cssi/SciSciGPT-SciSciNet huggingface dataset:
Fabrication and Characterization of Chitosan-Hyaluronic Acid Scaffolds with Varying Stiffness for Glioblastoma Cell Culture

The invasive and recurrent nature of glioblastoma multiforme (GBM) is linked to a small subpopulation of cancer cells, which are self-renewing, resistant to standard treatment regimens, and induce formation of new tumors. Matrix stiffness is implicated in the regulation of cell proliferation, drug resistance, and reversion to a more invasive phenotype. Therefore, understanding the relationship between matrix stiffness and tumor cell behavior is vital to develop appropriate in vitro tumor models. Here, chitosan-hyaluronic acid (CHA) polyelectrolyte complex scaffolds are fabricated with statistically significant stiffness variances to characterize the effect of scaffold stiffness on morphology, proliferation, drug resistance, and gene expression in human glioblastoma cells (U-87 MG). All scaffolds support GBM proliferation over a 12-day culture period, yet larger spheroids are observed in scaffolds with higher stiffness. Additionally, GBM cells cultured in stiffer CHA scaffolds prove significantly more resistant to the common chemotherapeutic temozolomide. Moreover, the stiffer 8% CHA scaffolds exhibit an increase in expression of drug resistance and invasion related genes compared to 2D culture. CHA scaffolds present a tunable microenvironment for enhanced tumor cell malignancy and may provide a valuable in vitro microenvironment for studying tumor progression and screening anticancer therapies.
KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia.

High-risk B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge despite advances in the use of tyrosine kinase inhibitors and chimeric-antigen-receptor engineered T cells. Lymphoblastic-leukemia precursors are highly sensitive to oxidative stress. KLF5 is a member of the Kruppel-like family of transcription factors. KLF5 expression is repressed in B-ALL, including BCR-ABL1+ B-ALL. Here, we demonstrate that forced expression of KLF5 in B-ALL cells bypasses the imatinib resistance which is not associated with mutations of BCR-ABL. Expression of Klf5 impaired leukemogenic activity of BCR-ABL1+ B-cell precursors in vitro and in vivo. The complete genetic loss of Klf5 reduced oxidative stress, increased regeneration of reduced glutathione and decreased apoptosis of leukemic precursors. Klf5 regulation of glutathione levels was mediated by its regulation of glutathione-S-transferase Mu 1 (Gstm1), an important regulator of glutathione-mediated detoxification and protein glutathionylation. Expression of Klf5 or the direct Klf5 target gene Gstm1 inhibited clonogenic activity of Klf5∆/∆ leukemic B-cell precursors and unveiled a Klf5-dependent regulatory loop in glutamine-dependent glutathione metabolism. In summary, we describe a novel mechanism of Klf5 B-ALL suppressor activity through its direct role on the metabolism of antioxidant glutathione levels, a crucial positive regulator of leukemic precursor survival.
Spectral Approximation on the Square

Before extensions to complex geometries are considered, Chapter 5 derives and shows how to implement spectral methods on the square domain Ω=[−1,1]×[−1,1]. Spectral approximations are developed for three canonical problems in mathematical physics: The solution of steady potentials, transport with and without diffusion, and wave propagation. These physical processes are modeled by the Poisson equation, the advection-diffusion equation, the scalar advection equation, and systems of conservation laws. Benchmark solutions include potentials on the square, advection and diffusion of a circular spot in a uniform flow, planewave propagation with and without reflection, and propagation of a circular sound wave.
“And Send Her Well-Dos’d to the Grave”: Literary Medical Horror

Medical horror includes autonomous changes in the body by natural or accidental occurrences—disease, injury, age, death—as well as interactions with medical institutions and their authorities. Kremmel argues that the figure of the physician and location of the medical space inherit many characteristics of the tyrant and the castle found in classic horror texts. These literary tropes become subsumed onto scientific settings and situations that shift horror from external supernatural threat to internal anatomical threat. Medical horror draws from and heightens fears of the body, as well as of medical institutions and authorities. Kremmel surveys a variety of medical horror texts from the eighteenth through the twenty-first centuries, including focused discussions of authors Matthew Lewis, Samuel Warren, Mrs. Carver, Ira Levin, Robin Cook, and Catriona Ward.
Effects of removing woody cover on long‐term population dynamics of a rare annual plant (Agalinis auriculata): A study comparing remnant prairie and oldfield habitats

Worldwide, grasslands are becoming shrublands/forests. In North America, eastern red cedar (Juniperus virginiana) often colonizes prairies. Habitat management can focus on woody removal, but we often lack long-term data on whether removal leads to population recovery of herbaceous plants without seeding. We undertook a long-term study (17 years) of numbers of the rare annual plant Agalinis auriculata in a gridwork of 100 m2 plots in adjacent prairie and oldfield sites in Kansas, USA. We collected data before and after removal of Juniperus virginiana at the prairie. Plant population sizes were highly variable at both sites and over time. High numbers of plants in a plot 1 year were often followed by low numbers the following year, suggesting negative density-dependence. Plant numbers were lowest with extensive woody cover and with low precipitation. After woody plant removal, A. auriculata increased dramatically in abundance and occupancy in most years; increases were also seen at the oldfield, suggesting later survey years were overall more favorable. Synthesis and applications: Removal of woody plants led to increased numbers of a rare annual prairie plant, without seeding. Multiple years of data were essential for interpretation given extreme temporal variability in numbers. The largest prairie population was 7 years following tree removal, showing that positive effects of management can last this long. This species also fared well in oldfield habitat, suggesting restoration opportunities. Given that land managers are busy, time-efficient field methods and data analysis approaches such as ours offer advantages. In addition to general linear models, we suggest Rank Occupancy-Abundance Profiles (ROAPs), a simple-to-use data visualization and analysis method. Creation of ROAPs for sites before and after habitat management helps reveal the degree to which plant populations are responding to management with changes in local density, changes in occupancy, or both.
2018 Langley Award for Basic Research on Nicotine and Tobacco: Bringing Precision Medicine to Smoking Cessation.

INTRODUCTION Large segments of the world population use combustible cigarettes, and our society pays a high price for smoking, through increased healthcare expenditures, morbidity and mortality. The development of combustible cigarette smoking requires the initiation of smoking and a subsequent chain of behavioral transitions from experimental use, to established regular use, to the conversion to addiction. Each transition is influenced by both environmental and genetic factors, and our increasing knowledge about genetic contributions to smoking behaviors opens new potential interventions. METHODS This review describes the journey from genetic discovery to the potential implementation of genetic knowledge for the treatment of tobacco use disorder. RESULTS AND CONCLUSIONS The field of genetics applied to smoking behaviors has rapidly progressed with the identification of highly validated genetic variants that are associated with different smoking behaviors. The large scale implementation of this genetic knowledge to accelerate smoking cessation represents an important clinical challenge in precision medicine.
On the central role of mitochondria dysfunction and oxidative stress in Alzheimer's disease.

Alzheimer’s disease (AD) is the commonest cause of dementia, with approximately 5 million new cases occurring annually. Despite decades of research, its complex pathophysiology and etiopathogenesis presents a major hindrance to the development of an effective treatment and prevention strategy. Aging is the biggest risk factor for the development of AD, and the total number of older people in the population is going to significantly increase in the next decades, suggesting that AD incidence and prevalence is likely to increase in the future. This makes the need for a better understanding of the disease to be extremely urgent. A search was done by accessing PubMed/Medline, EBSCO, and PsycINFO databases. The search string used was “(dementia* OR Alzheimer’s) AND (pathophysiology* OR pathogenesis)”. New key terms were identified (new term included “vitamin D, thyroid hormone, mitochondria dysfunction, oxidative stress, testosterone, estrogen, melatonin, progesterone, luteinizing hormone, amyloid-β (Aβ), and hyperphosphorylated tau”). The electronic databases were searched for titles or abstracts containing these terms in all published articles between January 1, 1965, and January 31, 2019. The search was limited to studies published in English and other languages involving both animal and human subjects. Mitochondria dysfunction and oxidative stress play a critical role in AD etiopathogenesis and pathophysiology. AD treatment and prevention strategies must be geared towards improving mitochondrial function and attenuating oxidative stress.
Multi-year and Multi-site Establishment of the Perennial Biomass Crop Miscanthus × giganteus Using a Staggered Start Design to Elucidate N Response

Much field research on perennial bioenergy crops confounds effects of plant age with those of the growing season, which increases uncertainty and the potential for erroneous conclusions, particularly in maturing stands. Most studies rely on stands planted in a single year and measured across multiple subsequent seasons. These “single-start” designs lack statistical power to separate temporal from environment effects. We used a staggered start experimental design to learn if increased statistical power clarified understanding of Miscanthus × giganteus nitrogen (N) needs. We conducted a staggered start experiment with three planting years and five N rates during the M. × giganteus yield-building phase at three sites across IA, USA. Third-year yields were 21.0, 25.0, and 27.1 Mg dry matter (DM) ha−1 at the northwest (NW), central, and southeast (SE) sites, respectively. Nitrogen fertilization effects changed with establishment conditions, but not with plant age. At the most N responsive site, N fertilizer changed yields at all stand ages, but not in every year. Yield increases of 150%, 36%, and 40% were observed in 1-, 2-, and 3-year-old stands, respectively, with N addition. Nitrogen effects on 1-year-old stands were positive in SE IA (2.7 kg DM kg−1 N added), negative (− 2.3 kg DM kg−1 N) in NW IA, and variable in central IA (− 2.2–9.6 kg DM kg−1 N), suggesting a site–year-specific response. Yield increases between the first and second years varied by > 100% depending on establishment conditions, highlighting the need for repeated planting before determining economic and agronomic crop viability.
Electrolytes for microsized silicon

Microsized battery anodes such as silicon offer cost advantages over nanosized counterparts but suffer from poor cycling stability. Now, an electrolyte design is reported to enable a LiF-rich solid–electrolyte interphase that stabilizes microsized silicon over a reasonably long cycle life.
A tutorial on Bayesian parameter inference for dynamic energy budget models

Mechanistic representations of individual life-history trajectories are powerful tools for the prediction of organismal growth, reproduction and survival under novel environmental conditions. Dynamic energy budget (DEB) theory provides compact models to describe the acquisition and allocation of organisms over their full life cycle of bioenergetics. However, estimating DEB model parameters, and their associated uncertainties and covariances, is not trivial. Bayesian inference provides a coherent way to estimate parameter uncertainty, and propagate it through the model, while also making use of prior information to constrain the parameter space. We outline a Bayesian inference approach for energy budget models and provide two case studies -- based on a simplified DEBkiss model, and the standard DEB model -- detailing the implementation of such inference procedures using the open-source software package deBInfer. We demonstrate how DEB and DEBkiss parameters can be estimated in a Bayesian framework, but our results also highlight the difficulty of identifying DEB model parameters which serves as a reminder that fitting these models requires statistical caution.
The only difference between a jail and a psychiatric hospital is a pillow

This is an article looking at the problems I have noticed in psychiatric hospitals as a patient with schizophrenia.
Technoecologies: The Interplay of Space and Its Perception

The essay presents how Technoecologies exhibition at the intersection of art, architecture, and humanities reconceives the relationship between humans and their environment in architecture through prototypes and models that explore emerging forms of bioarchitecture, living systems, and evolving environments. Technoecologies exhibition proposes a metabolic architecture as a provocative alternative approach, being manifested by speculative yet tangible ways (technoutopia vision). Metabolic architecture is contemplated here both literally, and metaphorically. Literally, it deals with material transformations caused by either growth or decay of organic matter. Metaphorically, it relates to immaterial transformations of light or sound caused by environmental or artificial stimuli. Through these processes, metabolism within architecture becomes an apparatus that produces constant changes in form, space, and in user perception. Through a series of concepts/modes such as metamaquettes and installations, the notion of experiment and experience, metabolic aesthetics, the binary of ordinary and illusionary, empathy and vulnerability, as well as public participation and user engagement, Technoecologies exhibition let us envision the possibility of this future world, and its positive and playful aspects.
ProSPECT: Proactive Storage Using Provenance for Efficient Compute and Tiering

AI and analytics applications are good at deriving meaningful insights from data, but they do not always cope well with the storage management challenges that come with a high pace of data generation. At the same time, a conventional data storage and management layer is not optimized to derive timely insights and value from huge volumes of data. This problem is rooted in a classical cross-layer dilemma wherein neither the application nor the storage layer has the deep knowledge needed to optimize the whole system. We resolve this omniscience dilemma by introducing ProSPECT, a set of techniques to proactively optimize analytics computations and data storage. ProSPECT enables a data fabric to become aware of the purpose and relevance of stored data by intercepting the lineage of workflows under execution within existing analytics frameworks. Partial analytics computations can then be initiated proactively by the data fabric layer, where data is stored and managed. ProSPECT provides analytics applications with relevant data or precomputed insights and alleviates storage management challenges using proactive tiering and data approximation. We describe experiments with application case studies using Apache Spark and Alluxio to demonstrate an order of magnitude reduction in the storage space occupied in the fastest tier and in time to value for analytics applications.
Leucine Pulses during Long-term Continuous Feeding Enhance mTORC1 and mTORC2 Activation in Skeletal Muscle of Neonatal Pigs

Infants who are unable to feed normally may be nourished continuously by orogastric tube. We recently showed that continuous feeding reduces lean accretion in neonatal pigs but this can be improved by administration of intermittent leucine pulses. However, the molecular mechanism of this phenomenon has not been fully assessed. In this study, neonatal piglets (n=23) were fed continuously a milk replacement formula via orogastric tube for 21 d with an additional parenteral infusion of either leucine (800 μmol•kg–1•h–1, Leu) or alanine (Ala) for 1 h every 4 h. To evaluate leucine action towards the protein synthesis regulator, mTOR, we determined mTORC1 and mTORC2 activation by analyzing intrinsic mTORC-specific catalytic activity (mTORC1- and mTORC2-associated mTOR Ser-2481 autophosphorylation). We also measured the protein abundance of regulatory components within and upstream of mTORC1 and mTORC2. Activation of mTORC1 and mTORC2 was higher in the Leu than Ala group. Deptor abundance was lower in the Leu t...
Bovine liver flutamate dehydrogenase. Sequence of a hexadecapeptide containing a lysyl residue reactive with pyridoxal 5'-phosphate.

Glutamate dehydrogenase is reversibly inhibited by the reaction of 1 mole of pyridoxal 5'-phosphate per mole of subunit polypeptide chain of the enzyme. Reduction of the pyridoxal 5'-phosphate-inactivated enzyme with NaBH4, followed by alkylation of the thiol groups and subsequent tryptic digestion, yielded a single fluorescent peptide which after acid hydrolysis, gave approximately 1 eq of e-pyridoxyllysine. This peptide was recognized by its amino acid composition as an overlap of two tryptic peptides which had been isolated and sequenced independently. The hexadecapeptide has the sequence: Cys-Ala-Val-Val-Asp-Pro-Val-Phe-Gly-Gly-Ala-Lys*-Ala-Gly-Val-Lys.
Probability Modeling and Statistical Inference in Periodic Cancer Screening

Early detection and efficient treatments are the most effective ways to increase the cure rate or prolong survival of cancer patients. The primary technique for implementing early detection is screening exams, by which the disease may be found before symptoms are present. There are many different kinds of cancer screenings in the world, such as mammogram and clinical breast exam (CBE) for breast cancer, chest X-ray or computed tomography (CT) scanning for lung cancer, fecal occult blood test (FOBT) for colon cancer, prostate-specific antigen (PSA) for prostate cancer, etc. Probability modeling in cancer screening was dated back to 1969, right after the Health Insurance Plan of Greater New York (HIP) study was close to an end. The HIP study, which began at the end of 1963, was the first randomized clinical trial to examine regular screening exams that include mammography as a diagnostic screening test for breast cancer. The study randomized initially asymptomatic women aged 40 to 64 years without a history of breast cancer to two groups: the study group and the control group. Each group consisted of about 31,000 women. The screening program for the study group called for up to 4 annual breast cancer screening exams, with each screening exam including both a mammogram and a clinical breast exam. The control group received usual care [16]. Zelen and Feinleib [32] in their first paper on screening proposed the disease progressive model: the disease develops by progressing through 3 states, denoted by S0 → Sp → Sc (Fig. 10.1). S0 refers to the disease-free state or the state in
The Goldilocks Dilemma: Homework Policy Creating a Culture Where Simply Good Is Just Not Good Enough.

Abstract Throughout the decades of educational reform cycles, the value of homework has proven either meaningful or meaningless depending on the reforming framework. Questions about homework as simply busy work or knowledge work, mere content distraction or content extension, ambivalence toward importance, or discipline of character all cloud any conclusions about homework, good or bad. Our research is a case study of one rural, high school that has created a No Excuses Homework expectation that is embedded in the school's culture. Focus groups of faculty and students, interviews with both the principal and assistant principal, combined with quantitative data reveal a cultural shift within the organization. Three themes emerge as contributors to a cultural transformation around homework expectations: initial and ongoing professional development exploring the creation of meaningful homework assignments and consistent quality expectations, continuous support for students and parents in meaningful homework s...
A Study of the Moraxella Group II. Oxidative-negative Species (Genus Acinetobacter)

A number of nutritional and biochemical properties of more than 100 strains of the oxidase-negative moraxellas (the Mima-Herellea-Acinetobacter group of bacteria) were studied. These properties included the range of carbon sources that can support growth, the utilization of nitrate, the production of proteolytic and lipolytic enzymes, and the reactions involved in the oxidation of sugars and of aromatic compounds. No evidence could be obtained for the accumulation of either poly-beta-hydroxybutyrate or polysaccharide as intracellular reserve materials. Of 158 different compounds tested, the group as a whole could use 85 as sole carbon sources for growth. The nutritional spectra of the individual strains, however, differed widely, with a range of from 17 to 74 alternative substrates. On the basis of 56 selected nutritional and physiological characters used for a numerical analysis, the collection could be divided into two major groups of strains comprising at least seven less clearly defined clusters. Neither the hydrolysis of gelatin nor acid production from aldose sugars was found to be a reliable index of strain affinities indicated by the phenotypic analysis, although both properties were of some use in distinguishing between the subgroups. For reasons that are discussed, we propose that the oxidase-negative moraxellas be placed in the genus Acinetobacter Brisou and Prevot, for which a modified description is presented. A. calco-aceticus (Beijerinck) is proposed as the type species, of which anitratum is regarded as a synonym or variety. On the basis of the present studies and unpublished supporting evidence provided by M. Mandel on deoxyribonucleic acid (DNA) composition and by J. Johnson on DNA homologies, it is proposed that two other species in the genus, A. lwoffi (Audureau) and A. hemolysans (Henriksen), as well as one subspecies, A. hemolysans haemolyticus (Stenzel and Mannheim), be recognized provisionally.
Mobile Tech and the Librarian: The iTest iPad Project

A 2012 project provided forty-eight health sciences librarians from primarily hospital and academic health sciences libraries with an Apple iPad2 along with training and support on its use. Project objectives were to determine how participants would adopt the iPad into their daily operations and what form of leadership role they would play while participating in the project. By project's end eighty-nine percent indicated they would continue using the iPad primarily as a productivity tool and to provide point of need services. Project data indicated that librarians assumed a leadership role promoting the use of mobile technology and the applications available.
Contemporary Results of Aortic Coarctation Repair Through Left Thoracotomy

Background Although surgical results for repair of coarctation of the aorta (CoA) have steadily improved, management of this condition remains controversial. The purposes of this study were to analyze the long-term outcomes of patients undergoing CoA repair through left thoracotomy and to define risk factors for reintervention. Methods All patients who were less than 18 years old and who underwent initial repair of CoA through left thoracotomy from 1995 to 2013 at Texas Children's Hospital (Houston, TX) were included. Patients were classified into 3 groups: 143 (42%) neonates (0 to 30 days old), 122 (36%) infants (31 days to 1 year old), and 78 (23%) older children (1 to 18 years old). Univariate and multivariate analyses were performed. Results A total of 343 patients (129 [38%] girls) with median age of 53 days (interquartile range [IQR],12 days to 9 months) and weight of 4.1 kg (IQR, 3.1 to 8.0) underwent repair with extended end-to-end anastomosis (291 patients [85%]), end-to-end anastomosis (44 patients [13%]), interposition graft (2 patients [0.6%]), or subclavian flap (6 patients [2%]). Concomitant diagnoses included genetic abnormalities (48 patients [14%]), isolated ventricular septal defects (58 patients [17%]), small left-sided structures (53 patients,16%), or other complex congenital heart disease (18 patients [5%]). Perioperative mortality was 1% (n = 4, all neonates). At a median follow-up of 6 years (7 days to 19 years), only 14 (4%) patients required reintervention (10 catheter-based procedures, 6 surgical repairs). A postoperative peak velocity of 2.5 m/s or greater was an independent risk factor for reintervention (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.4 to 11.6). Within the cohort, 95 (33%) patients were hypertensive or remained on cardiac medications a median of 12 years (6 months to 19 years) after the surgical procedure. Development of perioperative hypertension was associated with higher risk of chronic hypertension or cardiac medication dependency (OR, 1.9; 95% CI, 1.1 to 3.3). Conclusions CoA repair through left thoracotomy is associated with low rates of morbidity, mortality, and reintervention. Aortic arch obstruction should be completely relieved at the time of surgical intervention to minimize the risk of long-term recoarctation.
Focused and Model Average Estimation for Regression Analysis of Panel Count Data

Panel count data arise in many fields and a number of estimation procedures have been developed along with two procedures for variable selection. In this paper, we discuss model selection and parameter estimation together. For the former, a focused information criterion (FIC) is presented and for the latter, a frequentist model average (FMA) estimation procedure is developed. A main advantage, also the difference from the existing model selection methods, of the FIC is that it emphasizes the accuracy of the estimation of the parameters of interest, rather than all parameters. Further efficiency gain can be achieved by the FMA estimation procedure as unlike existing methods, it takes into account the variability in the stage of model selection. Asymptotic properties of the proposed estimators are established, and a simulation study conducted suggests that the proposed methods work well for practical situations. An illustrative example is also provided. © 2014 Board of the Foundation of the Scandinavian Journal of Statistics
Examining the Role of Antisocial Personality Disorder in Intimate Partner Violence Among Substance Use Disorder Treatment Seekers With Clinically Significant Trauma Histories

This study examined the associations among posttraumatic stress disorder (PTSD) symptom severity, antisocial personality disorder (ASPD) diagnosis, and intimate partner violence (IPV) in a sample of 145 substance abuse treatment-seeking men and women with positive trauma histories; sex was examined as a moderator. ASPD diagnosis significantly predicted both verbal and physical aggression; sex moderated the association between ASPD diagnosis and physical violence. PTSD symptom severity significantly predicted engaging in verbal, but not physical, aggression. Overall, these results suggest that an ASPD diagnosis may be an important risk factor for engaging in IPV among women seeking treatment for a substance use disorder.
Skin Advanced Glycation End Products Glucosepane and Methylglyoxal Hydroimidazolone Are Independently Associated With Long-term Microvascular Complication Progression of Type 1 Diabetes

Six skin collagen advanced glycation end products (AGEs) originally measured near to the time of the Diabetes Control and Complications Trial (DCCT) closeout in 1993 may contribute to the "metabolic memory" phenomenon reported in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. We have now investigated whether the addition of four originally unavailable AGEs (i.e., glucosepane [GSPNE], hydroimidazolones of methylglyoxal [MG-H1] and glyoxal, and carboxyethyl-lysine) improves associations with incident retinopathy, nephropathy, and neuropathy events during 13-17 years after DCCT. The complete 10-AGE panel is associated with three-step Early Treatment of Diabetic Retinopathy Study scale worsening of retinopathy (P ≤ 0.002), independent of either mean DCCT or EDIC study A1C level. GSPNE and fructose-lysine (furosine [FUR]) correlate with retinopathy progression, independently of A1C level. The complete panel also correlates with microalbuminuria (P = 0.008) and FUR with nephropathy independently of A1C level (P ≤ 0.02). Neuropathy correlates with the complete panel despite adjustment for A1C level (P ≤ 0.005). MG-H1 and FUR are dominant, independent of A1C level (P < 0.0001), whereas A1C loses significance after adjustment for the AGEs. Overall, the added set of four AGEs enhances the association of the original panel with progression risk of retinopathy and neuropathy (P < 0.04) but not nephropathy, while GSPNE and MG-H1 emerge as the principal new risk factors. Skin AGEs are robust long-term markers of microvascular disease progression, emphasizing the importance of early and sustained implementation of intensive therapy.
CONTRIBUTION OF O6-METHYLGUANINE-DNA METHYLTRANSFERASE TO MONOFUNCTIONAL ALKYLATING-AGENT RESISTANCE IN HUMAN BRAIN TUMOR-DERIVED CELL LINES

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been implicated in resistance of human brain tumors to alkylating agents. We observed that 14 human medulloblastoma- and glioma-derived cell lines differ in sensitivity to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), as shown by their 28-fold range in 10% survival dose (LD10). By using the substrate analogue inhibitor O6-benzylguanine (O6-BG), we showed that the contribution of MGMT to resistance varies widely, as evidenced by 3- to 30-fold reductions in LD10 among the lines, and varies up to 20-fold among subpopulations of individual lines. Importantly, variability in resistance, manifested as a 20-fold range in LD10, persists after measurable MGMT is eliminated, disclosing differential contributions of other resistance mechanisms to survival. Cells exposed to MNNG while suspended in growth medium are more resistant than cells alkylated as subconfluent monolayers, and MGMT accounts for a smaller proportion of their resistance. Notably, the MGMT content of the lines is not statistically correlated with MNNG resistance or with potentiation of killing by O6-BG, even though MGMT is a biochemically demonstrated determinant of resistance. In contrast, the same lines vary less in resistance to the ethylating agent N-ethylnitrosourea (ENU), and MGMT makes only a small contribution to resistance. Our results strongly indicate that resistance to both MNNG and ENU is multifactorial.
A water-soluble fraction from adult bone stimulates the differentiation of cartilage in explants of embryonic muscle

Abstract A water-soluble fraction of a 4 M , guanidine HCI extract of demineralized adult bovine bone stimulated the differentiation of cartilage in explants of minced skeletal muscle from embryonic chick legs; cartilage was also induced by a semipurified protein preparation. Cartilage could be identified in treated cultures at 1 week with muscle from day-9 embryos, not before 2 weeks with muscle from day-12 embryos, and not before 3 weeks with muscle from day-19 embryos. The ability to respond to this water-soluble fraction by exhibiting cartilage differentiation was dosedependent, but not confined to any particular muscle region of the day-12 embryonic leg. These observations indicate that bone-derived soluble chondroinductive agents act on cells in minced embryonic muscle preparations. The induction of cartilage is dependent upon the accessibility of the responding cells to the agents, on the concentration of inductive agents, and on the developmental age of the responsive tissue.
Toward a Methodology for the Measurement of Knowledge Structures of Ordinary People: The Conceptual Content Cognitive Map (3CM)

Mental models guide people's perceptions, decisions, and behavior regarding environmental problems and other issues. Hence, understanding these models would aid in understanding how people perceive problems, in determining how information may be most effectively shared, and in designing strategies for behavior change. Given this need for assessment, it would be helpful to expand the repertoire of available measurement approaches. The 3CM method, based on an extended theory of cognitive maps, is proposed as a new approach to assessing people's mental models. This approach is unique in its emphasis on the notion of "ownership" of the concepts that serve as landmarks in the cognitive map. Two recently developed implementations of the approach, each suited to different contexts and purposes, are described. Preliminary results suggest that the approach meets the criteria of construct validity, of being user friendly, and of providing information complementary to that obtained using traditional measures.
Team roles and team performance: Is there ‘really’ a link?

Belbin's (1981, 1993) team role theories are evaluated in terms of the claim that high team performance is associated with teams which are balanced in terms of the team roles represented amongst team members. Eleven teams from a mixture of private and public organizations were surveyed to test the proposition that a balanced team will be a high performing team and vice versa. Issues of measurement of team balance and team performance are addressed. The research is believed to be unique in including a number of criteria for team role balance rather than the single, simplistic measure frequently used. An innovative measure of team performance is used. The results of the investigation give some support to the link Belbin makes between team role balance and team performance. These are discussed in the light of the paucity of rigorous research in this area to date.
Transoesophageal echocardiography in cardiac anaesthesia and intensive care

Abstract Transoesophageal echocardiography (TOE) is being increasingly used throughout the field of anaesthesia and intensive care and nowhere has its impact been greater than in cardiac practice. This article outlines the main uses for TOE in current practice and explores the different ways in which it may affect anaesthetic and surgical management. Use of TOE for diagnostic purposes includes the assessment of valvular and other pathologies as well as for the rapid diagnosis of acute hypotension. Its use as a monitor for ischaemia and haemodynamic disturbances is also discussed. The importance of training and quality assurance are examined from a user's perspective and lastly a glimpse into the future reveals the enticing prospect of real-time 3 dimensional cardiac imaging.
A comparison of attitudes toward meat and animals among strict and semi-vegetarians

Abstract A number of studies have documented a phenomenon whereby individuals self-identify as vegetarians but then simultaneously acknowledge that they eat red meat, chicken, and/or fish. Despite being a consistent and fairly robust effect, there has been little attempt to explain these semi-vegetarians, why they would define themselves in a category whose membership criteria they violate, and ways they might differ from strict vegetarians. The present research highlights possible reasons for the discrepancy and focuses on several dimensions that may demarcate semi-from strict vegetarians: belief in human–animal similarity and liking of and disgust toward meat. Survey results indicated that semi-vegetarians ( n = 57) were less likely to dislike meat and to find meat disgusting than were strict vegetarians ( n = 157), even accounting for diet motives. There were no differences between the groups in their beliefs about human–animal similarity although semi-vegetarians who consumed a wider range of animal products perceived marginally less human–animal similarity than those who consumed only fish. The results suggest that semi-vegetarians are distinct from strict vegetarians primarily in their evaluation of and disgust toward meat, likely as a cause or consequence of their occasional consumption of animal flesh.
Mechanistic aspects of in vitro fatigue-crack growth in dentin

Although the propagation of fatigue cracks has been recognized as a problem of clinical significance in dentin, there have been few fracture mechanics-based studies that have investigated this issue. In the present study, in vitro cyclic fatigue experiments were conducted over a range of cyclic frequencies (1-50 Hz) on elephant dentin in order to quantify fatigue-crack growth behavior from the perspective of understanding the mechanism of fatigue in dentin. Specifically, results obtained for crack extension rates along a direction parallel to the dentinal tubules were found to be well described by the stress-intensity range, DeltaK, using a simple Paris power-law approach with exponents ranging from 12 to 32. Furthermore, a frequency dependence was observed for the crack-growth rates, with higher growth rates associated with lower frequencies. By using crack-growth experiments involving alternate cyclic and static loading, such fatigue-crack propagation was mechanistically determined to be the result of a "true" cyclic fatigue mechanism, and not simply a succession of static fracture events. Furthermore, based on the observed frequency dependence of fatigue-crack growth in dentin and observations of time-dependent crack blunting, a cyclic fatigue mechanism involving crack-tip blunting and re-sharpening is proposed. These results are deemed to be of importance for an improved understanding of fatigue-related failures in teeth.
X-ray photoelectron angular distributions with dispersion-compensating x-ray and electron optics

Abstract A general model for predicting instrumental effects on intensifies and line-shapes in angle-resolved X-ray photoemission experiments is presented. This
Self-consistent relaxation-time models in quantum mechanics

ABSTRACT. This paper is concerned with the relaxation-time von Neumann- Poisson (or quantum Liouville-Poisson) equation in three spatial dimensions which describes the self-consistent time evolution of an open quantum me- chanical system that includes some relaxation mechanism. This model and the equivalent relaxation-time Wigner-Poisson system play an important role in the simulation of quantum semiconductor devices. For initial density matrices with finite kinetic energy, we prove that this problem, formulated in the space of Hermitian trace class operators, admits a unique global strong solution. A key ingredient for our analysis is a new generalization of the Lieb-Thirring inequality for density matrix operators.
Cryostat design for the superconducting super collider dipole

The vacuum vessel, thermal shields, mechanical supports, and interconnections are described for cryostats used in SSC magnets. (AIP)
On the use and misuse of profit functions for measuring the price responsiveness of peasant farmers: A comment

The standard profit function approach has been applied successfully in a number of LDCs to measure the price responsiveness of peasant farmers. Yet, various problems afflict this approach including, but not restricted to, the existence of non‐competitive market structures, zero‐valued observations, exclusion of relevant variables, lack of participation in output and/or input markets, and endogeneity of input and/or output prices. The impact of these problems on estimation results, however, can be minimised through modifications and adaptations of the standard approach, better specification of the underlying technology, and the use of selected functional forms.
Arctic sea ice albedo from AVHRR

The seasonal cycle of surface albedo of sea ice in the Arctic is estimated from measurements made with the Advanced Very High Resolution Radiometer (AVHRR) on the polar-orbiting satellites NOAA-10 and NOAA-11. The albedos of 145 200-km-square cells are analyzed. The cells are from March through September 1989 and include only those for which the sun is more than 10 deg above the horizon. Cloud masking is performed manually. Corrections are applied for instrument calibration, nonisotropic reflection, atmospheric interference, narrowband to broadband conversion, and normalization to a common solar zenith angle. The estimated albedos are relative, with the instrument gain set to give an albedo of 0.80 for ice floes in March and April. The mean values for the cloud-free portions of individual cells range from 0.18 to 0.91. Monthly averages of cells in the central Arctic range from 0.76 in April to 0.47 in August. The monthly averages of the within-cell standard deviations in the central Arctic are 0.04 in April and 0.06 in September. The surface albedo and surface temperature are correlated most strongly in March (R = -0.77) with little correlation in the summer. The monthly average lead fraction is determined from the mean potential open water, a scaled representation of the temperature or albedo between 0.0 (for ice) and 1.0 (for water); in the central Arctic it rises from an average 0.025 in the spring to 0.06 in September. Sparse data on aerosols, ozone, and water vapor in the atmospheric column contribute uncertainties to instantaneous, area-average albedos of 0.13, 0.04, and 0.08. Uncertainties in monthly average albedos are not this large. Contemporaneous estimation of these variables could reduce the uncertainty in the estimated albedo considerably. The poor calibration of AVHRR channels 1 and 2 is another large impediment to making accurate albedo estimates.
Neighborhood socioeconomic status predictors of physical activity through young to middle adulthood: The CARDIA study

Neighborhood socioeconomic status (SES) is related to a wide range of health outcomes, but existing research is dominated by cross-sectional study designs, which are particularly vulnerable to bias by unmeasured characteristics related to both residential location decisions and health-related outcomes. Further, little is known about the mechanisms by which neighborhood SES might influence health. Therefore, we estimated longitudinal relationships between neighborhood SES and physical activity (PA), a theorized mediator of the neighborhood SES-health association. We used data from four years of the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 5115, 18-30 years at baseline, 1985-1986), a cohort of U.S. young adults followed over 15 years, and a time-varying geographic information system. Using two longitudinal modeling strategies, this is the first study to explicitly examine how the estimated association between neighborhood SES (deprivation) and PA is biased by (a) measured characteristics theorized to influence residential decisions (e.g., controlling for individual SES, marriage, and children in random effects models), and (b) time-invariant, unmeasured characteristics (e.g., controlling for unmeasured motivation to exercise that is constant over time using repeated measures regression modeling, conditioned on the individual). After controlling for sociodemographics (age, sex, race) and individual SES, associations between higher neighborhood deprivation and lower PA were strong and incremental in blacks, but less consistent in whites. Furthermore, adjustment for measured characteristics beyond sociodemographics and individual SES had little influence on the estimated associations; adjustment for unmeasured characteristics attenuated negative associations more strongly in whites than in blacks.
Endoluminal gastroplication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies.

Background: Patients with classic gastroesophageal reflux disease (GERD) symptoms and borderline 24‐h pH studies are not considered to be good candidates for surgical fundoplication. Endoluminal gastroplication (ELGP) is a new endoscopic treatment for patients with GERD. The aim of this study was to evaluate the efficacy of ELGP in these patients. Methods: Patients with heartburn, regurgitation symptoms and a DeMeester score of less than 30 were studied. ELGP involved placement of two or three plications within 2 cm of the gastroesophageal junction. Clinical outcomes measured were heartburn symptom score (HSS), regurgitation frequency score (RFS) and medication use. Results: Twenty‐five patients (11 M, 14 F, mean age of 51 years) had a medication use of 11.5 doses of proton‐pump inhibitors per week prior to ELGP. Average lower esophageal sphincter pressure measured 15 ± 8 mmHg, and average DeMeester score was 18 ± 8. Nine patients had hiatal hernias and 11 had esophagitis. Twenty‐four patients were availa...
Forming doublons by a quantum quench

Repulsive interactions between particles on a lattice may lead to bound states, so called doublons. Such states may be created by dynamically tuning the interaction strength, e.g. using a Feshbach resonance, from attraction to repulsion. We study the doublon production efficiency as a function of the tuning rate at which the on-site interaction is varied. An expectation based on the Landau-Zener law suggests that exponentially few doublons are created in the adiabatic limit. Contrary to such an expectation, we found that the number of produced doublons scales as a power law of the tuning rate with the exponent dependent on the dimensionality of the lattice. The physical reason for this anomaly is the effective decoupling of doublons from the two-particle continuum for center-of-mass momenta close to the corners of the Brillouin zone. The study of doublon production may be a sensitive tool to extract detailed information about the band structure.
Changes in α-adrenergic receptors in dog livers during endotoxic shock

The effects of endotoxin administration on α-adrenergic receptors in dog liver plasma membranes were studied using [3H]dihydroergocryptine as a radioactive ligand. The Scatchard analysis revealed a two-component binding characteristic both in control and endotoxin-injected dogs. The Kd (dissociation constant) of the high-affinity component was increased by 32.5% (0.4 ± 0.04 nM for control vs 0.53 ± 0.06 nM for endotoxic; P < 0.05) with no significant change in the Kd for the low-affinity component (3.0 ± 0.44 nM for control vs 3.4 ± 0.44 nM for endotoxic) 2 hr following endotoxin administration. The maximum binding capacity of the high-affinity component was decreased by 38.1% (460 ± 19.3 and 285 ± 14.8 fmole/mg protein for control and endotoxic, respectively; P < 0.01) and that of the low-affinity component was decreased by 34.2% (1050 ± 66.4 and 690 ± 44.6 fmole/mg protein for control and endotoxic, respectively; P < 0.05) 2 hr after endotoxin injection. The competitive inhibition studies show that the apparent Kd values for (−)-epinephrine, (−)-norepinephrine, and prazosin were increased 15, 13, and 25 times, respectively, with no significant change in the apparent Kd values for yohimbine or phentolamine 2 hr postendotoxin. These data demonstrate that the binding affinity of the high-affinity component and the number of α-adrenergic receptor binding sites were decreased in endotoxic shock. A modification of the α-adrenergic receptors in dog livers induced by endotoxin administration may play an important role in the development of hepatic glucose dyshomeostasis during shock.