cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulatory mechanisms in the induction of glutamine synthetase in the embryonic retina: Immunochemical studies

Abstract The precocious induction of glutamine synthetase (GS) by hydrocortisone in embryonic chick neural retina tissue in vitro was studied by immunochemical procedures. The rate of GS synthesis was followed in cultures pulse-labeled for 15 min at various times after the beginning of induction, by measuring the precipitation with anti-GS serum of radioactively labeled enzyme. The induced accumulation of GS activity was found to be due to progressive increase in the rate of enzyme synthesis, not to cessation of enzyme turnover or to activation of preformed enzyme precursors. The data are consistent with the view that the induced increase in the rate of GS synthesis is due to accumulation of active RNA templates for the enzyme. The requirement for continued presence of the inducer on accumulation of GS activity and on the rate of its synthesis were studied in cultures from which the inducer was withdrawn simultaneously with complete and partial inhibition of RNA synthesis (with actinomycin D). The results indicate that in the absence of the inducer the expressivity of preformed mRNA for GS is suppressed and that the inducer prevents this indirectly by eliciting transcription of short-lived regulatory RNA (desuppressor). A hypothetical model for regulatory events in GS induction is described and discussed in terms of further analysis of this system.
Act, Aim, and Unscientific Explanation

Against the claim that folk psychology is a theory, I contend thatfolk psychology is not empirically vulnerable in the same way theories are, and has evaluative functions that make it irreplaceable by a scientific theory. It is neither would-be nor has-been science.
Transactions preprint of technical papers comprising pages 563–602 of the 1940 volume: Restoration of service on a metropolitan power system

THE purpose of this paper is to outline procedures and discuss pertinent problems that arise when restoring service to a metropolitan system following a major shutdown. In the discussion, consideration is given to the fundamental plan of the system, pointing out the inherent features in the design which prevent such failures. Several cases of trouble which have been the cause of service curtailment have been discussed and the service restoration procedure outlined. A brief outline of the essential procedure is given for two types of service restoration.
Repertory grid: investigating personal constructs of novice programmers

In this paper, the repertory grid is presented as a technique to explore novice programmers' experiences within the context of an action research project. The theoretical and methodological aspects of the technique are discussed. The findings from the technique that combined quantitative and qualitative data analysis methods are provided. These findings relate to the learning process, learning content, and learning support as experienced by the students in an introductory object-oriented programming course. The repertory grid technique is then appraised for its relevance and usefulness to the project, and for its contribution to the diversity of computer science research methods. Insights gained from the use of the technique are shared with the community of computer science educators.
Response of rat ovarian cholesterol to gonadotropins and anterior pituitary hormones.

The ester and free cholesterol fractions in the immature rat ovary have been studied following administration of gonadotropins and anterior pituitary hormones. Pregnant mare‘s serum (PMS) and human chorionic gonadotropin (HCG) caused a great increase in ovarian size with a marked accumulation of cholesterol. Two to 3 times more ester cholesterol was present than free cholesterol. The largest ovaries with the highest free cholesterol values were seen in ovaries treated with HCG in addition to PMS. Luteinizing hormone (NIH-LH-S9) caused a marked depletion of ester cholesterol in 3–5 hr, which was followed by a reaccumulation 18 hr after LH administration. A small change in free cholesterol occurred during this time. A single reproducible area of ester cholesterol depletion was noted with LH doses from 0.02 to 2.0 pig. Free cholesterol concentration remained relatively constant over the dosage interval. Doses of LH above 2 μg did not cause further reduction in ester cholesterol. Other pituitary hormones did ...
Assessing student perceptions of the underserved at a Federally Qualified Health Center

Abstract The purpose of this evaluation is to determine student perceptions of caring for underserved patients. Doctor of Pharmacy candidates participating in an experiential rotation at a community health center were assigned to write a semistructured reflection paper upon rotation completion. Retrospective review of the reflections was done to identify common themes and provide insight into students' perceptions of caring for the underserved. Six main themes were identified. Students expressed positive changes in their perceptions toward underserved patients and prior negative misconceptions diminished as a result of rotation completion. A clinical rotation that focused on improving care of underserved patients positively impacted student learning, provided new perspectives, and dispelled prior misconceptions. Experiential rotations involving the care of underserved patients should be emphasized to foster future pharmacists' roles in the reduction of health care disparities and addressing unmet needs in high-poverty communities.
Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo

Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production and cellular calcium overload are believed to contribute to the damage and death of neurons that occurs following cerebral ischemia in victims of stroke. We now report that uric acid protects cultured rat hippocampal neurons against cell death induced by insults relevant to the pathogenesis of cerebral ischemia, including exposure to the excitatory amino acid glutamate and the metabolic poison cyanide. Confocal laser scanning microscope analyses showed that uric acid suppresses the accumulation of reactive oxygen species (hydrogen peroxide and peroxynitrite), and lipid peroxidation, associated with each insult. Mitochondrial function was compromised by the excitotoxic and metabolic insults, and was preserved in neurons treated with uric acid. Delayed elevations of intracellular free calcium levels induced by glutamate and cyanide were significantly attenuated in neurons treated with uric acid. These data demonstrate a neuroprotective action of uric acid that involves suppression of oxyradical accumulation, stabilization of calcium homeostasis, and preservation of mitochondrial function. Administration of uric acid to adult rats either 24 hr prior to middle cerebral artery occlusion (62.5 mg uric acid/kg, intraperitoneally) or 1 hr following reperfusion (16 mg uric acid/kg, intravenously) resulted in a highly significant reduction in ischemic damage to cerebral cortex and striatum, and improved behavioral outcome. These findings support a central role for oxyradicals in excitotoxic and ischemic neuronal injury, and suggest a potential therapeutic use for uric acid in ischemic stroke and related neurodegenerative conditions. J. Neurosci. Res. 53:613–625, 1998. © 1998 Wiley-Liss, Inc.
Abstract 3596: Comparison of intravenous microdialysis sampling to standard blood sampling to determine free etoposide exposure in non-human primates

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Microdialysis (MD) is a method for continuously sampling small molecules in tissue extracellular fluid in vivo. To determine if free (non-protein bound) drug exposure (AUC) in plasma could be accurately measured by MD under non-steady state conditions, we compared intravenous MD to standard serial plasma sampling during and after a short infusion of etoposide. Methods: CMA IView 64 catheters (10 mm PAES membrane with 20 kD MWT cutoff) were surgically implanted into the external jugular vein of Rhesus monkeys (Macaca mulatta). Catheter inflow and outflow tubing was tunneled subcutaneously from neck to the area on back between shoulder blades, brought through skin and attached to a MD pump (CMA 106 pump with fixed flow rate of 0.3 μL/min). The MD pump was secured in a fitted mesh jacket on the dorsum of the awake animal. Retrodialysis using 10 µM etoposide was used to measure in vivo relative recovery (RR) in each catheter. Following retrodialysis and catheter re-equilibration with normal saline, etoposide (5 mg/kg) was administered IV over 1 h. Serial plasma samples were collected during the infusion and for 8 h post-infusion. Free etoposide was extracted by ultrafiltration. MD samples were collected continuously over a single collection interval (0-9 h) or split into two collection intervals (0-3 h and 3-9 h). Etoposide was quantified using HPLC-electrochemical detection (linear range 0.05 - 10 μM). The etoposide concentration in MD samples was corrected for in vivo RR. The AUC was calculated by the linear trapezoidal method for serial plasma sampling and by summation of the concentration x time intervals for MD. Results: Simultaneous MD and serial plasma sampling was performed in 5 animals. The in vivo RR of etoposide ranged from 86.9 - 99.4%. The mean AUC0-9h for plasma free etoposide was 3.27 (median 3.81, range 2.11 - 5.15) μM·h. The mean AUC0-9h for MD sampling was 2.68 (median 3.02, range 1.75 - 3.65) μM·h. The mean ratio of AUCMD:AUCplasma was 0.81. The mean (95% CI) for the difference in the paired MD and plasma AUC was − 0.7 (−1.94, 0.54) µM·h. Conclusions: Quantitative MD sampling for pharmacokinetic studies is feasible and the in vivo RR of etoposide is high. Free etoposide exposure by MD slightly underestimates the AUC compared to serial plasma sampling. Intravenous MD sampling may be a promising alternative to standard plasma sampling for calculating free etoposide exposure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3596.
Hunchback sequence binding protein suppresses mouse TGF-β3 promoter in vitro

Abstract Transforming growth factor-β3 (TGF-β3) has a specific role in vivo in the patterning of embryonic and tissue-specific gene expression. We have cloned and sequenced the mouse TGF-β3 5′-flanking region to study the transcriptional regulation of this gene. Promoter fragments were cloned into a promoterless luciferase reporter plasmid to study functional activity in a human skin melanoma cell line A375 (A375). Sequential 5′-deletion encompassing DNA sequences from −2297 to −1003 bp exhibited high promoter activity in A375 cells, whereas the promoter activity decreased to minimal in the −742 to 104 bp regions, suggesting both positive and negative transcriptional regulation in the TGF-β3 promoter. The fragment containing 1.8 kb had the highest luciferase activity. Characterization of this 1.8 kb 5′-flanking region upstream of the translation start site showed a putative hunchback-binding site consensus sequence. The electrophoretic mobility shift assay (EMSA) and transient transfection experiments showed that the putative hunchback-binding site is functional and regulated TGF-β3 promoter transcriptional activity. The DNA-complex including the hunchback sequence binding protein (HbSBP) was important for suppression of the promoter activity in A375 cells. Mutation of the hunchback consensus sequence resulted in up to 2-fold higher promoter activity than the wild type construct. There was an absence of HbSBP in other cell lines tested including 3T3 fibroblast and B-16 mouse skin melanoma as determined by EMSA and Western blot analysis. HbSBP may function as a TGF-β3 gene transcriptional regulator and may be expressed in a cell type-specific manner.
Transcription ability of nuclear DNAs from different developmental stages of the sea urchin

Abstract Bulk nuclear DNAs from different stages of developing sea urchin embryos and sperm DNA were compared in molecular hybridization experiments. The comparison of the DNAs was for possible quantitative stage-specific differences in nucleotide sequences normally transcribed in vivo at the gastrula stage. The method of comparison was that of testing the ability of unlabeled early stage (morula) RNA to compete with labeled later stage (gastrula) RNA for hybridization sites on the different DNAs. Three postblastulation nuclear DNAs produced similar competition curves with a plateau after 25–30 % competition. Morula DNA produced a curve showing that greater than 90 % of the labeled RNA can be competed with the unlabeled RNA. Sperm DNA produced a curve also competed to a low value. These results suggest the possibility that there is an increase in availability of transcription sequences during blastulation.
A Markov Chain Process in Industrial Replacement

IN the manufacture of rubber tyres a machine is used which contains two "bladders", and which produces one tyre on each bladder simultaneously. Bladders can fail in service, a faulty bladder being discovered when a tyre fails to pass inspection. Thus there is a cost of a scrap or "second" tyre associated with a bladder which fails in service. Further, when a bladder fails the machine must be stripped down before replacement can be made, a process requiring fitters, labour, and production time with an associated cost. However, once a machine has been stripped, both bladders can be replaced at the same time. The cost of replacing the second bladder is virtually the cost of purchasing the bladder alone. It is found that the probability of failure is a function of the number of tyres made with a particular bladder. It thus seems likely that the cost of replacing bladders could be kept at a minimum with the following policies: (A) Replace bladders which have made a predetermined number of tyres without failure. (B) When a machine is stripped to replace one bladder, replace the other bladder if it has produced more than a given number of tyres. For brevity the number of tyres produced on a given bladder will be called the "age" of the bladder. Normal production records show the number of tyres produced on each bladder, and a curve of the probability of failure with age is readily obtained. It is the purpose of this paper to show how the ages required in A and B can be determined so as to minimize the average costs of replacing bladders per useful tyre produced; that is, to minimize the sum of: (i) The costs of stripping a machine for bladder replacement. (ii) The costs of lost production time due to a bladder failing and being replaced on a production shift. (iii) The costs of "second" or scrap tyres produced. (iv) The costs of purchasing bladders.
Two-photon excitation in laser scanning fluorescence microscopy

Simultaneous absorption of two red photons from a strongly focused subpicosecond colliding pulse mode4ocked dye laser stimulates visible fluorescence emission from fluorophores having their normal absorption in the ultraviolet1. The quadratic increase of the two-photon excitation rate with excitation intensity restricts fluorescence emission to the focal volume thus providing the same depth resolution as does confocal microscopy. Image degradation due to out of focus backround is thus avoided. Photobleaching and most cellular photodamage are similarly confined to the focus thereby minimizing sample degredation during acquisition of the multiple sections required for 3-d image reconstruction. Fluorescence images of living cells and other thick photolabile fluorescence labled assemblies illustrate the depth discrimination of both two-photon fluorescence excitation and photobleaching. The quadratic intensity dependence of two-photon excitation allows 3-d spatially resolved photochemistry in particular the photolytic release of caged compounds such as neurotransmitters nucleotides fluorescent dyes and second messengers such as 1P3 and Ca. The two-photon release of cased ATP has been measured and release of a caged fluorescent dye has been shown. Point photobleaching and a 3-d " write once read many" optical memory have been demonstrated. Two-photon excitation of photo-initiated polymerization with a sharply focused single beam allows microfabrication of complex structures of arbitrary form. By scanning the focused beam through a liquid polymer with a UV excited initiator it is possible to harden the polymer only at the focus thereby creating© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Thermal Conductivity of Single-Walled Carbon Nanotube/PMMA Nanocomposites

Single-walled carbon nanotubes (SWNTs) are considered as promising filler materials for improving the thermal conductivity of conventional polymers. We carefully investigated the thermal conductivity of SWNT poly(methylmethacrylate) (PMMA) nanocomposites with random SWNT orientations and loading up to 9 vol % using the comparative technique. The composites were prepared by coagulation and exhibit ∼250% improvement in the thermal conductivity at 9 vol %. The experimental results were analyzed using the versatile Nielsen model, which accounts for many important factors, including filler aspect ratio and maximum packing fraction. In this work, the aspect ratio was determined by atomic force microscopy (AFM) and used as an input parameter in the Nielsen model. We obtained good agreement between our results and the predictions of the Nielsen model, which indicates that higher aspect ratio fillers are needed to achieve further enhancement. Our analysis also suggests that improved thermal contact between the SWNT network and the matrix material would be beneficial.
Minimal infeasible constraint sets in convex integer programs

In this paper we investigate certain aspects of infeasibility in convex integer programs, where the constraint functions are defined either as a composition of a convex increasing function with a convex integer valued function of n variables or the sum of similar functions. In particular we are concerned with the problem of an upper bound for the minimal cardinality of the irreducible infeasible subset of constraints defining the model. We prove that for the considered class of functions, every infeasible system of inequality constraints in the convex integer program contains an inconsistent subsystem of cardinality not greater than 2n, this way generalizing the well known theorem of Scarf and Bell for linear systems. The latter result allows us to demonstrate that if the considered convex integer problem is bounded below, then there exists a subset of at most 2n−1 constraints in the system, such that the minimum of the objective function subject to the inequalities in the reduced subsystem, equals to the minimum of the objective function over the entire system of constraints.
Robert Nisbet on Images of History

The tendency to ascribe patterns to history must be grounded in the evidence. Otherwise, the pattern one devises can become mistaken for reality. Paradoxically, Robert Nisbet described a pattern in the history of writing history, from the ancient metaphor of history as a series of life cycles to the modern image of linear progress. The usefulness of such images can be outweighed by their limitations, which Nisbet set forth, in large part because history simply is not finished yet. We today—and especially leaders—should not find ourselves trapped within any one paradigm. Images of history do not control leaders.
Loss mechanism and high-low doping profile effects of silicon substrate with different resistivities at High frequency

In this paper, coplanar waveguide (CPW) lines are measured up to 110 GHz to characterize 8000 Ω-cm, 15 Ω-cm and 0.015 Ω-cm silicon substrates. The characteristic impedance and attenuation constant for the three substrates are compared and analyzed. The effects of the conductor surface roughness are investigated. The attenuation as a function of high-low doping profile has been investigated for 8000 Ω-cm and 15 Ω-cm substrates. Based on the simulation results, a thin layer of high doping concentration is shown to dominate the attenuation.
The Role of Tidal Vortices in Material Transport around Straits

The strong tidal current (tidal jet) in straits generates tidal vortices with a scale of several kilometers. The role of the vortices in material transport was investigated in the Neko Seto Sea, located in the western part of the Seto Inland Sea of Japan. A clockwise vortex with a diameter of about 0.8 km was observed in Nigata Bay (lying between two straits, the Neko Seto Strait and the Meneko Seto Strait). It was concluded that the clockwise vortex was the tidal vortex which was generated by the tidal jet in the Meneko Seto Strait. The vortex moved into the bay with the tide, but tended to stay on the sand bank in the bay. It was confirmed by current measurement with an ADCP and turbidity measurement that the secondary convergent flow was generated in the bottom layer of the vortex. This secondary flow seemed to contribute to the formation of the sand bank. It was suggested that tidal vortices may play an important role in the sediment transport and formation of topography in and around straits.
Plasminogen acceleration of urokinase thrombolysis.

Abstract Purpose: A relative deficiency of plasminogen within the thrombus may be the rate limiting factor in clot lysis. Methods: To investigate this hypothesis, we used an in vitro perfusion system and expanded polytetrafluoroethylene graft segments filled with radiolabeled human thrombus. Three groups of five perfusions were compared: (1) urokinase infusion (333 IU/min) into clots laced with buffer, (2) urokinase infusion (333 IU/min) into clots laced with plasminogen (44 CU), and (3) control, D5W infusion into clots laced with buffer. Two end points were measured over time: the amount of lysed thrombus and the flow through the graft. Results: Urokinase infusion resulted in augmented flow through the graft when compared with control ( p p p Conclusions: These results suggest that plasminogen supplementation of urokinase thrombolysis may result in significant clinical benefits with respect to the rate of clot lysis and the uniformity of clot dissolution with a lower likelihood of secondary embolization. (J VASC SURG 1994;19:298-305.)
A coupled mode examination of irregular waveguides including the continuum spectrum

Summary. A coupled mode theory is used to examine surface wave propagation in a laterally inhomogeneous acoustic waveguide. The theory is developed from the equations of motion for the pressure and velocity fields. The presence of lateral inhomogeneities in the form of varying layer thickness causes coupling among the discrete modes of the waveguide and radiation to the continuum. Expressions for the coupling coefficients among all mode types including coupling to the continuum spectrum are derived. The coupling coefficients are proportional to the horizontal derivative of the function describing the interface between layers of constant material properties but varying thickness. The coupled mode equations are solved in approximation for the case of a sinusoidal boundary and a sloping boundary. The results for radiation losses due to interaction with the irregular boundary of the waveguide are presented in analytical form, which clearly show the primary physical effects on the wavefield of the interaction. The far field amplitude of the scattered modes, excited by the interaction of some incident signal with a weak boundary irregularity, is modulated by the spatial Fourier transform of the irregularity.
The effect of a robot-assisted surgical system on the kinematics of user movements

Teleoperated robot-assisted surgery (RAS) offers many advantages over traditional minimally invasive surgery. However, RAS has not yet realized its full potential, and it is not clear how to optimally train surgeons to use these systems. We hypothesize that the dynamics of the master manipulator impact the ability of users to make desired movements with the robot. We compared freehand and teleoperated movements of novices and experienced surgeons. To isolate the effects of dynamics from procedural knowledge, we chose simple movements rather than surgical tasks. We found statistically significant effects of teleoperation and user expertise in several aspects of motion, including target acquisition error, movement speed, and movement smoothness. Such quantitative assessment of human motor performance in RAS can impact the design of surgical robots, their control, and surgeon training methods, and eventually, improve patient outcomes.
Student-to-Student Interaction Revisited: A Case Study of Working Adult Business Students in Online Courses*

Faculty teaching in online environments are universally encouraged to incorporate a variety of student-to-student learning activities into their courses. Although there is a body of both theoretical and empirical work supporting this, adult professional students participating in an online MBA program at an urban business school reported being at best indifferent and often negative regarding these learning activities. A case study was performed to explore how pervasive this attitude was and the possible reasons for it. Through various sources of data and exploration, we discovered that common interactive modalities are not associated with either perceived learning or satisfaction. A content analysis of a data analysis course revealed that 64.5% of responses recalled student-to-student interactivities when responding to a “learned least from” query. We identified three possible reasons for these negative responses: time inefficiency, interaction dysfunction, and flexibility intrusion. We conclude that, although some working professional students probably do learn from student-to-student interactivity, the costs incurred may be too great. If working adult students present a different profile than those students typically represented in academic research and thus have different needs and expectations, we may need to rethink the design of online education delivered to them.
A computational tool for the efficient analysis of dose-volume histograms from radiation therapy treatment plans.

A Histogram Analysis in Radiation Therapy (HART) program was developed to increase the efficiency and accuracy of dose–volume histogram (DVH) analysis for radiation therapy research. HART was written in MATLAB to analyze patient plans exported from the treatment planning system (Pinnacle 3 ) in the American Association of Physicists in Medicine/Radiation Therapy Oncology Group (AAPM/RTOG) format. DVH data were converted from differential histograms to cumulative histograms and compared with those manually extracted from the planning system for five patients treated with the IMRT technique. HART calculated over 4000 parameters from the differential DVH curves for each patient in approximately 10–15 minutes. Manual extraction of this amount of data required 5 to 6 hours. The normalized root mean square deviation (NRMSD) for the HART–extracted DVH outcomes was less than 1% or within 0.5% distance-to-agreement (DTA). HART is supported with various user-friendly options and graphical features, and can be efficiently and precisely applied for the DVH analysis of large quantities of patient data. HART also performs higher order polynomial simulations for DVH curves, and can identify the optimal dose response models for critical organs. It also offers various plan specific outcome analysis features.
Video. Micromanipulation of gametes and embryos: biopsy of a blastomere from an 8-cell human embryo

The preimplantation diagnosis of genetic disease in preimplantation human embryos was introduced several years ago. It involves removing one or more cells from a cleaving embryo or a blastocyst, and then assessing the isolated cells for evidence of chromosomal anomalies or genetic disease, usually by means of fluorescence in-situ hybridization (FISH), the polymerase chain reaction (PCR) and variants of it. The whole diagnostic procedure can be completed within one day, and correctly diagnosed embryos then replaced in the mother’s uterus. The number of correctly-diagnosed children is now accumulating as more clinics introduce this procedure into their practice. Details of PCR and FISH can be found in various publications (e.g. Delhanty and Handyside,1995). One form of operation is to remove a single blastomere from an 8-cell embryo, and this is the procedure shown in this video. This procedure is demonstrated on two approximately 8-cell human embryos growing in vitro. A series of steps are involved in the process. The initial step is to make a hole in the zona pellucida, and so permit the passage of pipettes through this investment. Access is thus gained to the enclosed embryo. Two examples are shown on this video. The first example illustrates a standard operation, from the drilling of the zona pellucida to the gentle loosening and withdrawal of a single blastomere. The second example is concerned with the problems arising when the first blastomere is damaged during the procedure, and it becomes essential to biopsy a second blastomere.
Using graphical representation of user interfaces as visual references

Many user interfaces use indirect references to identify specific objects and devices. My thesis investigates using graphical representations of user interfaces (i.e. screenshots) as direct visual references to support various kinds of applications. Sikuli Script enables users to programmatically control GUIs without the support from the underlying applications. Sikuli Test lets GUI developers and testers create test scripts without coding. Deep Shot introduces a framework and interaction techniques to migrate work states across heterogeneous devices in one action, taking a picture. In addition to these pure pixel-based systems, PAX associates the pixel representation with the internal structures and metadata of the user interface. Based on these building blocks, we propose to develop a visual history system that enables users to search and browse what they have seen on their computer screens. We outline some interesting use cases and discuss the challenges in this ongoing work.
Optimal promoter usage for lentiviral vector-mediated transduction of cultured central nervous system cells

Lentiviral vectors transduce both dividing and non-dividing cells and can support sustained expression of transgenes. These properties make them attractive for the transduction of neurons and other neural cell types in vitro and in vivo. Lentiviral vectors can be targeted to specific cell types by using different promoters in the lentiviral shuttle vector. Even with identical constructs, however, levels of expression can vary significantly in different types of neurons and different culture preparations; expression levels in the same neuronal subtypes can be very different in primary cell culture and in vivo. We systematically assessed the ability of different promoters to direct expression of foreign transgenes in primary murine neocortical neurons, cerebellar granule cells and in undifferentiated and differentiated neuroblastoma cells. In primary cortical neurons, constructs using the ubiquitin C promoter directed the highest level of transgene expression; the phosphoglycerate kinase (PGK) promoter also directed robust transgene expression, while the cytomegalovirus (CMV) and MND (a synthetic promoter that contains the U3 region of a modified MoMuLV LTR with myeloproliferative sarcoma virus enhancer) promoters resulted in the expression of the transgenes in only limited number of neurons. In contrast, in cerebellar granule cells and in differentiated SH-SY5Y neuroblastoma cultures, the CMV promoter directed the most robust transgene expression. There was similar variability in transgene expression directed by these promoters in primary cultures of oligodendrocytes and astrocytes. These findings may prove useful in the design of lentiviral vectors for use in cell culture models of the nervous system.
Gaps, Tensions, and Conflicts in the FDA Approval Process: Implications for Clinical Practice

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.
Biodegradability of nonaqueous‐phase liquids affects the mineralization of phenanthrene in soil because of microbial competition

A study was conducted to determine the effects of biodegradability of nonaqueous-phase liquids (NAPLs) and microbial competition on the biodegradation in soil of a constituent of the NAPLs. The rates of mineralization of phenanthrene dissolved in 8 mg of 2,2,4,4,6,8,8-heptamethylnonane (HMN), di(2-ethylhexyl) phthalate (DEHP), or pristane per g of soil were faster than the rates when the compound was dissolved in hexadecane or dodecane. Addition of inorganic N and P to the soil increased the mineralization rate in the first two but not the last two NAPLs. N and P addition did not enhance mineralization of phenanthrene when added in 500 {micro}g of hexadecane, pristane, or HMN per g of soil. Hexadecane was rapidly degraded, pristane was slowly metabolized, DEHP was still slower, and HMN was not mineralized in the test period. Mixing the soil stimulated mineralization of phenanthrene dissolved in HMN but not in hexadecane. Mineralization of phenanthrene dissolved in HMN was the same if the gas phase contained 21%, 2.1%, or traces of O{sub 2}. In contrast, the biodegradation of phenanthrene dissolved in hexadecane, although the same at 21 and 2.1% O{sub 2}, was not observed if traces of O{sub 2} were present. The mineralization was slower inmore » unshaken soil-water mixtures if phenanthrene was added in hexadecane than in HMN or pristane, but the rates with the 3 NAPLs were increased by shaking the suspensions. The authors suggest that the biodegradability of major components of NAPLs and microbial competition for N, P, or O{sub 2} will have a major impact on the rate of transformation of minor constituents of NAPLs.« less
Copy number variation influences gene expression and metabolic traits in mice

Copy number variants (CNVs) are genomic segments which are duplicated or deleted among different individuals. CNVs have been implicated in both Mendelian and complex traits, including immune and behavioral disorders, but the study of the mechanisms by which CNVs influence gene expression and clinical phenotypes in humans is complicated by the limited access to tissues and by population heterogeneity. We now report studies of the effect of 19 CNVs on gene expression and metabolic traits in a mouse intercross between strains C57BL/6J and C3H/HeJ. We found that 83% of genes predicted to occur within CNVs were differentially expressed. The expression of most CNV genes was correlated with copy number, but we also observed evidence that gene expression was altered in genes flanking CNVs, suggesting that CNVs may contain regulatory elements for these genes. Several CNVs mapped to hotspots, genomic regions influencing expression of tens or hundreds of genes. Several metabolic traits including cholesterol, triglycerides, glucose and body weight mapped to three CNVs in the genome, in mouse chromosomes 1, 4 and 17. Predicted CNV genes, such as Itlna, Defcr-1, Trim12 and Trim34 were highly correlated with these traits. Our results suggest that CNVs have a significant impact on gene expression and that CNVs may be playing a role in the mechanisms underlying metabolic traits in mice.
Educational Accountability in Michigan: Root and Branch:

Chester L Barnard postulated four criteria by virtue of which organizational communications achieve authoritativeness: (1) the recipient can and does understand the communication; (2) the recipient believes the communication consistent with the purposes of the organization; (3) the recipient believes the communication compatible with his personal interest; and (4) the recipient is able mentally and physically to comply with the communication. These criteria of authoritativeness were made operational in a four-scale instrument (one for each principle) and mailed to 500 K-8 Michigan teachers to determine their perceptions of the authoritativeness of the state's educational accountability program. It was found that the teachers did not regard the communications of educational accountability as authoritative, and the theory predicts that the teachers will withhold their vital cooperation from the program.
Giovanni Arrighi: Systemic Cycles of Accumulation, Hegemonic Transitions, and the Rise of China

This article surveys and critically assesses the life work of Giovanni Arrighi, a renowned historical sociologist and world-systems scholar who passed away in 2009. In a trilogy of books published between 1994 and 2007 Arrighi develops the master concept of his theoretical legacy, systemic cycles of accumulation, and advances an original reading of the history and dynamics of world capitalism as a succession of hegemonic episodes, each one more expansive than the previous and culminating in crises and chaotic transitions. He anticipated the rise of a Chinese-led East Asia as the emergent twenty-first century centre of a reorganised world economy and society. Arrighi is faulted for failing to develop any theory of politics, the state and collective agency in his construct, for his lack of attention to social forces from below, and for his dismissal of recent theorising on globalization.
Sample Efficient Reinforcement Learning with Gaussian Processes

This paper derives sample complexity results for using Gaussian Processes (GPs) in both modelbased and model-free reinforcement learning (RL). We show that GPs are KWIK learnable, proving for the first time that a model-based RL approach using GPs, GP-Rmax, is sample efficient (PAC-MDP). However, we then show that previous approaches to model-free RL using GPs take an exponential number of steps to find an optimal policy, and are therefore not sample efficient. The third and main contribution is the introduction of a model-free RL algorithm using GPs, DGPQ, which is sample efficient and, in contrast to model-based algorithms, capable of acting in real time, as demonstrated on a fivedimensional aircraft simulator.
A Sensitive phage-based capture ELISA for sub-femtomolar detection of protein variants directly from biological samples

To determine the role of proteins, and in particular protein variants, in human health, it may often be necessary to quantitatively determine the concentration of a specific protein variant present in complex biological samples such as blood, cerebral spinal fluid (CSF), or tissue. Many protein variants are present only at trace levels and therefore a simple assay with very high sensitivity and reliability would greatly facilitate correlation of the presence of particular protein variants with the progression of specific diseases. We have developed a simple phage based capture ELISA system that enables femtomolar or better detection of individual protein variants directly from complex biological samples. The protocol utilizes a capture reagent that selectively recognizes a unique epitope of the protein variant and a phage based detection reagent that binds to a second epitope present in all forms of the target protein. The phage based detection reagent is essentially a self-assembling nanoparticle consisting of several thousand coat proteins that can each be labeled to amplify the detection signal by several orders of magnitude. Here we demonstrate that we can achieve subfemtomolar detection of individual protein variants that have been implicated in neurodegenerative disease directly from complex tissue homogenates and sera. The ELISA system should facilitate identification of disease specific protein variants or other compounds even when present at trace amounts in samples including blood, CSF, saliva and urine. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:289–298, 2015
Sphingolipid Long-Chain Base Hydroxylation Is Important for Growth and Regulation of Sphingolipid Content and Composition in Arabidopsis

Sphingolipids are structural components of endomembranes and function through their metabolites as bioactive regulators of cellular processes such as programmed cell death. A characteristic feature of plant sphingolipids is their high content of trihydroxy long-chain bases (LCBs) that are produced by the LCB C-4 hydroxylase. To determine the functional significance of trihydroxy LCBs in plants, T-DNA double mutants and RNA interference suppression lines were generated for the two Arabidopsis thaliana LCB C-4 hydroxylase genes Sphingoid Base Hydroxylase1 (SBH1) and SBH2. These plants displayed reductions in growth that were dependent on the content of trihydroxy LCBs in sphingolipids. Double sbh1 sbh2 mutants, which completely lacked trihydroxy LCBs, were severely dwarfed, did not progress from vegetative to reproductive growth, and had enhanced expression of programmed cell death associated–genes. Furthermore, the total content of sphingolipids on a dry weight basis increased as the relative amounts of trihydroxy LCBs decreased. In trihydroxy LCB–null mutants, sphingolipid content was ∼2.5-fold higher than that in wild-type plants. Increases in sphingolipid content resulted from the accumulation of molecular species with C16 fatty acids rather than with very-long-chain fatty acids, which are more commonly enriched in plant sphingolipids, and were accompanied by decreases in amounts of C16-containing species of chloroplast lipids. Overall, these results indicate that trihydroxy LCB synthesis plays a central role in maintaining growth and mediating the total content and fatty acid composition of sphingolipids in plants.
Atrial fibrillation or sinus rhythm? Controversy and contradiction in quality of life outcomes.

Attempts to improve quality of life by restoring sinus rhythm will usually be unsuccessful. —The AFFIRM Trial Investigators ([1][1]) Restoration and maintenance of sinus rhythm was associated with significant increases in a number of quality of life measurements. —The SAFE-T Study Investigators
A High‐Altitude Site Survey for SOFIA

ABSTRACT The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a modified Boeing 747‐SP equipped with a 2.5 m telescope dedicated to astronomical research. Currently under joint development by the US (NASA) and Germany (DLR), it is scheduled to begin operations in late 2001. The ability of SOFIA to carry out its mission will depend strongly on the meteorological conditions at and above flight altitudes in the vicinity of its home base. The most important meteorological factors are the frequency of high‐altitude clouds and the magnitude of the water vapor overburdens. This paper performs a high‐altitude site survey by gathering together the best available meteorological data, defining metrics, and evaluating them for a variety of sites. These metrics are found to corroborate past airborne experience and to be consistent with well‐known global circulation patterns, convection, and upper tropospheric dynamics. They indicate that there are significant variations in the weather at SOFIA flight altitu...
Religion, Division, and the First Amendment

Nearly thirty-five years ago, in Lemon v. Kurtzman, Chief Justice Warren Burger declared that state programs or policies could excessive(ly) - and, therefore, unconstitutionally - entangle government and religion, not only by requiring or allowing intrusive public monitoring of religious institutions and activities, but also through what he called their divisive political potential. Chief Justice Burger asserted also, and more fundamentally, that political division along religious lines was one of the principal evils against which the First Amendment was intended to protect. And from this Hobbesian premise about the inten(t) animating the First Amendment, he proceeded on the assumption that the Constitution authorizes those charged with its interpretation to protect our normal political process from a particular kind of strife and to purge a particular kind of disagreement from politics and public conversations about how best to achieve the common good. This Article provides a close and critical examination of the argument that observations or predictions of political division along religious lines should supply the content, or inform the interpretation and application, of the Religion Clause. The examination is timely, not only because of the sharp polarization that is said to characterize contemporary politics, but also because of the increasing prominence of this political division argument. The inquiry and analysis that follow have empirical, doctrinal, and normative components: What, exactly, is religiously based social conflict - or, as the Court put it in Lemon, political . . . divisiveness on religious lines? What, exactly, is the relevance of such conflict to the wisdom, morality, or constitutionality of state action? How plausible, and how normatively attractive, are the political-divisiveness argument and the principle it is intended to vindicate? How well do this argument and this principle cohere with the relevant text, history, traditions, and values? And what does the recent resurfacing of this argument in the Religion Clause context reveal and portend about the state and trajectory of First Amendment theory and doctrine more generally? Working through these questions, I am mindful of John Courtney Murray's warning that we should cherish only modest expectations with regard to the solution of the problem of religious pluralism and civic unity, and also of his observations that pluralism (is) the native condition of American society and the unity toward which Americans have aspired is a unity of a limited order. Those who crafted our Constitution believed that both authentic freedom and effective government could be secured through checks and balances, rather than standardization, and by harnessing, rather than homogenizing, the messiness of democracy. It is both misguided and quixotic, then, to employ the First Amendment to smooth out the bumps and divisions that are an unavoidable part of the political life of a diverse and free people.
Variation in Aedes aegypti larval indices over a one year period in a neighborhood of Mérida, Yucatán, México

Surveys for Aedes aegypti larvae were conducted to provide an estimate of the magnitude and timing of seasonal variations in larval indices in one colonia in Merida, Yucatan, Mexico, and to assess how the proportion of disposable and non-disposable containers as larval production sites varies. Breteau indices exceeded 200 during the months of July and August, and disposable containers were important year-round larval production sites.
Glocalisation: An international communication framework?

(2003). Glocalisation. The Journal of International Communication: Vol. 9, Intercultural Relations, pp. 29-49.