cssi/SciSciGPT-SciSciNet huggingface dataset:
Epidermal expression of an Elovl4 transgene rescues neonatal lethality of homozygous Stargardt disease-3 mice

Elongase of very long chain fatty acids-4 (ELOVL4) is the only mammalian enzyme known to synthesize C28-C36 fatty acids. In humans, ELOVL4 mutations cause Stargardt disease-3 (STGD3), a juvenile dominant macular degeneration. Heterozygous Stgd3 mice that carry a pathogenic mutation in the mouse Elovl4 gene demonstrate reduced levels of retinal C28-C36 acyl phosphatidylcholines (PC) and epidermal C28-C36 acylceramides. Homozygous Stgd3 mice die shortly after birth with signs of disrupted skin barrier function. In this study, we report generation of transgenic (Tg) mice with targeted Elovl4 expression driven by an epidermal-specific involucrin promoter. In homozygous Stgd3 mice, this transgene reinstates both epidermal Elovl4 expression and synthesis of two missing epidermal lipid groups: C28-C36 acylceramides and (O-linoleoyl)-omega-hydroxy C28-C36 fatty acids. Transgene expression also restores skin barrier function and rescues the neonatal lethality of homozygous Stgd3 mice. These studies establish the critical requirement for epidermal C28-C36 fatty acid synthesis for animal viability. In addition to the skin, Elovl4 is also expressed in other tissues, including the retina, brain, and testes. Thus, these mice will facilitate future studies to define the roles of C28-C36 fatty acids in the Elovl4-expressing tissues.
Studies with chlorinated dibenzo-p-dioxins, polybrominated biphenyls, and polychlorinated biphenyls in a two-stage system of mouse skin tumorigenesis: potent anticarcinogenic effects.

The chlorinated dibenzo-p-dioxins and chlorinated dibenzo-furans are among the most potent teratogens and toxins that are found as environmental contaminants. The polychlorinated biphenyls and polybrominated biphenyls are not nearly as toxic as the dioxins, but they are environmentally more prevalent than the dioxins. Both classes of compounds are inducers of cytochrome P/sub 450/-mediated microsomal monooxygenases and of aminolevulinic acid synthetase. The dioxins induce aryl hydrocarbon hydroxylase, the enzyme system responsible for converting polycyclic aromatic hydrocarbons to active and inactive metabolites. PCB's and PBB's induce the monooxygenase system with properties similar to both phenobarbital and 3-MC. Timing is important in the application of PCB to the diets of laboratory animals. Treatment with PCB's prior to the administration of carcinogen results in reduction of tumor response whereas treatment subsequent to application of the carcinogen results in enhancement of the tumorogenic response. The two-stage system of mouse skin tumorigenesis allows one to evaluate critically the initiation and promotion phases of carcinogenesis individually. (DLS)
An evaluation of higher-order single crystal strength models for constrained thin films subjected to simple shear

Abstract An evaluation of different dislocation density-based strength models for a theory of micropolar single crystal plasticity is presented through detailed comparison with discrete dislocation dynamics simulations of a constrained thin film subjected to simple shear. The principal component of the evaluation is determining the most appropriate way to incorporate scale-dependent strengthening due to geometrically necessary dislocations (GNDs) within the model. We find that some models give results consistent with the discrete dislocation simulations, yet it is shown that models based on a generalized Taylor relation do not. Additionally, we briefly discuss the differences between models derived from unified (single) and independent (multiple) flow criteria, and demonstrate that single criterion models provide comparable predictive capability while introducing fewer nonlocal constitutive parameters.
PharmGKB update: I. Genetic variants of the organic cation transporter 2 (OCT2, SLC22A2).

Category: genotype PharmGKB Submission Number: PS202784 Project: Pharmacogenetics of Membrane Transporters HGNC Symbol: SLC22A2 HGNC Name: solute carrier family 22 (organic cation transporter), member 2 Synonyms: OCT2 Gene Ontology
Service robots in the domestic environment: a study of the roomba vacuum in the home

Domestic service robots have long been a staple of science fiction and commercial visions of the future. Until recently, we have only been able to speculate about what the experience of using such a device might be. Current domestic service robots, introduced as consumer products, allow us to make this vision a reality.This paper presents ethnographic research on the actual use of these products, to provide a grounded understanding of how design can influence human-robot interaction in the home. We used an ecological approach to broadly explore the use of this technology in this context, and to determine how an autonomous, mobile robot might "fit" into such a space. We offer initial implications for the design of these products: first, the way the technology is introduced is critical; second, the use of the technology becomes social; and third, that ideally, homes and domestic service robots must adapt to each other.
Cnidarian Toxins Acting on Voltage-Gated Ion Channels

Voltage-gated ion channels generate electrical activity in excitable cells. As such, they are essential components of neuromuscular and neuronal systems, and are targeted by toxins from a wide variety of phyla, including the cnidarians. Here, we review cnidarian toxins known to target voltage-gated ion channels, the specific channel types targeted, and, where known, the sites of action of cnidarian toxins on different channels.
AN ALGORITHM FOR CANCER RECOGNITION OF ULTRASOUND IMAGES

An algorithm of cancer recognition of ultrasound images is developed in this paper. As we pointed out in our previous work, in order for cancer to survive it develops its own blood supply system, which is different than the supply system of normal tissue. The velocity of the blood flowing through the cancerous blood vessels is different than the velocity of the blood flowing through blood vessels of normal tissue. Due to this fact the ultrasound signal is absorbed differently in the cancerous areas than in the normal tissue areas. The energy of the signal, the continuity of the signal, the autocorrelation function and frequency domain properties are different in the normal tissue than in cancerous tissue. All of these indicators are weighted here for the purpose of classifying the image of the tissue as being cancerous or non cancerous. Preliminary results based on limited number of ultrasound images show that our method has the ability to recognize cancer in ultrasound images.
Evaporative lithographic patterning of binary colloidal films

Evaporative lithography offers a promising new route for patterning a broad array of soft materials. In this approach, a mask is placed above a drying film to create regions of free and hindered evaporation, which drive fluid convection and entrained particles to regions of highest evaporative flux. We show that binary colloidal films exhibit remarkable pattern formation when subjected to a periodic evaporative landscape during drying.
Gender Mainstreaming Principles in Indonesia's REDD+ Program A Document Analysis

This paper analyzes publically available, published documents to conduct a systematic review of the inclusion of gender mainstreaming principles in documents related to one of the largest, most important international forest-preservation projects, Reducing Emissions from Deforestation and Forest Degradation (REDD+). Although more than 60 countries have adopted REDD+ initiatives, this document analysis focuses specifically on REDD+ in Indonesia, both because of its early adoption of REDD+ and as one of the most ecologically diverse and environmentally important countries in the world. Of the 383 documents reviewed, only 88 were found to include any mention of gender, and of those, very few included gender mainstreaming principles to a level that could be considered integrated and substantive. The distinct lack of these widely touted but seldom implemented principles should be of concern to international and national policy makers, and taken under serious consideration during the forthcoming Conference of the Parties (COP) 21 meetings in Paris. Moreover, this analysis is the first step to identifying where women’s voices may still be silent, and lays the groundwork for more extensive, on the ground research of REDD+ project sites to evaluate the extent to which gender mainstreaming is or is not incorporated into actual project implementation in Indonesia.
A Semantic Lexicon for Medical Language Processing

Objective: Construction of a resource that provides semantic information about words and phrases to facilitate the computer processing of medical narrative. Design: Lexemes (words and word phrases) in the Specialist Lexicon were matched against strings in the 1997 Metathesaurus of the Unified Medical Language System (UMLS) developed by the National Library of Medicine. This yielded a “semantic lexicon,” in which each lexeme is associated with one or more syntactic types, each of which can have one or more semantic types. The semantic lexicon was then used to assign semantic types to lexemes occurring in a corpus of discharge summaries (603,306 sentences). Lexical items with multiple semantic types were examined to determine whether some of the types could be eliminated, on the basis of usage in discharge summaries. A concordance program was used to find contrasting contexts for each lexeme that would reflect different semantic senses. Based on this evidence, semantic preference rules were developed to reduce the number of lexemes with multiple semantic types. Results: Matching the Specialist Lexicon against the Metathesaurus produced a semantic lexicon with 75,711 lexical forms, 22,805 (30.1 percent) of which had two or more semantic types. Matching the Specialist Lexicon against one year's worth of discharge summaries identified 27,633 distinct lexical forms, 13,322 of which had at least one semantic type. This suggests that the Specialist Lexicon has about 79 percent coverage for syntactic information and 38 percent coverage for semantic information for discharge summaries. Of those lexemes in the corpus that had semantic types, 3,474 (12.6 percent) had two or more types. When semantic preference rules were applied to the semantic lexicon, the number of entries with multiple semantic types was reduced to 423 (1.5 percent). In the discharge summaries, occurrences of lexemes with multiple semantic types were reduced from 9.41 to 1.46 percent. Conclusion: Automatic methods can be used to construct a semantic lexicon from existing UMLS sources. This semantic information can aid natural language processing programs that analyze medical narrative, provided that lexemes with multiple semantic types are kept to a minimum. Semantic preference rules can be used to select semantic types that are appropriate to clinical reports. Further work is needed to increase the coverage of the semantic lexicon and to exploit contextual information when selecting semantic senses.
Symbolic Simulation: An ACL2 Approach

Executable formal specification can allow engineers to test (or simulate) the specified system on concrete data before the system is implemented. This is beginning to gain acceptance and is just the formal analogue of the standard practice of building simulators in conventional programming languages such as C. A largely unexplored but potentially very useful next step is symbolic simulation, the "execution" of the formal specification on indeterminant data. With the right interface, this need not require much additional training of the engineers using the tool. It allows many tests to be collapsed into one. Furthermore, it familiarizes the working engineer with the abstractions and notation used in the design, thus allowing team members to speak clearly to one another. We illustrate these ideas with a formal specification of a simple computing machine in ACL2. We sketch some requirements on the interface, which we call a symbolic spreadsheet.
Transcription of viral genes in chromatin from adenovirus 2 transformed cells by exogenous eukaryotic RNA polymerases

Abstract The transcription of chromatin from adenovrius 2 transformed rat cells by murine plasmacytoma RNA polymerases I, II and III has been studied. Both the total RNA synthesis and transcription of the integrated adenovirus 2 genes by RNA polymerase II represent de novo DNA transcription as assessed by their sensitivity to actinomycin D. It is shown that each RNA polymerase class has characteristic ionic strength activation profiles and metal ion requirements. RNA polymerase II transcribes the integrated adenovirus 2 genes in chromatin at a frequency 25- to 50-fold higher than their sequences are represented in the genome. In contrast, no detectable viral RNA is synthesized when deproteinized DNA is transcribed. In the presence of Mn2+, all three RNA polymerases (I, II and III) transcribe the integrated viral genes at approximately the same relative frequencey. However, the Mg2+ as divalent cation, the proportion of the total RNA which represents viral gene transcripts is increased 3- to 4-fold with RNA polymerase II, while it remains unchanged for RNA polymerases I or III.
Teacher Nomination: German Version of the Scales for Rating the Behavioral Characteristics of Superior Students

Teacher nomination is often used as one criterion of a multidimensional approach towards identifying students with high abilities. Multiple criteria can be useful to identify students for gifted programs who may be overlooked using traditional methods. The teacher rating scales discussed in this study have been extensively used in the United States and have been translated into twelve other languages for use in identification of talented students in other countries. The purpose of this study was to develop teacher-rating scales for schools in the German speaking part of Switzerland. Therefore, the Scales for Rating the Behavioral Characteristics of Superior Students revised (SRBCSS-R) were translated from English into German and data were collected from certified teachers in public schools in Switzerland. Factor analysis confirmed the original four-factor structure from the American SRBCSS-R with a comparative fit index (CFI) of .89 and a root mean square residual of .07. Alpha reliability coefficients ra...
Identification and Estimation of Level-K Auctions

I develop a structural econometric framework for first-price auctions by generalizing the assumption of Bayesian Nash Equilibrium within the context of a level-k behavioral model, which nests equilibrium by allowing bidders to hold heterogeneous beliefs about opponents' bidding strategies. While behavioral heterogeneity causes identification to fail under benchmark equilibrium conditions, independence and exclusion restrictions recover identification of the joint distribution over valuations and bidder-types in heterogeneous populations. Establishing consistent maximum likelihood sieve estimation with an upper semicontinuous population log-likelihood function leads to a natural semi-nonparametric maximum likelihood estimator based on Legendre polynomials. The level-k model introduces a mixture structure to the estimation problem, requiring a generalized expectation maximization algorithm. Presenting evidence from a pilot study of vintage computer auctions, I find a high level of bidder sophistication in the field. To further apply the econometric framework, I characterize expected revenues in first price auctions with level-k bidders, establishing a partial identification result for expected revenues in unidentified models. An empirical analysis of USFS timber auctions finds that a misspecified equilibrium optimal reserve price could reduce expected revenues up to 30% relative to an unbinding reserve price.
Improvements in well-being and vagal tone following a yogic breathing-based life skills workshop in young adults: Two open-trial pilot studies

Background: While efficacy of Sudarshan Kriya Yoga (SKY) has been demonstrated in a number of prior studies, little is known about the effects of SKY taught as part of the Your Enlightened Side (YES+) workshop designed for college students and other young adults. Aims: This study aimed to assess the effects of YES+, a yogic breathing-based life skills workshop, on multiple measures of well-being and physiological stress response. Materials and Methods: Two nonrandomized open-trial pilot studies were conducted with a total of 74 young adults (age 25.4 ± 6.6 years; 55% female). Study 1 collected a variety of self-report questionnaires at baseline, postworkshop, and 1-month follow-up. Study 2 collected self-report questionnaires in addition to electrocardiography with a stationary cycling challenge at baseline and 1-month follow-up. Results: Study 1: Improvements in self-reported depression (P's ≤ 0.010), perceived stress (P's ≤ 0.002), life satisfaction (P's ≤ 0.002), social connectedness (P's ≤ 0.004), and gratitude (P's ≤ 0.090) were observed at postworkshop and 1-month after workshop relative to baseline. Study 2: Improvements in self-reported emotion regulation were observed at 1-month follow-up relative to baseline (P = 0.019). Positive and Negative Affect Schedule-Expanded Form positive affect increased (P = 0.021), while fatigue and sadness decreased (P's ≤ 0.005). During the stationary cycling challenge, rate to recovery of electrocardiography inter-beat interval also increased from baseline to 1-month follow-up (P = 0.077). Conclusions: These findings suggest that a life skills workshop integrating yogic breathing techniques may provide self-empowering tools for enhancing well-being in young adults. Future research is indicated to further explore these effects, particularly in regards to vagal tone and other aspects of stress physiology.
Preservation of intestinal gene expression during hibernation

The role of luminal nutrients in regulating enterocyte gene expression was studied in a natural model for long-term fasting, the hibernating ground squirrel. Squirrels were studied during the active season and during the hibernation season when they had not eaten for at least 12 wk. The specific activities of sucrase, isomaltase, and intestinal alkaline phosphatase in jejunal brush-border membranes were similar in hibernating and active squirrels, whereas amino-oligopeptidase was reduced in hibernators. Na(+)-K(+)-adenosinetriphosphatase activity in jejunal mucosa was unchanged by hibernation. Densitometric analysis of Western blots showed that abundance of sucrase-isomaltase (SI), amino-oligopeptidase, and the Na(+)-glucose cotransporter SGLT1 was similar in the two activity states. Preservation of SI abundance in hibernation was confirmed by immunocytochemistry. Slot-blot analysis revealed no differences in mRNA levels for these proteins between hibernating and active squirrels. Enterocyte proliferation and migration rates were greatly suppressed in torpid squirrels but increased immediately upon rewarming during arousals. These results demonstrate the striking constancy of enterocyte gene expression despite long-term fasting in a hibernating mammal.
An internally pressurized aerostatic journal bearing for thermoacoustic engines

Abstract An internally pressurized aerostatic journal bearing suitable for thermoacoustic power converters is designed and experimentally demonstrated using a free piston oscillating in a cylinder between two gas springs. The oscillating pressures in a thermoacoustic power converter׳s cavities can be used to create a near constant flow through an air gap between piston and cylinder. By selectively supplying and draining gas from gas reservoirs to the converter׳s gas cavities, separate reservoirs inside the piston can be maintained below and above the engine mean pressure. A continuous flow of gas between these reservoirs in the air gap creates an aerostatic gas bearing between the converter׳s piston and cylinder. The results show that, under the operating conditions of thermoacoustic power converter, a robust passive gas bearing is feasible.
Evolution of expert systems

Expert systems are computer programs for providing expertise emulative of that which might be expected from human experts in solving complex problems for which analytical solutions are not available. Evolution of an expert system refers to the initial development of the system and its continuing modification in order to improve its performance. Any modifications made to an expert system have the potential of producing undesirable logical errors and side-effects that are difficult to find or prevent. Although much research has focused on facilitating the evolution of expert systems, most of the limitations still exist. This dissertation proposes an approach for structuring and evolving expert systems for applications in which the provision of the desired expertise is beyond the reach of either analytical or traditional heuristic approaches, but in which the knowledge domain is causally connected and the relevant causality can be expressed in procedural form. The research vehicle used is that of a hypothetical manufacturing system in which products of different types use some of the same workstations, and some of the product types loop back to workstations that they have previously used. The expertise sought is that of scheduling starts of products into the first stage of production so as to yield a stream of output that satisfies a user-specified balance among a variety of business performance measures including timeliness of production output. An approach for structuring and evolving expert systems is introduced. The main system elements are: A simulation model of the causal relations of the knowledge domain; a collection of heuristic algorithms, each guaranteed to produce a feasible solution to any problem lying within the scope of the system's expertise; and a module that determines, from user-supplied criteria, the best of the alternative solutions. The evolution approach is based on adding new heuristic algorithms rather than modifying existing ones. That approach is used to develop, and evolve through several steps of evolution, an expert system for the subject application. The experimental results assess the expert system's initial capability, and demonstrate the evolution of the system's expertise through addition of more heuristic algorithms.
A Cyclotron Magnet Case Study: Would Replacing the LTS Coils With HTS Coils Make Sense?

The cyclotron gas-stopper magnet (CGSM) at Michigan State University (MSU) was used as model for a study for whether HTS conductor is feasible for use in cyclotrons. The outside diameter of the CGSM split warm iron magnet yoke is 4 m, with a pole radius of 1.1 m. The desired field shape is obtained by shaping the iron pole profile. Each superconducting coil is in a separate cryostat. The two coils are connected in series through the warm electrical connection. Each coil is wound and potted within an 80 mm × 80 mm cross section and mounted within a 304 stainless steel helium vessel that is designed to carry magnetic forces to the magnet cold mass supports without excessive deflection. The iron is split, so that the cyclotron chamber and RF extraction system can be mounted between the two poles. This magnet has been successfully cooled down and tested at MSU to its 180-A operating current. One can ask the following question, “If one built a cyclotron magnet the size of the MSU cyclotron gas-stopper magnet, would replacing the existing LTS coils with HTS coils using a standard second generation HTS tape make technical sense or economic sense?” The report will explore the technical and economic issues of replacing an existing LTS coil with an HTS coil of the same size and shape, using 2G YBCO tape conductor commercially available in 2015 in place of the Nb-Ti used in the magnet.
Origins of Selectivity in Brønsted Acid-Promoted Diazoalkane−Azomethine Reactions (The Aza-Darzens Aziridine Synthesis)

The mechanism of the Bronsted acid-catalyzed aza-Darzens reaction is explored by charting the stereochemical outcome of the triflic acid-promoted conversion of trans-triazolines to cis-aziridines. These experiments are consistent with the intermediacy of an α-diazonium-β-amino ester intermediate.
Preserving the internal mammary artery: end-to-side microvascular arterial anastomosis for DIEP and SIEA flap breast reconstruction.

Background: Microvascular breast reconstruction often sacrifices the internal mammary artery by means of an end-to-end anastomosis. However, an end-to-side anastomosis to the internal mammary artery will maintain the option of using the internal mammary artery for future coronary artery bypass. The authors' goal was to show the feasibility and reliability of the end-to-side arterial anastomosis by comparing it with the end-to-end anastomosis in terms of associated ischemia time, flap weight, incidence of thrombosis and fat necrosis, and overall flap survival. Methods: The authors reviewed the medical records of 22 consecutive patients who underwent 30 autologous breast reconstructions performed by one surgeon at The Johns Hopkins Hospital Avon Foundation Breast Center and whose deep inferior epigastric artery perforator or superficial inferior epigastric artery flap pedicles were anastomosed using an arterial end-to-side hand-sewn technique (15 anastomoses) or an arterial end-to-end hand-sewn technique (15 anastomoses). The authors compared the identified parameters and set the level of significance at the 0.05 alpha level. Results: The only significant difference between the end-to-side and end-to-end groups was mean ischemia time: 85.3 ± 18.1 minutes (range, 55 to 113 minutes) and 64.4 ± 23.6 minutes (range, 30 to 113 minutes), respectively. Conclusions: Although ischemia times were increased in the end-to-side group, they remained within acceptable limits. Therefore, this technique is a reliable and technically feasible method of preserving the internal mammary artery system for future potential cardiac surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
A Numerical Scheme for the Quantum Fokker-Planck-Landau Equation Efficient in the Fluid Regime

We construct an efficient numerical scheme for the quantum Fokker-Planck- Landau (FPL) equation that works uniformly from kinetic to fluid regimes. Such a scheme inevitably needs an implicit discretization of the nonlinear collision operator, which is difficult to invert. Inspired by work [9] we seek a linear operator to penalize the quantum FPL collision term QqFPL in order to remove the stiffness induced by the small Knudsen number. However, there is no suitable simple quantum operator serving the purpose and for this kind of operators one has to solve the complicated quantum Maxwellians (Bose-Einstein or Fermi-Dirac distribution). In this paper, we propose to penalize QqFPL by the "classical" linear Fokker-Planck operator. It is based on the observation that the classical Maxwellian, with the temperature replaced by the internal energy, has the same first five moments as the quantum Maxwellian. Numerical results for Bose and Fermi gases are presented to illustrate the efficiency of the scheme in both fluid and kinetic regimes.
FDA labeling of NSAIDs: Review of nonsteroidal anti-inflammatory drugs in cardiovascular disease

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively used worldwide for both chronic and acute musculoskeletal and inflammatory conditions. Extensive evidence has linked NSAID use with adverse cardiovascular events. This review article aims to review the existing evidence on the risk of cardiovascular and coronary events in both selective and nonselective NSAIDs, the time course of NSAIDs associated with cardiovascular risk, and specific populations that may be at increased risk.
Calcium Malabsorption in Hyperthyroidism

Two-hour isotopic 45calcium absorption measurements were determined in 23 thyrotoxic patients, 27 normal subjects, and in 10 treated hyperthyroid patients. Defective calcium absorption was clearly evident (P
DFWM and phase conjugation in absorbing liquids at 1 jim with 1‒20-ms-duration pulses

The use of a thermal nonlinearity for phase conjugation (PC) has been demonstrated for wavelengths from 0.25 to 10.6 μm.1−3 The advantages of the thermal nonlinearity are that it is universal in wavelength, it has a strong nonlinearity, it tolerates wide-bandwidth pulses (several cm−1), and its parameters can be chosen so that pulse durations from nanoseconds to milliseconds (or cw) can be used. The disadvantage of the thermal nonlinearity is that a considerable fraction (10% or more) of the optical power must be dissipated in the absorbing medium.
Signal Transduction by the PDGF Receptor

Publisher Summary Platelet-derived growth factor (PDGF) was discovered as a component present in platelets that promote growth of smooth muscle cells (SMCs) and cells from connective tissue in culture. PDGF is a 30,000-kDa protein. It is composed of two polypeptide chains linked by disulfide bonds. The A-chain and the B-chain of PDGF are encoded by different genes located on chromosomes 7 and 22 in the human genome, respectively. PDGF exists in human plasma predominantly as an AB heterodimer with two homodimeric forms. Both homodimeric forms of PDGF have been identified in several normal and transformed cell types. This chapter describes the primary structures of both PDGF receptors by molecular cloning. The experiments using an IL-3-dependent cell type, transfected with each of the receptor types, shows that both receptors are able to confer the mitogenic and chemotactic response to PDGF. An addition of PDGF to PDGF receptor-bearing cells promotes receptor dimerization. The intracellular domain or the receptor kinase activity is dispensable for ligand-induced dimerization. The receptor tyrosine kinase activity is essential for several functions of the receptor.
Carotenoids and Retinoids: Nomenclature, Chemistry, and Analysis

Carotenoids are polyenes synthesized in plants and certain microorganisms and are pigments used by plants and animals in various physiological processes. Some of the over 600 known carotenoids are capable of metabolic conversion to the essential nutrient vitamin A (retinol) in higher animals. Vitamin A also gives rise to a number of other metabolites which, along with their analogs, are known as retinoids. To facilitate discussion about these important molecules, a nomenclature is required to identify specific substances. The generally accepted rules for naming these important molecules have been agreed to by various Commissions of the International Union of Pure and Applied Chemistry and International Union of Biochemistry. These naming conventions are explained along with comparisons to more systematic naming rules that apply for these organic chemicals. Identification of the carotenoids and retinoids has been advanced by their chemical syntheses, and here, both classical and modern methods for synthesis of these molecules, as well as their analogs, are described. Because of their importance in biological systems, sensitive methods for the detection and quantification of these compounds from various sources have been essential. Early analyses that relied on liquid adsorption and partition chromatography have given way to high-performance liquid chromatography (HPLC) coupled with various detection methods. The development of HPLC coupled to mass spectrometry, particularly LC/MS-MS with Multiple Reaction Monitoring, has resulted in the greatest sensitivity and specificity in these analyses.
Comparison of Two Mycophenolate Mofetil Dosing Regimens Following Hematopoietic Cell Transplantation (HCT).

Mycophenolate mofetil (MMF) is frequently used as part of the immunosuppressive regimen after allogeneic nonmyeloablative HCT. We and others have previously shown that low mycophenolic acid (MPA) exposure, the active component of MMF, is associated with poorer rates of engraftment and increased risk of graft-vs-host disease (GVHD). As therapeutic plasma targets are difficult to achieve in adult HCT recipients with doses of MMF 2 gm/day, higher doses are required. To determine if higher MMF doses of 3 gm/day would achieve the therapeutic plasma targets we conducted a prospective pharmacokinetic study in adult recipients of nonmyeloablative HCT treated with cyclophosphamide 50 mg/kg, fludarabine 200 mg/m2 and total body irradiation 200 cGy in combination with cyclosporine and MMF as either 1.5 gm every 12 hours (n=15) or 1 gm every 8 hours (n=15). MMF was initiated on day -3 intravenously and switched to the oral form within the first week at the same dose. Pharmacokinetic sampling at steady state was performed once in each patient between days -1 and +5 while on intravenous therapy and then repeated once between days 5 and 14 posttransplant after oral administration. There were no differences in total or unbound MPA 24 hour cumulative area under the curve (AUC), concentration at steady state (Css) or troughs between the two dosing regimens. Total MPA 24 hour AUC (median, [range]) exposures were not different between intravenous 1 gm every 8 hours (53.59 [22.86–101.99] mcg*hr/mL) and intravenous 1.5 gm every 12 hours (60.90 [35.89–127.24] mcg*hr/mL) regimen (p=0.34). Unbound MPA 24 hour AUC exposures were also not different between the intravenous 1 gm every 8 hours (0.942 [0.389–1.722] mcg*hr/mL) and intravenous 1.5 gm every 12 hours (1.081 [0.610–2.194] mcg*hr/mL)(p=0.25). Following oral therapy, total and unbound MPA 24 hour AUC exposures after 1 gm every 8 hours and 1.5 gm every 12 hours were also not different (p≥0.43). Total MPA Css after intravenous 1 gm every 8 hours, oral 1 gm every 8 hours, intravenous 1.5 gm every 12 hours, oral 1.5 gm every 12 hours were 2.23 [0.95–4.25], 2.05 [1.32–3.24], 2.53 [1.46–5.24] and 2.35 [1.47–4.05] mcg/ml, respectively (p≥0.15). We previously found that an unbound 24 hour cumulative MPA AUC 0.600 mcg*hr/mL in 87–100% of subjects. All patients with the every 8 hour dosing had neutrophil recovery (ANC >500 cells/uL x 3 consecutive days) at a median [range] of day 10 [6–38] as compared to day 12 [0–31] in those with every 12 hour dosing. Acute GVHD grades II–IV developed in 3 (20%) and 6 (40%) patients in the MMF every 8 hour and every 12 hour dosing cohorts, respectively. When compared to our historical controls, MPA exposure is higher with MMF 3 gm/day compared to 2 gm/day regardless of dosing schedule and achieves adequate exposure in most adult patients. In conclusion, MMF 3 g/day should be considered the standard starting dose for adult patients undergoing nonmyeloablative HCT.
Kazakhstan's Nonprofit Sector at a Crossroad on the Great Silk Road

The Republic of Kazakhstan is developing a nonprofit sector, albeit slowly. It still suffers from the experience of 70 years of Communism but is now moving forward with development. This survey reviews the history, evolution, scope, and currency with a focus on the legal underpinnings of the nonprofit sector in Kazakhstan. In addition to discussing the traditions and cultures affecting development, the survey mainly concentrates on the legal and legislative obstacles that discourage rather than encourage more rapid development of the third sector in this Central Asian state.
Modeling the effects of topography and wind on atmospheric dispersion of CO2 surface leakage at geologic carbon sequestration sites

Abstract Understanding the potential impacts of unexpected surface releases of CO 2 is an essential part of risk assessment for geologic carbon sequestration sites. We have extended a mesoscale atmospheric model to model dense gas dispersion of CO 2 leakage. The hazard from CO 2 leakage is greatest in regions with topographic depressions where the dense gas can pool. Simulation of dispersion in idealized topographies shows that CO 2 can persist even under high winds. Simulation of a variety of topographies, winds, and release conditions allows the generation of a catalog of simulation results that can be queried to estimate potential impacts at actual geologic carbon sequestration sites.
Market and Non Market Mechanisms for Procuring Human and Cadaveric Organs

In the United States, as well as throughout the world, current demands for organ transplants far exceed the actual supply. Nonconsensual human donations, taken from minors, incompetents and prisoners are regulated carefully by the courts. The Uniform Anatomical Gift Act and the National Organ Transplant Act serve also as statutory frameworks for organ retrievals and allocations and place various restrictions upon each. Altruistically motivated donations at death continue to be an inadequate mechanism for meeting the growing demands of the market. Included among the various approaches to resolving the critical shortage of human organs for transplantation are post mortem harvesting, escheatage, prospective contingent sales and standard death benefit payments – with the latter being perhaps the most attractive in the United States. While ethical and moral principles can help develop a construct for resolving harvesting and transplantation conflicts, they must be tempered – in the final analysis – by a standard of practical need that recognizes unnecessary suffering and premature death from diseased and replaceable organs as undesirable.
Angewandte lineare Algebra

Eine m × n-Matrix hat m Zeilen, n Spalten und nm Elemente. Wir bearbeiten diese Zeilen und Spalten, um lineare Gleichungssysteme Ax=b und Eigenwertprobleme Ax=λ x zu losen. Aus den Eingaben A und b erhalten wir (mithilfe solcher Software wie MATLAB) die Ausgaben x und λ. Ein schneller und stabiler Algorithmus ist dabei auserordentlich wichtig. Genau das finden Sie in diesem Buch.
Who benefits most from property assessment taxes? Evidence from Los Angeles County

ABSTRACTAssessment caps on property taxes are often assumed to benefit affluent homeowners the most with little gains for low-income households. Quantile regression results for Los Angeles County show that on average effective property tax rates decrease by $1994 per year due to length of ownership in the 50th percentile because of California’s Proposition 13 assessment cap. There is evidence of both horizontal and vertical inequity across the entire sample. Low-income households do benefit from California’s assessment cap as they are typically infrequent movers but their effective tax rates decrease over time. However, the most affluent households by market value do not gain the most and there is no evidence of horizontal inequity for these homeowners. There is also no evidence of horizontal inequity for middle-income households. Property tax savings vary between $18,000 and $40,000, depending on the assessed value decile and percentage quantile.
Approaches to measure protein binding of enzymatically unstable compounds in plasma.

Aim: To develop approaches to measure plasma protein binding (PPB) of enzymatically unstable compounds. Methodology: Bis-para-nitrophenyl phosphate (BNPP) was used to inhibit enzyme activity and stabilize two model compounds (diltiazem and oseltamivir) that are subject to enzyme-catalyzed hydrolysis in plasma. Protein binding of the compounds in BNPP-treated rat plasma was measured using equilibrium dialysis or ultrafiltration. Conclusion: PPB measurement of unstable compounds was improved by using enzyme inhibitor to stabilize the compounds in plasma during the assay. The effect of BNPP concentration on drug-protein binding appeared to be compound dependent. Given the compound's nonspecific binding to the assay device can be accounted for in the unbound fraction measurement, ultrafiltration can be a viable alternative or complementary approach for PPB assay of unstable compounds while minimizing the potential impact of enzyme inhibitor on drug-protein binding.
Elements of viral cartography

Making and sharing maps is easier than ever, and social media platforms make it possible for maps to rapidly attain widespread visibility and engagement. Such maps can be considered examples of vir...
SRT is as easy as 12AKDB3.

Sequence learning — how we learn that one event or item follows another — has been studied mostly focusing on the effects of relatively simple relationships between elements. Using network science, a new study shows that in complex probabilistic sequences, some relationships are more easily learned than others.
Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: a case report and review of imaging findings.

Abstract Fingolimod is an oral medication approved by the Food and Drug Administration in 2009 for the treatment of relapsing remitting multiple sclerosis (RRMS). Initial clinical trials did not show a significantly increased rate of serious infections with fingolimod therapy. However, a mildly increased risk of less serious infections, such as varicella zoster virus and herpes simplex virus, was reported. Recently, however, several instances of serious opportunistic infections have been reported. In the years following approval of fingolimod for use in multiple sclerosis (MS), seven cases of cryptococcal meningitis in patients undergoing treatment have been described in the literature. We present a 40-year old woman with RRMS on fingolimod therapy presenting with a rare case of cryptococcal meningitis exhibiting alterations of consciousness, which was initially diagnosed as an MS relapse.
Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies

Introduction Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non–human leukocyte antigen (HLA) antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different pathway than HLA donor-specific antibodies (DSAs). Our aim was to examine serum cytokine profiles associated with AT1R-Ab and distinguish them from those associated with HLA DSA in serially collected blood samples from a cohort of pediatric renal transplant recipients. Methods Blood samples from 65 pediatric renal transplant recipients drawn during the first 3 months posttransplant, at 6, 12, and 24 months posttransplant, and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-8, IL-1β, IL-6, and IL-17). Associations between antibodies and cytokines were evaluated. Results AT1R-Ab, but not HLA DSA, was associated with elevations in TNF-α, IFN-γ, IL-8, IL-1β, IL-6, and IL-17. This relationship remained significant even after controlling for relevant clinical factors and was consistent across all time points. In contrast to HLA DSA, AT1R-Ab was associated with elevations in vascular inflammatory cytokines in the first 2 years posttransplant. Conclusions This profile of vascular cytokines may be informative for clinical monitoring and designing future studies to delineate the distinct pathophysiology of AT1R-Ab–mediated allograft injury in kidney transplantation.
Mycobacterium tuberculosis: Bacterial fitness within the host macrophage

Mycobacterium tuberculosis has evolved to become the single greatest cause of death from an infectious agent. The pathogen spends most of its infection cycle in its human host within a phagocyte. The bacterium has evolved to block the normal maturation and acidification of its phagosome and resides in a vacuole contiguous with the early endosomal network. Cytokine-mediated activation of the host cell can overcome this blockage, and an array of antimicrobial responses can limit its survival. The survival of M. tuberculosis in its host cell is fueled predominantly by fatty acids and cholesterol. The ability of M. tuberculosis to degrade sterols is an unusual metabolic characteristic that was likely retained from a saprophytic ancestor. Recent results with fluorescent M. tuberculosis reporter strains demonstrate that bacterial survival differs with the host macrophage population. Tissue-resident alveolar macrophages, which are biased towards an alternatively activated, M2-like phenotype, are more permissive to bacterial growth than monocyte-derived, inflammatory, M1-like interstitial macrophages. The differential growth of the bacterium in these different phagocyte populations appears to be linked to host cell metabolism.
Economistes and the Reinvention of Empire: France in the Americas and Africa, c.1750–1802

Exploring the myriad efforts to strengthen colonial empire that unfolded in response to France's imperial crisis in the second half of the eighteenth century, Pernille Roge examines how political economists, colonial administrators, planters, and entrepreneurs shaped the recalibration of empire in the Americas and in Africa alongside the intensification of the French Caribbean plantation complex. Emphasising the intellectual contributions of the Economistes (also known as the Physiocrats) to formulate a new colonial doctrine, the book highlights the advent of an imperial discourse of commercial liberalisation, free labour, agricultural development, and civilisation. With her careful documentation of the reciprocal impacts of economic ideas, colonial policy and practices, Roge also details key connections between Ancien Regime colonial innovation and the French Revolution's republican imperial agenda. The result is a novel perspective on the struggles to reinvent colonial empire in the final decades of the Ancien Regime and its influences on the French Revolution and beyond.
Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Background The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA− T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results Although CLA+ TH1 frequencies were significantly lower in infants with AD versus all older patients (P Conclusions The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.