cssi/SciSciGPT-SciSciNet huggingface dataset:
The transition model of RTK activation: A quantitative framework for understanding RTK signaling and RTK modulator activity

Here, we discuss the transition model of receptor tyrosine kinase (RTK) activation, which is derived from biophysical investigations of RTK interactions and signaling. The model postulates that (1) RTKs can interact laterally to form dimers even in the absence of ligand, (2) different unliganded RTK dimers have different stabilities, (3) ligand binding stabilizes the RTK dimers, and (4) ligand binding causes structural changes in the RTK dimer. The model is grounded in the principles of physical chemistry and provides a framework to understand RTK activity and to make predictions in quantitative terms. It can guide basic research aimed at uncovering the mechanism of RTK activation and, in the long run, can empower the search for modulators of RTK function.
Cooperación internacional para el desarrollo e iniciativas de paz de la sociedad civil en Cali y Buenaventura, 2001-2015

Objetivo/contexto: El articulo se enfoca en la relacion entre cooperacion internacional e iniciativas de paz de la sociedad civil en Cali y Buenaventura, e indaga la forma en la que la primera inci...
Robust p53 Stabilization Is Dispensable for Its Activation and Tumor Suppressor Function.

p53 is a short-lived protein with low basal levels under normal homeostasis conditions. However, upon DNA damage, levels of p53 dramatically increase for its activation. Although robust stabilization of p53 serves as a “trademark” for DNA damage responses, the requirement for such dramatic protein stabilization in tumor suppression has not been well addressed. Here we generated a mutant p53KQ mouse where all the C-terminal domain lysine residues were mutated to glutamines (K to Q mutations at K367, K369, K370, K378, K379, K383, and K384) to mimic constitutive acetylation of the p53 C-terminus. Because of p53 activation, p53KQ/KQ mice were perinatal lethal, yet this lethality was averted in p53KQ/− mice, which displayed normal postnatal development. Nevertheless, p53KQ/− mice died prematurely due to anemia and hematopoiesis failure. Further analyses indicated that expression of the acetylation-mimicking p53 mutant in vivo induces activation of p53 targets in various tissues without obviously increasing p53 levels. In the well-established pancreatic ductal adenocarcinoma (PDAC) mouse model, expression of the acetylation-mimicking p53-mutant protein effectively suppressed K-Ras–induced PDAC development in the absence of robust p53 stabilization. Together, our results provide proof-of-principle evidence that p53-mediated transcriptional function and tumor suppression can be achieved independently of its robust stabilization and reveal an alternative approach to activate p53 function for therapeutic purposes. Significance: Although robust p53 stabilization is critical for acute p53 responses such as DNA damage, this study underscores the important role of low basal p53 protein levels in p53 activation and tumor suppression.
Overcoming an Annotation Hurdle: Digitizing Pen Annotations from Whole Slide Images.

Background: The development of artificial intelligence (AI) in pathology frequently relies on digitally annotated whole slide images (WSI). The creation of these annotations – manually drawn by pathologists in digital slide viewers – is time consuming and expensive. At the same time, pathologists routinely annotate glass slides with a pen to outline cancerous regions, for example, for molecular assessment of the tissue. These pen annotations are currently considered artifacts and excluded from computational modeling. Methods: We propose a novel method to segment and fill hand-drawn pen annotations and convert them into a digital format to make them accessible for computational models. Our method is implemented in Python as an open source, publicly available software tool. Results: Our method is able to extract pen annotations from WSI and save them as annotation masks. On a data set of 319 WSI with pen markers, we validate our algorithm segmenting the annotations with an overall Dice metric of 0.942, Precision of 0.955, and Recall of 0.943. Processing all images takes 15 min in contrast to 5 h manual digital annotation time. Further, the approach is robust against text annotations. Conclusions: We envision that our method can take advantage of already pen-annotated slides in scenarios in which the annotations would be helpful for training computational models. We conclude that, considering the large archives of many pathology departments that are currently being digitized, our method will help to collect large numbers of training samples from those data.
MIF is a 3' flap nuclease that facilitates DNA replication and promotes tumor growth.

How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3’ flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3’ nuclease, excises flaps at the immediate 3’ end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth. Replication stress is associated with cancer formation and progression. Here the authors reveal that the macrophage migration inhibitory factor (MIF) functions as 3’ flap nuclease involved in resolving replication stress affecting overall tumor progression.
Patterns and Pathways of Peer Victimization Across the Transition to Middle School

Peer victimization is a widespread and heterogeneous phenomenon, especially during the transition to middle school, and is associated with numerous negative consequences. However, previous research...
Using Sankey diagrams to visualize drag and drop action sequences in technology-enhanced items

We propose a Sankey diagram-based visualization method to illustrate test-takers’ action sequences in technology-enhanced, drag-and-drop items. This method extends existing studies focusing only on initial or last attempt(s) of answer formulation, and extracts, at the item level, comprehensive information of test-takers’ drag-and-drop actions. Using the process data from three mathematical items in the National Assessment of Educational Progress, we exemplify how to develop Sankey diagrams, discover frequent actions at each stage of problem solving, deduce test-takers’ response strategies, and discuss the relationship among domain (i.e., mathematics) knowledge, response strategy, and item performance. The applications and future extensions of this method can contribute to process-based problem-solving research in educational assessments.
Disease Severity and Motor Impairment Correlate With Health-Related Quality of Life in AP-4-Associated Hereditary Spastic Paraplegia.

Objective AP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a childhood-onset neurogenetic disease and mimic of cerebral palsy. Data on health-related quality of life (HRQoL) are lacking. To establish a metric for HRQoL and caregiver priorities, we used the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire to assess HRQoL in correlation with disease severity in 64 patients with AP-4-HSP. Methods A cross-sectional analysis of caregiver-reported HRQoL was performed using the CPCHILD questionnaire in combination with a detailed clinical characterization. Results HRQoL was impaired in all domains in patients with AP-4-HSP (mean score: 59.6 ± 12.6 [SD]), with no significant difference between the 4 subtypes. Age, as a surrogate for disease duration, and Spastic Paraplegia Rating Scale scores, as an indicator for corticospinal tract dysfunction and motor impairment, correlated with lower CPCHILD scores (Pearson r = −0.31, p = 0.01 and r = −0.52, p Conclusions We show that the CPCHILD questionnaire, developed for use in children with cerebral palsy, can be used to assess HRQoL in patients with childhood-onset complex hereditary spastic paraplegia. HRQoL is reduced in patients with AP-4-HSP and correlates with the degree of motor impairment. These results provide a framework for medical decision making and a baseline for the future development of treatment guidelines and interventional trials.
A Tutorial on One-Way Analysis of Circular-Linear Data

Some industrial applications lead to observations that are characterized by a bivariate response where one observation is an angle or direction and the other is linear. These data are frequently called cylindrical data since they can be represented by p..
Are the Best solutions to a real optimization problem always found in the noninferior set? evolutionary algorithm for generating alternatives (EAGA)

Evolutionary algorithms (EAs) continue to offer an effective, powerful, and sometimes exclusive way to search for solutions to real optimization problems. While these algorithms can help solve a complex optimization problem, whether the results represent the “best” choices for making decisions about a solution to a real problem is questionable. In decision-making problems that are ill posed, all objectives may not be defined clearly and therefore not quantitatively captured in the optimization model [1]. The noninferior set of solutions to the optimization model being solved may not necessarily contain the best solution to the actual problem.
Fluorescence in Living Systems: Applications in Chemical Biology

Increasingly, studies of biomolecules are progressing from understanding how isolated biomolecules work in vitro to asking how macromolecular machines, signaling pathways, and other biological networks function in the complex environment of the living cell. Just as chemical methods greatly impacted fundamental studies of the structure and function of biomolecules in vitro in the last century, chemical methods are now being developed to study biomolecule function in vivo. This review focuses on chemical biology tools being developed to provide fluorescent reporters for biomolecules in living cells. The wealth of in vitro fluorescent reporters is the underpinning of much of this research, but it is beyond the scope of this review. Emphasis is placed on protein tagging, beginning with the fluorescent proteins and more recently moving to chemical tagging methods. In addition, chemical tools for fluorescence imaging of other classes of biomolecules and dynamic modifications to biomolecules in living cells are also overviewed.
Averaged and cycle by cycle switching models for buck, boost, buck-boost and Cuk converters with common average switch model

This paper shows computer models for common switch-mode converters with averaged and conventional cycle by cycle switching operation. Models for the buck, boost, buck-boost, and Cuk converter are presented. Also shown are buck and boost converters with integrated magnetic components. All time averaged models are using an identical averaged model for the PWM switch. The models are implemented using PSpice(R) for Windows(R). The advantage of averaged models are much faster execution time as well as the ability to perform frequency domain (bode plots) analysis in addition to time domain analysis.
The effect of dynamic retail experiences on experiential perceptions of value: an Internet and catalog comparison

Abstract The authors introduce cognitive continuum theory (CCT) as a theoretical framework to examine the effect of consumer shopping tasks and retail information display properties on consumer perceptions of experiential value. In this empirical investigation, the nature of a consumer’s shopping task is found to exert a direct influence on consumer perceptions of efficiency, economic value, and shopping enjoyment, all active dimensions of value. In addition, congruent interactions between shopping task and retail information display properties exert an enhancing effect on the reactive dimensions of value, as evidenced by perceptions of visual appeal, entertainment value, and service excellence. Future application of CCT is outlined and managerial implications are discussed.
A Review of “Fair and Affordable Housing in the US: Trends, Outcomes, Future Directions”

In the US, fair housing has remained an issue despite the passing of the Fair Housing Act in 1968 and the Fair Housing Amendments Act of 1988. Affordable housing has also remained an issue, especia...
Profession at the crossroads: A dialog concerning the preparation of nursing scholars and leaders

The purpose of a practice discipline's terminal degree is to develop wise scholars to guide the profession in anticipating and meeting the health-related needs of those served via philosophical, conceptual/theoretical, and empirical inquiry on behalf of professional practice. Each of these dimensions is important for the discipline's ability to meet its obligations to society. However, contemporary circumstances have created a context within which the maturation of the profession may be threatened by an imbalance among the three dimensions of PhD education. Specifically, we discuss the possibility of a tilt toward the empirical at the expense of the other two. Yet, the philosophical and conceptual/theoretical dimensions are those that have permitted core disciplinary knowledge to be developed. We aim to create a dialog about current challenges and the responsibilities of the discipline's scholars for stewardship of the discipline and offer some strategies to ensure balance among the three equally important dimensions.
Investigation of Computer-Aided Control of a Waterjet Robotic Workcell

This paper is concerned with the cutting of complex flat shapes by the use of a waterjet robotic workcell. Results of processing different materials (Kelvar, glass, titanium) are presented. The various modes of control of waterjet cutting are discussed and the results of their applications are compared. The principal defects of cutting for each mode of motion control are identified and methods of the prevention of defects generation are suggested. The specific features of the control of a waterjet robotic workcell are discussed.
Quantum-defect analysis of 3 p and 3 d H 3 Rydberg energy levels

In this work, Rydberg energy levels of the triatomic hydrogen molecule (${\mathrm{H}}_{3}$) are studied with multichannel quantum-defect theory. We extract the body-frame $p$-wave quantum defects from highly accurate ab initio electronic potential surfaces and calculate the quantum defects of higher angular-momentum states in a long-range multipole potential model. Laboratory-frame quantum-defect matrices emerge from a rovibrational-frame transformation carried out with accurate rovibrational states of ${\mathrm{H}}_{3}^{+}$. Finally, we use the laboratory-frame quantum defects to calculate Rydberg energy levels for the fundamental neutral triatomic molecule ${\mathrm{H}}_{3}$.
Utilization of Mechanical Circulatory Support in Patients Undergoing Percutaneous Coronary Intervention: Insights From the NCDR

Limited data is available on contemporary use of intra-aortic balloon pump (IABP) and other mechanical circulatory support (O-MCS) devices in patients undergoing percutaneous coronary intervention (PCI) with cardiogenic shock (CS). Patients undergoing PCI in CS at 1,429 NCDR CathPCI® participating
Visually Exploring Transportation Schedules

Public transportation schedules are designed by agencies to optimize service quality under multiple constraints. However, real service usually deviates from the plan. Therefore, transportation analysts need to identify, compare and explain both eventual and systemic performance issues that must be addressed so that better timetables can be created. The purely statistical tools commonly used by analysts pose many difficulties due to the large number of attributes at trip- and station-level for planned and real service. Also challenging is the need for models at multiple scales to search for patterns at different times and stations, since analysts do not know exactly where or when relevant patterns might emerge and need to compute statistical summaries for multiple attributes at different granularities. To aid in this analysis, we worked in close collaboration with a transportation expert to design TR-EX, a visual exploration tool developed to identify, inspect and compare spatio-temporal patterns for planned and real transportation service. TR-EX combines two new visual encodings inspired by Marey's Train Schedule: Trips Explorer for trip-level analysis of frequency, deviation and speed; and Stops Explorer for station-level study of delay, wait time, reliability and performance deficiencies such as bunching. To tackle overplotting and to provide a robust representation for a large numbers of trips and stops at multiple scales, the system supports variable kernel bandwidths to achieve the level of detail required by users for different tasks. We justify our design decisions based on specific analysis needs of transportation analysts. We provide anecdotal evidence of the efficacy of TR-EX through a series of case studies that explore NYC subway service, which illustrate how TR-EX can be used to confirm hypotheses and derive new insights through visual exploration.
Influence of testosterone and dihydrotestosterone on bone-matrix induced endochondral bone formation.

A bone matrix-induced endochondral bone development model has been used to study the effects of androgens on different stages of bone development in castrated young adult rats. Androgen treatment, especially with dihydrotestosterone (DHT) for 7 days, inhibited35SO4 incorporation by the developing cartilage in the induced plaques. Castrated control animals maintained for 11 days after implantation of bone matrix showed significantly lower calcium levels in the induced implant than was observed earlier in the unoperated controls. DHT treatment for 11 days caused dramatic increases in levels of calcium in the implants. Testosterone had little effect. When androgen treatment was continued for 21 days, while levels of alkaline phosphatase in the implants were unaffected, levels of calcium in the implants were significantly higher than on day 11 for both castrated control and androgen-treated animals. Peak alkaline phosphatase activity (day 10) is known to precede peak calcium mineralizing activity (day 12) in this model and it is also known that calcium levels remain high thereafter. Evaluation of calcium and alkaline phosphatase levels in the proximal tibial metaphyses of castrated control and androgen-treated groups of animals showed no changes after 11 days treatment. Prolonged treatment (21 days) elevated the levels of alkaline phosphatase whereas no change was observed in calcium levels in the tibial metaphyses. These findings demonstate that androgens stimulate mineralization and that DHT is more active when used for short periods of time and in early stages of bone development in matrix-induced implants.
Antibodies to estrophilin: comparison between rabbit and goat antisera.

Abstract The immunochemical similarity of mammalian estrophilins has been demonstrated by the ability of immunoglobulin (Ig-i) obtained from rabbits and a goat immunized with purified estradiol-receptor complex of calf uterine nuclei to cross-react with all radioactive estradiol-receptor complexes (E∗R) tested to date, as determined by sucrose gradient, gel filtration and double antibody precipitation techniques. Rabbit antibodies to the nuclear receptor of calf uterus react with 5.2 S nuclear E∗R from calf, rat, rabbit and sheep uterus, as well as from rat endometrial and pituitary tumors to give two more rapidly sedimenting E∗R-Ig-i complexes (7–8 S and 10–12 S). Extranuclear E∗R (4 S) from uteri and tumors of several mammalian species, and from rat and human mammary cancers, as well as nuclear and extranuclear E∗R (3.5 S) from MCF-7 human breast tumor cells, give a single major sedimentation peak (7–8 S) with rabbit Ig-i. The hormone specificity of rabbit Ig-i has been demonstrated by the absence of any interaction between Ig-i and androgen receptors of rat prostate, or mammalian and non-mammalian progesterone receptors. Also, there is no reaction with free estradiol, with non-specific binding components in human breast cancer cytosol, or with 125I-labeled mouse or rat a-fetoprotein. Goat antibodies to calf uterine E∗R react with nuclear and extranuclear E∗R of all tested tissues, including uterus, tumor and human breast cancer, to give a major new entity sedimenting at 11–14 S. The titer of antibodies to estrophilin in goat Ig-i is considerably higher than in rabbit Ig-i. Unlike rabbit antibody, interaction of goat Ig-i with extranuclear estrophilin causes a decrease in affinity and a reduction in the number of binding sites for estradiol. Fab fragments from both rabbit and goat Ig-i react with nuclear E∗R from calf uterus to give a product sedimenting slightly ahead of the original E∗R complex.
Halotolerant aerobic heterotrophic bacteria from the Great Salt Plains of Oklahoma

The Salt Plains National Wildlife Refuge (SPNWR) near Cherokee, Oklahoma, contains a barren salt flat where Permian brine rises to the surface and evaporates under dry conditions to leave a crust of white salt. Rainfall events dissolve the salt crust and create ephemeral streams and ponds. The rapidly changing salinity and high surface temperatures, salinity, and UV exposure make this an extreme environment. The Salt Plains Microbial Observatory (SPMO) examined the soil microbial community of this habitat using classic enrichment and isolation techniques and phylogenetic rDNA studies. Rich growth media have been emphasized that differ in total salt concentration and composition. Aerobic heterotrophic enrichments were performed under a variety of conditions. Heterotrophic enrichments and dilution plates have generated 105 bacterial isolates, representing 46 phylotypes. The bacterial isolates have been characterized phenotypically and subjected to rDNA sequencing and phylogenetic analyses. Fast-growing isolates obtained from enrichments with 10% salt are predominantly from the gamma subgroup of the Proteobacteria and from the low GC Gram-positive cluster. Several different areas on the salt flats have yielded a variety of isolates from the Gram-negative genera Halomonas, Idiomarina, Salinivibrio, and Bacteroidetes. Gram-positive bacteria are well represented in the culture collection including members of the Bacillus, Salibacillus, Oceanobacillus, and Halobacillus.
Sister chromatid gene conversion is a prominent double‐strand break repair pathway in mammalian cells

In mammalian cells, repair of DNA double-strand breaks (DSBs) occurs by both homologous and non-homologous mechanisms. By definition, homologous recombination requires a template with sufficient sequence identity to the damaged molecule in order to direct repair. We now show that the sister chromatid acts as a repair template in a substantial proportion of DSB repair events. The outcome of sister chromatid repair is primarily gene conversion unassociated with reciprocal exchange. This contrasts with expectations from the classical DSB repair model originally proposed for yeast meiotic recombination, but is consistent with models in which recombination is coupled intimately with replication. These results may explain why cytologically observable sister chromatid exchanges are induced only weakly by DNA-damaging agents that cause strand breaks, since most homologous repair events would not be observed. A preference for non-crossover events between sister chromatids suggests that crossovers, although genetically silent, may be disfavored for other reasons. Possibly, a general bias against crossing over in mitotic cells exists to reduce the potential for genome alterations when other homologous repair templates are utilized.
Research and Education Needed on Milk and Milk Products in Developing Countries

There is a close relationship between education and develpoment. Education is the single most important element in modernization; in fact, the process of modernization is fundamentally a process of education. These thoughts were expressed by David E. Bell, Administrator, A.I.D. Any contribution which may be made to the educational program of another country must be motivated by the desire to enhance the efforts of those people affected to do all the things enabling them to achieve a better life. The need for research and education on milk and milk products has been established. Excellent proposals have been made designating programs which will be effective in developing countries. I f we accept these statements we may conclude that our principal efforts should now be directed toward implementation of the proposals. Believing that many of our members may not have familiarized themselves with the contents of the numerous excellent reports containing pert inent information, possibly a greater number should be assigned to panels such as this one which, in itself, stimulates a careful reading of these reports. The title assigned to me prompts me to divide my remarks--first , on the basis of the need for research and education; secondly, on how this need may be met. The importance o£ milk and milk products as a source of adequate human nutrition and part icularly in overcoming protein deficiency appears to be paramount. This is the basis for the need for education and research. Any efforts which would result in increased volume of milk per animal in the developing country would have an immediate effect in meeting the human nutritional problem. Increased production per animal may be brought about principal ly by improved nutrit ion or improved genetic ability. However, pasture management, utilization of available water supplies for irrigation, cropping practices, feed
Single-shell direct-drive capsule designs to study effects of perturbations on burn

The effect of small localized perturbations, such as fill tubes and mounting tents, on the NIF ignition capsule and the effect of hemi-joints on high gain double shell capsules are an important issue in achieving ignition on NIF. Our codes have difficulty modeling small features and their effect on mix. Because of issues of symmetry, shock timing, high-z shells, mix etc. trying to understand the effect of localized perturbations ("defect") on these high gain NIF capsules will be difficult. To begin the study of defects on DT burn, a direct-drive exploding pusher is used. Experimental results are presented for capsules with and without defects. The unperturbed capsules give reproducible yields while the perturbed capsules show significant drops in yield. Both AMR and Lasnex codes over predict the unperturbed capsule yield
Relationships Between Job Mobility and Perceived Success of Black Managers

The purposes of this investigation were to determine the role of career mobility and perceived career success by Black managers and to describe common career and personal traits among successful Black managers.
Plateletapheresis Using Single Vein Access: A Comparison of Haemonetics V‐50 and Fenwal CS‐3000 Blood Cell Separators

Donors were randomly selected for plateletapheresis using either the Haemonetics V-50 surge procedure or the Fenwal CS-3000 with special modifications. Six procedures using the V-50 were performed with 6 collection cycles. Platelet yields averaged 3.9 X 10(11) with an average white cell contamination of 3.8 X 10(8). Ten procedures were performed with 8 collection cycles. Platelet yields averaged 4.5 X 10(11) with an average white cell contamination of 1.2 X 10(8). CS-3000 procedures were performed using either 4,000 or 4,800 ml whole blood processed as the endpoint. Concentrates obtained using 4,000 ml (n = 10) as the endpoint contained 3.9 X 10(11) platelets with a white cell contamination of 9.2 X 10(8). A 4,800 ml (n = 5) endpoint produced concentrates with a yield of 4.5 X 10(11) and white cell contamination of 10.4 X 10(8).
Relationship of gestational age and cervical dilation to the timing of delivery.

Abstract Objective: To determine the effect of gestational age and cervical dilation on pregnancy continuation in women with idiopathic preterm labor who were treated with parenteral tocolysis. Method: A total of 950 women with singleton gestations, intact membranes and preterm labor treated with tocolysis prior to 34 weeks' gestation were retrospectively studied. These women were identified from the March of Dimes prematurity prevention program database. For analysis, women were categorized into five gestational age groups and three cervical dilation groups. The primary outcomes measured were the percentage of women who remained undelivered at 48 h and at 14 days post-initiation of therapy. Result: Overall, 82% of women remained undelivered after 48 h and 65% remained undelivered at 14 days. As cervical dilation advanced, the number of women remaining undelivered at 48 h and 14 days significantly decreased. However, even at ≥4 cm, 52% of women remained undelivered at 48 h. If the cervix was dilated
Proteasome inhibition induces hepatic stellate cell apoptosis

Induction of hepatic stellate cell (HSC) apoptosis attenuates hepatic fibrosis, and, therefore, mechanisms to induce HSC cell death are of therapeutic interest. Proteasome inhibitors induce apoptosis in transformed cells, especially those cells dependent upon nuclear factor kappa B (NF-kappaB) activation. Because stimulated HSCs also trigger NF-kappaB activation, the aim of this study was to determine if proteasome inhibitors induce HSC apoptosis. The immortalized human HSC line, LX-2, and primary rat HSCs were treated with the proteasome inhibitors bortezomib and MG132. Both proteasome inhibitors induced HSC apoptosis. Proteasome inhibition blocked NF-kappaB activation and, more importantly, NF-kappaB inhibition by Bay11-7082-triggered HSC apoptosis. Activated HSC survival is dependent upon the NF-kappaB target gene A1, an anti-apoptotic Bcl-2 family member, as siRNA targeted knockdown of A1-induced HSC apoptosis. In contrast, proteasome inhibition-induced alterations in TRAIL, death receptor 5, and Bim could not be implicated in the apoptotic response. The relevance of these findings was confirmed in the bile-duct-ligated mouse where bortezomib reduced hepatic markers of stellate cell activation and fibrosis. In conclusion, proteasome inhibition is a potential therapeutic strategy for inducing HSC apoptosis and inhibiting liver fibrogenesis.
Housing inequality in urban China in the 1990s

Access to housing of sufficient space and quality has been a central element in social stratification in urban China. We examine the sources of housing inequality in 1993 in Shanghai and Tianjin, when a market reform process had been underway in the national economy for nearly fifteen years. The Chinese housing allocation system favors people with political position and connections, those of higher socio-economic background, and those whose work units have greater organizational authority. There is only slight evidence that market reform has undermined this stratification order. To the contrary, there are reasons to believe that in some respects inequalities rooted in socialism are strengthened by institutional changes. These conclusions are reinforced by comparison to results of analyses of income inequality in the same cities. L'acces aux logements suffisamment spacieux et de bonne qualite est un element central de la stratification sociale en Chine urbaine. Nous examinons les origines de l'inegalite du logement en 1993 a Shangai?? et Tianjin alors qu'un processus de reforme du marche dans l'economie nationale est en cours depuis presque quinze ans. Le systeme d'allocation de logements favorise les personnes qui ont une position et des contacts politiques, les personnes d'un milieu socio-economique eleve et celles des unites de travail qui ont une plus grande autorite d'organisation. Il y a peu de preuves que les reformes du marche aient ebranle cette stratification. Au contraire, il y a des raisons de penser que certaines inegalites dont l'origine remonte au socialisme sont fortifies par les changements institutionnels. Ces conclusions sont renforcees par la comparaison des resultats des analyses des inegalites des revenus dans les memes villes.
Pharmacokinetics of Digoxin in Normal Subjects After Intravenous Bolus and Infusion Doses

Normal subjects were given 0.75 mg of intravenous digoxin as a bolus and a 1-hr infusion, Radio-immunoassayed serum concentrations obtained over 48 hr and urinary excretion rates over 6 days were simultaneously fitted to a two- compartment open model by computer nonlinear least-squares regression. Serum concentration data alone were also fitted by this program. There was good agreement in calculated parameters between the two routes of administration in five of eight subjects, but the infusion mode of administration produced less variability in the apparent pharmacokinetic constants. The β half-life values obtained from serum concentration data alone (24.2 hr) underestimated the half-lives obtained by the simultaneous fit (44.1 hr). The steady-state volume of distribution of digoxin averaged 590±164 liters (±1sd).The renal clearance of digoxin (140±41 ml/min/1.73 m 2 )was significantly higher than creatinine clearance (101±13 ml/min/ 1.73 m 2 ),indicating tubular secretion of the drug. Digoxin body clearances were 188±44 ml/min/ 1.73 m 2 ,indicating elimination of 25% of the dose by nonrenal mechanisms. Urinary excretion data are essential for proper pharmacokinetic analysis of digoxin disposition and reveal a slower rate of elimination than that suggested by earlier studies which determined only serum concentrations.
GENE EXPRESSION IN HETEROZYGOTES AND SYNTHESIS OF PLASMA ANTIHAEMOPHILIC FACTOR.

IN commenting on a communication with this title from Dr. L. J. Woolf1, we would at the outset aver that there is little or no direct evidence which bears on the points at issue. This does not preclude speculation; but the speculative nature of the comments of both Dr. Woolf and ourselves should be kept in mind.
Learning Disabilities and Eligibility for Vocational Rehabilitation Services: A Chronology of Events.

Historically, learning disabled (LD) individuals have been excluded from vocational rehabilitation services because of eligibility criteria that did not recognize learning disabilities as a mental or physical disability. Several significant events including the recognition of learning disabilities by the Diagnostic Statistical Manual III of the American Psychiatric Association, the World Health Organization's International Classification of Diseases, and the California Department of Rehabilitation created an atmosphere of acceptance in the rehabilitation community. After initial efforts to maintain the traditional posture towards learning disabilities in the rewriting of the Rehabilitation Comprehensive Services and Developmental Disabilities Amendments of 1978 (PL 95–602), the Rehabilitation Services Administration yielded to a new conceptualization which will now allow the severely learning disabled (SLD) access to rehabilitation services.
New Useful Polymers by Ring-Opening Polymerization

Abstract Recent research in ring-opening polymerizations offers promising new practical developments in polycarbonate copolymers, reaction injection molding, high-impact nylon 6, polyacetals, engineering-grade polystyrenes, polyphosphazenes, degradable plastics for biomedical products and solid waste reduction, novel thermosetting resins, and high-performance elastomers.
Laparoscopic Heller myotomy and Dor fundoplication for esophageal achalasia in children.

Background/Purpose: In the past, surgical treatment in achalasia usually has been reservedfor patients whose d ysphagia does not respond to pneumatic dilatation. The success of minimally invasive myotomy, however, has resultedin a shift in practice in adult patients, whereby laparoscopic surgery is becoming preferredas primary treatment by most gastroenterologists andsurgeons. The aim of this study was to assess the efficacy of laparoscopic Heller myotomy and Dor fundoplication for esophageal achalasia in children. Methods: Thirteen patients with esophageal achalasia (median age, 15 years; 6 boys and 7 girls; median duration of symptoms, 24 months) underwent laparoscopic Heller myotomy andDor fund oplication between 1996 and1999. Two patients hadbeen treatedpreviously by pneumatic d ilatation, and1 patient hadreceivedintrasphincteric Botulinum toxin injections. Results: Median duration of the operation was 130 minutes. The patients were fedafter an average of 33 hours, andthey all left the hospital within 2 days. At a median follow-up of 19 months, there was no residual dysphagia in any patient. Conclusions: Laparoscopic Heller myotomy andDor fundoplication were effective and safe for children with esophageal achalasia. Hospital stay andrecovery time was short, andthe functional results were excellent. These data support the notion that laparoscopic Heller myotomy shouldbecome the primary treatment of esophageal achalasia in children. J Pediatr Surg 36:1248-1251. Copyright © 2001 by W.B. Saunders Company.
NextSlidePlease: navigation and time management for hyperpresentations

Slide-ware presentations typically involve an uninterrupted progression of bulleted slides introduced by a lone figure before a passive audience. This format does not encourage active discussion or facilitate improvisational presentation of material. Two studies were conducted to evaluate how presenters author, rehearse for and deliver presentations. From these studies, feature recommendations for a prototype hyperpresentation system were developed.
Downward water flow through sloping layers in the vadose zone: time-dependence and effect of slope length

Abstract We develop a 2-D numerical model to simulate both steady-state and transient downward water flow through sloping layers in the vadose zone with a deep water table. The horizontal flow component obtained with the 2-D numerical model varies with position along the slope, but was nearly the same as the 1-D analytical solution once beyond a few meters from blocked vertical boundaries at the upper or lower end of the slope. Under time-variable precipitation, both the time delay and the peak magnitude of the response deep within the profile are not simply proportional or in one-to-one correspondence to the strength of each rainfall event, but rather depend on the initial moisture status in the profile as well as the previous rainfall events. An interesting phenomenon for the transient case is that the horizontal flow component reversed direction to upslope during the time of heavy rain. This is due to the flow pattern near the upper surface boundary (a sloping wetting front), and is a consequence of the sloping geometry. Previous studies (Warrick et al., 1996) have shown that multidimensional steady-state water flow through a sloping interface can essentially be solved by a one-dimensional analytical solution for an infinite long slope. The simulations suggest that a 1-D numerical analysis should also be valid for 2-D transient flow cases, if the slope is of sufficient length and the point of evaluation is sufficiently far from the beginning or end of the slope.
DNA polymerase activity of hepatitis B virus particles : differential inhibition by L-enantiomers of nucleotide analogs

Abstract DNA polymerase activity was assayed in hepatitis B virus (HBV) and core particles isolated from chronic producer lines. The particle-associated DNA polymerase activity, which was found to be limited to incorporation of only a few nucleotides, was inhibited by the 5′-triphosphates of nucleoside analogs. The 1-β- l (1S,4R) and 1-β- d (1R,4S) enantiomers of antiviral nucleoside analogs were compared for the ability to inhibit incorporation of natural nucleoside triphosphates into the viral DNA. Previously, both enantiomers of several analogs were found to be substrates for human immunodeficiency virus type 1 reverse transcriptase (HIV RT); the 1-β- d enantiomers of some pairs were preferred as substrates. In contrast, the 1-β- l enantiomers of all pairs tested were the more potent inhibitors of labeled substrate incorporation into hepatitis B virus DNA; the concentration required to inhibit the incorporation of the natural substrate by 50% was 6-fold to several hundred-fold lower than the concentration of the 1-β- d enantiomer required for the same inhibitory effect. This preference for the 1-β- l enantiomers was observed for both RNA-directed synthesis in core particles and DNA-directed synthesis in viral particles. The observed antiviral effect of the nucleoside analogs in cell culture seemed to be limited chiefly by their phosphorylation in cells.
Assessing long-term impacts of increased crop productivity on atmospheric CO2.

Abstract A full assessment of the impacts of land clearance and crop production on atmospheric CO2 requires a systems approach. By considering long-term soil carbon changes and fossil fuel energy inputs, we show that increased crop productivity will alleviate CO2 release to the atmosphere primarily by preventing additional land cultivation. Each hectare of cropland undergoing a simulated threefold crop productivity increase here prevents a net release on the order of 150–200 Mg C to the atmosphere over 100 years by avoiding additional land cultivation which would otherwise be required. This effective carbon sink would slowly diminish with time due to fossil fuel energy input requirements. However, future self-containment of the energy needs of high-yield crop production may displace on the order of 1.0 Pg C per year of fossil fuel carbon, in addition to the carbon sink attributable to avoided land cultivation. By avoiding land cultivation, high yield crop systems also preserve natural ecosystems.
The Networked Local Library: Developing the Vision Thing

Offers a particular forecast of library networking in coming years, within the context of individual libraries. Foresees library networking as being completely dependent on computer client/server approaches; library patrons or staff should be able to go to a single workstation and access all resources local or remotely as needed; systems will be patron friendly, and there will be less dependence on the printed word. Asserts that library networking will be based on a wireless environment that will facilitate highly mobile computing and access to information services.
Efficient evaluation of treatment effects in the presence of missing covariate values

In clinical trials, treatment comparisons are often performed by models that incorporate important prognostic factors. Since these models require complete covariate information on all patients, statisticians frequently resort to complete case analysis or to omission of an important covariate. A probability imputation technique (PIT) is proposed that involves substituting conditional probabilities for missing covariate values when the covariate is qualitative. Simulation results are presented which demonstrate that the method neither violates the size of the treatment test nor introduces additional bias for the estimation of the treatment effect. It allows use of standard software. A clinical trial of breast cancer treatment, in which an important covariate was partly missing, was analysed by Cox's model. The use of PIT resulted in smaller observed error probability compared with case deletion, and sensitivity analysis supported these results.
Reactions of trivacant Wells-Dawson heteropolytungstates. Ionic strength and Jahn-Teller effects on formation in multi-iron complexes.

Reaction of α-P2W15O5612- and Fe(III) in a saturated NaCl solution produces a trisubstituted Wells−Dawson structure with three low-valent metals, α-(FeIIICl)2(FeIIIOH2)P2W15O5911- (1). Dissolution of this species into 1 M NaBr (Br- is noncoordinating) gives the triaquated species α-(FeIIIOH2)3P2W15O599- (2). Ionic strength values of 1 M or greater are necessary to avoid decomposition of 1 or 2 to the conventional sandwich-type complex, αββα-(FeIIIOH2)2FeIII2(P2W15O56)212- (3). If the pH is greater than 5, a new triferric sandwich, ααβα-(NaOH2)(FeIIIOH2)FeIII2(P2W15O56)214- (4), forms rather than 3. Like the previously reported Wells−Dawson-derived sandwich-type structures with three metals in the central unit ([TMIIFeIII2(P2W15O56)(P2TMII2W13O52)],16- TM = Cu, Co), this complex has a central α-junction and a central β-junction. Thermal studies suggest that 4 is more stable than 3 over a wide range of temperatures and pH values. The intrinsic Jahn−Teller distortion of d-electron-containing metal ions incor...
The tree projection theorem and relational query processing

Abstract The class of relational database schemas can be partitioned into two subclasses: tree schemas and cyclic schemas. This partitioning has consequences in several areas of database theory, including query processing, dependency theory, and schema design. Query processing consequences of the partitioning are examined. Queries, called natural join queries, that compute the natural join of all relations in the database projected onto a prescribed set of attributes are considered. Also programs that solve natural join queries by applying joins, semijoins, and projections in some order are considered. It is shown that if such a program solves a natural join query then it must create an “embedded” tree schema, called a tree projection. Conversely, if a program creates a tree projection then the program augmented with a small number of semijoins solves the query. Thus, forming a tree projection is the crux of the query processing problem for natural join queries.
An overview of healthcare standards

There exists a multitude of standards with regards to health information systems (HIS) and the electronic exchange of commercial transactions containing private data that must be used amongst various service providers to adequately perform their duties to patients. The evolution of health information systems has been guided by business interests as well as from government legislation creating a somewhat fragmented system with many marginally compatible components exchanging patient sensitive information electronically. The many standards in use today include: HIPAA, EDI, HL7, DICOM, IEEE 11073, ICD-9, and CPT. This paper is a broad overview of the standards listed above as well as a brief discussion of the immediate history of healthcare standards.
Pairwise and variance balanced incomplete block designs

The purpose of this paper is three-fold. The first purpose is to compile and to systematize published and dispersed results on two aspects of balancing in incomplete block designs, i.e., pairwise balance and variance balance. This was done in order to establish the status of these two concepts of balance in published literature and to put them in a form which is useful for further work in this area. Also, the results in this form are necessary for the development of the remainder of the paper.
THE SPECTROSCOPY AND PHOTOCHEMISTRY OF ENAMINONITRILES INCLUDING THE SYNTHESIS AND IDENTIFICATION OF CIS‐β‐AMINOACRYLONITRILE

— The absorption spectral and photochemical properties of β-aminoacrylonitrile (AAN), β-aminocrotonitrile (ACN) and three other enaminonitriles have been studied. The synthesis and identification of cis-β-aminoacrylonitrile are also included. Each enaminonitrile has one intense absorption band (1–2 × 104M-1cm-1) in the 254–273 nm region. Photoisomerization and photocyclization to imidazoles are observed. Imidazole formation is quite strongly inhibited by oxygen and the presence of oxygen can cause wavelength dependent photochemistry, other reactions and destruction of the reactant. The quantum yield of formation of imidazoles is low (<10-4) for β-aminoacrylonitrile and β-aminocrotonitrile and photoisomerization dominates in those four cases where it can occur. Imidazole formation from a dimethylamino compound proves that the presence of H atoms on the amino group is not a prerequisite for photocyclization.