as biomaterials in tissue engineering applications. In this work, we show that PEG-based hydrogels prepared by photopolymerization of PEG macromonomers functionalized with either acrylate or acrylamide end-groups generate networks with cross-link junctions of high functionality. Although the cross-link functionality is not well controlled, the resultant networks are sufficiently well ordered to generate a distinct correlation peak in the small-angle X-ray scattering (SAXS) related to the distance between cross-link junctions within the PEG network. The cross-link spacing is a useful probe of the PEG chain conformation within the hydrogel and ranges from approximately 6 to 16 nm, dependent upon both the volume fraction of polymer and the molecular weight of the PEG macromonomers. The presence of a peak in the scattering of photopolymerized PEG networks is also correlated with an ...
Improved Four-Stage Accel-Decel Production of Low Energy Highly Stripped Heavy Ions

The two model MP Tandem Van de Graaff accelerators at Brookhaven have been used in a four-stage acceldecel configuration to produce highly stripped low energy heavy ions. The performance in this mode of operation has now been substantially improved by modifications of the second accelerator. The inclined field acceleration tube electrodes at the exit of this accelerator were replaced by straight electrodes, the vacuum was improved and the maximum negative terminal potential was increased. Higher intensity beams of heavier highly stripped ions can now be produced at lower energies than before.
Digital library support for scholarly research

Taking an iterative design approach, a user-centered field study investigated requirements to support remote scholarship. By observing scholars' use of a library special collection, a requirements analysis study established a model of scholarly inquiry and specified the initial design requirements for a web-based research library. Upon implementing a prototype providing intelligent information retrieval capabilities to access the full text and page image representations of twenty-eight books from the special collection, its use was evaluated by observing scholars conducting research remotely. Supporting the evaluation study, a web-based field laboratory administered survey instruments and instruction to participants. Promotional activities attracted an international group of scholars to use the prototype and participate in its evaluation. The results provide insight into web-based inquiry and requirements for remotely supporting scholarship.
Cloning and characterization of the cDNA and gene encoding the γ-subunit of cGMP-phosphodiesterase in canine retinal rod photoreceptor cells

Abstract Rod photoreceptor cyclic GMP-phosphodiesterase (cGMP-PDE) is one of the key enzymes of the visual phototransduction cascade in the vertebrate retina. The enzyme is composed of α- and β-catalytic subunits and two identical inhibitory γ-subunits. A defect in any of the subunits may potentially alter the activity of the enzyme, leading to aberration in the visual phototransduction. We have cloned and sequenced both the cDNA and gene for the canine γ-subunit of cGMP-PDE (PDEγ). The 952-bp cDNA has a coding region of 261 bp which is very similar to those of the PDEγ cDNAs from human, mouse and bovine retinas. Among the 87 amino acids encoded by the transcribed region, differences in only three residues located within the first 17 amino acids were identified. The carboxyl terminus of PDEγ, involved in interaction with the catalytic subunits of cGMP-PDE and the a-subunit of transducin, is conserved through evolution. The single polyadenylation signal (AATAAA) present in human and bovine PDEγ cDNAs is replaced by AGTAAA in the canine sequence. The canine gene (2.8 kb) consists of four exons and is much smaller than the human gene (6 kb). The larger size of the human gene is primarily due to the presence of AluI repetitive elements in its first two introns.
252Cf-plasma desorption time-of-flight mass spectrometry☆

Abstract Details of a 252 Cf-plasma desorption time-of-flight mass spectrometer are described. Fission fragments from 252 Cf decay are used to produce rapid heating and ionization in thin solid samples. Time-of-flight measurements are made by single ion counting using fast pulse electronics techniques. An electrostatic particle guide is used to produce an 8-m flight path for high-resolution mass measurements.
Nucleation and Growth of Microtubules from γ-Tubulin-Functionalized Gold Surfaces

Microtubules are protein filaments that are emerging as potential building blocks in manufacturing nanoscale structures and systems such as interconnecting nanowires. Future development in using microtubules necessitates a control of their nucleation and growth. We report the controlled nucleation and growth of microtubules from functionalized gold on a hydrophilic oxidized silicon wafer. The gold substrate is functionalized with γ-tubulin, a natural nucleating agent for microtubule growth. We show that the attached γ-tubulin retains its biological functionality and leads to nucleation and assembly of microtubules from the functionalized gold surface. We also analyze the interplay between the geometry of the nucleating substrates and the morphology of microtubules arrays and networks grown from them. We consider two geometrical arrangements of the substrates: (a) a square lattice of small gold pads on a hydrophilic oxidized silicon wafer and (b) a large flat surface. Fluorescence microscopy and scanning electron microscopy are employed to provide a detailed characterization of the length and morphology of the nucleated and grown microtubules. The observed microtubule morphologies are modeled, analyzed and discussed within the context of reaction-diffusion and nucleation controlled processes.
Reinforcement of inhibition.

A differential-reinforcement-of-other-behavior (DRO) schedule with trials and delayed reinforcement was investigated. Periodically a wheel was briefly available to rats, followed six seconds later by brief availability of a bar. Variable-ratio food reinforcement of wheel turns was adjusted to give 95% turns. After variable-ratio-five reinforcement of bar presses produced 100% pressing, then separate ratio schedules were used for presses following turns (turn presses) and presses following nonturns (nonturn presses). Increasing nonturn-press reinforcements decreased turns, even though total reinforcements increased. Reversal by decreasing nonturn-press reinforcements raised turns, though with hysteresis. Thus food reinforcement increased nonturns even though delayed six to ten seconds after nonturns, a delay that greatly reduces response reinforcement. Those and other results indicate that the turn decrease was not due to reinforcement of competing responses. Evidence against other alternatives, and the reduction of responding by increased reinforcement, indicate that the term inhibition is appropriate for the phenomenon reinforced. Response-specific inhibition appears appropriate for this particular kind, since its effects are more specific to particular responses than Pavlovian conditioned-inhibition. Response-specific inhibition seems best considered a behavioral output comparable to responses (e.g., both reinforcible) but with important properties different from responses (e.g., different reinforcement-delay gradients).
The Renaissance Engineer: Educating Engineers in a Post-9/11 World.

Technology that fuels the economy and adds to the quality of life can also bring with it unexpected complexities. The events of 11 September bring into sharp relief some of the vulnerabilities that exist in the world, and also challenge us to re-examine the role of engineers in society. To date, the traditional responsibilities of the engineering communities in preventing future catastrophes have been defined purely in terms of technological advances. However, it is clear that engineering must go beyond pure technology to consider also the causes of vulnerabilities and examine if and how engineering can address matters that are often embedded in the social and economic fabric of society. Moreover, engineers must go beyond being technical experts who understand and consider social, financial and political factors in their work, and become leaders in all arenas of society. These expectations call for renaissance engineers and the need for a renaissance in engineering education. Recommendations to cultivate ...
Miniemulsion copolymerization of styrene–methyl methacrylate

Miniemulsion copolymerization of 50 : 50 weight fraction of styrene–methyl methacrylate monomer, using hexadecane as the cosurfactant, was carried out in both unseeded and seeded polymerizations. Effects of the hexadecane concentration and the ultrasonification time on the conversion–time curves and particle size of the final latex were investigated for unseeded polymerization. The kinetic and particle size distribution results showed that an increase in hexadecane concentration and ultrasonification time cause faster polymerization rate and smaller particle size. The mechanism of mass transport from miniemulsion droplets to polymer particles was also investigated for seeded polymerization. For this purpose a monomer miniemulsion was mixed with a fraction of a previously prepared miniemulsion latex particles prior to initiation of polymerization, using residual oil-soluble initiator in the seed latex. The concentration of hexadecane and a water-insoluble inhibitor (2,5 di-tert-butyl hydroquinone) in the miniemulsions were the main variables. Seeded polymerizations were also carried out in the presence of miniemulsion droplets containing a water-insoluble inhibitor and water-soluble initiator. The inhibitor concentration and the agitation speed during the course of polymerization were the experimental variables. The kinetic and particle size results from these seeded experiments suggested that collision between miniemulsion droplets and polymer particles may play a major role in the transport of highly water-insoluble compounds.
A Semi-implicit Numerical Scheme for Reacting Flow

An additive semi-implicit projection scheme for the simulation of unsteady combustion in two dimensions is constructed. The scheme relies on a zero-Mach number formulation of the compressible conservation equations with detailed chemistry. The governing equations are discretized in space using second-order differences and integrated in time using a semi-implicit approach. Time integration of the evolution equations for species mass fraction, thermodynamic pressure, and density is performed using a semi-implicit, nonsplit scheme that combines a second-order predictor?corrector treatment of convection and diffusion terms, and a stiff integrator for the reaction source terms. Meanwhile, the momentum equations are integrated using a second-order projection scheme. The projection scheme is based on a predictor?corrector approach that couples the evolution of the velocity and density fields in order to stabilize computations of reacting flows with large density variations. A pressure Poisson equation is inverted following both the predictor and corrector steps using a fast solver. The advantages of the stiff integration of reaction source terms are analyzed by comparing the performance of the scheme to that of a predictor?corrector scheme in which reaction and diffusion are integrated in a similar nonstiff fashion. The comparison in based on both one-dimensional (1D) unsteady tests of a premixed methane?air flame, and unsteady two-dimensional tests of the same flame interacting with a counterrotating vortex pair. In both cases, the GRImech1.2 reaction mechanism with 32 species and 177 elementary reactions is used. Computed results show that the stiff reaction scheme enables selection of larger time steps and thus leads to substantial improvement in the performance of the computations. For the present reaction mechanism and flame conditions, speedup factors of about 10 are achieved in the 1D tests and about five in two dimensions. Possible extensions of the present scheme to further improve efficiency are also discussed.
The infrared spectra of methylchloro- and methylbromodiazirine

Abstract The vapor phase infrared spectra of methylchloro- and methylbromodiazirine have been observed in the 250–4000 cm−1 region. Vibrational assignments are given to all the bands observed and all fundamentals are established with the exception of the torsion and the carbon-carbon-halogen twist and wag, which are expected to occur below 250 cm−1. The A′ vibrations exhibit A, B, or A-B hybrid type contours; however, the type-C contour expected from the A″ vibrations is not as obvious.
A PERFORMANCE EVALUATION OF HEURISTICS-BASED TEST CASE GENERATION METHODS FOR SOFTWARE BRANCH COVERAGE

Software testing is an important step in the development of complex systems. The construction of test cases using traditional methods usually requires considerable manual effort. QUEST/Ada—Query Utility Environment for Software Testing of Ada, is a prototype test case generation system that uses various heuristics-based approaches to generate test cases. The system, which is designed for unit testing, generates test cases by monitoring the branch coverage progress and intelligently modifying existing test cases to achieve additional coverage. Three heuristics-based approaches along with a random test case generation method were studied to compare their branch coverage performance. Although some constraints are imposed by the prototype, the framework provides a useful foundation for further heuristics-based test case generation research. The design of the system, the heuristic rules used in the system, and an evaluation of each rule’s performance are presented.
Accommodation to current ramps in motoneurons of fast and slow twitch motor units.

1. The response of triceps surae motoneurons to linearly rising ramps of depolarizing current injected through intracellular micropipette electrodes has been studied in cats. Most of the data were obtained in animals anesthetized with pentobarbital but some units were studied in spinal unanesthetized preparations with anemic destruction of the brain. There were no essential differences in results from the two types of preparations.2. The speed of contraction of the muscle fibers innervated by the motoneurons studied was measured following stimulation of the cell through the intracellular micropipette. Motor units could then be classified into two groups, fast twitch or type F and slow twitch or type S, on the basis of the speed of contraction of the muscle fibers innervated.3. The presence or absence of accommodation in each motoneuron was determined based on the shape of the current-latency curve obtained during passage of linearly rising depolarizing currents of widely varying slope. About one half of t...
The differential effects of body fat distribution on insulin and glucose metabolism during pregnancy

Abstract Objective: Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy. Study Design: A longitudal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese ( n = 6, waist/hip ratio n = 8, waist/hip ratio ≥0.9). Results: Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p p p p r = 0.70, p r = 0.76, p Conclusions: Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.
The symmetry groups of periodic isonemal fabrics

An isonemal fabric is a weaving in which the symmetry group is transitive on the strands. Its symmetry groups is a layer group. In this paper we determine the 21 possible layer groups which occur as symmetry groups of (2-way, 2-fold) periodic isonemal fabrics. In addition, utilizing the induced strand subgroup, we classify the fabrics into 42 symmetry types.
Self-Organizing WSN Protocol for Real-Time Communication Requirements

In this paper we propose a distributed, low-power, self-organizing MAC scheme for low-power wireless sensor and control applications. In such applications, nearly periodic traffic needs to be handled so that the communication delays are minimized and the transmission is as predictable as possible. We propose Asynchronous Random Schedules with Collision Forecast (ARS/CF) for this purpose, together with a multichannel extension based on an improved modulation scheme to improve capacity scaling of the basic ARS/CF scheme. We analyze and simulate the basic single-hop ARS/CF implementation with regard to throughput and delay when used both in single- and multi-channel settings. Finally, we consider the implementation of ARS/CF in a multi-hop setting.
Doctors for Democracy: Health Professionals in the Nepal Revolution; East African Doctors: A History of the Modern Profession; Immigrant Physicians: Former Soviet Doctors in Israel, Canada, and the United States

Doctors for Democracy: Health Professionals in the Nepal Revolution. Vincanne Adams. Cambridge and New York: Cambridge University Press, 1998. xii. 251 pp. East African Doctors:. History of the Modern Profession. John lliffe. Cambridge and New York: Cambridge University Press, 1998. xii+ 336 pp. Immigrant Physicians: Former Soviet Doctors in Israel, Canada, and the United States. Judith T. Shuval and Judith H. Bernstein. eds. Westport, CT: Praeger, 1997. + 220 pp.
Predicting Patients' Expectations of Hospital Chaplains: A Multisite Survey

OBJECTIVE To identify patient expectations regarding chaplain visitation, characteristics of patients who want to be visited by a chaplain, and what patients deem important when a chaplain visits. PARTICIPANTS AND METHODS Three weeks after discharge, 4500 eligible medical and surgical patients from hospitals in Minnesota, Arizona, and Florida were surveyed by mail to collect demographic information and expectations regarding chaplain visitation. The survey was conducted during the following time periods: Minnesota participants, April 6 until April 25, 2006; Arizona participants, October 16, 2008, until January 13, 2009; Florida participants, October 16, 2008, until January 20, 2009. Categorical variables were summarized with frequencies or percentages. Associations between responses and site were examined using χ2 tests. Multivariate logistic regression was used to assess the likelihood of wanting chaplain visitation on the basis of patient demographics and perceived importance of reasons for chaplain visitation. RESULTS About one-third of those surveyed responded from each site. Most were male, married, aged 56 years or older, and Protestant or Catholic. Of the respondents, nearly 70% reported wanting chaplain visitation, 43% were visited, and 81% indicated that visitation was important. The strongest predictor of wanting chaplain visitation was denomination vs no indicated religious affiliation (Catholic: odds ratio [OR], 8.11; 95% confidence interval [CI], 4.49-14.64; P CONCLUSION The results of this study suggest the importance medical and surgical patients place on being visited by a chaplain while they are hospitalized. Those who valued chaplains because they reminded them of God's care and presence and/or because they prayed or read scripture with them were more likely to desire a visit. Our results also suggest that being religiously affiliated is a very strong predictor of wanting chaplain visitation.
The influence of short-term firefighting activity on information processing performance

This study examined the following: effects of simulated firefighting (FF) activities under heat stress on sustained attention; whether incident rehabilitation (IR) influences performance; and relationships between performance, affect and personality. Firefighters performed ∼18 min of FF. Attention, physiological, perceptual and psychological assessments were made before and after FF, IR and recovery. IR had no effects. Self-rated Energy increased, Tiredness decreased and Anxiety increased immediately post-FF; all returned to baseline 120 min post. The immediate effect of FF was faster reaction time (RT) followed by slowing after recovery. Perceived Energy at baseline was associated (p-values < 0.05) with faster and Tiredness with slower post-FF RTs; Accuracy was unaffected. Conscientiousness was negatively associated with RT before and 120 min following FF. RTs were faster following FF, accuracy was unchanged. Higher baseline Energy/lower Tiredness were associated with faster, less variable RTs at baseli...
The relationship of active and passive smoking to carotid atherosclerosis 12-14 years later.

Abstract Background. Active and passive smoking have been found to be associated with clinical atherosclerotic disease. To explore the effects of smoking on atherogenesis, we investigated the relationship of past and current active and passive smoking to carotid atherosclerosis in middle-aged adults. Methods. The study population consisted of 2,073 middle-aged residents of Washington County, Maryland. Information on active smoking and exposure to environmental tobacco smoke (ETS) was obtained from a 1975 census and from the baseline visit of the Atherosclerosis Risk in Communities (ARIC) Study in 1987-1989. Carotid artery intimal-medial wall thickness, measured by B-mode ultrasound methods in 1987-1989, was used as an indicator of carotid atherosclerosis. Mean intimal-medial wall thickness (IMT) was adjusted for age, gender, cardiovascular risk factors, and education using multiple linear regression. Results. The lowest mean IMT was found among never smokers who had never been exposed to ETS (mean ± standard error: 0.706 ± 0.013 mm). Exposure to ETS in one or both time periods was associated with increased IMT among never smokers (ETS in 1975 only: 0.731 ± 0.022; ETS in 1987-1989 only: 0.738 ± 0.011; ETS in both periods: 0.734 ± 0.012). Active smoking in 1975 was also associated with increased IMT. The greatest mean intimal-medial wall thickness was found among persons who were current smokers in both time periods (0.807 ± 0.009). Conclusions. Both past and current passive and active smoking are associated with increased carotid intimal-medial wall thickness.
Orthotic intervention in forefoot and rearfoot strike running patterns.

Objective. To compare the differential effect of custom orthoses on the lower extremity mechanics of a forefoot and rearfoot strike pattern. Design. Fifteen subjects ran with both a forefoot and a rearfoot strike pattern with and without orthoses. Lower extremity kinematic and kinetic variables were compared between strike pattern and orthotic conditions. Background. Foot orthoses have been shown to be effective in controlling excessive rearfoot motion in rearfoot strikers. The effect of orthotic intervention on rearfoot motion in forefoot strikers has not been previously reported. Methods. Five trials were collected for each condition. Peak rearfoot eversion, eversion excursion, eversion velocity, peak inversion moment, and inversion work were compared between conditions. Kinematic variables in the sagittal plane of the rearfoot and in the frontal and sagittal plane of the knee were also determined. Results. Increased rearfoot excursions and velocities and decreased peak eversion were noted in the forefoot strike pattern compared to the rearfoot strike pattern. Orthotic intervention, however,did not significantly change rearfoot motion in either strike pattern. Reductions in internal rotation and abduction of the knee were noted with orthotic intervention. Conclusions. Foot orthoses do not differentially effect rearfoot motion of a rearfoot strike and a forefoot strike running pattern. Orthotic intervention has a larger and more systematic effect on rearfoot kinetics compared to rearfoot kinematics. Relevance
Hot embossed polyethylene through-hole chips for bead-based microfluidicdevices

Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications force cost considerations to be kept low and throughput high. As such, materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 min with the ability to scale up 4 times by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby demonstrating that the approach is compatible with high performance, real-world clinical measurements in the context of point-of-care testing.
Errors in volumetric respirometry: description of an improved microrespirometer.

Abstract 1. 1. When the capabilities for simplicity of construction and operation of the capillary volumeter are carried to extremes, certain random and constant errors appear which render the instrument unstable and insensitive. Some implications of these errors for respiration data in the literature are discussed. 2. 2. A modified microrespirometer is presented which utilizes some of the useful features of existing volumeters, but without certain of their limitations. This instrument has a capacity of 8 vessels, each calibrated to 200 μl; and volume changes, at the rate of 70 μl/hr or greater, can be measured to the nearest 1.0 μl with a precision of 2%.
Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab

Immunologists have long hypothesized that particular 'molecular addresses' govern lymphocyte entry to a given organ. In 1992, alpha4beta1 integrin was identified as the key molecule involved in homing to inflamed regions of the brain. An antibody to alpha4beta1integrin blocked paralysis in an animal model of multiple sclerosis, and the humanized monoclonal antibody natalizumab, which binds alpha4beta1 integrin, reduced relapses 66% in clinical trials in multiple sclerosis. Three months after its expedited approval by the FDA, natalizumab was removed from the market after two cases of deadly progressive multifocal leukoencephalopathy were reported among the few thousand patients who had taken this drug in those clinical trials.
Infusion of very hypertonic saline to bled rats: membrane potentials and fluid shifts.

Abstract Anesthetized rats were subjected to a moderate degree of hemorrhagic shock, lowering their mean arterial pressure to approximately 50 mm Hg for approximately 100 min. At the end of the shock period, resting skeletal muscle transmembrane potentials had depolarized from a baseline value of −82 mV to −65 mV; intracellular water had increased by 13%; and intracellular sodium and chloride contents had doubled. Eight rats were then given an infusion of very hypertonic saline (2400 mOsmole/kg, calculated osmolality) in a volume equal to only 10% of the volume of shed blood; another eight rats were given the equivalent amount of sodium and chloride in an isotonic solution (volume equal to 80% of shed blood). The mean arterial pressure in the rats that were given the very hypertonic saline returned to 81 mm Hg, compared to 55 mm Hg in the animals given normal saline. The membrane potentials in the hypertonic group polarized back to near normal— −78 mv—compared to no changes in the normal saline group. Intracellular water returned to preshock values in the hypertonic group as did intracellular sodium and chloride contents. Cellular contents in the normal saline group remained at shock levels. It was concluded that, in rats, infusion of small amounts of hypertonic saline can reverse some of the cellular abnormalities induced by hemorrhagic shock.
The economics of Third World arms imports

The international trade with weapons and its effects on the Third World are rarely mentioned in papers on international trade. This is not really surprising, given the fact that military affairs are kept very secret. Of all social science data it is probably that of the military sector which is the most scarce and unreliable. Despite these difficulties the author of the following article describes some recent trends in the international trade in major weapons and analyses their negative effects on Third World countries.
The expanding spectrum of robotic gynecologic surgery: A review

Abstract Minimally invasive surgical approaches in gynecology have evolved considerably in the last 30 years. The integration of robotic technology represents significant progression along the continuum of minimally invasive operative techniques in gynecology utilized to treat both benign and malignant conditions. Robotic systems have the potential to convert surgical procedures that we presently perform by laparotomy to laparoscopy and are currently utilized in the fields of reproductive endocrinology and fertility, gynecologic oncology and female pelvic medicine/reconstructive surgery. Robotic-assisted procedures may help overcome some of the cited limitations associated with standard laparoscopy, including longer operative times, counterintuitive and limited instrument maneuverability, and lack of formal training and/or a steep learning curve. However, a critical appraisal of robotic systems is essential due to technological limitations. These limitations include a system that is bulky and costly to maintain and does not give haptic feedback, uncertainty about the long-term outcomes following robotic surgery, and the need for a greater number of larger incisions when compared to standard laparoscopy.
Dissemination of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Pediatric Intensive Care Units

To study the growing trend of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in pediatric intensive care units (PICUs), 88 nonrepetitive ESBL-producing isolates were prospectively collected and analyzed by molecular methods during a 16-month period. The emergence and dissemination of ESBL-producing Enterobacteriaceae in PICUs are the consequence of the clonal dissemination of a few epidemic strains along with the horizontal transmission of resistance gene-carrying plasmids among bacterial organisms.
The Electrocardiogram in Infarction of the Lateral Wall of the Left Ventricle A Clinicopathologic Study

This reappraisal of the electrocardiographic manifestations of infarction of the lateral wall of the left ventricle is based on data acquired by simple and conventional technics. Categories of cases have been determined by the age of the infarct and the distribution of the lesion with respect to the circumference of the left ventricular wall and its epicardial and endocardial boundaries. Significant data have been presented in the form of illustrative diagrams and reproductions. The results do not establish a simple pattern common to all cases of infarction of the lateral wall; they do illustrate the varied yet limited electrocardiographic consequences of such lesions.
RAPID INHIBITION OF THE C-JUN PROTO-ONCOGENE EXPRESSION IN AVIAN OVIDUCT BY ESTROGEN

The c-jun proto-oncogene codes for an important component of the AP-1 transcription factor complex which regulates the expression of many genes. This paper demonstrates that the steady state c-jun mRNA level in the avian oviduct is markedly decreased to 50% of control values within 30 minutes after estrogen injection into the animals. In the avian liver, the level is rapidly increased over 10 fold. Nuclear run-off transcription analysis demonstrates that the decrease in the c-jun mRNA levels in the avian oviduct occurs at least in part at the level of transcription. These changes are reproducible in repeat experiments. This response in the avian oviduct is unique since 1) it is the first demonstration of a steroid effect on c-jun expression in any animal system, 2) the changes in c-jun mRNA occur much more rapidly than most steroid responsive genes, and 3) it is the rare demonstration of an estrogen inhibition of the expression of a gene. A role for the c-jun proto-oncogene as an early regulatory gene in ...
Menstrual cycle-dependent variations of breast cyst fluid proteins and sex steroid receptors in the normal human breast.

Menstrual cycle dependent variations in cytosol levels of estrogen receptor (ER), progesterone receptor (PR), and two breast cyst fluid glycoproteins, gross cystic disease fluid protein (CDP) and nonreceptor progesterone binding protein (PBP), were demonstrated in epithelial-enriched “normal” breast tissues from 56 premenopausal women. Criteria for normalcy were: (1) normal menstrual history; (2) absence of drug use or debilitating disease; (3) normal adrenal, ovarian and pituitary function; and (4) no clinical, gross or histologic evidence of breast disease. Highest mean levels of CDP (8180 ± 2850 ng/mg protein) and PBP (17750 ± 6320 ng/mg protein) were noted during the follicular phase (days 8–14) of the menstrual cycle, while lowest levels of CDP (450 ± 260) and PBP (1810 ± 380) were observed during the luteal phase (days 15–20). Both CDP and PBP had peak values on days 10–12 with a smaller peak on days 20–23. The number of samples with ER > 3 fmole/mg protein (8/14; 57%) and mean ER level (7.5 ± 2.9 fmole/mg protein) were significantly higher during the proliferative phase (days 3–7) than during other menstrual phases. Maximum ER values occurred on days 5–8. The greatest number of samples with PR > 3 fmole/mg protein (5/15, 33%) and highest mean levels of PR (36 ± 27.8 fmole/mg protein) were noted during the follicular phase of the menstrual cycle. These data demonstrate that the normal human breast has menstrual cycle variations of CDP and PBP which may be useful as markers of sex steroid receptor integrity. These data also documented that appreciable ER levels were found during the proliferative phase with low levels at other times in the menstrual cycle.
Congress moves to address emergency cardiac care issues.

Over the past year, emergency cardiac care and related issues have increasingly moved to the forefront of debate in the Congress. Legislators are becoming more sensitized to emergency care issues. In the May 1991 edition of Circulation , the American Heart Association (AHA) unveiled its “chain of survival” concept. The chain details the sequence of events needed to ensure that more people can survive sudden cardiac arrest. The links of the chain included early access to the emergency system, early cardiopulmonary resuscitation (CPR), early defibrillation, and early advanced cardiac life support. In the article, the Emergency Cardiac Care Committee of the AHA set forth a series of recommendations to strengthen the chain of survival. Among the suggestions with public policy ramifications are the following: (1) all communities should implement an enhanced 911 system; (2) communities should adopt more widespread and effective targeted CPR programs; (3) communities should implement programs to establish dispatcher-assisted CPR; and (4) all communities should adopt the principle of early defibrillation, including making automatic external defibrillators (AEDs) available to first responders trained in their use. Legislation will soon be introduced, drafted in large part by the AHA, that would remove barriers to the “chain of survival” to increase the likelihood of people surviving sudden cardiac arrest. The legislation, sponsored by Gerry E. Studds (D-10-MA), directs the Secretary of Health and Human Services to provide states with recommendations on a variety of issues, including lifesaving first aid and CPR training for 911 dispatchers, firefighters, teachers, and day-care providers. Further, recommendations regarding AEDs would address the placement of the devices in emergency vehicles and large buildings, stadiums, and arenas; the need for removing barriers to expanding the pool of emergency personnel and first responders authorized to use the device; and the modification of tort laws regarding its use. The …
Ecdysteroid receptors in the neuroendocrine-endocrine axis of a moth

With a combination of thaw-mount autoradiography using a tritiated 20-hydroxyecdysone agonist, ponasterone A, and immunocytochemistry with a monoclonal antibody to 29 K-prothoracicotropic hormone, high affinity binding sites for ecdysteroids were identified in the tissues of the neuroendocrine-endocrine axis inManduca sexta larvae. At specific times during larval-pupal development in fifth stadium larvae, nuclear ecdysteroid binding sites were present in the cerebral prothoracicotropes, the corpora allata and prothoracic glands, the main axis for the regulation and production of ecdysteroids. A stage-specific appearance of ecdysteroid receptors also occurred in cells of fat body, midgut and Malpighian tubules, tissues which convert ecdysone into 20-hydroxyecdysone. Our data identify new target tissues for ecdysteroids and suggest that ecdysteroids could affect their own production at the genomic level via long and short feedback loops.
A procedure for the isolation of specific point mutants of influenza virus

Abstract Procedures were developed for the screening and isolation of RNA viruses that vary from the consensus population by a single point mutation and are present in low abundance. We tested these procedures using a mixture of the vaccine donor line cold-adapted (ca) B/Ann Arbor/1/66 and its wild type (wt) progenitor at a ratio of 1,000:1. A 13-mer oligodeoxynucleotide was prepared as a [32P]-radiolabeled probe which specifically hybridized to wt viral RNA (vRNA) at a region that varied between the ca and wt sequence by a single base at position 1,320 of the PA gene. This probe was able to detect as little as 88 pg of total wt vRNA blotted to nitrocellulose, while giving no positive signal with as much as 1 μg of total ca vRNA. We were able to isolate virus containing the wt PA gene sequence from the mixed pool of ca and wt viruses by two successive rounds of amplification in embryonated eggs inoculated with a controlled number of infectious virions. During each round of amplification the abundance of the virus containing the wt PA gene sequence was increased about ten-fold. Once a relative abundance of 1:10 was reached, the virus was cloned by plaquing in Madin-Darby canine kidney cells. These procedures, which allow the isolation of specific point mutants, utilize no selective pressure conditions and are suitable for analyzing the phenotypic importance of known mutations in biologically important viruses.
Stress Initiated During Isolation of Rat Renal Proximal Tubules Limits in Vitro Survival

The effects of oxidative damage were assessed in rat proximal tubule fragments (isolated by collagenase perfusion) by monitoring lactate dehydrogenase release (LDH-R) to measure cell viability and thiobarbituric acid (TBA) reactive material to follow oxidative damage. Increasing the oxygen content in the incubation atmosphere from 10 to 95% significantly increased LDH-R and TBA reactants. Addition of butylated hydroxytoluene or deferoxamine (DF) to the medium prevented these changes, but ascorbic acid or mannitol had no positive effect. Lima bean trypsin inhibitor also reduced LDH leakage significantly when added to the medium, but not when added to the perfusion buffers. In contrast, adding DF to the perfusate during tubule isolation produced the most pronounced benefit; net LDH-R after 4 hr was about 10% in tubules prepared this way compared to 20% when DF was omitted. Basal oxygen consumption declined to approximately the same extent as LDH-R increased. Maintenance of nystatin-stimulated respiration, A...