cssi/SciSciGPT-SciSciNet huggingface dataset:
Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review.

Abstract Background Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). Materials and Methods This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. Results There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. Conclusion Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib.
Partial Atrioventricular Canal Defect With an Anomalous Left Circumflex Coronary Artery in an Elderly Veteran

AbstractThis study reports a case of partial atrioventricular canal defect with an anomalous left circumflex coronary artery in an elderly veteran presenting with unexplained dyspnea on exertion. T...
Does Body Shape in Fundulus Adapt to Variation in Habitat Salinity

Understanding the ecological pressures that generate variation in body shape is important because body shape profoundly affects physiology and overall fitness. Using Fundulus, a genus of fish that exhibits considerable morphological and physiological variation with evidence of repeated transitions between freshwater and saltwater habitats, we tested whether habitat salinity has influenced the macroevolution of body shape at different stages in development. After accounting for phylogenetic inertia, we find that body shape deviates from the optimal streamlined shape in a manner consistent with different osmoregulatory pressures exerted by different salinity niches at every stage of ontogeny that we examined. We attribute variation in body shape to differential selection for osmoregulatory efficiency because: (1) saline intolerant species developed body shapes with relatively low surface areas more conducive to managing osmoregulatory demands and (2) inland species that exhibit high salinity tolerances have body shapes similar to saline tolerant species in marine environments.
spc4sts: Statistical process control for stochastic textured surfaces in R

Stochastic textured surface (STS) data (e.g., material microstructure microscopy images) are increasingly common in many quality control settings. Because of their stochastic nature, performing sta...
38 – Ureteral Pacemaker

Publisher Summary The ureter can be made to peristalse by mechanical stimulation anywhere along its course. It can be stimulated electrically by means of a peacemaker. In a study described in the chapter, pigs, constant stimulation of the ureter up to 12 V did not produce any signs of scar after several months. The clinical results in three children ranged from excellent to failure. After electrical stimulation, the intraureteral pressures returned to normal, but when the electrical stimulation was discontinued, the pressures in the ureter slowly fell to the same low levels seen before stimulation. The child subsequently had bilateral ileal sleeve procedures, together with Politano–Leadbetter ureteroneocystostomy. The excellent result was a child with moderate ureteral dilatation and reflux, and abnormally low intraureteral pressures. After 3 months of constant electrical pacing, the stimulator was turned off and the intraureteral pressures were normal.
Clinical trials and group sequential testing

Abstract This chapter considers the design of controlled clinical trials. We begin with motivation and the need for well-designed randomized controlled clinical trials. Fundamental elements of clinical trial design are presented, including the definition of target populations, intervention definitions, and the choice of trial endpoints. Randomization strategies are explained and group sequential testing procedures are introduced as methods for increasing trial efficiency.
Equity in Sugar-Sweetened Beverage Taxes: Who Pays for Obesity Control?

While the burden of infectious disease is still great in many regions of the world, public health concern has recently begun to shift toward non-communicable diseases (NCDs). Research has revealed distinct preventable and modifiable risk factors associated with NCDs. Metabolic risk factors linked to unhealthy diet, inactivity, and obesity have been implicated in diabetes and cardiovascular disease. The health risks associated with unhealthy diets are relatively well known, but on whom does the burden fall to regulate and improve eating practices? Is it the responsibility of the individual to self-regulate, or does the government have a role in protecting its citizens from dangerous eating practices? In the past decade, an increasing number of governments have begun taking steps to influence the nutritional habits of their citizens through the development of taxes levied on foods linked to obesity and cardiovascular disease (often called a “sin tax” or “fat tax”). Popular in recent news is the implementation of taxes on sugar-sweetened beverages (SSBs), designed to reduce their purchase and consumption. Economic analyses have shown that such SSB taxes are likely to have a greater impact on low-income individuals, in what is referred to as a “regressive income effect." Theoretically, the entire US tax-paying population would benefit from lower healthcare spending on obesity-related diseases. Is it fair, then, that those at the bottom of the US income system should disproportionately bear the burden of such a tax? Perhaps government approaches to taxes aimed at improving nutrition should be two-fold: the implementation of a Pigouvian tax aimed at reducing unhealthy dietary consumption (like sugar, fat, or salt) and the use of funds from such a tax to provide subsidies for healthier foods, nutritional education programs, or local community gardens, particularly in low-income communities most affected by these taxes. This approach would limit the financial burden placed upon any one segment of the population and continue to encourage healthy lifestyle habits.
The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer : a prospective comparative trial

AbstractWe assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100mg./M.2 cisplatin, 60mg./M.2 doxorubicin and 600mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive tra...
Friends with Beneficence: Asymmetry and Teacher Identity

Amy Shuffelton’s essay provides convincing responses to some common fears regarding teacher–student friendships, including inequality, partiality, and motivation. In refuting these arguments and outlining some positive potentials in pedagogical friendships, she also references another characteristic of character friendships, namely a mutuality of knowledge and recognition between friends, which remains unexamined in relation to pedagogical relationships, and may benefit from consideration. By contrasting our expectations of mutual knowledge in friendship and in pedagogical relationships, I suggest that the student’s lack of knowledge about the teacher plays an important role in learning, and may also shape what is possible in teacher–student friendships.
Cell Volume Modifies an ATP-Sensitive Anion Conductance in Cultured Hippocampal Astrocytes

282, C494-C500 (2002). 2. N. Perrotti, R.A. He, S.A. Phillips, C.R. Haft and S.I. Taylor, Activation of serumand glucocorticoidinduced protein kinase (sgk) by cyclic AMP and insulin, J. Biol. Chem. 276, 9406-9412 (2001). 3. H.H. Ussing and K. Zerahn, Active transport of sodium as the source of electric current in the shortcircuited isolate frog skin, Acta. Physiol. Scand. 23, 110-127 (1951). _______________________________________ * Nathan Kast and Bonnie L. Blazer-Yost, Biology Department, Indiana University–Purdue University at Indianapolis, IN 46202. Nicola Perrotti, Dipartimento di Medicina Sperimentale e Clinica, Universita Magna Graecia, Catanzaro, Italy
Design and Implementation of Instructional Computer Systems

AbstractBy using macroscopic planning models, school decision makers can help ensure that dollars spent on educational computing will yield optimal results. One such model is presented to facilitate the design and implementation of instructional micro- and minicomputer systems in school districts. The model is based on a comprehensive literature review which was refined by the results of a survey of school districts across the nation with outstanding micro- or minicomputer systems. A systems approach was used to organize the model, which consists of prescribed concepts and practices for selecting computer system inputs and maximizing computer system processes and outputs.
Design and Application of Two Rapid Screening Techniques for Isolation of Mn(IV) Reduction-Deficient Mutants of Shewanella putrefaciens

Chemical mutagenesis procedures and two newly developed rapid plate assays were used to identify two Mn(IV) reduction-deficient (Mnr) mutants of Shewanella putrefaciens. All eleven members of a set of previously isolated Fe(III) reduction-deficient (Fer) mutants displayed Mnr-positive phenotypes on the plate assays and were also capable of anaerobic growth on Mn(IV) as the sole terminal electron acceptor.
Rostrocaudal differences within the somites confer segmental pattern to trunk neural crest migration.

Neural crest cells are one of the most migratory and pleiotropic of embryonic cells types. These cells originate within the central nervous system, but emigrate from the neural tube shortly after its closure. They subsequently migrate along well characterized pathways to populate numerous and diverse derivatives ranging from sensory and autonomic ganglia of the peripheral nervous system to the cartilage and bone of the face. It is reported that neural crest migration is intimately linked to both the formation and segmentation of the somites. After differentiation of somites into dermomyotome and sclerotome, the sclerotomal compartment is subdivided into rostral and caudal halves. Although overtly similar, the caudal half sclerotome has a higher cell density and different molecular markers. Notably, ephrins (Eph) are selectively expressed in the caudal half sclerotome whereas their cognate Eph receptors are expressed on neural crest cells and rostral sclerotomal cells. Functional interactions between Eph receptors and ligands appear to restrict neural crest cells to the rostral half sclerotomal domain. This in turn leads to their segmental migration and the subsequent metameric distribution of neural crest-derived sensory and sympathetic ganglia.
A critical evaluation of inoculums in composting.

The practice of producing organic fertilizer through the biological decomposition of organic wastes has been carried on for centuries as an art generally known as composting. The widest application of the practice has occurred in the Orient and in Europe where dense populations have for generations placed a great burden on soil fertility. Until recently, interest in composting in the United States has been limited to the amateur gardener and the organic farming enthusiast. At present, two important factors are contributing to a broadening interest in composting in this country. One is the possibility of composting as an answer to the increasingly complex and serious problem of municipal refuse disposal. The other is the growing concern over the depletion of our agricultural soils by our present intensive farming practices which fail to return organic humus to the earth. The especial importance of both of these factors to the state of California prompted the Sanitary Engineering Research Laboratory of the University of California to begin a study of the application of composting to the reclamation of municipal refuse. It soon became apparent that in spite of the antiquity of composting there existed very little scientific knowledge of the process. Because there is a widespread conviction that an "inoculum" of some sort is needed for successful and rapid composting, one of the problems studied in the investigation was the effect of such an additive on the process. Since composting is a biological process, its course should be determined by the magnitude and nature of the microbial population present. It is easy, therefore, to assume that by artificially increasing the numbers of organisms, the process should be accelerated. Refuse is a mixture of relatively undecomposed heterogenous material. During the composting of such material there appears a succession of environments, especially with regard to temperature and substrate, with a corresponding series of microbial populations. Since the environmental conditions at any one time are suitable to a limited variety of bacteria, it would seem doubtful that organisms added as an inoculum could be any more effective than similar organisms indigenous to mixed refuse. To determine the validity of this reasoning a series of experiments were conducted concurrently with a broader investigation of composting to learn what benefit, if any, would accrue to the process from the use of an inoculum. Materials which have often been considered as inocul-ums essential to the composting process include: animal manures, garden soil, decomposing material, and a variety of proprietary bacterial cultures. In the experiments, inoculums consisting of soil, of horse manure, and of partially composted material, as well as a commercial preparation of bacterial cultures were tested.
Resolution of Inflammation: Prostaglandin E2 Dissociates Nuclear Trafficking of Individual NF-κB Subunits (p65, p50) in Stimulated Rheumatoid Synovial Fibroblasts

NF-κB transcription factors regulate inflammatory responses to cytokines such as IL-1β and TNF-α. We tested whether PGE 2 regulated nuclear localization of individual NF-κB subunits, p65 and p50, in synovial fibroblasts harvested from patients with rheumatoid arthritis (RA). IL-1β/TNF-α stimulated the translocation of p65 and p50 from the cytosol to the nucleus of human RA synovial fibroblasts, as well as NF-κB activation measured by luciferase reporter assay. PGE 2 (10 nM, 6 h) enhanced p50, but inhibited p65 translocation and NF-κB activation. In contrast, depletion of endogenous PGE 2 by ibuprofen (100 μM) and celecoxib (5 μM) enhanced p65, but inhibited p50 nuclear translocation as well as binding to NF-κB DNA binding sites. PGE 2 also blocked IL-1β/TNF-α-stimulated ERK activation, and the ERK inhibitor, PD98059, mimicked PGE 2 in blocking p65, but enhancing p50 nuclear translocation, suggesting that the effects of PGE 2 on p65 and p50 are mediated via effects on ERK. PGE 2 also enhanced the expression of IκBα in an ERK-independent manner, suggesting that PGE 2 inhibits NF-κB activation by both ERK-dependent and -independent mechanisms. Our data indicate that PGE 2 may act to attenuate cytokine-induced inflammatory responses in RA synovial fibroblasts via regulation of the localization of specific NF-κB family dimers.
Equity, Emotion, and Household Division of Labor Response.

Building upon insights generated by social psychological scholarship on equity, emotions, and identity, we use the General Social Survey (1996) Modules on Emotion and Gender and the National Survey...
Beyond the prescription: medication monitoring and adverse drug events in older adults

Whether a person will suffer harm from a medication or how severe that harm will be is difficult to predict precisely. As a result, many adverse drug events (ADEs) occur in patients in whom it was reasonable to believe that the drug's benefits exceeded its risks. Improving safety and reducing the burden of ADEs in older adults requires addressing this uncertainty by not only focusing on the appropriateness of the initial prescribing decision, but also by detecting and mitigating adverse events once they have started to occur. Such enhanced monitoring of signs, symptoms, and laboratory parameters can determine whether an adverse event has only mild and short-term consequences or major long-term effects on morbidity and mortality. Although current medication monitoring practices are often suboptimal, several strategies can be leveraged to improve the quality and outcomes of monitoring. These strategies include using health information technology to link pharmacy and laboratory data, prospective delineation of risk, and patient outreach and activation, all within a framework of team-based approaches to patient management. Although many of these strategies are theoretically possible now, they are poorly used and will be difficult to implement without a significant restructuring of medical practice. An enhanced focus on medication monitoring will also require a new conceptual framework to re-engineer the prescribing process. With this approach, prescribing quality does not hinge on static attributes of the initial prescribing decision but entails a dynamic process in which the benefits and harms of drugs are actively monitored, managed, and reassessed over time.
Molecular cloning, functional expression, tissue distribution, and in situ hybridization of the renal sodium phosphate (Na+/P(i)) transporter in the control and hypophosphatemic mouse.

The current studies were designed to isolate a cDNA encoding the control mouse renal sodium phosphate (Na+/P(i)) transporter and to determine mRNA levels encoding this transporter in control and (Hyp) mice. A 2.4 kb cDNA was isolated from a control mouse kidney cDNA library using a PCR-amplified 850 base pair (bp) fragment of rat cDNA. The cDNA encoding the mouse renal Na+/P(i) transporter shows sequence similarity to the rat and human Na+/P(i) transporters. The predicted protein exhibits 98% and 91% amino acid sequence identity with the rat and human proteins, respectively. A cRNA was synthesized from the cDNA and showed an expression of sodium-dependent phosphate transport in Xenopus laevis oocytes. Northern blot analysis of renal poly(A)+ RNA from (Hyp) and control mice showed a threefold decrease in mRNA level in the (Hyp) mice compared with control mice. In situ hybridization analysis localizes the Na+/P(i) transporter message to the renal proximal tubule, with message levels distinctly lower in the ...
Optimal polarization states determination of the Stokes reflection matrices [Mp] for the coherent case, and of the Mueller matrix [M] for the partially polarized case

A problem originating in radar polarimetry is considered for which the radar target is to be characterized by its 4x4 Mueller matrix [M] properties in terms of a partially polarized wave treatment for the monostatic reciprocal and non-reciprocal cases. In order to compare our results with previous coherent treatments of optimizing the corresponding 2x2 Sinclair matrix [S], first the vector formalism for the coherent case is introduced. The coherent formulation is then extended via the coherency matrix (vector) approach to the partially polarized case with the aid of the Kronecker expansion matrix and the Stokes vector formulism. Distinction of the Stokes Reflection Matrices is made between the one-antenna and the two-antenna cases. For the one-antenna case, the reception of the optimal energy densities and powers is accomplished separately for the co-polarized and the cross-polarized channels which is a natural approach in radar polarimetry. For the two-antenna case, the reception of the optimal power is accomplished by adjusting the polarization state of the receiving antenna to match or mismatch the polarization state of the scattered wave. The “degen- erate Mueller matrix case” for purely coherent wave reception is analyzed first to facilitate comparison with previous methods of optimizing the corresponding Sinclair matrix [S]. Here, the Lagrangian multiplier method is used for determining the characteristic optimal polarization states subject to the constraint that the incident wave is purely polarized.
How to Count the States of Extremal Black Holes in N = 8 Supergravity

The basic technique for counting the states of extremal black holes in string theory is to represent the black hole as a bound state of p-brane solitons. The horizon area of the resulting supergravity solution is related to an entropy by the Bekenstein-Hawking formula S = A/4G N . At weak coupling, p-branes charged under the Ramond-Ramond fields of Type II string theory are easily quantized as D-branes [1]. This fact was exploited in the seminal paper of Strominger and Vafa who showed that for some black holes corresponding at weak coupling to systems of D-branes, the collective coordinate degeneracy of the bound state can be easily calculated [2]. If the bound state in question is a BPS state, this degeneracy can be extrapolated back to strong coupling since the representation theory of supersymmetry protects it from corrections. To summarize, the program for counting the states of black holes amounts to treating the black hole as a bound state of solitons, quantizing the solitons at weak coupling, and extrapolating the resulting collective coordinate degeneracy back to strong coupling via an appeal to supersymmetry.
Role of laccase in the biology and virulence of Cryptococcus neoformans

Laccase is an important virulence factor for the human pathogen, Cryptococcus neoformans. In this review, we examine the structural, biological and genetic features of the enzyme and its role in the pathogenesis of cryptococcosis. Laccase is expressed in C. neoformans as a cell wall enzyme that possesses a broad spectrum of activity oxidizing both polyphenolic compounds and iron. Two paralogs, CNLAC1 and CNLAC2, are present in the fungus, of which the first one expresses the dominant enzyme activity under glucose starvation conditions. Regulation of the enzyme is in response to various environmental signals including nutrient starvation, the presence of multivalent cations and temperature stress, and is mediated through multiple signal transduction pathways. Study of the function and regulation of this important virulence factor has led to further understanding of mechanisms of fungal pathogenesis and the regulation of stress response in the host cell environment.
Proceedings of the first international conference on Neutrosophy, neutrosophic logic, neutrosophic set, neutrosophic probability and statistics

Neutrosophy is a new branch of philosophy, introduced by Florentin Smarandache in 1980, which studies the origin, nature, and scope of neutralities, as well as their interactions with different ideational spectra. Neutrosophic Logic is a general framework for unification of all existing logics. The main idea of NL is to characterize each logical statement in a 3D Neutrosophic Space, where each dimension of the space represents respectively the truth (T), the falsehood (F), and the indeterminacy (I) of the statement under consideration, where T, I, F are standard or non-standard real subsets of ]-0, 1+[. Moreover, in NL each statement is allowed to be over or under true, over or under false, and over or under indeterminate by using hyper real numbers developed in the non-standard analysis theory. It is the foundation for a new theory of paradoxical and plausible reasoning [i.e. Dezert-Smarandache Theory (ref. n.)] has been developed, that takes into account in the combination process itself the possibility for uncertain and paradoxical information. The basis for the development of this theory is to work with the hyper-power set of the frame of discernment relative to the problem under consideration rather than its classical power set since, in general, the frame of discernment cannot be fully described in terms of an exhaustive and exclusive list of disjoint elementary hypotheses. In such general case, no refinement is possible to apply directly the Dempster-Shafer Theory (DST) of evidence. In our new theory [i.e. DSmT (ref. n.)], the rule of combination is justified from the maximum entropy principle and there is no mathematical impossibility to combine sources of evidence even if they appear at first glance in contradiction (in Shafer's sense) since the paradox between sources of evidence yields unavoidable paradoxes. This theory has shown, through many illustrated examples, that conclusion drawn from it provides results which agrees perfectly with the human reasoning and is useful to take a decision on complex problems where DST usually fails. This book has been devoted to the development of a theoretical bridge between neutrosophic logic and this new theory, in order to solve the delicate problem of combination of neutrosophic evidences. The neutrosophic logic serves as the most general framework (prerequisite) for dealing with uncertain and paradoxical sources of information through this new theory (DSmT).
Physical Activity as Reinforcement for Classroom Calmness of ADHD Children: A Preliminary Study.

Contingent reward procedures have been found beneficial in improving classroom conduct of ADHD children. Based on the conceptualization of the Premack Principle, a previous single-subject study of an ADHD Autistic child suggested the novel use of physical activity availability as a reinforcer for attentive calmness of the Attention Deficit Hyperactivity Disorder (ADHD) child in a laboratory situation. The present study extended this finding to two older ADHD children in a typical special education classroom. The result is an increase of attentive calmness for the duration of the class for both children. These results suggest the possible use of this special type of reinforcer for general classroom usage in behavioral contingency management programs for ADHD children.
It Takes Three to Tango Genes Complicate the Association Between Birth Weight and Cardiovascular Disease

The risk factors of cardiovascular disease (CVD) are thought to be well known, but the relative importance of nature versus nurture continues to be debated. Although sex, family history, and genetic susceptibility are recognized as playing a major role, most attention has focused on lifestyle risk factors because of the substantial clinical benefits achievable—and achieved—by preventing or treating hypercholesterolemia, diabetes mellitus, hypertension, obesity, and smoking. In addition to genetically determined and postnatal risk factors, during the past 2 decades, developmental programming has emerged as a potential determinant of CVD. The concept that adult CVD is influenced by the conditions encountered by the developing fetus in utero originated largely from the observation by Barker and colleagues1 that low birth weight was associated with increased CVD. This prompted a flurry of epidemiological studies, the majority of which supported the association of birth weight with CVD and hypertension,2,3 whereas the association with type 2 diabetes mellitus remains more controversial.4,–,6 Later studies highlighted the need to differentiate low birth weight resulting from premature birth from true intrauterine growth restriction and established that the CVD risk is in fact associated with birth weight adjusted for gestational length.7 Article see p 2792 Unfortunately, the original Barker hypothesis has yielded only limited mechanistic insights and no translational benefits as of yet. The difficulty in identifying the underlying mechanisms stems largely from the fact that birth weight is an outcome of pregnancy and does not result from a uniform pathogenic condition in utero. Epidemiological studies of populations born during prolonged hunger periods established undernutrition as a cause of low birth weight,8 but many other pathogenetically diverse factors can result in low birth weight, such as severely protein-deficient diets, mechanical obstructions of the uterine artery, corticosteroid treatment, and …
Trbp Sliding Promotes Dicer's Cleavage Activity

Transactivation response (TAR) RNA binding protein (TRBP) is an essential cofactor of Dicer in the RNA interference pathway. TRBP enhances Dicer's processing of both microRNA (miRNA) and small interfering RNA (siRNA) precursors, yet the mechanistic basis of this effect has not been elucidated. Here we report a robust sliding activity of TRBP exclusively on double stranded RNA (dsRNA). TRBP exhibits ATP-independent motion selectively on double stranded RNA in a length dependent manner. We find that the first two double stranded RNA binding domains (dsRBDs) of TRBP, which stimulate the dicing activity, are also directly responsible for the sliding motion, whereas the third dsRBD is dispensable. The same sliding motion was also observed in two other dsRBD-possessing proteins, PACT, and R3D1, implying a universality of sliding activity in this family of proteins. When in complex, Dicer-TRBP displayed two modes of binding to dsRNA: static interaction and dynamic sliding. Upon stimulation of RNA cleavage, the sliding molecules, not the static molecules, disappeared selectively, strongly suggesting that the sliding motion of Dicer-TRBP promotes dicing activity. Our study demonstrates a novel mode of motion, sliding on dsRNA exhibited by dsRBD containing proteins, and suggests that such activity of TRBP leads to an enhanced catalytic cleavage of Dicer.
Collisional Quenching and Energy Transfer in OH

David R. Crosley and Richard A. CopelandMolecular Physics DepartmentSRI InternationalMenlo Park, California 94025AbstractStudies of energy transfer in the OH molecule are of both fundamental and practicalimportance. A recent series of measur9ments in this laboratory, on collisional processesinvolving the electronically excited A-E state of OH, has generated several interestingand surprising results. We find the total removal (electronic quenching) cross section ofthe y' = 0 level to decrease with increasing initially excited rotational level N' andtemperature. These observations strongly suggest long range attractive forces dominatethe quenching mechanism. Vibrational transfer y' =
DOC-2/DAB2 is the binding partner of myosin VI.

Myosin VI is a molecular motor that moves processively along actin filaments and is believed to play a role in cargo movement in cells. Here we found that DOC-2/DAB2, a signaling molecule inhibiting the Ras cascade, binds to myosin VI at the globular tail domain. DOC-2/DAB2 binds stoichiometrically to myosin VI with one molecule per one myosin VI heavy chain. The C-terminal 122 amino acid residues of DOC-2/DAB2, containing the Grb2 binding site, is identified to be critical for the binding to myosin VI. Actin gliding assay revealed that the binding of DOC-2/DAB2 to myosin VI can support the actin filament gliding by myosin VI, suggesting that it can function as a myosin VI anchoring molecule. The C-terminal domain but not the N-terminal domain of DOC-2/DAB2 functions as a myosin VI anchoring site. The present findings suggest that myosin VI plays a role in transporting DOC-2/DAB2, a Ras cascade signaling molecule, thus involved in Ras signaling pathways.
Growth rate of nonthermodynamic emittance of intense electron beams

The nonlinear free-energy concept has been particularly useful in estimating the emittance growth resulting from any excess energy of electron beams in periodic and uniform channels. However, additional emittance growth, that is geometrical rather than thermodynamic in origin, is induced if the particles have different kinetic energies and axial velocities, which is common for mildly relativistic, very intense electron beams. This effect is especially strong if particles lose or gain significant kinetic energy due to the beam's potential depression, as the beam converges and diverges. In this paper we analyze these geometric emittance growth mechanisms for a uniform, continuous, intense electron beam in a focusing transport channel consisting of discrete solenoidal magnets, over distances short enough that the beam does not reach equilibrium. These emittance growth mechanisms are based on the effects of (1) energy variations leading to nonlinearities in the space-charge force even if the current density is uniform, (2) an axial velocity shear radially along the beam due to the beam's azimuthal motion in the solenoids, and (3) an energy redistribution of the beam as the beam compresses or expands. The geometric emittance growth is compared in magnitude with that resulting from the nonlinear free energy, for the case of a mismatched beam in a uniform channel, and is shown to dominate for certain experimental conditions. Rules for minimizing the emittance along a beamline are outlined.
Are there environmental forms of systemic autoimmune diseases

A large number of drugs and an increasing number of environmental agents reportedly result in the appearance of a number of autoantibodies and in many instances in the appearance of a range of autoimmune clinical syndromes. The major disorders so recognized have marked resemblances to the autoimmune disease systemic lupus erythematosus. The commonly used term is drug-induced lupus; a better term is drug-related lupus. There is considerable interest at the present time in an increasing number of environmental agents. There have been two epidemics in recent years--one in Spain to a contaminant of rapeseed oil and one in the United States to a contaminant of l-tryptophan that caused an eosinophilic myositis. It is important for physicians and others involved in health care to recognize the potential associations of these diseases of unknown cause or causes.
Creative Work and Health.

Employees with greater control over their own activities have better health. People who are employed give up some control over their own activities for pay, yet employment is associated with better health. Perhaps paid jobs provide resources for productive self-expression that make up for the loss of autonomy. We find that paid employment is associated with lower autonomy but greater creativity of one's work or other main daily activities. Both have positive associations with health. Creativity's association is larger more statistically significant, and found in follow-up models as well as cross-sectional ones. The health advantage of being at the 60th versus the 40th percentile of creative work is equivalent to that of being 6.7 years younger or having two more years of education or 15 times greater household income. Education reduces the amount of autonomy lost in employment. Managerial authority and occupational attributes influence autonomy and creativity but otherwise have little or no association with health.
The thioxanthone system as a template in free radical relaychlorination of a steroid

Abstract The 3-α-cholestanyl ester of thioxanthone-3-carboxylic acid undergoes selective chlorination of the steroid C-9 carbon by a radical relay mechanism directed by the thioxanthone template.
Embracing dissemination and implementation research in cardiac critical care.

In both high- and low-resource settings, high-quality health care can be ensured when routine clinical practices are based on high-quality evidence that underpins trustworthy clinical practice guidelines (CPGs). The United States Institute of Medicine (IOM) has defined CPGs as statements that include recommendations for patient care that are informed by a rigorous systematic review of the evidence and an assessment of the benefits and harms of alternative care options [1,2]. Typically, however, many routine practices and guideline recommendations are based on insufficient or low-quality evidence, while others are based solely on expert opinion. For example, in a review of all CPGs issued by the American College of Cardiology and American Heart Association from 1984 to September 2008, Tricoci et al. [3] showed that recommendations based solely on expert opinion, case studies, or “standard of care” (level of evidence C) were the most frequently encountered. Although important improvements have been proposed in the CPG development process [4] since the publication of the IOM standards, many challenges persist, including gaps in available evidence and also CPG implementation. The field of cardiac critical care (CCC) is no exception to these challenges [5]. Embracing dissemination and implementation (D&I) research is one approach to improving the quality of care delivered in CCC. As shown in Figure 1, our conceptualization of implementation research begins with (1) a rigorous systematic review of available evidence to identify interventions and practices of proven effectiveness that can inform the writing of CPG recommendations [6], (2) the identification of gaps in the available evidence that can inform new knowledge generation in the pre-clinical and clinical translational research arena (T1 to T3), and (3) the identification of gaps in CPG implementation that can inform post-clinical D&I research (T4 translation research) [7,8]. In this schema, T4 research includes specific observational or interventional studies to identify strategies that lead to a sustained, increased uptake of evidence-based practices and deimplementation of “evidence-free” practices. From this perspective, 2 examples are presented whereby embracing D&I research can help accelerate improvements in the quality of care delivered in critical care settings. A third example that serves as a model for successful D&I research is also provided. FIGURE 1 The National Heart, Lung, and Blood Institute is committed to supporting rigorous systematic review and synthesis of available evidence to underpin a collaborative partnership model for developing clinical practice guidelines
Economic versus social exchange in marketing places: An empirical study among manufacturing firms

This paper examines the relative role of relationships in shaping business satisfaction with, and commitment to, a business location. Economic and social exchange provides the theoretical perspectives for this study. In particular, this paper addresses the question: is social exchange valued in its own right (as a separate element alongside economic benefits) or does it rather add value to the economic exchange process? That is, is social exchange a benefit, or is it a facilitating condition? These issues are tested using path analysis with data from a survey among executives of manufacturing firms located in a 10-county area of the southeastern United States. The results support a model wherein social exchange facilitates the relationship between location factors (in particular, transportation access, labor quality, and government support) and location satisfaction.
Countertrade practices in Japan

Abstract This article investigates countertrade transactions in Japan. An analysis of 104 reported countertrade transactions revealed that compensation was the most frequently used form of countertrade. The former Soviet Union, the People's Republic of China, Indonesia, India, Turkey, and the United States were the major trading partners. The data on countertrade were compiled from Countertrade Outlook (weekly) and Financial Times (daily), two major sources of information on global countertrade transactions. The various forms of countertrade covered in this study are explained and illustraded with recently reported Japanese countertrade transactions. Current data on countertrade transactions with Japan for 1987, 1988, and the first half of 1989 were then analyzed. The analysis covered the frequency and relative importance of the countries involved, forms of countertrade used, and types of products imported and exported by Japan consistent with earlier studies on countertrade [1–4]. A familiarity with recent trends in Japanese countertrade enable international marketing managers to identify, and to take advantage of, emerging opportunities in the Japanese marketplace.
The After-School Needs and Resources of a Low-Income Urban Community: Surveying Youth and Parents for Community Change

Using a collaborative research approach, this project describes a partnership between community residents and university researchers to develop a comprehensive survey of the after-school needs of a low-income urban community in a large Midwestern city. Surveying parents and children was considered particularly important because the current literature on after-school does not include much input from them, the key stakeholders in programming. By surveying pre- and young adolescent youth (N = 416) and parents (N = 225) in the community, information was gathered to document the need for after-school programming, tap program preferences, and uncover barriers to participation and enrollment. Survey findings revealed significant differences between youth and parent perspectives. Disagreements between youth and parent survey responses suggest that after-school programs in the community should offer a balance of academic, recreational, and social activities, as well as a tutoring or homework component. Further, in order to increase participation and attendance rates, community after-school programs need to address the following barriers to participation: safety, transportation, family responsibilities (e.g., care for siblings, household chores), and access to information about available programs. These findings guided the planning of future after-school programs. The survey results and comparisons between youth and parent data will be presented.
Process Elongation of Oligodendrocytes Is Promoted by the Kelch-related Protein MRP2/KLHL1

Oligodendrocytes (OLGs) are generated by progenitor cells that are committed to differentiating into myelin-forming cells of the central nervous system. Rearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by OLGs. Here, we have characterized a new member of the Kelch-related protein family termed MRP2 (for Mayven-related protein 2) that is specifically expressed in brain. MRP2/KLHL1 is expressed in oligodendrocyte precursors and mature OLGs, and its expression is up-regulated during OLG differentiation. MRP2/KLHL1 expression was abundant during the specific stages of oligodendrocyte development, as identified by A2B5-, O4-, and O1-specific oligodendrocyte markers. MRP2/KLHL1 was localized in the cytoplasm and along the cell processes. Moreover, a direct endogenous association of MRP2/KLHL1 with actin was observed, which was significantly increased in differentiated OLGs compared with undifferentiated OLGs. Overexpression of MRP2/KLHL1 resulted in a significant increase in the process extension of rat OLGs, whereas MRP2/KLHL1 antisense reduced the process length of primary rat OLGs. Furthermore, murine OLGs isolated from MRP2/KLHL1 transgenic mice showed a significant increase in the process extension of OLGs compared with control wild-type murine OLGs. These studies provide insights into the role of MRP2/KLHL1, through its interaction with actin, in the process elongation of OLGs.
Particle-induced indentation of the alveolar epithelium caused by surface tension forces.

Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submerging a hydrophilic particle has been suggested by Gehr and Schurch's group (e.g., Respir Physiol 80: 17–32, 1990). In this paper, we extended their studies by developing a further comprehensive and mechanistic analysis. The analysis reveals that the mechanics operating in the particle-tissue interaction phenomena can be explained on the basis of a balance between surface tension force and tissue resistance force; the former tend to move a particle toward alveolar epithelial cell surface, the latter to resist the cell deformation. As a result, the submerged particle deforms the tissue and makes a noticeable indentation, which creates unphysiological stress and strain fields in tissue around the particle. This particle-induced microdeformation could likely trigger adverse mechanotransduction and mechanosensing pathways, as well as potentially enhancing particle uptake by the cells.
Mechanistic mathematical model of kinesin under time and space fluctuating loads

Kinesin-1 is a processive molecular motor that converts the energy from ATP hydrolysis and Brownian motion into directed movement. Single-molecule techniques have allowed the experimental characterization of single kinesins in vitro at a range of loads and ATP concentrations, and shown that each kinesin molecule moves processively along microtubules by alternately advancing each of its motor domains in a hand-over-hand fashion. Existing models of kinesin movement focus on time and space invariant loads, and hence are not well suited to describing transient dynamics. However, kinesin must undergo transient dynamics when external perturbations (e.g., interactions with other kinesin molecules) cause the load on each motor to change in time. We have developed a mechanistic model that describes, deterministically, the average motion of kinesin under time and space varying loads. The diffusion is modeled using a novel approach inspired by the classical closed form solution for the mean first-passage time. In the new approach, the potential in which the free motor domain diffuses is time varying and updated at each instant during the motion. The mechanistic model is able to predict experimental force-velocity data over a wide range of ATP concentrations (1 μM–10 mM). This mechanistic approach to modeling the mechanical behavior of the motor domains of kinesin allows rational and efficient characterization of the mechanochemical coupling, and provides predictions of kinesin with time-varying loads, which is critical for modeling coordinated transport involving several kinesin molecules.