cssi/SciSciGPT-SciSciNet huggingface dataset:
Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans

Aims Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). Materials and methods We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg−1 min−1) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Results Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. Conclusions These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.
High power microwave window breakdown under vacuum and atmospheric conditions

Microwave window breakdown is investigated in vacuum and atmospheric conditions. An S-band resonant ring with a frequency of 2.85 GHz and a power of 80 MW with a 4 MW magnetron as a source is used. Window breakdown on the vacuum side is simulated using a dielectric slab partially filling an evacuated waveguide. Various high-speed diagnostic methods yield a complete picture on the breakdown phenomenology, with far reaching similarities to de surface flashover. During the initiation phase, free electrons are present, which can be influenced by magnetic fields, followed by a saturated secondary electron avalanche with electron-induced outgassing. Final breakdown occurs in the desorbed gas layer above the surface. In order to simulate window breakdown on the gas-side, a segment of the resonant ring separated by two windows was filled with gas at variable pressure, and breakdown was initiated by field-enhancement tips on one of the gas-side surfaces. Threshold power densities for breakdown are measured, and. first results on the phenomenology of this gas breakdown are compared with the processes of flashover in vacuum.
De Novo Glycan Sequencing by Electronic Excitation Dissociation and Fixed-Charge Derivatization

Detailed glycan structural characterization is frequently achieved by collisionally activated dissociation (CAD) based sequential tandem mass spectrometry (MSn) analysis of permethylated glycans. However, it is challenging to implement MSn (n > 2) during online glycan separation, and this has limited its application to analysis of complex glycan mixtures from biological samples. Further, permethylation can reduce liquid chromatographic (LC) resolution of isomeric glycans. Here, we studied the electronic excitation dissociation (EED) fragmentation behavior of native glycans with a reducing-end fixed charge tag and identified key spectral features that are useful for topology and linkage determination. We also developed a de novo glycan sequencing software that showed remarkable accuracy in glycan topology elucidation based on the EED spectra of fixed charge-derivatized glycans. The ability to obtain glycan structural details at the MS2 level, without permethylation, via a combination of fixed charge deriva...
Not All Polyaxial Locking Screw Technologies Are Created Equal: A Systematic Review of the Literature.

Background Locking plate fixation strength relies on axial alignment of the screw axis and plate hole, with small deviations in alignment substantially decreasing the load to failure. In an effort to overcome this technical deficiency, polyaxial locking plates were designed to provide increased flexibility of screw positioning with the intent of not sacrificing fixation strength. The purpose of this article is to review the variety of polyaxial locking mechanisms currently available, to compare the biomechanical performance of these designs, and to highlight their differences, which may have clinical implications. Methods A systematic review using the search terms "polyaxial locking," "variable angle locking," "polyaxial screws," and "variable angle screws" was conducted to identify all English-language articles assessing variable-angle locking screw technology. All articles directly comparing the biomechanical performance of polyaxial locking technologies were included. Results Polyaxial locking is achieved by 5 described mechanisms: point-loading thread-in, cut-in, locking cap, expansion bushing, and screw-head expansion. With increasing insertion angulation, point-loading thread-in and cut-in designs demonstrate reduced failure strength. However, locking-cap fixation maintains consistent failure strength with increasing off-axis insertion angles. Conclusions Reports comparing polyaxial locking technologies are limited. The current biomechanical literature raises concerns that these mechanisms have various strengths and performance characteristics. Based on the results of the few studies that exist, it appears that locking-cap fixation provides superior biomechanical strength when compared with point-loading and cut-in designs. Additional studies are needed to assess variable-angle locking mechanisms more completely.
Fungal, Viral, and Other Oddball Infections and the Immunosuppressed Patient

Infections with fungal and viral pathogens in the surgical intensive care unit (ICU) are not uncommon. Often, however, diagnosis tends to be either delayed or superimposed on bacterial infections. In some scenarios, definitive diagnosis can be challenging and a high index of suspicion is warranted to promptly manage critically ill patients. This approach is critical especially in immunosuppressed patients given their relative vulnerability to a multitude of infectious processes. Although rare, oddball infections with rare viruses and fungi can significantly affect the clinical course and recovery of patients if timely diagnosis is delayed. This chapter highlights important fungal, viral, and rare infections in the context of critically ill and high-risk patients, including the immunosuppressed patients, in the surgical ICU.
Toward an Extended AC OPF-Based Approach to Wind Power Integration and Pricing

This chapter is motivated by the difficult questions concerning the integration and operation of wind and solar power plants in the existing electric power systems. It describes how the value of these new resources critically depends on their locations and on how the dispatchable equipment is operated. It is suggested that the most efficient and reliable utilization of existing assets requires on-line resource management as system conditions vary. An extended AC Optimal Power Flow (AC XOPF) is used as a means of computing such online resource management. Illustrations of value brought about by adding new wind power plants in the islands of Flores and Sao Miguel are provided. It is also illustrated how short-term efficiency measured in terms of total generation cost depends on optimizing both real power generation and voltage-controllable equipment. It is finally shown that different pricing methods, O&M cost- and locational marginal price (LMP)-based approaches in particular, have very different implications on capital cost recovery of wind power plants, electricity tariffs to the customers, total generation cost, and the grid congestion cost. These findings point into the need for technology-agnostic incentives to all candidate technologies which contribute to enhanced performance.
In ovo intraperitoneal administration of bromodeoxyuridine to avian fetuses.

The embryological development of skeletal muscle begins with the fusion of mononucleated myoblasts that form myotubes, which then mature into myo-fibers (1). By late embryogenesis, myo-blasts found in the chicken fetus may be referred to as satellite cells, and they have predominantly adult characteristics (2). Satellite cells are located underneath the myofiber basal lamina along the entire length of the myofiber (3). Satellite cells are a mitotically active cell population (4), making it possible to label the cells with
Wh-clefts as evidence of resultatives in ASL

Abstract The status of syntactic resultative constructions has been disputed in the American Sign Language (ASL) literature. These are single sentences such as “Mary hammered the metal flat,” where two predicates share the same object and an event (hammered) causes the affected object (the metal) to change state (flat) as a result. While not all languages permit such constructions, this study shows that (several) alternate multi-sentential analyses can be ruled out. WH-clefts are used to provide a test for independent clausal boundaries, providing additional support that American Sign Language (ASL) permits resultative constructions. We also observe possible word order variations and note common features of the result predicates in these constructions.
Integrating air pollution exposure in a mechanistic agent-based model of asthma: Model development and application to childhood asthma outcomes

Introduction: Air pollution exposure is associated with adverse health outcomes among asthmatics. A mechanistic understanding of this association may identify optimal public health interventions to...
The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella

Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC. We hypothesized that 1) overexpressing flhDC in Salmonella increases intracellular bacterial accumulation in tumor cell masses, and 2) intracellular accumulation of Salmonella drives tumor colonization in vitro. To test these hypotheses, we transformed Salmonella with genetic circuits that induce flhDC and express green fluorescent protein after intracellular invasion. The genetically modified Salmonella was perfused into an in vitro tumor-on-a-chip device. Time-lapse fluorescence microscopy was used to quantify intracellular and colonization dynamics within tumor masses. A mathematical model was used to determine how these mechanisms are related to each other. Overexpression of flhDC increased intracellular accumulation and tumor colonization 2.5 and 5 times more than control Salmonella, respectively (P < 0.05). Non-motile Salmonella accumulated in cancer cells 26 times less than controls (P < 0.001). Minimally invasive, ΔsipB, Salmonella colonized tumor masses 2.5 times less than controls (P < 0.05). When flhDC was selectively induced after penetration into tumor masses, Salmonella both accumulated intracellularly and colonized tumor masses 2 times more than controls (P < 0.05). Mathematical modeling of tumor colonization dynamics demonstrated that intracellular accumulation increased retention of Salmonella in tumors by effectively causing the bacteria to bind to cancer cells and preventing leakage out of the tumors. These results demonstrated that increasing intracellular bacterial density increased overall tumor colonization and that flhDC could be used to control both. This study demonstrates a mechanistic link between motility, intracellular accumulation and tumor colonization. Based on our results, we envision that therapeutic strains of Salmonella could use inducible flhDC to drive tumor colonization. More intratumoral bacteria would enable delivery of higher therapeutic payloads into tumors and would improve treatment efficacy.
Hypertension 2008, refining our treatment.

Clinical studies continue to modify our approach to the older hypertensive patient. The pathophysiology of hypertension is now better understood from data derived from ambulatory blood pressure monitoring, the assessment of central arterial pressure and of vascular stiffness. This is altering both the ways we assess, monitor, and treat our older hypertensive patients as well as our choice of pharmacological agents. New data have confirmed the importance of treating the very elderly patient's blood pressure and of modifying the increasing incidence of atrial fibrillation. Resistant hypertension is frequently the result of excessive aldosterone production, a situation easily treated. Several investigators have raised the question of the prehypertensive state and the of possible therapy.
Completion-Completeness for NULL Convention Digital Circuits Utilizing the Bit-Wise Completion Strategy.

Delay-Insensitive paradigms, such as NULL Convention Logic (NCL), require an additional condition, referred to herein as Completion-Completeness, in order to ensure delay-insensitivity when the bit-wise completion strategy is used along with one or more components that are not complete with respect to all of their inputs. Completion-completeness requires that completion signals only be generated such that no two adjacent DATA wavefronts can interact within any combinational component. Correctly applying the bit-wise completion strategy to a circuit with input-incomplete components does not ensure completion-completeness; instead this may require either modifying one or more completion sets or changing the input-completeness of one or more inputincomplete components. Examples of completionincompleteness, and their solutions, are shown when applying the bit-wise completion strategy to circuits utilizing input-incomplete components, for an array of AND functions, the final stage of an unsigned multiplier, and the partial product generation for an unsigned multiplier.
Clinical Applications of Estimating Reliability of Within-Person Couplings in a Multilevel Framework

Neubauer and colleagues (this issue) highlight the importance of identifying within-person couplings, and then detail a method of assessing the reliability of these couplings. They focus on the wit...
The Role of Adjuvant Therapy in Patients With Margin-Positive (R1) Esophagectomy: A National Analysis

Abstract Background We performed a nationwide analysis to assess the impact of adjuvant therapy on survival after a microscopically margin-positive (R1) resection for esophageal cancer. Methods The National Cancer Database was used to identify patients with R1 resection for esophageal cancer (2004-2015). Patients were grouped by type of adjuvant therapy. Patients who had other margin status, M1 disease, neoadjuvant chemotherapy and radiation, missing survival, and no or unknown treatment were excluded. The primary outcome was overall survival. A 1:1 propensity score–matched sensitivity analysis was also performed comparing patients who received no adjuvant therapy with those who received adjuvant chemoradiation. Results Of 546 patients, 279 (51%) received adjuvant therapy and 267 (49%) did not. Patients receiving adjuvant therapy were more likely to be younger, have more advanced pathologic stage, have nonsquamous histology, and have shorter hospitalization. In multivariable analysis, adjuvant chemotherapy, radiation, and chemoradiation were all associated with improved survival compared with no adjuvant therapy. In a propensity score–matched analysis of 123 patient pairs, adjuvant chemoradiation was associated with improved survival compared with no adjuvant therapy (adjusted HR: 0.30; 95% CI: [0.22, 0.40]). Conclusions Adjuvant therapy is associated with improved survival compared with no adjuvant therapy in patients with R1 resection for esophageal cancer even after adjustment for pathologic stage. Adjuvant therapy should be considered in patients with incompletely resected esophageal cancer in concordance with national guidelines.
EXPLORATIONS IN PLACE ATTACHMENT. Edited by JEFFREY S. SMITH. xvi and 244 pp.; maps, diagrs., ills., notes, index. New York, NY.: Routledge, 2018. $112.00 (cloth), ISBN 9781138729742.

Explorations in Place Attachment is part of geography's long fascination with understanding how human beings interact with their surroundings and the emotional attachments they form as a result. Ed...
Using Coding Interviews as an Organizational and Evaluative Framework for a Graduate Course in Programming

Objective: In a Statistical Analysis System (SAS) coding interview, job applicants are typically presented with data management and data analysis problems and asked to solve them using the programming language of SAS. Interviewers not only assess technical competence, but also algorithm design and more generally how applicants approach computer programming. In the language of constructivism, the problems are designed to assess the depth and soundness of the applicant’s mental model of SAS programming. We asked whether a SAS course, embedded within a Master of Biostatistics program, could reasonably be structured using a coding interview for the final examination as its organizing framework. Methods: This is a case study, where we describe how our content delivery was structured in order to prepare students for their coding interviews. It additionally relies on the metaphor of learning a second language through immersion. Results: Using a constructivist approach enhanced with active learning exercises, a course could in fact be designed around a coding interview. Course content can be mapped to the metaphor of foreign language immersion. Student response has been positive, and the formative evaluation has been encouraging to date. Conclusions: Coding interviews are a novel and potentially promising way to design a course in SAS programming.
The Characterization of the Toll of Caring for Coronavirus Disease 2019 on ICU Nursing Staff

Objectives: Coronavirus disease 2019 pandemic exercised a significant demand on healthcare workers We aimed to characterize the toll of caring for coronavirus disease 2019 patients by registered nurses Design: An observational study of two registered nurses cohorts Setting: ICUs in a large academic center Subjects: Thirty-nine ICU registered nurses assigned to coronavirus disease 2019 versus noncoronavirus disease 2019 patients Interventions: None Measurements and Main Results: Skin temperature (t [degreeC]), galvanic skin stress response (GalvStress), blood pulse wave, energy expenditure (Energy [cal]), number of steps (hr-1), heart rate (min-1), and respiratory rate (min-1) were collected using biosensors during the shift National Aeronautics and Space Administration Task Loading Index measured the subjective perception of an assignment load Elevated skin temperatures during coronavirus disease 2019 shifts were recorded (DELTAtCOVID vs tnon-COVID = +1 3 [degreeC];95% CI, 0 1-2 5) Registered nurses staffing coronavirus disease patients self-reported elevated effort (DELTAEffortCOVID vs Effortnon-COVID = +28 6;95% CI, 13 3-43 9) concomitant with higher energy expenditure (DELTAEnergyCOVID vs Energynon-COVID = +21 5 [cal/s];95% CI, 4 2-38 7) Galvanic skin stress responses were more frequent among coronavirus disease registered nurse (DELTAGalStressCOVID vs GalvStressnon-COVID = +10 7 [burst/hr];95% CI, 2 6-18 7) and correlated with self-reported increased mental burden (DELTATLXMentalCOVID vs DELTATLXMentalnon-COVID = +15 3;95% CI, 1 0-29 6) Conclusions: There are indications that registered nurses providing care for coronavirus disease 2019 in the ICU reported increased thermal discomfort coinciding with elevated energy expenditure and a more pronounced self-perception of effort, stress, and mental demand
Modern Band: A Review of Literature:

The recent increase in popular music education in K–12 school music programs is in part due to the expansion of modern band programming throughout the United States. Modern band is a term used to d...
Preschoolers’ Intimate Partner Violence Exposure and Their Speeded Control Abilities Eight Years Later: A Longitudinal Mediation Analysis:

Executive functioning (EF), or a set of related cognitive skills that facilitate goal-oriented behavior, is a critical aspect of adaptive development. Mounting research indicates that exposure to e...
A Review of “The Intimate University: Korean American Students and the Problems of Segregation”

The Intimate University tells the story of Korean American students at the University of Illinois, Urbana-Champaign (UIUC), during the late 1990s and early 2000s. The book operates around the tensi...
Semantically-triggered reading epilepsy: an experimental case study

Primary reading epilepsy (PRE) is a rare syndrome in which epileptic seizures are electively provoked by reading. Cognitive neuropsychology has demonstrated the existence of at least two pathways for reading, the sublexical pathway involved in converting graphemes to phonemes, and the lexical pathway used when meaning is conveyed. Which of these specific pathways is relevant in triggering epileptic discharges remains largely unknown. We report the case of a patient suffering from PRE in which the two routes were distinguished on the basis of the reading material employed. Significantly less epileptic discharges were observed when the patient read non-words than words. In view of our findings, we tentatively contrast a lexical form of PRE, triggered by the activation of semantic knowledge structures, with a sublexical form, triggered by non-word reading. Evidence from the literature suggests that the former is characterized by bilateral EEG activating patterns, whereas the latter involves preferentially the left hemisphere.
Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: The cellular basis of LPS-stimulated metabolism

The rate of glucose utilization has been used as a measure of LPS-induced activation of cultures of C3H/HeN and C3H/HeJ spleen cells, peritoneal cells, and purified peritoneal adherent cells. Peritoneal cells utilized 40 to 60 times more glucose than did spleen cells and purified adherent monolayers were more active than mixed peritoneal cells, suggesting that only macrophage metabolism was being measured. The cell preparations for C3H/HeJ mice were not activated by Escherichia coli K235 LPS prepared by extensive phenol extraction, whereas C3H/HeN cells were activated by that LPS. Cells from both strains were activated by a commercially obtained E. coli 0111:B4 LPS and butanol-extracted K235 LPS. The addition of 10% C3H/HeN spleen cells to C3H/HeJ peritoneal cells resulted in a marked enhancement of glucose utilization. These findings suggest that LPS-induced enhancement of macrophage metabolism occurs both by direct action of LPS on macrophages as well as indirectly through activated lymphocytes.
Where Does Star Formation End in NGC1058

As part of a large project to study the rate, distribution and history of star formation in the outer parts of galactic disks (Ferguson, PhD thesis), we have obtained very deep Ha and B-band images of the nearby face-on spiral NGC1058. Our images reveal extremely low surface brightness outer spiral arms in the B-band which extend well beyond the Holmberg radius and appear to be aligned with underlying HI spiral arms. These features contrast greatly to the flocculent appearance of the innermost regions of the disk and the complete absence of any well defined-arms in the Ha image. The surface brightness profile derived from the B-band image exhibits a sharp fall off in the inner regions of the disk followed by a much shallower decline beyond ∼ R 25 and consequently a single exponential disk cannot be fit to the entire profile.
Levels of microbial agents in floor dust during remediation of a water-damaged office building.

Abstract We examined the effects of remediation on loads of culturable fungi in floor dust collected from a large water-damaged office building during four cross-sectional surveys (2002, 2004, 2005, and 2007, respectively). We created a binary remediation variable for each year for each sampled workstation using information on remediation associated with water damage obtained from building management and used generalized linear mixed-effects models. We found significantly lower levels of culturable total and hydrophilic fungi at remediated workstations than at non-remediated workstations in 2004 and 2005 after completion of major remediation. The remediation effect, however, disappeared in 2007. The fraction of hydrophilic to total fungal concentrations was lowest in 2004, increased in 2005, and was highest in 2007. Our results indicate that the 2003 remediation lowered dust indices of dampness temporarily, but remediation was incomplete, consistent with a building assessment report of water infiltration. This study demonstrates the utility of longitudinal evaluation of microbial indices during remediation of water damage in this building, in which elimination of sources of moisture was not fully addressed. Our findings indicate that the fraction of hydrophilic fungi derived from concentrations of fungal species may be a useful index for assessing the long-term effectiveness of remediation. Practical Implications This study demonstrates the utility of longitudinal evaluation of microbial indices during remediation of water damage in this building, in which elimination of sources of moisture was incomplete. Our findings indicate that the fraction of hydrophilic fungi derived from concentrations of fungal species may be a useful index for assessing the long-term effectiveness of remediation.
Subdivided procedures: a language extension supporting extensible programming

An extension of conventional procedures in which procedure bodies handling multiple cases can be subdivided into separate bodies handling a single case each is described. Subdivision is based on criteria specified by the programmer. Underlying call support selects the body to execute in response to each call. Subdivided procedures support a programming style in which great attention is paid to facilitating subsequent extensions. Normally, extensions have to be made by changing source code; subdivided procedures allow them to be made instead by adding new bodies. Subdivided procedures can be implemented on top of procedural languages with a preprocessor that examines just a file of definitions; it does not need to examine procedure code. A restricted version of the mechanism implemented within the RPDE/sup 3/ environment framework has been in constant use for more than two years. Experience has shown that it facilitates extensible programming at little or no cost in call-time overhead. >
POLARIZATION CHARACTERISTICS OF Pc 1 MICROPULSATIONS AT COLLEGE.

Abstract Polarizations of Pc 1 ( T ∼ 1–5 sec) micropulsations were recorded intermittently at College from September 1965 to November 1966 by (1) photographing an x - y storage oscilloscope during the event, and by (2) recording the two horizontal components on FM magnetic tape with subsequent playback into the x - y scope. The characteristics of the data suggest that both right-hand and left-hand polarized waves are simultaneously present. Some events had persistent sense, right or left. The structured Pc 1 polarization data and sonagrams are consistent with the concept of an inter-hemisphere-reflecting packet of hydromagnetic waves, but do not give direct support to theories which require that the packet propagates in L mode.
Using British Trial Procedures in American Cases: A More Civil Trial?

A number of attorneys, judges, and legal scholars have asserted that the overly combative nature of American trials may impact on the actual quality of justice and bring the legal system into disrepute. In contrast, many who witness criminal and civil trials conducted in Great Britain are struck by the greater apparent civility of the courtroom atmosphere. Closer examination of the English system reveals seven specific procedural differences that may contribute to this perceived change in atmosphere. In this study, these procedural differences were manipulated and their effect on verdict and on perceptions of trial participants measured. In addition, opinions about these differences were elicited. Results showed that while the trial was perceived as more civil, and the judge viewed more positively, participants tended to indicate preferences for the American style. Implications of these results are discussed.
Effect of cyclosporine on colchicine secretion by a liver canalicular transporter studied in vivo

The multidrug resistance transport protein is a normal constituent of the liver canalicular membrane, although its function has not been defined in vivo. Colchicine, a multidrug resistance substrate, is eliminated mainly by the liver. Cyclosporine reverses multidrug resistance in vitro, presumably by inhibiting the multidrug resistance transporter. This study assesses biliary colchicine elimination and the effect of cyclosporine on this process. After cyclosporine administration biliary colchicine clearance decreased from 11.6 ± 0.8 to 2.2 ± 0.4 ml/min ± kg (p < 0.05), and the colchicine bile/plasma ratio decreased from 166 ± 9 to 38 ± 5 (p < 0.05). Cremophor EL (a cyclosporine vehicle) transiently inhibited biliary colchicine clearance and colchicine bile/plasma ratio, but to a much smaller extent than cyclosporine in vehicle. Biliary cyclosporine clearance was 0.122 and 0.024 ml/min · kg after bolus doses of 2 or 10 mg/kg intravenously, respectively. Cyclosporine bile/plasma ratio was 1.3 to 5.2. When cyclosporine was given 16 hr before colchicine infusion, biliary colchicine clearance decreased 39% (p < 0.05), and colchicine bile/plasma ratio decreased 51% (p < 0.05). Thus colchicine is actively secreted into bile and will be useful in the study of the multidrug transporter in vivo. Cyclosporine profoundly inhibits colchicine secretion into bile but is itself mainly metabolized rather than secreted. If competition for a common carrier is the basis for the interaction, then cyclosporine represents a drug that binds to but is not transported by the canalicular transporter. (HEPATOLOGY 1992;15:899–903).
Comparison of the spectra of genetic damage in N4-hydroxycytidine-induced ad-3 mutations between nucleotide excision repair-proficient and -deficient heterokaryons of Neurospora crassa.

Abstract A comparison has been made of the mutagenic effects of N4-hydroxycytidine (HC) in the adenine-3 (ad-3) region of two-component heterokaryons of Neurospora crassa: nucleotide excision repair-proficient (uvs-2+ / uvs-2+) heterokaryon 12 (H-12) and nucleotide excision repair-deficient (uvs-2 / uvs-2) heterokaryon 59 (H-59). HC was found to produce mutations predominantly, if not exclusively, by AT to GC base-pair transitions in Escherichia coli strain K12 by Janion and Glickman (1980, Mutation Res., 72, 43–47) and Sledziewska-Gojska et al. (1992, Mutagenesis, 7, 41–46). The ad-3 forward-mutation, specific-locus assay system permits the recovery of ad-3A and/or ad-3B mutants resulting from gene/point mutation, multiple-locus mutation, and multilocus deletion mutation. Uvs-2, which is homokaryotic in H-59, results in a recovery of HC-induced ad-3 forward mutations at a frequency in H-59 that is comparable to that found in H-12. Genetic analysis of ad-3 mutants recovered from experiments with HC treatment demonstrates that predominantly gene/point mutations were found in both strains: 99.3% (540/544) in H-12, and 97.4% (531/545) in H-59. Genetic analysis of allelic complementation among the ad-3BR mutations demonstrated that HC induced the highest percentage of complementing mutants ever found with base analogs both in H-12 (99.7% [328/329]) and H-59 (91.2% [290/318]). As a result of these findings, the majority of HC-induced ad-3 mutations are postulated to have resulted from missense mutations. Thus, we conclude that the results in Neurospora are consistent with the observations in E. coli strain K-12, where HC induces predominantly AT to GC base-pair transitions.
Main bronchus occlusion for treatment of congenital diaphragmatic hernia in fetal lambs.

Abstract Purpose The present study investigates a new surgical approach in the treatment of left diaphragmatic hernia in fetal sheep. We postulated that unlike tracheal occlusion where both lungs are occluded, selective left main bronchus occlusion (LMBO) would accelerate growth of only the left lung, reduce left visceral herniation, and recover space in the both thoraces necessary for lung development. Methods Left-sided congenital diaphragmatic hernia (CDH) was surgically created in 8 fetal lambs at approximately 65 days of gestation; in 4 of these animals, LMBO was performed at approximately 118 days. Four sham-operated animals served as controls. Lambs were delivered by hysterotomy at 137 days. We measured lung-to-body weight ratios, alveolar surface area, septal wall thickness, and AE2 cell density in the left and right lungs. Results Left main bronchus occlusion increased ( P Conclusions Left main bronchus occlusion failed to restore normal pulmonary development in CDH.
The metastability of gold-antimony phases prepared by splat cooling

Abstract The metastable gold-antimony phases ζ (h.c.p. Mg-A3 type) containing 15.0 at. % antimony and π (simple cubic α-Po-Ah type) containing 76.6% antimony were prepared by splat cooling. The heats of formation of these phases were measured by solution ealorimetry and their free energies of formation were estimated. An analysis of the free energies of the relevant phases leads to the following conclusions, (i) The phases ζ and π are unstable at all temperatures, (ii) Liquid alloys containing 15.0% and 76.6% antimony, respectively, must be undercooled by at least 150° and 200°K for the phases ζ and π to form, (iii) The temperature below which the π phase can form (600°K) is about 250°K lower than the temperature below which the ζ phase can form, (iv) Although the free energies indicate that the π phase is more unstable than the ζ phase, the calculated degrees of undercooling required and the calculated temperature of formation of the two phases indicate that the π phase is less difficult to produce by splat cooling than the ζ phase. This agrees with experimental observations.
What is the role of free clinics in the safety net

BACKGROUND Free clinics play an important role in the safety net but little is known about what factors drive their existence within a given community. The anecdotal literature suggests that they exist due to growing numbers of uninsured and a lack of affordable care. OBJECTIVE To determine whether unmet needs explain the existence of free clinics. MATERIALS AND METHODS The relationship between demographics, Medicaid policy, and ambulatory safety-net care on the geographical distribution of all known free clinics (n=1007) across all metropolitan statistical areas (n=361) in the United States is investigated cross sectionally. Drawing from numerous secondary data sources and an original dataset of all known free clinics, a negative binomial model is used to examine whether free clinic prevalence is higher in communities with larger proportions of uninsured patients, poor adults, and African Americans and is lower in communities with greater availability of federally qualified health centers (FQHCs), FQHC look-alikes, and health departments, and more generous Medicaid eligibility for working parents and Medicaid beneficiary/provider payment levels. RESULTS AND DISCUSSION None of the demographic variables has a positive, statistically significant relationship to the number of free clinics in a metropolitan statistical area. However, the number of FQHC grantees per 10,000 uninsured individuals [incidence rate ratios (IRR)=0.69, P<0.05], the number of FQHC look-alike sites per 10,000 uninsured individuals (IRR=0.46, P<0.05), Medicaid beneficiary payments (IRR=0.9998, P<0.05), and Medicaid eligibility levels (IRR=0.998, P<0.10) are negatively associated with the number of free clinics. Thus, free clinics seem to respond to particular gaps left by safety-net providers and Medicaid but do not seem to respond to direct need.
Multi-Agent Customer Allocation in a Stochastic Service System

In many service systems, customers interact with an agent who directs customers to specific service facilities. Each agent, as a decision maker, seeks to allocate his/her customers to the service centers so as to optimize a measure of performance based on the customers' expected waiting time and the expected number of customers in service. In this paper, the problem of multiple agents, each optimizing his/her customer allocation decision in a stochastic service system, is analyzed as a noncooperative game. It is shown that an equilibrium point to such a game exists and sufficient conditions for which this equilibrium point is unique are also given. Finally, the relative efficiency of the multi-agent system is examined by comparing the customers' average waiting time in the multi-agent system to the one-agent case. It is shown that, in general, the multi-agent system is not as efficient as the one-agent one in terms of customer welfare.
Lower extremity injuries in youth sports.

The lower extremity is the anatomic area most commonly injured in sports. Injuries may occur from repetitive stresses associated with running and jumping or from acute traumatic events [1]. Overuse injuries such as tendinitis, apophysitis, patellofemoral pain, shin splints, and stress fractures are discussed in the article on chronic musculoskeletal pain elsewhere in this issue. This article focuses on common injuries that occur to the hip, pelvis, leg, thigh, knee, and ankle. Discussion of each injury includes a review of relevant anatomy, injury mechanisms, presenting symptoms, pertinent physical findings, radiologic evaluation, treatment, and return to play criteria. Special emphasis is placed on injuries that are unique to the pediatric age group [2] and injuries that can be evaluated and managed by pediatricians or other nonorthopedic specialists. Hip and pelvis Injuries to the hip and pelvis are the least common of the lower extremity injuries but include many of the more serious conditions [3]. The articulation between the femoral head and acetabulum has a high degree of bony stability and, hence, is protected from many of the ligamentous or soft tissue injuries that occur in other joints. Hip fractures and hip dislocations, when they do occur, are typically a result of major trauma such as motor vehicle accidents. Many of the conditions presenting as acute ‘‘hip pain’’ are actually injuries to the pelvis. Contusions to the iliac crest known as ‘‘hip pointers’’ cause pain, localized tenderness, and discomfort with weight bearing activity. Treatment includes rest, limiting impact activity, and antiinflammatory measures followed by exercises to restore flexibility and strength in the affected muscle groups. When the patient can run, jump, and quickly change directions without pain, he or she can return to full activity. Additional padding over the iliac crest may be helpful for participants in contact or collision sports.
High-Level Abstractions and Modular Debugging for FPGA Design Validation

Design validation is the most time-consuming task in the FPGA design cycle. Although manufacturers and third-party vendors offer a range of tools that provide visibility and control of the different stages of a design, many require that the design be fully re-implemented for even simple parameter modifications or do not allow the design to be run at full speed. Designs are typically first modeled using a high-level language then later rewritten in a hardware description language, first for simulation and then later modified for synthesis. IP and third-party cores may differ during these final two stages complicating development and validation. The developed approach provides two means of directly validating synthesized hardware designs. The first allows the original high-level model written in C or C++ to be directly coupled to the synthesized hardware, abstracting away the traditional gate-level view of designs. A high-level programmatic interface allows the synthesized design to be validated directly by the software reference model. The second approach provides an alternative view to FPGAs within the scope of a traditional software debugger. This debug framework leverages partially reconfigurable regions to accelerate the modification of dynamic, software-like breakpoints for low-level analysis and provides a automatable, scriptable, command-line interface directly to a running design on an FPGA.
Macroeconomic Impacts of the California Global Warming Solutions Act on the Southern California Economy

We evaluate the potential regional macroeconomic impacts of a set of ten greenhouse gas mitigation policy options intended to enable the Southern California Association of Governments to comply with the State's greenhouse gas reduction targets. The Regional Economic Models, Inc. Policy Insight Plus Model, was applied in the analysis by carefully linking technical and microeconomic aspects of each mitigation option to the workings of the regional economy. We took into account key considerations, such as how investment in mitigation options would displace ordinary private business investment and the time-phasing of renewable electricity generation. Our results indicate that the combined ten mitigation policy options could create an annual average employment gain of 21 thousand jobs over the entire planning period from now to 2035, but could also have a negative net present value impact of $17 billion in regional GDP. In the paper, we explain this and other anomalies. Sensitivity analyses of key assumptions and parameters for the Renewable Portfolio Standard indicate that the results are robust. They also provide policy-makers with insights into how to improve the macroeconomic impact of this major policy option.
Allergy in duodenal ulcer: Incidence and significance of food hypersensitiveness as observed in 32 patients

Abstract Evidence has been presented which tends to show that food hypersensitiveness may be an etiologic factor in a small but appreciable percentage of cases of duodenal ulcer. Especially in those cases in which ulcer recurs after operation should an allergic factor be suspected. Its recognition in any case puts the treatment of that patient upon the sound and successful basis of removing a cause.
A multi‐director formulation for elastic—viscoelastic layered shells

A linear finite element formulation for the analysis of multi-layered shells comprised of linear elastic and viscoelastic layers is presented. The elastic and viscoelastic layers may occupy arbitrary locations and the formulation is appropriate for thick and thin shells. The concept of a multi-director field defined over a reference surface is employed for the description of the initial geometry and motion of the multi-layered shell. The kinematical theory incorporated in the three-dimensional variational formulation describes, within individual layers, the effects of transverse shear and transverse normal strain to arbitrary orders in the layer thickness co-ordinate. These kinematics have ‘local support’ over a layer and prove to be convenient and accurate in application. All stresses are computed through three-dimensional constitutive equations and the usual ‘zero normal stress’ shell hypothesis is not employed. Layer material properties are assumed to be isotropic, although this is not a restriction of the formulation. Sufficiently general constitutive equations for the viscoelastic layers are presented in rate form and an accurate and efficient product algorithm is introduced for their temporal integration. Finite element formulations using both resultant and continuum approaches are developed and compared. Observations and suggestions on the use of reduced/selective integration in the presence of high-order kinematics are made and a number of numerical examples are presented to illustrate the capability of the formulation.
The External Proton Beam for the Princeton-Pennsylvania Accelerator

The beam extraction system being built for the Princeton-Pennsylvania 3-Bev weak foccussing proton synchrotron is a resonant system using the ?r = 2/3 resonance. This system has the advantages of high efficiency and small emittance, and requires that only the final extraction magnet, or septum magnet, need be plunged.
NFATc2 and NFATc3 regulate T(H)2 differentiation and modulate TCR-responsiveness of naïve T(H)cells.

The NFAT family of transcription factors are key regulators of inducible gene expression in the immune system. We examined the function of two NFAT proteins after naive T helper (T(H)) cell activation. We found that naive T(H) precursors that are doubly deficient in NFATc2 and NFATc3 intrinsically differentiate into TH(2)-secreting cells, even in the absence of interleukin 4 (IL-4) production. We also found that lack of NFATc2 and NFATc3 obviates the necessity for engagement of CD28 on naive cells and controls the time required to reach the first cell division upon activation. These results demonstrate a key role for NFATc2 and NFATc3 in modulating T cell receptor responsiveness and regulating subsequent cell division and T(H)2 differentiation.