cssi/SciSciGPT-SciSciNet huggingface dataset:
Merodiploidy in ESCHERICHIA COLI-SALMONELLA TYPHIMURIUM Crosses: The Role of Unequal Recombination between Ribosomal RNA Genes

Previous workers have shown that intergeneric crosses between Salmonella typhimurium and Escherichia coli produce a high proportion of merodiploid recombinants among the viable progeny. We have examined the unequal crossover event that was responsible for a number of intergeneric merodiploids. The merodiploids that we studied were all heterozygous for the metB–argH interval and were the products of intergeneric conjugal crosses. We found that when the S. typhimurium donor had its transfer origin closely linked to metB and argH, all recombinants examined were merodiploid, and they generally arose as F-prime factors. Many of these F-prime factors had been created by recombination between flanking rrn genes in the donor. When the S. typhimurium Hfr transfer origin was more distant from the selected markers, quite different results were obtained. (1) Depending on the donor, 19–47% of the recombinants that acquired the donor argH+ or metB+ genes were merodiploid for these loci, but none of the recombinants were F-prime. (2) A majority of the merodiploids had a novel (nonparental) rrn gene, indicating that unequal recombination between nonidentical rrn genes was a prevalent mechanism for establishing the merodiploidy. (3) Both tandem and nontandem duplications were found. (4) Some of the merodiploids duplicated E. coli genes in addition to acquiring S. typhimurium genes. (5) Some merodiploids contained the oriC region from each parent. Of a total of 118 intergeneric merodiploids characterized from all donors, 48 different genotypes were observed, and 38 of the 48 had one or more nonparental rrn operons.
Books before Chocolate? The Insufficiency of Mill's Evidence for Higher Pleasures

Recent attempts to defend Mill's account of higher and lower pleasures have overlooked a critical flaw in Mill's argument. Mill considers the question of pleasure and preference as an empirical one, but the evidence he appeals to is inconclusive. Yet, this distinction plays an essential role in Mill's utilitarianism because Mill uses this evidence to support his argument that most people actually prefer pleasures resulting from higher faculties over pleasures resulting from lower faculties. If this proves to be insufficient, then Mill's claim that these pleasures are clearly of a higher quality than others is left unsubstantiated. This article highlights the problematic nature of Mill's evidence, thereby exposing a significant problem for his, and for any utilitarian system which assumes Mill's distinction without providing additional argumentation for it.
Two-photon microscopy of oxygen distributions in mouse cerebral microvasculature

The two-photon microscopy imaging was used to obtain high-density PO2 maps in cortical microvasculature in anesthetized mice. The detailed PO2 distributions were presented as functions of various microvascular morphological parameters.
A study of a Hurricane Katrina–induced phytoplankton bloom using satellite observations and model simulations

[1] Satellite observations of sea surface temperature (SST) and chlorophyll-a concentration from the Moderate Resolution Imaging Spectroradiometer (MODIS) on Aqua revealed a phytoplankton bloom event in the vicinity of the Loop Current (LC) in the Gulf of Mexico after Hurricane Katrina's passage in August 2005. The sea surface height (SSH) anomaly data derived from satellite altimetry measurements indicated that the phytoplankton bloom coincided with a LC frontal eddy and thus suggested that the cold-core eddy may have played a critical role in the phytoplankton bloom event. Using the Hybrid Coordinate Ocean Model (HYCOM), we have carried out numerical simulations to understand the mechanism that triggers the phytoplankton bloom after Katrina passage. The model study shows that the preexisting cold-core eddy strengthens the upper ocean dynamics and nutrient responses with significant increase of nutrient concentration after the passage of Hurricane Katrina, because of the uplift of nutrient fields within the cold-core eddy. The Hurricane Katrina–triggered phytoplankton bloom is attributed to the preexisting cold eddy as well as the slowly passing hurricane. The nutrient distribution after Hurricane Katrina indicates that the increase of nitrate concentration plays a dominant role in the development of the phytoplankton bloom.
Spouses of spinal cord injury survivors: The added impact of caregiving

Abstract Objective: To better understand the needs of spouses who provide care to spinal cord injury (SCI) survivors, by comparing their self-perceptions and complaints with those of their partners with disabilities and with those of spouses who do not provide care. Design: Survey, including demographics, health concerns questionnaire, and administration of the Center for Epidemiologic Studies Depression Scale (CES-D), the Perceived Stress Scale (PSS), the Life Satisfaction Index (LSI-Z), and the Quality of Life and Individual Needs Questionnaire. Setting: Two British SCI treatment centers, serving a defined population-based catchment area. Participants: One hundred twenty-four spouses of a longitudinally followed sample of SCI survivors, all of whom had been injured 23 or more years when the study was conducted in 1993. Outcome Measures: Scores on the above standardized tests, and responses to survey questions. Results: Spouses had more depressive affect ( p p = .005), emotional stress ( p = .011), burnout ( p = .007), fatigue ( p = .002), and anger and resentment ( p = .029). On the CES-D, they had more symptoms of depressive affect ( p = .004) and somatic depression ( p = .005). Conclusions: Spouses of long-term SCI survivors who fulfill a caregiving role report more symptoms of stress and depression than their partners with disabilities and other spouses who are not caregivers.
Reciprocal Interactions of Pit1 and GATA2 Mediate Signaling Gradient–Induced Determination of Pituitary Cell Types

The mechanisms by which transient gradients of signaling molecules lead to emergence of specific cell types remain a central question in mammalian organogenesis. Here, we demonstrate that the appearance of four ventral pituitary cell types is mediated via the reciprocal interactions of two transcription factors, Pit1 and GATA2, which are epistatic to the remainder of the cell type-specific transcription programs and serve as the molecular memory of the transient signaling events. Unexpectedly, this program includes a DNA binding-independent function of Pit1, suppressing the ventral GATA2-dependent gonadotrope program by inhibiting GATA2 binding to gonadotrope- but not thyrotrope-specific genes, indicating that both DNA binding-dependent and -independent actions of abundant determining factors contribute to generate distinct cell phenotypes.
Hierarchical Linear Modeling of Creative Artists' Problem Solving Behaviors.

College art students were videotaped creating original drawings from an array of objects. Judges reliably assessed the creativity of the drawings. Videos of the creation of ten high- and ten low-rated drawings were coded frame-by-frame to quantify the extent to which artists engaged in several categories of activities (selecting objects, selecting media, pausing, drawing objects, drawing other visible elements, and drawing imaginary elements) plus reworking the drawing (erasing and revising). Video coding was used to model how the frequency of each measure varied throughout the sessions. Behaviors were analyzed by hierarchical linear modeling, a regression technique that permits individual- and group-level analyses simultaneously. Analyses revealed substantial individual and group differences in the behavioral trajectories, especially in the drawing measures and in reworking the drawing. The results support a positive association between creativity and opportunistic problem solving strategies, and a negative association between creativity and the pre-planned application of default problem representations.
Febrile neutropenia in adjuvant docetaxel and cyclophosphamide (TC) with prophylactic pegfilgrastim in breast cancer patients: a retrospective analysis

US Oncology Research Trial 9735 reported that TC improved overall survival when compared to doxorubicin and cyclophosphamide in early-stage breast cancer. Despite 61% grades 3–4 neutropenia in the TC arm, only 5% of patients developed febrile neutropenia (FN) without primary prophylactic GCSF (ppGCSF). TC has risen in popularity, particularly in older patients or in those where an anthracycline is contraindicated. Other studies examining the toxicity of TC without ppGCSF reported a higher incidence of FN between 23 and 46%. We reviewed our institutional experience with ppGCSF and the TC regimen. Women treated with adjuvant TC and pegfilgrastim at Roswell Park Cancer Institute were identified from the pharmacy database between 8/2006 and 11/2010. Patient characteristics and comorbidities were abstracted. Endpoints included incidence of FN, hematologic toxicities, relative dose intensity (RDI), and other acute complications. Docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 were given every 21 day/cycle for a planned four cycles. All patients received pegfilgrastim 6 mg on day 3. One hundred and eleven women with median age of 56 years (27–79) were identified. Twenty-two percent of patients were ≥65 at diagnosis. Eight patients developed FN (7%). Ninety-five patients (86%) were able to complete four cycles. Completion rate was significantly lower in patients with age ≥65 (71% vs. 90%; P = 0.02). Incidence of hospitalization, delay, RDI <85%, and dose reduction were not significantly different between the age groups. The overall incidence of FN was 7%. Older patients were significantly less likely to complete four cycles of TC as planned. ppGCSF should be strongly considered in breast cancer patients receiving adjuvant TC chemotherapy.
Limitations in plasticity of the T-cell receptor repertoire.

Abstract How constrained is T-cell recognition? Is a truncated T-cell receptor (TCR) repertoire, missing half of its V beta components (where V indicates variable), still broad enough to produce an antigen-specific T-cell response to all determinants? These questions can be answered for certain T-cell antigenic determinants whose response in the wild type is limited to specific gene segments. Our results show that mice with such a deletion in their TCR V beta genes (V beta truncated haplotype, Va beta) are unable to respond to two antigen determinants (sperm whale myoglobin 111-121/I-Ed and myelin basic protein 1-11/I-Au) whose response in the wild type is restricted to the missing V beta (V beta 8.2 in the case of 111-121/I-Ed and V beta 8.2 and V beta 13 in the case of 1-11/I-Au) gene segments. Fundamentally, this restriction could have been attributed to another aspect of immunodominance--that a favored TCR with high affinity would dominate the response, but in its absence, a hierarchy of T cells with lesser efficiency and expressing alternate TCR V genes could take over. However, from our experiments it has become evident that there is an absolute limit to the flexibility inherent in the TCR repertoire. Since it is clear that mouse populations have many ambient deletion ligands (such as self-superantigens) that can result in the loss of multiple V beta gene segments during normal T-cell development, these deletions can have serious consequences, such as unresponsiveness to the antigen as a whole--a hole in the repertoire--if a dominant determinant of that antigen normally shows restricted TCR V beta gene usage.
Deconstructing the Physical and Molecular Basis of Touch and Pain Sensation

Touch is the first sense to develop and the last to fade. To investigate the molecular and physical basis of this crucial sensory modality, we exploit the nematode C. elegans and in vivo cellular physiology.
A finite element alternating method for evaluation of stress intensity factors fpr part-circular cracks subjected to arbitrary loadings

Abstract The stress intensity factor solution for embedded circular cracks, semicircular and part-circular surface cracks in plates, quartercircular corner cracks in rods, and semicircular surface cracks at a hole in a plate are evaluated using a finite element alternating method. This method of superposition employs the standard 20-noded solid element solution for the uncracked solid, and the complete analytical solution for an embedded circular crack in an infinite elastic medium, so that arbitrary pressures on the fracture surface can be modelled. The numerical results indicate that the alternating technique is quite cost efficient and effective. Convergence studies based on finite element meshes of 425 to 4499 nodes show that a good estimate of the stress intensity factor variation along the flaw border can be obtained with the coarsest mesh. Also, the natural-basis influence functions for a fixed crack and boundary geometry can be efficiently derived by the alternating process, to extract stress intensity factors for multiple loading problems.
The cyclo-oxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulum Ca2+-ATPases: a plausible link with its anti-tumour effect and cardiovascular risks

Substantial evidence indicates that the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib, a widely prescribed anti-inflammatory agent, displays anti-tumour effect by sensitizing cancer cells to apoptosis. As part of our effort to understand the mechanism by which celecoxib mediates apoptosis in androgen-independent prostate cancer cells, we investigated its effect on intracellular calcium concentration ([Ca(2+)](i)). Digital ratiometric imaging analysis indicates that exposure of PC-3 cells to celecoxib stimulates an immediate [Ca(2+)](i) rise in a dose- and time-dependent manner. Kinetic data show that this Ca(2+) signal arises from internal Ca(2+) release in conjunction with external Ca(2+) influx. Examinations of the biochemical mechanism responsible for this Ca(2+) mobilization indicate that celecoxib blocks endoplasmic reticulum (ER) Ca(2+)-ATPases. Consequently, inhibition of this Ca(2+) reuptake mechanism results in Ca(2+) mobilization from ER stores followed by capacitative calcium entry, leading to [Ca(2+)](i) elevation. In view of the important role of Ca(2+) in apoptosis regulation, this Ca(2+) perturbation may represent part of the signalling mechanism that celecoxib uses to trigger rapid apoptotic death in cancer cells. This Ca(2+)-ATPase inhibitory activity is highly specific for celecoxib, and is not noted with other COX inhibitors tested, including aspirin, ibuprofen, naproxen, rofecoxib (Vioxx), DuP697 and NS398. Moreover, it is noteworthy that this activity is also observed in many other cell lines examined, including A7r5 smooth muscle cells, NIH 3T3 fibroblast cells and Jurkat T cells. Consequently, this Ca(2+)-perturbing effect may provide a plausible link with the reported toxicities of celecoxib such as increased cardiovascular risks in long-term anti-inflammatory therapy.
A Chemical Screen Identifies Small Molecules that Regulate Hepcidin Expression

Abstract Hepcidin, a peptide hormone produced in the liver, decreases intestinal iron absorption and macrophage iron release via effects on ferroportin. Bone morphogenic protein and Stat3 signaling regulate Hepcidin 's transcription. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. To generate a tool for identifying small molecules that modulate Hepcidin expression, we stably transfected human hepatocytes (HepG2) cells with a reporter construct containing 2.7 kb of the human Hepcidin promoter upstream of a firefly reporter gene. We used high throughput methods to screen 10,169 chemicals in duplicate for their effect on Hepcidin expression and cell viability. Regulators were identified as chemicals that caused a change > 3 standard deviations above or > 1 standard deviation below the mean of the other chemicals (z-score > 3 or Hepcidin expression. All of the chemicals identified increased expression of bone morphogenic protein-dependent and/or Stat3-dependent genes, however none of them strongly increased phosphorylation of Smad1,5,8 or Stat3.
Macul: Influences of Tasks on the Development of Social and Physical Spaces

by JOSEPH J. VALADEZ WITH ESMEE BELLALTA Physical Determinists Joseph J. Valadez is currently a visiting scholar at the Center for International Stud~es, MIT; he is on leavefiom the University of Maryland where he is Assistant Professor of International Cornmunity Development. Esmee Bellalta is Assoc~ate Professor of Arch~tecture at Notre Dame University. Funds to support this project were provided by the Institute for the Research and Development of Holistic Designs, a University of Maryland Summer Research Grant, and the University of Maryland Computer Science Center. Though a Chilean city, Macul was winner of the 1981 Merit Research Award from the American Society of Landscape Architects, and the 1981 Design Award for Unique Community Solutions from the American Institute of Landscape Architects. W e give special thanks to Remi Clignet for his wisdom and enthusiasm, to Donald T. Campbell for sharing his creativity and knowledge, and to Allan Schnaiberg for inviting Valadez to spend his seminal 1977-1979 years at North western University's Sociology Department.
Using satellite and real-time weather data to predict maize production

Large-scale assessments of crop conditions prior to harvest are critical for providing early estimates of production. Satellite and weather information provide the opportunity for near real-time crop monitoring. The objective of this research was to develop an operational assessment system for crop production utilizing data from these sources. Maize (Zea mays) production was assessed in 42 Crop Reporting Districts (CRDs) across the United States Corn Belt, which produce 60% of all maize grown in the United States. Satellite, climatolocal, and agricultural data were collected for 8 years, 1985–1992, and aggregated into CRDs. A model predicting the normalized maize yields for each CRD was developed that included as independent variables a satellite data variable, the Vegetation Condition Index, and a climatological variable, the Crop Moisture Index. This model explained approximately three-quarters (R 2=0.73) of the variation observed in the normalized yields, and was examined both for its accuracy and its timeliness in providing production estimates. Predicted seasonal yields were summed to provide a maize production estimate for the entire Corn Belt study region. Production estimates deviated from the final USDA statistics, which become available several months after harvest, by less than 10% for all eight growing seasons. In addition, the production estimates were available approximately 2 months prior to the completion of the maize harvest. This system has the potential for providing timely in-formation to organizations monitoring regional or global agricultural production for humanitarian or economic benefits.
Border Pedagogy and die Politics of Modernism/Postmodernism

Education may well be, as of right, the instrument whereby every individual, in a society like our own, can gain access to any kind of discourse. But we all know that in its distribution, in what it permits and prevents, it follows the well-trodden battle lines of social conflict. Every educational system is a political means of maintaining or modifying the appropriation of discourse with the knowledge and powers it carries with it.1
Asian international students’ socio-cultural adaptation: Influence of multicultural personality, assertiveness, academic self-efficacy, and social support

Abstract In this study examining the influence of multicultural personality, assertiveness, social support, and academic self-efficacy on Asian international students’ (ISs) socio-cultural adjustment in the U.S., 330 Asian ISs completed a web-survey. Structural Equation Modeling (SEM) analysis revealed that both Multicultural Personality and Assertiveness were associated with Socio-cultural Adaptation, which was mediated by Academic Self-efficacy. Although Multicultural Personality was associated with Social Support, bootstrapping results indicated that there was no indirect effect from Social Support to Socio-cultural Adaptation, therefore mediation paths between Multicultural Personality to Social Support and Social Support to Socio-cultural Adaptation were not supported. Implications are discussed.
Perceptions of Professional Growth: A Mathematics Teacher Educator in Transition.

To meet the need for reform in mathematics teacher preparation courses, two cycles of changes made in an elementary mathematics methods course are presented. Using action research, teaching approaches were developed, implemented, and evaluated as a meaningful way to continue my professional development. Results suggested that I improved my teaching practices and focused more on teaching tasks that engaged my students to “think like teachers.” Three critical components of teacher preparation courses are identified that are important for teacher educators to acknowledge when implementing change: (a) using reflective verbal and written communication, (b) establishing a collaborative mathematical community, and (c) focusing on a narrower selection of mathematical content.
Three-dimensional head anthropometric analysis

Currently, two-dimensional photographs are most commonly used to facilitate visualization, assessment and treatment of facial abnormalities in craniofacial care but are subject to errors because of perspective, projection, lack metric and 3-dimensional information. One can find in the literature a variety of methods to generate 3-dimensional facial images such as laser scans, stereo-photogrammetry, infrared imaging and even CT however each of these methods contain inherent limitations and as such no systems are in common clinical use. In this paper we will focus on development of indirect 3-dimensional landmark location and measurement of facial soft-tissue with light-based techniques. In this paper we will statistically evaluate and validate a current three-dimensional image-based face modeling technique using a plaster head model. We will also develop computer graphics tools for indirect anthropometric measurements in a three-dimensional head model (or polygonal mesh) including linear distances currently used in anthropometry. The measurements will be tested against a validated 3-dimensional digitizer (MicroScribe 3DX).
Correlation time expansion for non-markovian, gaussian, stochastic processes

Abstract Ordered operator cumulants and van Kampen's lemma are used to obtain a correlation time expansion for colored noise, stochastic processes. An explicit result to first order in the correlation time is obtained, and confirms the result of Dekker obtained by application of Novikov's theorem. The operator cumulant approach is much more direct, systematically yielding the desired result, and systematically provided any higher order correction. The origin of each explicit order of correction is accounted for in a natural manner in terms of the cluster property for ordered operator cumulants.
Quasi-melting of small particles

Abstract We investigate the energetics of structural fluctuations in small particles, a phenomenon recently observed by high resolution electron microscopy. Using a continuum model with anisotropic surface energies and isotropic inhomogeneous elasticity, we estimate the activation energy for these transformations. The results indicate that the primary cause of the structural fluctuations is the reduction of the surface energy anisotropy as the temperature is raised, either the thermal or electronic temperature.
Insulin Resistance Induces Posttranslational Hepatic Sortilin 1 Degradation in Mice

Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions. Background: Sortilin 1 mediates lysosome-dependent apoB100 degradation in hepatocytes. Results: Blocking insulin/PI3K/AKT signaling caused posttranslational hepatic sortilin 1 degradation. Conclusion: Insulin resistance is an underlying cause of decreased hepatic Sort1 in diabetes. Significance: This study suggests a new mechanism underlying altered hepatic apoB100 metabolism in type 2 diabetes.
A tale of the prichard (AL) pension program

On 22 December 2010, The New York Times reported that ‘Prichard did something that pension experts say they have never seen before: it stopped sending monthly pension checks to its 150 retired workers’. Prichard is a small city in southwest Alabama. Thirty-five per cent of Prichard residents live below the poverty level, and 85 per cent are African-Americans. This article introduces the progression of the Prichard pension from its inception to the unprecedented temporary halt in payment and then resumption of payment in reduced amount.
Ethical Standards Within Organizational behavior

The results of a study of the ethics of publishing and reviewing research indicated (1) substantial dissensus about whether standards exist; (2) vague or nonexistent mechanisms for communicating st...
Caring for patients with limited health literacy: a 76-year-old man with multiple medical problems

Health literacy is the degree to which individuals have the capacity to obtain, process, and understand health information, skills, and services needed to make informed health decisions and take informed actions. Narratives from Mr J, a 76-year-old man with multiple medical problems and limited health literacy, and his physician exhibit some of the difficulties experienced by patients with limited health literacy. Clinicians can help patients with limited health literacy by removing unneeded complexity in their treatment regimens and in the health care system and by using teach-back methods to assess and improve understanding. Rather than a selective screening approach for limited health literacy, a patient-based universal precaution approach for confirming patient comprehension of critical self-care activities helps ensure that all patients have their health literacy needs identified.
Enhanced Conversational Recall and Reduced Conversational Interference as a Function of Cognitive Complexity

This study examines the relationship between cognitive complexity and conversational recall. Three hypotheses are put forward arguing that individuals high in cognitive complexity will (a) recall more person-oriented conversational information, (b) recall more person-oriented information in an interference condition, and (c) recall more total information from a conversation than subjects low in cognitive complexity. Subjects were 72 college students who observed a video taped conversation. Recall was elicited by means of a free recall task and an 18-item multiple choice test. MANOVA and canonical discriminant-analysis results support each hypotheses.
Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease.

Purification and in vitro protein-folding schemes were developed to produce monodisperse samples of the mature wild-type HIV-2 protease (PR2), enabling a comprehensive set of biochemical and biophysical studies to assess the dissociation of the dimeric protease. An E37K substitution in PR2 significantly retards autoproteolytic cleavage during expression. Furthermore, it permits convenient measurement of the dimer dissociation of PR2E37K (elevated Kd ∼20 nM) by enzyme kinetics. Differential scanning calorimetry reveals a Tm of 60.5 for PR2 as compared with 65.7°C for HIV-1 protease (PR1). Consistent with weaker binding of the clinical inhibitor darunavir (DRV) to PR2, the Tm of PR2 increases by 14.8°C in the presence of DRV as compared with 22.4°C for PR1. Dimer interface mutations, such as a T26A substitution in the active site (PR2T26A) or a deletion of the C-terminal residues 96–99 (PR21–95), drastically increase the Kd (>105-fold). PR2T26A and PR21–95 consist predominantly of folded monomers, as determined by nuclear magnetic resonance (NMR) and size-exclusion chromatography coupled with multiangle light scattering and refractive index measurements (SMR), whereas wild-type PR2 and its active-site mutant PR2D25N are folded dimers. Addition of twofold excess active-site inhibitor promotes dimerization of PR2T26A but not of PR21–95, indicating that subunit interactions involving the C-terminal residues are crucial for dimer formation. Use of SMR and NMR with PR2 facilitates probing for potential inhibitors that restrict protein folding and/or dimerization and, thus, may provide insights for the future design of inhibitors to circumvent drug resistance.
Inflammatory Cytokines and the Development of Pulmonary Complications after Allogeneic Hematopoietic Cell Transplantation in Patients with Inherited Metabolic Storage Disorders

Abstract Patients with inherited metabolic storage disorders are at a higher risk of developing pulmonary complications after hematopoietic cell transplantation (HCT). This single-center prospective study of 48 consecutive inherited metabolic storage disorder patients was performed to identify risk factors for the development of pulmonary complications after HCT. Before HCT, subjects underwent bronchoalveolar lavage (BAL) for cell count, culture, nitrite levels, and analysis of proinflammatory cytokines and chemokines. The overall incidence of pulmonary complications was 52% (infectious, 23%; noninfectious, 29%) over a period of 4 years. Diffuse alveolar hemorrhage was the most frequent noninfectious complication and occurred in 19% of patients, all of whom had a diagnosis of mucopolysaccharidosis (Hurler and Maroteaux-Lamy syndromes). Levels of interleukin (IL)–1β, IL-6, IL-8, tumor necrosis factor α, macrophage inflammatory protein 1α, and granulocyte colony-stimulating factor in BAL fluid samples obtained before HCT were higher in patients with mucopolysaccharidoses than in patients with leukodystrophies. In addition, levels of IL-1β, IL-6, IL-8, and granulocyte colony-stimulating factor were increased in the BAL fluid of patients who developed noninfectious pulmonary complications compared with those who did not develop pulmonary complications. It is interesting to note that most noninfectious pulmonary complications occurred in patients with mucopolysaccharidoses, especially diffuse alveolar hemorrhage, which occurred exclusively in patients with mucopolysaccharidoses. Higher levels of bronchial proinflammatory cytokines and chemokines may be predictive of the development of subsequent posttransplantation noninfectious complications in patients with mucopolysaccharidoses, especially those with Hurler syndrome. Larger studies will be required to further elucidate etiologic mechanisms and predictive factors.
Soluble leptin receptor and leptin are associated with baseline adiposity and metabolic risk factors, and predict adiposity, metabolic syndrome, and glucose levels at 2-year follow-up: the Cyprus Metabolism Prospective Cohort Study

We examined the relationship between serum levels of leptin-binding protein (soluble leptin receptor [sOB-R]) and leptin with metabolic parameters at baseline and prospectively at 2-year follow-up in young healthy men. A total of 916 eighteen-year-old men were examined at baseline, with a subgroup of 91 participants examined again 2 years later. Anthropometric and metabolic measurements were performed at baseline and at follow-up. In the cross-sectional study, levels of sOB-R were significantly inversely correlated with all baseline measures of obesity and metabolic risk factors (blood pressure, total and low-density lipoprotein cholesterol, and fasting glucose), and significantly positively correlated with high-density lipoprotein cholesterol. After correcting for age, smoking status, and waist-to-hip ratio, the inverse correlation remained statistically significant for all measures of adiposity, fasting glucose, and the metabolic syndrome score. Correlations for leptin were similar in magnitude but opposite in direction to correlations for sOB-R. In prospective analyses, baseline levels of sOB-R were predictive at 2-year follow-up of fasting glucose, the metabolic syndrome score, and measures of adiposity in both unadjusted and adjusted models. Similarly, leptin was predictive of fasting glucose, the metabolic syndrome score, adiposity, and systolic blood pressure. We confirm correlations of leptin and sOB-R levels with measures of adiposity and metabolic risk factors at baseline, and demonstrate for the first time prospectively the role of sOB-R as an independent, although weak, predictor of metabolic syndrome and fasting glucose in young men.
Hydration of DNA

Abstract In the past year, some new experimental and theoretical studies have been published which show that many factors influence hydration structure. As the data emerge, it is clear that DNA sequence, size of the grooves, overall conformation and crystal packing are all related to the structural arrangements of water molecules around nucleic acids. Caution in relating these structures to macroscopic properties is still appropriate.
Crossotelos, an Early Permian nectridian amphibian

Crossotelos annulatus, an Early Permian nectridean amphibian, has been known previously only from isolated vertebrae. This last and largest end member of a Pennsylvanian urocordylid radiation is de...
Elective stenting of extracranial carotid arteries.

The efficacy of surgical carotid endarterectomy (CEA) for extracranial carotid stenosis has now been unequivocally demonstrated. The publication of several large worldwide trials1 2 3 4 has finally provided clinicians with critically important data for practical management of a group of patients at particularly high risk of stroke: those with transient ischemic attacks (TIAs) or minor strokes referable to a high-grade stenosis at the carotid bifurcation. These data come after more than 20 years of inconclusive, noncontrol case studies and are the result of cooperative efforts of neurologists, neurosurgeons, and vascular surgeons to address the question of the efficacy of CEA in proper prospective randomized trials. The field of angioplasty/stenting (AS) for carotid disease has much to learn from the CEA experience. In patients with TIAs or minor stroke, the CEA trials have shown the following: (1) if the symptoms are referable to a >70% diameter stenosis at the carotid bifurcation, CEA reduces the risk of subsequent ipsilateral stroke from 26% during the first 2 years with optimal medical management to 9% if CEA is added; (2) the risk of stroke without surgery is greater with increasing degrees of stenosis, reaching >30% during the first year for 90% to 95% stenosis; (3) surgery is not of benefit for <50% stenosis; (4) the risk/benefit of CEA for 50% to 70% stenosis remains unknown and is still under investigation; (5) although the best way to measure stenosis is debated, these degrees of stenosis assume a standard method of measurement comparing the narrowest lumen diameter at the bifurcation to the normal diameter of the internal carotid in a vertical distal segment; (6) benefit occurs with CEA with either hemispheric or retinal symptoms and in all relevant demographic subgroups; and (7) the benefit assumes a perioperative risk of stroke or death of ≤5% …
Compact Nuclei in Galaxies at Moderate Redshift. II. Their Nature and Implications for the Active Galactic Nucleus Luminosity Function

This study explores the space density and properties of active galaxies to z0.8. We have investigated the frequency and nature of unresolved nuclei in galaxies at moderate redshift as indicators of nuclear activity such as active galactic nuclei (AGNs) or starbursts. Candidates are selected by fitting imaged galaxies with multicomponent models using maximum-likelihood estimate techniques to determine the best model fit. We select those galaxies requiring unresolved point-source components in the galaxy nuclei, in addition to disk and/or bulge components, to adequately model the galaxies' light. We have searched 70 WFPC2 images, primarily from the Medium Deep Survey, for galaxies containing compact nuclei. In our survey of 1033 galaxies, the fraction containing unresolved nuclear components contributing ≥5% of the total galaxy light is 9%±1% corrected for incompleteness. In this second of two papers in this series, we discuss the nature of the compact nuclei and their hosts. We present the upper limit luminosity function (LF) for low-luminosity AGNs (LLAGNs) in two redshift bins to z=0.8. Mild number-density evolution of the form ∝(1+z)1.9 is detected for nuclei at -18MB-14. The LFs appear to flatten at MB≥-16 and this flatness, combined with the increase in number density, is inconsistent with pure luminosity evolution. Based on the amount of density evolution observed for these objects, we find that almost all present-day spiral galaxies could have hosted LLAGNs at some point in their lives. We also comment on the likely contribution of these compact nuclei to the soft X-ray background.
Hair Lead Levels Related to Children's Classroom Attention-Deficit Behavior

The goal of this study was to evaluate the relationship between hair lead levels of children and their attention-deficit behaviors in the classroom. Scalp hair specimens were obtained from 277 first-grade pupils, teachers completed the abbreviated Boston Teacher's Rating Scale for rating classroom attention-deficit behavior, and parents completed a short questionnaire. The children's hair lead concentrations ranged from less than 1 to 11.3 ppm (microg/g). The striking dose-response relationship between levels of lead and negative teacher ratings remained significant after controlling for age, ethnicity, gender, and socioeconomic status. An even stronger relationship existed between physician-diagnosed attention-deficit hyperactivity disorder and hair lead in the same children. There was no apparent 'safe' threshold for lead. Scalp hair should be considered a useful clinical and epidemiologic approach for the measurement of chronic low-level lead exposure in children.
In situ infrared study of NO reduction over Pd/Al2O3 and Ag-Pd/Al2O3 catalysts under H2-rich and lean-burn conditions

Abstract Catalytic reduction of NO under H2-rich and lean-burn conditions over Pd/Al2O3 and Ag-Pd/Al2O3 has been studied by temperature programmed reaction (TPR) coupled with in situ infrared (IR) and mass spectrometry (MS) techniques. Under H2-rich conditions, Pd/Al2O3 produces, Pd-NCO, Pd+-NO, Pd0-NO, and adsorbed nitrate at temperatures below 398 K. N2 and adsorbed NH3 are produced at temperatures above 400 K. Addition of Ag to Pd/Al2O3 suppresses the Pd+-NO formation and lowers the formation temperature of NH3 species to 373 K. Under lean-burn conditions, Pd/Al2O3 produces Pd-NCO, Pd+-NO, Pd0-NO, and adsorbed nitrate at temperatures below 373 K, while the addition of Ag suppresses the Pd-NCO and Pd+-NO formation, and enhances the Pd0-NO formation. Infrared results reveal that oxygen under lean-burn conditions does not oxidize Pd0 sites to Pd+ on the Ag-Pd/Al2O3 catalyst. Addition of Ag enhances NO2 formation and shifts the N2 formation to lower temperatures, suggesting that NO2 is effectively reduced to N2.
Implicit theories, self-schemas, and leader-member exchange

This study examined the relation of cognitive factors (implicit theories, self-schemas, and perceived similarity) to liking and leader-member exchange (LMX) in a field setting. Perceived similarity...
Intestinal microbiota are transiently altered during Salmonella-induced gastroenteritis

The mammalian GI tract contains a large and diverse ecosystem of microorganisms that play a profound role in our development and physiology. Interestingly, the microbial make-up within the intestine has been found to be altered in many clinically important diseases, including inflammatory bowel disease, irritable bowel syndrome, Types 1 and 2 diabetes, and obesity. Barman et al. used a Salmonella-induced murine model of gastroenteritis to show that the intestinal microbiota are transiently altered during the host inflammatory response to infection. These findings are of interest as understanding how the microbiota are altered during disease states may offer insight into which microbial populations are important in maintaining intestinal homeostasis. Recently, probiotics have been shown to modulate the mucosal immune system and improve intestinal barrier function, validating their potential as therapeutics for gastrointestinal-associated diseases. As we begin to understand the benefits conferred to the intestine by microbiota, the use of probiotics to modify its composition is an attractive option to improve human health.
PERSPECTIVE: 'Putting Patients First': A Philosophy In Practice

Humana's chairman and CEO explains the rationale and goals for the American Association of Health Plans' new initiative to show consumers that health plans are attentive to their concerns.
Spindle cell carcinoma of the larynx : Review of 26 cases including DNA content and immunohistochemistry

Spindle cell carcinoma (SpCC) is uncommon, with a predilection for the upper aerodigestive tract. Its histogenesis has not been resolved, although most authors support the sarcomatoid carcinoma concept. Ploidy analysis and proliferation indices have not been reported for laryngeal SpCCs. The authors examined the pathological and clinical features of 26 patients (25 men, 1 woman; mean age, 64 years) with laryngeal SpCC treated at the Mayo Clinic from 1960 to 1990. Twenty-three tumors were examined with digital image analysis for DNA content of the spindle cell population (13 tumors had a sufficient squamous component to be analyzed separately). The glottis was involved most frequently (19 patients); 21 tumors were grossly polypoid. Twenty-three tumors were biphasic, and three were monophasic. Overall, 17 tumors (65%) showed keratin positivity in the spindle cell component. Polyclonal antikeratin (15 positive cases), 34betaE12 (15 positive), and AE1/AE3 (12 positive) were the most sensitive markers. Spindle cells were diploid in 5 tumors (22%) and nondiploid in 18 (78%); conventional squamous cell carcinoma was diploid in 4 cases and nondiploid in 9. DNA ploidy results were concordant between the two populations in 11 of 13 tumors (85%). Mean percent MIB-1 staining was 31% in the sarcomatoid component and 45% in the squamous component. In our primary treatment group of 22 patients (median follow-up, 6.4 years), 4 (18%) had local recurrence, 3 (14%) had distant metastasis, and 4 (18%) died of disease. Presence of a nondiploid spindle cell population in 78% of cases of laryngeal SpCC is interpreted as evidence of a neoplastic rather than reactive process. Keratin positivity in nearly two thirds of tumors supports the theory of epithelial origin of these tumors (sarcomatoid carcinoma).
Automatic and continuous software architecture validation

Software systems tend to suffer from architectural problems as they are being developed. While modern software development methodologies such as Agile and Dev-Ops suggest different ways of assuring code quality, very little attention is paid to maintaining high quality of the architecture of the evolving systems. By detecting and alerting about violations of the intended software architecture, one can often avoid code-level bad smells such as spaghetti code. Typically, if one wants to reason about the software architecture, the burden of first defining the intended architecture falls on the developer's shoulders. This includes definition of valid and invalid dependencies between software components. However, the developers are seldom familiar with the entire software system, which makes this task difficult, time consuming and error-prone. We propose and implement a solution for automatic detection of architectural violations in software artifacts. The solution, which utilizes a number of predefined and user-defined patterns, does not require prior knowledge of the system or its intended architecture. We propose to leverage this solution as part of the nightly build process used by development teams, thus achieving continuous automatic validation of the system's software architecture. As we show in multiple open-source and proprietary cases, a small set of predefined patterns can detect architectural violations as they are introduced over the course of development, and also capture deterioration in existing architectural problems. By evaluating the tool on relatively large open-source projects, we also validate its scalability and practical applicability to large software systems.
Bonding technologies for chip level and wafer level 3D integration

This paper provides a comparison of bonding process technologies for chip and wafer level 3D integration (3Di). We discuss bonding methods and comparison of the reflow furnace, thermo-compression, Cavity ALignment Method (CALM) for chip level bonding, and oxide bonding for 300 mm wafer level 3Di. For chip 3Di, challenges related to maintaining thin die and laminate co-planarity were overcome. Stacking of large thin Si die with 22 nm CMOS devices was achieved. The size of the die was more than 600 mm 2 . Also, 300 mm 3Di wafer stacking with 45 nm CMOS devices was demonstrated. Wafers thinned to 10 μm with Cu through-silicon-via (TSV) interconnections were formed after bonding to another device wafer. In either chip or wafer level 3Di, testing results show no loss of integrity due to the bonding technologies.
New insights into minimum-variance reduced-order filters

The minimum-variance reduced-order (MVRO) filter is an algorithm that has become popular in the guidance and navigation community as a tool for designing and evaluating the performance of candidate reduced-order filters. Its utility rests on the assumption that the MVRO algorithm yields the optimum (in a minimum-varian ce sense) performance possible with a given reduced-order filter. The analysis and examples in this paper show that this is not the case and that the MVRO algorithm merely yields an optimal estimate immediately after the first measurement update. It is shown how a new MVRO gain matrix may be derived that will yield optimum results at some specified time in the future. The main point of the analysis is to prove that, in general, it is not possible to specify a discrete reduced-order filter that is always minimum-variance. The minimum-variance condition can only be achieved at a specific time-before and after that time, other filter gain histories could provide better performance.