cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of (Drug) Transporters in Imaging in Health and Disease

This report is the summary of presentations at the symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics, April 26-30, at Experimental Biology 2014 in San Diego, CA. The presentations focused on the role of transporters in imaging in health and disease and on assessing transporter function in vivo. Imaging is an important diagnostic tool in clinics and is a novel tool for in vivo visualization of transporter function. Many imaging substrates and endogenous markers for organ function are organic anions. In this symposium, the bile salt transporter sodium taurocholate cotransporting polypeptide and the liver organic anion transporting polypeptides (OATPs) as well as the renal organic anion transporters (OATs) were addressed in detail; e.g., OATPs mediate transport of contrast agents used for magnetic resonance imaging of the liver or transport agents used for hepatobiliary scintigraphy, and OATs transport substances used in renography. In addition, the symposium also focused on the multidrug-resistance transporter 1 (MDR1 or P-gp), which is the most important gatekeeper in epithelial or endothelial barriers for preventing entry of potentially harmful substances into organs. Novel substrates suitable for positron emission tomography (PET) allow the study of such transporters at the blood-brain barrier or while they are mediating uptake of drugs into hepatocytes, and, importantly, PET tracers also now allow renography. Finally, quantitative data on transporter expression in human organs allow the development of improved physiologically based pharmacokinetic (PBPK) models for drug disposition. Hence, the combined efforts using novel substrates for in vivo visualization of transporters and quantification of transporters will lead to a deeper understanding of transporter function in disease and allow development of novel PBPK models for disease states.
The existence of optimal consumption policies in optimal economic growth models with nonconvex technologies

Abstract An existence theorem for a class of continuous time infinite horizon optimal growth models is developed. The underlying technology set is not assumed to be convex, instead the “slices” of the technology set corresponding to a fixed capital stock vector are assumed convex and compact in the consumption and net investment variables. This allows consideration of the case of increasing returns to scale. Existence of an optimal capital stock and consumption policy is proved directly without consideration of the underlying Hamiltonian dynamical system that arises from applying Pontryagin's maximum principle.
Do Ethnic Differences Still Exist in Pain Assessment and Treatment in the Emergency Department

Although the provision of timely and appropriate analgesia is a primary goal of Emergency Department (ED) staff, pain continues to be undertreated and some evidence supports the existence of pain treatment disparities. Despite strong incentives from accreditation organizations, pain management in the ED may still be inconsistent and problematic. The purpose of this research study was to conduct a retrospective chart review to investigate pain assessment and treatment for 200 adults (≥18 years old) admitted to the ED suffering from long-bone fractures. An additional purpose was to investigate demographic variables, including ethnicity, to determine if they influenced pain assessment, pain treatment, and wait times in the ED. Although assessment and treatment of pain is universally recognized as being important and necessary to provide optimal patient care, only 52% of patients in this study were assessed using a pain intensity scale, with 43% of those assessed reporting pain as ≥5 on a 0-10 pain intensity instrument. Pain medication was administered to 75% of the patients, but 25% of the patients received no medication. Only 24% of those receiving a pain medication were reassessed to determine pain relief. Compounding these problems were wait times for analgesia of >1 hour. Although the influence on pain management related to ethnicity was not a factor in this study, other findings revealed that undertreatment of pain, inadequate assessment, lack of documentation of pain, and lengthy wait times persist in the ED.
Exploring sleep-wake experiences of mothers during maintenance therapy for their child's acute lymphoblastic leukemia

A qualitative study was designed to explore sleep-wake experience of mothers of children in maintenance treatment for Acute Lymphoblastic Leukemia. Interviews were conducted with 20 participants using open-ended, semi-structured questions and were transcribed verbatim. Two main themes emerged: "It's a whole new cancer world" and "I don't remember what it's like to have sleep." Mothers experience difficulty sleeping during their children's treatment, and expressed several serious issues. Although the mothers were able to employ various mechanisms to address sleep deprivation and disruption, interventions such as social support, journaling, spiritual guidance, and/or self-talk may be most beneficial.
Some remarks on Talcott Parsons’s family

It is no doubt very well known that Talcott Parsons was of New England ances try. It may be less well known how pure this ancestry was. His father, my grandfa ther Edward Smith Parsons (1863-1943), had a strong interest in genealogy and did quite a bit of work (evidently some of it with the help of other family mem bers)2 tracing his ancestry and that of his wife, Mary Augusta Ingersoll Parsons (1863-1944). He verified that every line of the ancestry of both could be traced back into seventeenth-century New England. Several ancestors apparently came to Massachusetts Bay Colony in its earliest years, and it appears that one came on the Mayflower. Grandfather wrote out handwritten copies of the genealogy for his chil dren. The one he gave to my father is now in my possession, but some years ago we gave a copy of it to the Harvard University Archives, so that some of you may have seen it. In this paper I will say something about the earlier history of the family up to Grandfather's generation, mentioning some individuals who might interest you. Then I will say something about my grandfather's life and his world as I perceive it. The aspects of it that have struck me most forcefully have not only vanished; they were beginning to vanish in the last years of his life, and I will mention some intra-family events that were part of that process. What I find most striking about my grandfather is the strength of his New England identification, even though neither he nor his wife was born or reared there. This seems to have been shared by others in his milieu and by other family members in the nineteenth and early twen tieth centuries. There was evidently for a long time a self-conscious New England diaspora to which Edward and Mary Augusta Parsons belonged. Although the phe nomenon seems to be recognized by historians, it has not been systematically stud ied, and my own efforts to obtain relevant readings have been largely frustrated, in spite of helpful responses to inquiries with Harvard historians.3
The Two Extremes of Cardiac Sarcoidosis and the Effect of Prednisone Therapy

Described herein are clinical and morphologic findings in 2 patients who underwent heart transplantation because of severe heart failure resulting from cardiac sarcoidosis. Although the explanted hearts in each patient had characteristic gross changes of cardiac sarcoidosis, one patient who had been treated with prednisone, had no residual sarcoid granulomas in the myocardium, whereas the other patient, in whom diagnosis was not made until heart transplantation, had innumerable sarcoid granulomas in her heart. This report suggests that prednisone can eliminate sarcoid granulomas in the heart but that their replacement is by dense fibrous tissue, something also likely the result of the granulomas themselves, creating a situation where the treated (prednisone) and the non-treated sarcoid heart may appear similar by gross examination.
Capillary isoelectric focusing-electrospray ionization mass spectrometry for transferrin glycoforms analysis.

Abstract On-line capillary isoelectric focusing (CIEF)–electrospray ionization mass spectrometry (ESIMS) as a two-dimensional separation system is employed for high-resolution analysis of bovine serum apotransferrin glycoforms. On the basis of their differences in isoelectric point (p I ), the di-, tri-, and tetrasialotransferrins are separated and resolved in CIEF. The focused protein zones of di-, tri-, and tetrasialotransferrins are eluted by combining gravity with cathodic mobilization. At the end of CIEF capillary, the mobilized transferrin zones are analyzed by mass spectrometry coupled on-line to an electrospray interface with a coaxial sheath flow configuration. Additional transferrin variants within each of di-, tri-, and tetrasialotransferrins, differing in their molecular weights, are easily distinguished by ESIMS. In combination with sialidase digestion, the distribution of p I and molecular weight of asialo-, mono-, di-, tri-, and tetrasialotransferrin variants was obtained from the CIEF–ESIMS measurements. In addition to the differences in the number of sialic acid, the microheterogeneity of bovine serum apotransferrin glycans might be complicated by the partial fucosylated structure and the α-Gal (1–3)-β-Gal on the α-Man-(1–6) antenna.
Do time perspectives predict unique variance in life satisfaction beyond personality traits

In this study we compared the relationships between time perspectives, the Big Five personality traits, and life satisfaction. Our results replicated past work in that personality traits and time perspectives were both associated with life satisfaction. Individuals high on extraversion and those having a past positive and a present hedonism time perspective were more satisfied with their lives; individuals high on neuroticism and those having a past negative time perspective were less satisfied with their lives. Further, hierarchical regression analyses demonstrated that time perspectives accounted for an additional 13.7% of the variance in life satisfaction beyond personality traits; whereas, personality traits accounted for an additional 4.4% of the variance in life satisfaction beyond time perspectives. Mediation models demonstrated that time perspectives partially accounted for the personality and life satisfaction relationship. We discuss the possibility that most of the association between personality traits and life satisfaction may be due to individual differences in cognitive time frames.
Plausibility, Manipulation, and Fischer and Ravizza

The manipulation argument poses a significant challenge for any adequate compatibilist theory of agency. The argument maintains that there is no relevant difference between actions or pro-attitudes that are induced by nefarious neurosurgeons, God, or (and this is the important point) natural causes. Therefore, if manipulation is thought to undermine moral responsibility, then so also ought causal determinism. In this paper, I will attempt to bolster the plausibility of John Martin Fischer and Mark Ravizza's semicompatibilist theory of moral responsibility by demonstrating how their account provides a distinctive line of response to three important types of manipulation.
Light-dependent modification of Photosystem II in spinach leaves

In dark-adapted spinach leaves approximately one third of the Photosystem II (PS II) reaction centers are impaired in their ability to transfer electrons to Photosystem I. Although these ‘inactive’ PS II centers are capable of reducing the primary quinone acceptor, QA, oxidation of QA − occurs approximately 1000 times more slowly than at ‘active’ centers. Previous studies based on dark-adapted leaves show that minimal energy transfer occurs from inactive centers to active centers, indicating that the quantum yield of photosynthesis could be significantly impaired by the presence of inactive centers. The objective of the work described here was to determine the performance of inactive PS II centers in light-adapted leaves. Measurements of PS II activity within leaves did not indicate any increase in the concentration of active PS II centers during light treatments between 10 s and 5 min, showing that inactive centers are not converted to active centers during light treatment. Light-induced modification of inactive PS II centers did occur, however, such that 75% of these centers were unable to sustain stable charge separation. In addition, the maximum yield of chlorophyll fluorescence associated with inactive PS II centers decreased substantially, despite the lack of any overall quenching of the maximum fluorescence yield. The effect of light treatment on inactive centers was reversed in the dark within 10–20 mins. These results indicate that illumination changes inactive PS II centers into a form that quenches fluorescence, but does not allow stable charge separation across the photosynthetic membrane. One possibility is that inactive centers are converted into centers that quench fluorescence by formation of a radical, such as reduced pheophytin or oxidized P680. Alternatively, it is possible that inactive PS II centers are modified such that absorbed excitation energy is dissipated thermally, through electron cycling at the reaction center.
Adrenergic stimulation of lens cytoskeletal phosphorylation.

Stimulation of lens fiber cytoskeletal phosphorylation by adrenergic drugs is described. The effect of isoproterenol on phosphorylation of the 47Kd beaded filament protein is dose-dependent, detectable as soon as one minute after treatment and blocked by propranolol. Epinephrine increases the phosphorylation of both 47Kd and the intermediate filament protein, vimentin. 47Kd phosphorylation is also increased by norepinephrine, dibutyryl-cAMP or forskolin. The results indicate that lens fiber cytoskeletal phosphorylation is regulated, at least in part, via a beta-adrenergic receptor coupled to cyclic AMP production.
The Functional Significance of FSH in Spermatogenesis and the Control of Its Secretion in Male Primates

The aim of this review is to provide an integrative analysis of the role of FSH in the control of testicular function in higher primates, including man. Attention is focused on the action of FSH during neonatal development, puberty, and adulthood. Whether FSH is the major determinant of the adult complement of Sertoli cells and whether FSH is obligatory for the initiation, maintenance, and restoration of spermatogenesis is evaluated. The mechanism whereby the circulating concentration of FSH regulates spermatogonial proliferation to dictate the sperm production rate under physiological conditions in the adult is discussed in detail. Inhibin B is the major component of the testicular negative feedback signal governing FSH beta gene expression and FSH secretion, and the evidence for this view is presented. The review concludes with the presentation of a model for the operation of the FSH-inhibin B feedback control system regulating sperm production postpubertally in monkey and man, and with speculation on issues of clinical interest.
Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers

Background Hepatitis C virus (HCV) is a major cause of chronic liver disease by infecting over 170 million people worldwide. Recent studies have shown that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, are involved in the regulation of HCV infection, but their functions have not been systematically studied. We propose an integrative strategy for identifying the miRNA-mRNA regulatory modules that are associated with HCV infection. This strategy combines paired expression profiles of miRNAs and mRNAs and computational target predictions. A miRNA-mRNA regulatory module consists of a set of miRNAs and their targets, in which the miRNAs are predicted to coordinately regulate the level of the target mRNA.
Salt-dependent heat capacity changes for RNA duplex formation.

Two short non-self-complementary RNA duplexes have been probed extensively to assess whether the heat capacity change (ΔCP) for RNA duplex formation is sensitive to the solution ionic strength. Isothermal titration calorimetry data for duplex formation were collected as a function of temperature to obtain the ΔCP values under each condition. Ionic strength was varied by repeating the measurements in the presence of 0.1−1.5 M added NaCl. In both cases, the ΔCP for duplex formation was shown to have a significant dependence on the solution ionic strength, varying linearly with the log of the added NaCl. In each case, the ΔCP became more negative at high ionic strength. Heat capacity changes have been much better studied in the area of protein folding where ΔCP is not strongly dependent upon ionic strength but instead depends primarily on the burial of hydrophobic surface. Whereas hydrophobic burial is almost certainly involved in RNA duplex formation as well, the polyanionic nature of the backbone and the a...
Nonpolar interactions in the maleimide inactivation of Haemophilus influenzae D-lactate dehydrogenase.

A series of N-alkylmaleimides varying in chain length from N-ethyl up to and including N-heptyl, was shown to effectively inactive Haemophilus influenzaeD-lactate dehydrogenase at pH 7.0 and 25°C in processes proposed to involve covalent modification of cysteine residues. The inactivation proceeded through an initial reversible binding of maleimides facilitated by nonpolar interactions with a hydrophobic region of the enzyme. Subsequent irreversible inactivation of the enzyme indicated the modification of a fast-reacting group leading to approx. 80% loss of enzyme activity followed by a second slower-reacting modification process. At saturating concentrations of maleimides, the second inactivation process exhibited a common pseudo-first-order rate constant of 0.6 min−1. The initial reversible binding of N-alkylmaleimides resulted in inhibition of the enzyme that was competitive with respect to NADH. Positive chain length effects were observed in the second-order rate constants for inactivation and in the 6-fold better binding of N-heptylmaleimide as compared to that for N-ethylmaleimide. It is suggested that the nonpolar interactions stabilizing the 1,4-dihydronicotinamide molety of the reduced coenzyme also facilitate the initial binding of N-alkylmaleimides.
Midsagittal facial soft-tissue growth of French Canadian adolescents.

This study examines changes in 12 midline soft-tissue thicknesses from the forehead, nose, lip, and chin regions in girls and boys from 10 to 16 years of age. The soft-tissue changes are compared to changes in two hard-tissue distances (sella-nasion and nasion-menton). The subjects are from a mixed-longitudinal sample studied at the Montreal Human Growth Research Center in the 1960s and 1970s. Total sample size is 242 (from lateral cephalographs of 124 males and 118 females), with numbers varying by age and measurement. For hard-tissues, boys show clearly defined adolescent spurts, while girls display small velocity increases indicative of only very minor spurts. Forehead tissue thicknesses for both sexes change little and show no demonstrable growth spurts. For the nose and philtrum region, which have the greatest absolute soft-tissue growth changes, both boys and girls show adolescent spurts. Peak velocities are attained between 13 and 14 years in boys and between 11.9 and 12.5 years in girls. Boys appear to have small adolescent spurts for upper (13.7 years) and perhaps lower lip thicknesses. Neither sex displays clear evidence for adolescent spurts in the chin region.
Dependence of Epithelial Intercellular Junction Biogenesis on Thapsigargin-sensitive Intracellular Calcium Stores

Perturbation of potentially regulatable endoplasmic reticulum (ER) calcium stores with the Ca-ATPase inhibitor, thapsigargin (TG), perturbs the formation of desmosomes and tight junctions during polarized epithelial cell biogenesis, despite the development of cell contact. In a Madin-Darby canine kidney cell model for intercellular junction assembly, TG treatment inhibited the development of transepithelial electrical resistance (TER), a measure of tight junction assembly, in a dose-dependent manner. The TG-induced inhibition of tight junction assembly was paralleled by a defect in the sorting of the tight junction protein, ZO-1. An even more dramatic delay in sorting of the desmosomal protein, desmoplakin, was observed in the presence of TG. In addition, while both ZO-1 and desmoplakin-I in control cells were shown to become associated with the Triton X-100 insoluble cytoskeleton during intercellular junction assembly, prior treatment with 100 nM TG diminished this biochemical stabilization into the detergent-insoluble fraction, particularly in the case of ZO-1. Although spectrofluorimetric measurements in fura-2 loaded Madin-Darby canine kidney cells confirmed the occurrence of TG-mediated release of calcium from internal stores, total cytosolic calcium during junction assembly remained similar to untreated cells. Therefore, the presence of cytosolic calcium alone is not sufficient for normal intercellular junction biogenesis if intracellular stores are perturbed by TG. The results indicate the presence of calcium-sensitive intracellular mechanisms involved in the sorting and cytoskeletal stabilization of both tight junction and desmosomes and suggest a role for calcium-dependent signaling pathways at an early (possibly common) step in polarized epithelial biogenesis.
Serum uric acid and self-reported rheumatoid arthritis in a multiethnic adult female population.

AbstractObjective:Studies suggest that serum uric acid (SUA) is significantly associated with cardiovascular disease (CVD) mortality among women and blacks. CVD rates are higher among patients with rheumatoid arthritis (RA) than the normal population. The objective of this study was to determine if there was an association between SUA levels and self-reported RA in a multiethnic female population in the United States.Methods:This cross-sectional study was conducted using data for 7374 women above 20 years of age in the Third National Health and Nutrition Examination Survey. Multiple and logistic regression methods were used to determine an association between SUA levels and self-reported RA.Results:Women self-reporting RA had significantly higher SUA levels (p < 0.0001) compared to women not self-reporting RA, also when adjusted for age and race (p < 0.0001). In a regression analysis, significant predictors of SUA levels were: self-reporting RA, race/ethnicity, being married, smoking, use of alcohol, high...
Tax enforcement: A public choice perspective

Federal income tax inforcement varies greatly across individual states. While it is not known if this interstate variation enhances efficiency, anecdotal evidence suggests it does not. In this paper we apply the Weingast/Moran model to the treasury and explore the relationship between the legislature and the IRS. Specifically, we model IRS audit rates by state as a function of both political and efficiency considerations. We find that the interstate differences in enforcement is influenced by efficiency considerations but also the IRS shifts enforcement away from states represented by legislators who sit on committees with oversight responsibility for the IRS.
Soil pH, extractable aluminum and tree growth on acid minesoils

Abstract Paper birch and hybrid poplar were grown in acid minesoils amended with different rates and types of lime. Growth of the trees was correlated with soil pH, Ca, Mg, K, P and three measures of extractable Al ‐ 1 N KCl, 0.01 M CaCl2 and H2O extractable Al. Correlations between soil pH and extractable Al and between the three measures of extractable Al were also determined. Soil pH accounted for the largest share of the total variation in root and shoot growth of both species over all soils. Correlations between tree growth and extractable Al for all soils combined were low and generally non‐significant. Significant correlations were obtained between soil pH and extractable Al and between the three measures of extractable Al, however, the relationships varied among soils.
Reconstructing the South: How Commercial Myths Compete for Identity Value through the Ideological Shaping of Popular Memories and Countermemories

This study explicates the coconstitutive relationships between commercial mythmaking and popular memory that arise through myth market competitions for identity value. We develop a genealogical analysis of the representational strategies and ideological rationales that two prominent New South mythmakers use to shape popular memories in relation to their competitive goals and to efface countermemories that contradict their mythologized representations. We then derive a conceptual model that highlights competitive, historical, and ideological influences on commercial mythmaking and their transformative effects on popular memory, which have not been addressed by prior theorizations of the meaning transfer process.
Transjugular intrahepatic portosystemic shunt--role in treating intractable variceal bleeding, ascites, and hepatic hydrothorax.

Transjugular ihtrahepatic portosystemic shunt (TIPS) patency can be improved by the use of covered stents. Although this technical advance may lower the costs associated with TIPS, the overall role of TIPS in the management of portal hypertension may not change. Currently, bare metal TIPS is indicated in the treatment of acute refractory variceal hemorrhage, in the secondary prevention of variceal hemorrhage, for the management of ascites refractory to both medical management and large-volume paracentesis, and in the control of hepatic hydrothorax refractory to medical management.
The Nature of Violence A Multilevel Analysis of Gun Use and Victim Injury in Violent Interpersonal Encounters

A large number of studies have examined predictors of crime quantities yet considerably less attention has been directed toward exploring patterns in the nature or quality of violence within and across communities. The current study adds to the literature on qualitative variations in violence by assessing the incident and contextual-level predictors of offender gun use and physical injuries sustained by victims of robbery and aggravated assault. Specifically, we examine incident-level data from the National Incident Based Reporting System in conjunction with contextual-level data on the cities in which the incidents occurred. We use hierarchical linear and nonlinear modeling techniques to explore variations in predictors of offender gun use and extent of victim injury. Supporting cultural effects explicated by Anderson, results reveal certain individual-level predictors are conditioned by community characteristics.
MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage.

Microcephalin (MCPH1) is one of the causative genes for the autosomal recessive disorder, primary microcephaly, characterized by dramatic reduction in brain size and mental retardation. MCPH1 also functions in the DNA damage response, participating in cell cycle checkpoint control. However, how MCPH1 is regulated in the DNA damage response still remains unknown. Here we report that the ability of MCPH1 to localize to the sites of DNA double-strand breaks depends on its C-terminal tandem BRCT domains. Although MCPH1 foci formation depends on H2AX phosphorylation after DNA damage, it can occur independently of MDC1. We also show that MCPH1 binds to a phospho-H2AX peptide in vitro with an affinity similar to that of MDC1, and overexpression of wild type, but not C-BRCT mutants of MCPH1, can interfere with the foci formation of MDC1 and 53BP1. Collectively, our data suggest MCPH1 is recruited to double-strand breaks via its interaction with γH2AX, which is mediated by MCPH1 C-terminal BRCT domains. These observations support that MCPH1 acts early in DNA damage responsive pathways.
Comparison of outcomes following open and laparoscopic esophagomyotomy for achalasia.

Background: Minimally invasive esophagomyotomy is replacing open surgery for achalasia, but data comparing these procedures performed by the same surgical team are sparse. The purpose of this study was to compare the morbidity and clinical outcome following laparoscopic and open esophagomyotomy.
Reach out or reach within? Performance implications of alliances and location in biotechnology

The extensive literature on geographical clusters has argued that firms stand to gain from the knowledge spillovers and the easy availability of skills in regional agglomerations. At the same time, the research on strategic alliances, particularly in technology-intensive industries, views alliances as vehicles for the transfer of technology and knowledge. Does membership in a geographical cluster or a network of alliances}an alliance cluster}benefit firms equally? More importantly, does it matter whether firms form alliances with firms within their geographical cluster, or do they do better by reaching out beyond their cluster? In this paper, we investigate these and other related questions in the context of technology-intensive industries such as biotechnology and argue that the high-level knowledge sensing and acquiring needs of firms in such industries may require combinations of both kinds of knowledge-access mechanisms. We use the BioScan database to obtain 648 alliances for the period 1985–1998 among 248 public companies, and complement it with COMPUSTAT data to examine the effect of clustering and alliances on market value. Our results suggest that merely being part of geographical clusters is not enough, and nor is it adequate for firms to join alliance clusters. Rather, firms gain by forming alliances both within and beyond their geographical clusters, which highlights the complexities of acquiring technology-intensive knowledge and suggests that the acquisition of knowledge in technology-intensive settings is best achieved through mechanisms both formal and informal, both proximate and distant. Copyright # 2004 John Wiley & Sons, Ltd.
Camptothecin in sterically stabilized phospholipid micelles: A novel nanomedicine

Abstract Background Camptothecin (CPT) is a well-established topoisomerase I inhibitor against a broad spectrum of cancers. However, poor aqueous solubility, instability, and toxic effects to normal tissues have limited CPT clinical development. Recently, sterically stabilized micelles (SSM) composed of polyethylene glycol (PEGylated) phospholipids have been introduced as safe, biocompatible nanocarriers for the delivery of poorly water-soluble drugs. It was the aim of this study to develop and evaluate in vitro camptothecin-containing SSM (CPT-SSM) as a novel nanomedicine for parenteral administration. Methods The solubilization potential, stability, and in vitro cytotoxicity of CPT in SSM were studied. Lyophilization of CPT-SSM under controlled conditions was also studied. Results The mean size of CPT-SSM was found to be ∼14 nm with a narrow size distribution. CPT-SSM were prepared by coprecipitation reconstitution. At a concentration of 15 mmol/L of PEGylated phospholipids where no micelle–micelle interaction was observed, CPT solubilization in SSM was 25-fold higher than CPT in buffer. We determined that CPT can be solubilized in SSM up to molar ratios of CPT/lipid = 0.0063:1. Above this critical molar ratio, heterogeneous systems of CPT-SSM and CPT self-aggregated particles were formed. CPT in SSM was at least 3 times more stable and 3-fold more cytotoxic to MCF-7 cells than CPT alone. Furthermore, CPT-SSM alone was lyophilized without additional lyoprotectants and cryoprotectants and reconstituted without any significant change in properties. Conclusion We have shown that CPT in SSM is a promising nanomedicine with improved drug solubility, stability, freeze-drying properties, and anticancer activity. It is anticipated that, because of the nanosize and steric stability of the micelles, CPT-SSM will be passively targeted to solid cancers in vivo, resulting in high drug concentration in tumors and reduced drug toxicity to the normal tissues.
Working through Sarah Polley's Stories We Tell (and the issue of creative expression).

The gifted Canadian director, film writer and actress Sarah Polley, at age 36, has written and directed three critically acclaimed films: Away From Her (2006), Take This Waltz (2011) and Stories We...
The spectrum of mucocutaneous manifestations in Adamantiades-Behçet's disease in Greece.

Background This is the largest specific demographic and clinical study performed until now in Greece. Objectives To analyse the spectrum of mucocutaneous manifestations in 202 patients with Adamantiades-Behcet’s disease (ABD) in Greece. Methods Any mucocutaneous symptom at disease onset and during the follow-up was recorded in a particular questionnaire that included 58 items. All patients fulfilled the International Study Group Criteria for BD. Results Consecutive patients (130 men and 72 women) were included in this study. Their mean age was 42.03 ± 12.41 and 44.96 ± 11.99 years for male and female patients respectively. Pathergy test was positive in 38%, whereas HLA-B5 (51) positivity was evident in 76% of patients. Onset signs: oral aphthous ulcers were found in 64.36%, genital ulcers in 6.93%, skin lesions in 8.91%, erythema nodosum in 7.42% and pseudofolliculitis in 1.5%. One patient had leg ulcers. During the follow-up, oral aphthous ulcers were found in 100%, genital ulcers in 65.4% and in 51.4%, erythema nodosum in 42.9% and in 78.1%, whereas pseudofolliculitis in 57.1% and in 21.9% in men and women respectively. Significant differences pointing to a different course of mucocutaneous disease were found between men and women. Conclusions The nature and frequency of mucocutaneous manifestations at presentation are important for the diagnosis of ABD, whereas significant differences were found between genders in this Greek patient cohort. Significant differences were also observed when our results were compared with those of four other series, probably explained by genetic and environmental factors.
The tL2 cluster of transcription termination sites between genes bet and ral of coliphage lambda.

Abstract The major leftward transcription of bacteriophage λ is controlled by several terminators ( t ), including t L1 , t L2 , t L3 , and others. The t L2 termination site, which was placed by Salstrom and Szybalski ( Virology 88 , 252–260, 1978) between λ genes bet and ral , was found to consist of a cluster of four leftward terminators. As not to change the numbering of other leftward terminators, these were designated as t L2a , t L2b , t L2c and t L2d As determined by S1 nuclease mapping of the t L2 -terminated in vitro transcripts, the normally p L- initiated major leftward λ transcription should encounter termination points at 1653 bp ( t L2a ; between genes Ea 10 and ral ), 2089 by ( t L2b ; between genes c III and Ea 10), 2441–2442 bp, and 2483 by ( t L2c and t L2d ; both within gene gam ) from the S L startpoint (= +1). All terminators were cloned in a pBR322-derived plasmid between the p ′ R promoter and the galK gene, and their in vivo termination efficiencies are 69% ( t L2a ), 53% ( t L2b ), and 38% ( t L2c + t L2a ), measured as reduction of galK expression in rho + galK − hosts at 30° The t L2a and t L2b terminators depend little on the rho factor, whereas the efficiency of t L2c + t L2d decreases from 38 to only 14% in the rho − host. When shifted to 42°, the termination efficiency of t L2b decreases from 53 to only 36%, while the other t L2 terminators are much less affected by increasing the temperature. The calculated joint efficiency of the entire t L2 cluster is 90%, which is in perfect agreement with the 90% termination efficiency reported by Salstrom and Szybalski (1978) for t L2 . However, the natural location of t L2c and t L2d within the actively translated gam gene may interfere with their termination function. Under in vitro conditions, t L2a and t L2b are active only in the presence of rho factor, whereas t L2a and t L2b do not require rho . The structure of the t L2 terminators resembles that of some other known termination sites: a perfect (8 by for t L2a and t L2a ) or imperfect (8–9 bp) dyad symmetry and a T 6 ( t L2a ), T 5 ( t L2b ), T 4 ( t L2c ), or TTATT sequence ( t L2d ) toward the 3′ end of the mRNA-like DNA strand.
Modeling and control of an LCL filter based three-phase active rectifier in grid emulator

An active rectifier with an LCL filter has been proved to be an effective approach to suppress switching harmonic current, guarantee unity power factor, and supply reliable dc voltage in power grids. This paper deals with the modeling and control of an active rectifier with low-volume coupled LCL filter for switching ripple attenuation. Specifically, the equivalent circuit model of three-phase three-column coupled inductors is built taking the variation of coupling coefficient into account. Based on the equivalent circuit, the average model of the active rectifier is derived under abc and dq0 coordinates to design a decoupled controller with excellent steady-state and dynamic performance. In addition, the influences of the coupled LCL filter on current total harmonic distortion (THD) and system stability are investigated under both resistive loads and paralleled inverter loads. Simulation and experimental results from a 30 kVA prototype verify the validity of the proposed model and the effectiveness of the designed controller.
Glycoconjugates and tumor metastasis.

Metastasis is one of the most dangerous characteristics of malignant tumors, and it seems to be a biological property separate from rapid and uncontrolled growth. The clinical significance of metastasis as opposed to tumor growth was suggested when we studied the records of 391 colorectal cancer patients surgically treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between 1959 and 1975 to see if there was any correlation between the size of a primary tumor and the incidence of local or distant metastasis. The mean size of primary tumors from patients having regional or distant metastasis was significantly smaller than the mean size of primary tumors from patients without metastasis (Miller et al., 1985), and the five-year survival rate of patients having metastasis at the time of surgery was much poorer than that of patients having no metastasis (Miller et al., 1985). These results indicated that metastatic capacity, not rapid proliferation, is the major cause of death by colorectal cancer. This hypothesis is presumably true for many other malignant tumors. The other important conclusion drawn from this study was that the tumor cells of each colorectal carcinoma may be unique in their metastatic potential. In addition, intratumoral heterogeneity may exist. These findings are consistent with the biological nature of metastatic tumors as determined in experimental tumor systems (Nicolson and Poste, 1982, 1983).
The ‘risk inventory for persons with spinal cord injury’: Development and preliminary validation of a risk assessment tool for spinal cord injury

Purpose. To present a new short instrument to measure perceived risks of common everyday activities engaged in by persons with spinal cord injury (SCI), and to provide preliminary data on its psychometric properties. Method. Community-dwelling men and women with SCI (N ¼ 139) in metropolitan Detroit completed the risk inventory for persons with spinal cord injury (RISCI). They also answered a risk-taking identity question (‘Are you a risk-taker’?) and completed the risk orientation questionnaire (ROQ) (Rohrmann, http://www.rohrmannresearch.net/, 2008), a risk propensity measure. Results. All items of the RISCI correlated positively with each other and the total score; internal reliability as measured by Cronbach’s a was 0.86. Principal components factor analysis confirmed a one-factor structure which explained 41% of the variance. A three-factor solution with readily interpretable factors explained 64% of the variance. Content validity was established through extensive consultations with persons with SCI in the development of the measure. Discriminant validity was supported by the ability of the RISCI to distinguish between subsamples (for example, between men and women, those with paraplegia and tetraplegia) for whom differences in risk assessment might be expected. Criterion validity was supported by significant relationships in the expected directions between the RISCI and risk-taking identity and between the RISCI and the ROQ. Conclusions. Findings suggest that the RISCI is a brief, easy to administer and psychometrically sound measure of perceived risk of activities common in daily life for use with persons with SCI.
How accurate channel prediction needs to be for adaptive modulation in Rayleigh MIMO channels

Adaptive modulation improves system throughput considerably by matching transmitter parameters to time-varying wireless fading channels. Crucial to adaptive modulation is the quality of channel state information (CSI) at the transmitter. We consider a channel predictor based on pilot symbol assisted modulation (PSAM) for multi-input multi-output (MIMO) Rayleigh fading channels. We analyze the impact of the channel prediction error on the bit error rate (BER) performance of an adaptive system assuming perfect CSI. Our numerical results reveal the critical value of the normalized prediction error, below which the predicted channels can be treated as perfect by the adaptive modulator; otherwise, explicit consideration of the channel imperfection must be accounted for at the transmitter.
Activation of Antiviral Protein Kinase Leads to Immunoglobulin E Class Switching in Human B Cells

An epidemiologic association between viral infections and the onset of asthma and allergy has been documented. Also, evidence from animal and human studies has suggested an increase in antigen-specific immunoglobulin E (IgE) production during viral infections, and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provide molecular evidence for the roles of viral infection and of activation of the antiviral protein kinase (PKR) (double-stranded-RNA [dsRNA]-activated protein kinase) in the induction of IgE class switching. The presence of dsRNA, a known component of viral infection and an activator of PKR, induced IgE class switching as detected by the expression of germ line ɛ in the human Ramos B-cell line. Furthermore, dsRNA treatment of Ramos cells resulted in the activation of PKR and in vivo activation of the NF-κB complex. Interestingly, infection of Ramos cells with rhinovirus (common cold virus) serotypes 14 and 16 resulted in the induction of germ line ɛ expression. To further evaluate the role of PKR in the viral induction of IgE class switching, we infected Ramos cells with two different vaccinia virus (cowpox virus) strains. Infection with wild-type vaccinia virus failed to induce germ line ɛ expression; however, a deletion mutant of vaccinia virus (VP1080) lacking the PKR-inhibitory polypeptide E3L induced the expression of germ line ɛ. Collectively, the results of our study define a common molecular mechanism underlying the role of viral infections in IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma.
POST-ABORTION ADJUSTMENT OF HEALTH CARE PROFESSIONALS IN TRAINING

Sixty-three women students of the health care professions were surveyed about their abortion and post-abortion experiences, feelings, and attitudes. Variables predictive of short- and long-term adjustment, belief in the wisdom of the choice, and right to choose were analysed, as were effects on emotional and attitudinal responses of passage of time and pressure to abort. Most reported mild, transient, short-term negative effects, and generally benign long-term effects. Implications of the findings are discussed.
Locus control regions

Locus control regions (LCRs) are operationally defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number–dependent manner at ectopic chromatin sites. Although their composition and locations relative to their cognate genes are different, LCRs have been described in a broad spectrum of mammalian gene systems, suggesting that they play an important role in the control of eukaryotic gene expression. The discovery of the LCR in the β-globin locus and the characterization of LCRs in other loci reinforces the concept that developmental and cell lineage–specific regulation of gene expression relies not on gene-proximal elements such as promoters, enhancers, and silencers exclusively, but also on long-range interactions of various cis regulatory elements and dynamic chromatin alterations.
Cerebellar Mutism and Reversible Cytotoxic Edema in Influenza B–Associated Encephalopathy

Abstract Background Influenza virus–associated neurological complications are rare, though well-documented, especially in children. Encephalopathy and seizures are the most common complications and are typically associated with influenza A infection. Cerebellar mutism has been rarely reported in association with influenza B infection. Patient We describe a 3-year-old boy who presented with cough, fever, altered mental status, seizure, hypotonia, and mutism. He tested positive for influenza B virus. His brain magnetic resonance imaging showed reversible cytotoxic edema limited to the middle cerebellar peduncles and the dentate nuclei. Other viral, vascular, toxic, and metabolic causes were ruled out. Conclusion Our patient represents a case of cerebellar mutism associated with influenza B encephalopathy in which the brain magnetic resonance imaging scan showed reversible cytotoxic edema limited to the middle cerebellar peduncles and the dentate nuclei. This clinicoradiological correlation supports other reports in which the dentate nuclei play a major rule in the pathogenesis of cerebellar mutism.
Investigating functionalized active coated nanoparticles for use in nano-sensing applications.

In this paper we investigate the use of active coated nano-particles (CNPs) for nano-sensing applications. Simulation results of the optical properties of an active CNP with a 24nm radius active silica core and 6nm thick plasmonic shell made of silver that has been functionalized by an additional spherical outer layer of varying thickness and refractive index are presented. In particular, the effects of the functional-layer thickness and refractive index on the super-resonant (SR) state of the active CNP are presented. It is shown that the wavelength and optical gain required to excite the SR state may provide both a spectral and a power signature usable for nano-scale sensing and that these signatures may be used to identify the dimensions and optical properties of the functional layer. These results are then applied to the case of a functional layer containing a solution of human hemoglobin. It is demonstrated that the concentration of hemoglobin may be remotely determined from these SR signatures.