cssi/SciSciGPT-SciSciNet huggingface dataset:
Integrated Safety Assessment of 2′-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers

The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2′-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2′-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied.
THE FUNCTIONS OF SCHOOLING: Perspectives from Rural Australia

(1989). THE FUNCTIONS OF SCHOOLING: Perspectives from Rural Australia. Discourse: Studies in the Cultural Politics of Education: Vol. 9, No. 2, pp. 1-21.
RasGRF Couples Nox4-Dependent Endoplasmic Reticulum Signaling to Ras

Objectives— In response to endoplasmic reticulum (ER) stress, endothelial cells initiate corrective pathways such as the unfolded protein response. Recent studies suggest that reactive oxygen species produced on the ER may participate in homeostatic signaling through Ras in response to ER stress. We sought to identify mechanisms responsible for this focal signaling pathway. Approach and Results— In endothelial cells, we found that ER stress induced by tunicamycin activates the NADPH oxidase Nox4 focally on the ER surface but not on the plasma membrane. Ras activation is also restricted to the ER, occurs downstream of Nox4, and is required for activation of the unfolded protein response. In contrast, treatment with the growth factor VEGF results in Ras activation and reactive oxygen species production confined instead to the plasma membrane and not to the ER, demonstrating local coupling of reactive oxygen species-Ras signals. We further identify the calcium-responsive, ER-resident guanyl exchange factors RasGRF1 and RasGRF2 as novel upstream mediators linking Nox4 with Ras activation in response to ER stress. Oxidation of the calcium pump sarcoendoplasmic reticulum calcium ATPase and increases in cytosolic calcium caused by ER stress are blocked by Nox4 knockdown, and reduction in cytosolic free calcium prevents both Ras activation and the unfolded protein response. Conclusions— ER stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF.
Characterization on latest-generation SiC MOSFET's body diode

This work evaluates the reverse recovery behavior of CREE's Gen 3 900V SiC MOSFET's body diode under different conditions. As the highest current rating discrete SiC MOSFET available up-to-now, CREE's Gen 3 900V 10 mΩ SiC MOSFET is the main device under test (DUT) in this work. Both static and dynamic characteristics of the DUT are presented. The factors that show effects on reverse recovery behavior in this work are forward conduction currents, junction temperatures, current commutation rates (gate resistors), supply voltages and die sizes. By comparing the CREE's Gen 3 900V 10 mΩ SiC MOSFET with the Gen 2 1200V ones (the main commercial products at present), the improvements in reverse recovery behavior of the Gen 3 900V over the Gen 2 1200V are discussed with several aspects. This work also discusses the junction capacitor and parasitic inductance effects on reverse behavior for SiC MOSFETs and how to clarify their effects in reverse recovery charge calculation.
Arrow Key Configurations on Laptop Keyboards: Performance and User Preference of the Inverted-T and Modified-T Layout

Over the years, many configurations of the navigation arrow keys have been developed and implemented. As laptops have become smaller, keyboard sizes have followed suit. Consequently, arrow key configurations have been looked at to help free up real estate on the keyboard. The most common configuration currently is the inverted-T; however, the modified-T is being investigated as a possible solution to provide more space on laptop keyboards. This study sought to understand how the inverted-T and the modified-T compare in terms of performance and user preference. Performance was defined by accuracy and speed of use on a series of tasks, where accuracy was measured by number of errors and speed was measured by task completion time. User preference was evaluated using the System Usability Scale. Results showed that user performance and preference did not differ significantly between the two keyboard designs. This has practical implications for laptop keyboard design.
The Impact of Reexcision and Residual Disease on Local Recurrence Following Breast-Conserving Therapy

Purpose Risk factors for local recurrence (LR) following breast-conserving therapy (BCT) inform the need for local therapy. A Danish population-based cohort study identified residual disease on reexcision as an independent risk factor for LR but was limited by incomplete data on biologic subtype (Bodilsen et al. 2015 in Ann Surg Oncol 22: S476–S485). We sought to elaborate this risk in an independent cohort with clearly defined biologic subtypes.
Molecular mechanisms of development of the human fetal female reproductive tract.

Human female reproductive tract development rests mostly upon hematoxilyn and eosin stained sections despite recent advances on molecular mechanisms in mouse studies. We report application of immunohistochemical methods to explore the ontogeny of epithelial and mesenchymal differentiation markers (keratins, homobox proteins, steroid receptors), transcription factors and signaling molecules (TP63 and RUNX1) during human female reproductive tract development. Keratins 6, 7, 8, 10, 14 and 19 (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19) were expressed in a temporally and spatially dynamic fashion. The undifferentiated Mullerian duct and uterovaginal canal, lined by simple columnar epithelia, expressed KRT7, KRT8 and KRT19. Glandular derivatives of the Mullerian duct (uterine tube, uterine corpus and endocervix) maintained expression of these keratins, while tissues that undergo stratified squamous differentiation (exocervix and vagina) expressed KRT6, KRT14 and KRT10 during development in an age-dependent fashion. TP63 and RUNX1 were expressed prior to KRT14, as these two transcription factors are known to be upstream from KRT14 in developing Mullerian epithelium. In the vagina, KRT10, a marker of terminal differentiation, appeared after endogenous estrogens transformed the epithelium to a thick glycogenated squamous epithelium. Uroplakin, a protein unique to urothelium, was expressed only in the bladder, urethra and vaginal introitus, but not in the female reproductive tract itself. Mesenchymal differentiation was examined through immunostaining for HOXA11 (expressed in uterine mesenchyme) and ISL1 (expressed in vaginal mesenchyme). A detailed ontogeny of estrogen receptor alpha (ESR1), progesterone receptor (PGR) and the androgen receptor (AR) provides the mechanistic underpinning for the teratogenicity of estrogens, progestins and androgens on female reproductive tract development. Immunohistochemical analysis of differentiation markers and signaling molecules advance our understanding of normal development of the human female reproductive tract. These observations demonstrate remarkable similarities in mouse and human female reproductive tract development, but also highlight some key differences.
Explosive and General Oxidative Characteristics of Fuels

This chapter discusses the explosive and general oxidative characteristics of fuels. There are two means by which the reaction can be initiated—thermally or photochemically. A thermal explosion occurs when a chemical system undergoes an exothermic reaction during which insufficient heat is removed from the system so that the reaction process becomes self-heating. The chapter highlights the explosive and general oxidative characteristics of fuels by giving illustrations through explosion limits and oxidation characteristics of carbon monoxide, hydrocarbons, and higher-order hydrocarbons such as aliphatic hydrocarbons, alcohols, and aromatic hydrocarbons. In hydrogen, flames of hydrogen in air or oxygen exhibit little or no visible radiation, what radiation one normally observes being due to trace impurities. The rate of carbon monoxide oxidation in the presence of species such as water is substantially faster than the “bone-dry” condition. The higher-order hydrocarbons, particularly propane and above, oxidize much more slowly than hydrogen and are known to form metastable molecules that are important in explaining the explosion limits of hydrogen and carbon monoxide. The chapter also reveals that a general pattern for oxidation of hydrocarbons in flames has two essential thermal zones: the primary zone, in which the initial hydrocarbons are attacked and reduced to products (CO, H 2 , H 2 O) and radicals (H, O, OH), and the secondary zone, in which CO and H 2 are completely oxidized.
Cesium Recognition by Supramolecular Assemblies of 2-Benzylphenol and 2-Benzylphenolate

Extraction experiments show that 2-benzylphenol is an efficient and selective extractant for cesium. The structures of cesium and potassium 2-benzylphenolate were determined. Both structures also contain 2-benzylphenol, which ligates the cation, through its phenolic oxygen atom and the benzyl ring. The phenolate oxygen atom does not directly contact the cation in either structure, but is a hydrogen-bond acceptor to the 2-benzylphenol ligands, forming a supramolecular assembly. For comparison to the bound ligands, the structure of 2-benzylphenol was also determined. Molecular mechanics and ab initio molecular orbital theory are used to rationalize several aspects of Cs/Na selectivity.
High-fidelity detection of crop biomass quantitative trait loci from low-cost imaging in the field.

Field-based, rapid, and nondestructive techniques for assessing plant productivity are needed to accelerate the discovery of genotype-to-phenotype relationships in next-generation biomass grass crops. The use of hemispherical imaging and light attenuation modeling was evaluated against destructive harvest measures with respect to their ability to accurately capture phenotypic and genotypic relationships in a field-grown grass crop. Plant area index (PAI) estimated from below-canopy hemispherical images, as well as a suite of thirteen traits assessed by manual destructive harvests, were measured in a Setaria recombinant inbred line mapping population segregating for aboveground productivity and architecture. A significant correlation was observed between PAI and biomass production across the population at maturity (r2 = .60), as well as for select diverse genotypes sampled repeatedly over the growing season (r2 = .79). Twenty-seven quantitative trait loci (QTL) were detected for manually collected traits associated with biomass production. Of these, twenty-one were found in four clusters of colocalized QTL. Analysis of image-based estimates of PAI successfully identified all four QTL hot spots for biomass production. QTL for PAI had greater overlap with those detected for traits associated with biomass production than with those for plant architecture and biomass partitioning. Hemispherical imaging is an affordable and scalable method, which demonstrates how high-throughput phenotyping can identify QTL related to biomass production of field trials in place of destructive harvests that are labor, time, and material intensive.
Open Resonator Microwave Sensor Systems for Industrial Gauging: A practical design approach

Open resonator microwave sensors allow accurate sensing, monitoring and measurement of properties such as dimension and moisture ontent in materials including dielectrics, rubber, polymers, paper, fabrics and wood veneers. This book presents a coherent and entirely practical approach to the design and use of systems based on these sensors in industrial environments, showing how they can provide meaningful, accurate and industrially-viable methods of gauging. Starting with an introduction to the underlying theory, the book proceeds through the entire design process, including simulation, experimentation, prototyping and testing of a complete system. It takes the reader through the development of a particular sensor, stressing the parameters that should be optimized and emphasizing practical aspects of a sensor and of its use. Two extended application case studies on the use of these systems for rubber thickness and fabric coating monitoring are included.
The Electronic Structure of Ag/Cu(100) and Pd/Cu(100) Surface Alloys Studied by Auger-Photoelectron Coincidence Spectroscopy

We have measured the Ag and Pd M 5 VV Auger spectrum in coincidence with Ag and Pd 4d 5/2 photoelectrons for the Ag/Cu(100) and PaVCu(l00) systems, respectively, as a function of admetal coverage. These systems form surface alloys (i.e. random substitutional alloys in the first atomic layer) for impurity concentrations in the 0.1 monolayer range. For these systems, the centroid of the impurity 4d levels is expected to shift away from the Fermi level by ~ 1 eV [Ruban et al., Journal of Molecular Catalysis. A 115 (1997) 421], an effect that should be easily seen in coincidence core-valence-valence Auger spectra. We find that the impurity Auger spectra of both systems shift in a manner that is consistent with d-band moving away from EF. However, the shift for Pd is considerably smaller than expected, and a shift almost absent for Ag. The disagreement between theory and experiment is most likely caused by the neglect of lattice relaxations in the calculations.
Accounting Certification in the Former Soviet Union and its Importance to the Energy Sector

The decline and fall of the Soviet empire has had profound effects on accounting and the accounting profession in the former Soviet republics. As the nations of the former Soviet Union have started to shift from central planning to a market economy they have encountered difficulties in adopting and implementing International Financial Reporting Standards (IFRS) and International Standards on Auditing (ISA). Accountants were not trained in IFRS and ISA and universities have only recently begun to add these subjects to their curriculum. Some national certification exams have started to test on these subjects but the national certifications do not have much credibility, especially in the international marketplace, because of corruption and the perception of poor quality. Lack of credibility is an especially important issue in the energy sector, since this is one of the sectors most in need of injections of foreign capital. Yet attracting foreign capital is made more difficult by lack of credible financial statements. The market is solving this credibility problem by offering several internationally recognized and respected certifications in the English language. There is also a regional certification program that offers a series of credible exams in the Russian language. This paper reports on these certification programs.
Phage therapy pharmacology: calculating phage dosing

Phage therapy, which can be described as a phage-mediated biocontrol of bacteria (or, simply, biocontrol), is the application of bacterial viruses-also bacteriophages or phages-to reduce densities of nuisance or pathogenic bacteria. Predictive calculations for phage therapy dosing should be useful toward rational development of therapeutic as well as biocontrol products. Here, I consider the theoretical basis of a number of concepts relevant to phage dosing for phage therapy including minimum inhibitory concentration (but also "inundation threshold"), minimum bactericidal concentration (but also "clearance threshold"), decimal reduction time (D value), time until bacterial eradication, threshold bacterial density necessary to support phage population growth ("proliferation threshold"), and bacterial density supporting half-maximal phage population growth rates (K(B)). I also address the concepts of phage killing titers, multiplicity of infection, and phage peak densities. Though many of the presented ideas are not unique to this chapter, I nonetheless provide variations on derivations and resulting formulae, plus as appropriate discuss relative importance. The overriding goal is to present a variety of calculations that are useful toward phage therapy dosing so that they may be found in one location and presented in a manner that allows facile appreciation, comparison, and implementation. The importance of phage density as a key determinant of the phage potential to eradicate bacterial targets is stressed throughout the chapter.
Flow in the Community College Classroom?: An Autoethnographic Exploration

Flow theory has not been previously applied to faculty experiences in higher education. Upon carrying out this autoethnographic self-study, I discovered that my experiences as a community college instructor were riddled with periods of being in flow. During the spring academic semester of 2010, I created weekly journals of my teaching life. Then, I coded and analyzed the journals and three themes were generated: preparation rituals, feedback, and solidarity. This self-study provided me with a wealth of knowledge about my own teaching and could assist others in understanding their own teaching experiences. It also highlighted the importance of affect in the college classroom. This study adds to the existing literature on flow theory, college teaching, and autoethnography.
Fluorescence, Absorption, and Optical Rotatory Behavior of Acridine Orange: Poly-L-Glutamic Acid Complexes

The work described below was actually carried out a few years ago at Iowa State University, but for the most part, it has not yet been published (Myhr 1968). This work was concerned with the use of metachromatic dyes as probes of polyanion conformation under test tube conditions, yet it now seems that the results and experience obtained may in some sense be useful to those who are interested in utilizing the optical properties of intracellular acridine orange, or another metachromatic dye, to derive polymer structural information or to follow regulatory changes.
SAT0180 Two-year consolidated safety data for abp 501 in patients with moderate to severe rheumatoid arthritis

Background: Biosimilars are expected to have similar long-term safety profiles as originator products. Objectives: To describe the consolidated, 2-year safety data on ABP 501, an approved biosimilar to adalimumab. Methods: We combined individual patient data from a 26-week randomized controlled head-to-head study (parent study) comparing ABP 501 with adalimumab (NCT01970475) and its 72-week open-label extension (OLE) study (NCT02114931) in which all patients received only ABP 501. Safety data were reported by exposure-adjusted incidence rate as the number of subjects with the specified adverse events *(AEs) per 100 person-years. AEs from the parent and OLE studies were summarized; for each category, patients were included only once based on the 1st event in that AE category. All comparisons were performed descriptively. Results: In the parent study, 264 patients received ABP 501 and 262 patients received adalimumab reference product (RP). Of these, 229 in the ABP 501 arm and 237 in the RP arm entered and were treated in the open-label extension study. The exposure-adjusted incidence rate for treatment-emergent AEs by treatment group are shown in the Table. Conclusions: Over the 2-year observation period, there were no meaningful differences in AEs between adalimumab reference product and ABP 501. Disclosure of Interest: E. Krishnan Shareholder of: Amgen Inc., Employee of: Amgen Inc., N. Zhang Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Wang Shareholder of: Amgen Inc., Employee of: Amgen Inc.
Exploratory syntheses and structures of SrAu(4.3)In(1.7) and CaAg(3.5)In(1.9): electron-poor intermetallics with diversified polyanionic frameworks that are derived from the CaAu4In2 approximant.

The phase regions around quasicrystals and approximants (QC/ACs) are rich pools for electron-poor intermetallics with novel, complex structures, and bonding patterns. The present SrAu(4.30(1))In(1.70(1)) (1) and CaAg(3.54(1))In(1.88(1)) (2) were synthesized through chemical tunings of the model CaAu(4)In(2) (YCd(6)-Type) AC. Single crystal X-ray diffraction analyses reveals that crystal 1 has Pnma (CeCu(6)-type) symmetry, with a = 9.102(1) A, b = 5.6379(9) A, and c = 11.515(2) A. The building block in 1 is a 19-vertex cluster Sr@Au(9)In(4)M(6) (M = Au/In), which vividly mimics Ca@(Au,In)(18) in Ca(3)Au(12.4)In(6.1) (YCd(6)-type) in geometry. These clusters aggregate into one-dimensional columns extending along the b axis. Crystal 2 (P6/mmm, a = 20.660(3) A, c = 9.410(2) A) is closely related to Na(26)Cd(141) (hP167) and Y(13)Pd(40)Sn(31) (hP168), which are differentiated by the selective occupation of Wyckoff 1a (0 0 0) or 2d (1/3 2/3 1/2) sites by Cd or Pd. Crystal 2 adopts the Na(26)Cd(141) structure, but the 1a site is split into two partially occupied sites. The synergistic disorder in the hexagonal tunnels along c is a major property. The valence electron count per atom (e/a) values for 1 and 2 are 1.63 and 1.74, respectively, the lowest among any other ternary phases in each system. These values are close to those of ACs in the Ca-Au-M (M = Ga, In) systems. Electronic structures for both are discussed in terms of the results of TB-LMTO-ASA calculations.
A Dharma Reader: Classical Indian Law , translated and edited by Patrick Olivelle

A Dharma Reader: Classical Indian Law, translated and edited by Patrick Olivelle. New York: Columbia University Press, 2017. xii + 410 pp., $80.00. ISBN 978-0-23117-956-0.
Contemporary indications for and outcomes of hepatic resection for neuroendocrine liver metastases

Contemporary indications for and outcomes of hepatic resection for neuroendocrine liver metastases
Orbital and Ocular Adnexal Manifestations of Adult T-Cell Leukemia/Lymphoma: a Case Report and Systematic Review.

Purpose To describe a patient with orbital adult T-cell leukemia/lymphoma (ATLL) and to review the literature on presentation, diagnostics, management, and clinical course of this rare disease. Methods A systematic literature review. PubMed/MEDLINE and Google Scholar databases were searched for all well-documented cases of orbital/ocular adnexal ATLL. Results Sixteen patients were included in the final analysis. The median age at diagnosis was 47 years (range, 20-85), 9/16 patients (56%) were male, and patients were of Japanese (10/16, 63%), Caribbean (5/16, 31%), or African (1/16, 6%) origin. Proptosis (6/15, 40%) and visual loss (5/15, 33%) were the most common presenting signs. Involvement of adjacent structures was documented in 8 of 16 (50%) patients. All patients had evidence of systemic ATLL, which was identified concurrently with orbital/ocular adnexal disease in 9 of 15 (60%) patients. Management included multi-agent chemotherapy with steroids (9/13, 69%), antivirals (2/13, 15%), biologic agents (4/13, 31%), and umbilical cord blood transplantation (1/13, 8%). Most patients (8/12, 67%) experienced at least partial remission with disease relapse occurring in 6 of 8 patients (75%). The median survival time was 28 months (95% CI, 5.5-50.5 months). Conclusions Adult T-cell leukemia/lymphoma should be considered in the differential diagnosis of orbital and ocular adnexal space-occupying lesions, particularly in male patients from endemic regions. Orbital disease is frequently locally aggressive and presents concurrently with systemic ATLL, highlighting the importance of comprehensive multimodal work-up and multidisciplinary management. Emerging targeted therapies and hematopoietic stem cell transplant may prolong survival.
Loneliness: The Cause or Consequence of Peer Victimization in Children and Youth

This article reviews the extant research literature on loneliness and peer victimization for children and youth, and explores the complex relationship between these two constructs. While lonely students who have few friends and receive limited peer support are vulnerable to being victimized by their peers, loneliness also emerges as a salient outcome of persistent and chronic peer victimization. The author discusses the phenomenon and incidence of bullying, the predictors of bullying and loneliness in children and youth, and reviews the literature associated with peer victimization in children and youth with disabilities, a population that is particularly vulnerable to being both the perpetrator and victim of bullying. The article concludes with a review of school-based intervention approaches to alleviate bullying in children and youth.
Matroid Secretary is Equivalent to Contention Resolution.

We show that the matroid secretary problem is equivalent to correlated contention resolution in the online random-order model. Specifically, the matroid secretary conjecture is true if and only if every matroid admits an online random-order contention resolution scheme which, given an arbitrary (possibly correlated) prior distribution over subsets of the ground set, matches the balance ratio of the best offline scheme for that distribution up to a constant. We refer to such a scheme as universal. Our result indicates that the core challenge of the matroid secretary problem lies in resolving contention for positively correlated inputs, in particular when the positive correlation is benign in as much as offline contention resolution is concerned. Our result builds on our previous work which establishes one direction of this equivalence, namely that the secretary conjecture implies universal random-order contention resolution, as well as a weak converse, which derives a matroid secretary algorithm from a random-order contention resolution scheme with only partial knowledge of the distribution. It is this weak converse that we strengthen in this paper: We show that universal random-order contention resolution for matroids, in the usual setting of a fully known prior distribution, suffices to resolve the matroid secretary conjecture in the affirmative. Our proof is the composition of three reductions. First, we use duality arguments to reduce the matroid secretary problem to the matroid prophet secretary problem with arbitrarily correlated distributions. Second, we introduce a generalization of contention resolution we term labeled contention resolution, to which we reduce the correlated matroid prophet secretary problem. Finally, we combine duplication of elements with limiting arguments to reduce labeled contention resolution to classical contention resolution.
Chopped ID and Bicycle Repair: Contrasting Values in Synchronous Graduate Instructional Designs for Design Learning

This article presents two similar design cases and a discussion of how like values resulted in dissimilar design moves. Both cases were gamified learning activities for graduate students in instructional design. Both interventions employed rapid prototyping and were delivered synchronously in an at-a-distance setting. This article compares the two designs, the two designs’ similar development narratives, and the two designs’ divergent features. We give special attention to the common values the designers brought to the act of designing. Contrasting crucial features in similar designs allowed us, as designers, to appreciate divergent design moves. A discussion of the two cases explains how designers arrived at different design decisions through similar rationale. The authors were both designers and instructors of the implementations; each presents their case in relation to the other. Our combined cases explore how designers might compare salient features of similar instructional interventions and appreciate design moves that one chose not to make.
Microfluidic based nanoparticle synthesis and their potential applications

A lot of substantial innovation in advancement of microfluidic field in recent years to produce nanoparticle reveals a number of distinctive characteristics for instance compactness, controllability, fineness in process, and stability along with minimal reaction amount. Recently, a prompt development, as well as realization in production of nanoparticles in microfluidic environs having dimension of micro to nanometers and constituents extending from metals, semiconductors to polymers, has been made. Microfluidics technology integrates fluid mechanics for production of nanoparticles having exclusive with homogenous sizes, shapes, and morphology, which are utilized in several bioapplications such as biosciences, drug delivery, healthcare, including food engineering. Nanoparticles are usually well-known for having fine and rough morphology because of their small dimensions including exceptional physical, biological, chemical, and optical properties. Though the orthodox procedures need huge instruments, costly autoclaves, use extra power, extraordinary heat loss, as well as take surplus time for synthesis. Additionally, this is fascinating in order to systematize, assimilate, in addition, to reduce traditional tools onto one platform to produce micro and nanoparticles. The synthesis of nanoparticles by microfluidics permits fast handling besides better efficacy of method utilizing the smallest components for process. Herein, we will focus on synthesis of nanoparticles by means of microfluidic devices intended for different bioapplications. This article is protected by copyright. All rights reserved.
Anti-aging Gene Klotho Deficiency Causes Arterial Calcification via Activating the Bone Morphogenetic Protein Signaling

Background. Arterial calcification is an important risk factor for arterial stiffening, hypertension, stroke, and coronary heart disease. Klotho-deficient mice display severe arterial calcification but the mechanism remains to be determined. Methods & Results. We found that Klotho-deficient mice developed elastin fiber fragmentation and smooth muscle cell (SMC) apoptosis and arterial calcification. Aortas of Klotho (-/-) mice demonstrate higher levels of bone morphogenetic proteins (BMP2 and BMP4) and runt-related transcription factor 2 (RUNX2, a key transcription factor for bone formation). Given that Klotho deficiency-induced hyperphosphotemia may cause arterial calcification, Klotho deficient mice were given low phosphate diet (0.2%). Interestingly, Low phosphate diet normalized blood phosphate levels and abolished calcification in lungs and kidneys, but it did not prevent the development of aortic calcification in Klotho-deficient mice. In cultured mouse aortic SMCs, KL-deficient serum promoted BMP2-i...
Biogeochemical Cycling of Iron Isotopes

Iron is the most abundant element on Earth that undergoes reduction-oxidation (redox) reactions. Moreover, the ratio of the iron isotopesFe andFe can change during these redox reactions. As Johnson and Beard discuss in their Perspective, this isotope fractionation has attracted interest as a way of understanding important biogeochemical processes on Earth over time. This isotope system may help unravel some of the questions surrounding changes in atmospheric oxygen and the origin and evolution of life over the past 4 billion years.
Prolapse of the umbilical cord. Analysis of 76 cases.

Abstract 1. 1. Ninety-six cases of prolapsed cord were recorded from August 1940, to January 1958. Twenty instances were not included because they occurred in late abortions. Seventy-six cases have been analyzed. 2. 2. One should be familiar with the predisposing factors leading to cord prolapse. 3. 3. Early diagnosis is important. A change in fetal heart rate or premature rupture of the membranes demands a vaginal examination. 4. 4. When prolapse of the cord is diagnosed, delivery should be accomplished immediately if the baby is still alive.
Growth hormone modulation of liver drug metabolic enzyme activity in the rat. I. Effect of the hormone on the content and rate of reduction of microsomal cytochrome P-450.

Abstract The liver metabolism of hexobarbital and aniline was decreased 48 hr after the first injection of growth hormone (GH) in adult male rats. The content and rate of reduction of hepatic microsomal cytochrome P-450 were lowered in these rats as compared with control animals. Liver NADPH-cytochrome c reductase showed a similar decrease in activity after GH treatment. The decrease in hexobarbital metabolism paralleled the change in cytochrome P-450 reductase activity as measured with or without addition of this drug substrate to a suspension of liver microsomes from GH-treated rats. The change in aniline metabolism approximated the extent and rate of cytochrome P-450 reduction after GH treatment only when cytochrome P-450 reductase activity was measured without addition of aniline. Injection of GH produced a parallel decrease in the metabolism of both drugs as compared with cytochrome c reductase activity. Differences in optimal requirements for drug substrates (hexobarbital or aniline) or NADPH for cytochrome P-450 reductase were not detected. Preincubation studies showed no differences in microsomal drug metabolic enzyme system stability in rats injected with GH. Inhibitors of this system in vitro were not demonstrated in liver from GH-treated rats. GH is presumed to affect the level of liver drug metabolism through mechanisms in vivo operative at the first stage transfer of reducing equivalents to cytochrome P-450. An additional effect of this hormone on the level or catalytic properties of the hemoprotein cytochrome P-450 may contribute to the decrease in aniline metabolism.
Isolated unilateral temporalis muscle hypertrophy: Case report

Isolated unilateral temporalis muscle hypertrophy is an extremely rare cause of swelling in the temple region, with only 7 cases reported in the literature. The authors report the eighth case of this unique occurrence in a 17-year-old boy and review the current literature.
Sympathetic effects on the steroidogenesis and proliferation of adrenocortical cells in vitro.

Recent evidence supports the hypothesis that sympathetic neurons play a significant role in the regulation of adrenocortical cell proliferation and steroidogenesis. Co-cultures of rat adrenocortical and sympathetic ganglion cells have been established to study sympatho-adrenal interactions. In these studies we have compared differentiation, growth and secretion of adrenocortical cells grown in co-culture with those grown alone. Adrenocortical cells were identified using 3s-hydroxysteroid dehydrogenase (3sHSD) histochemistry or immunocyto-chemistry; sympathetic neurons were identified using immunocytochemical localization of tyrosine hydroxylase. The sympathetic neurons usually form clusters of 3–10 cells, and extend neurites to adrenocortical cells. Adrenocortical cells continue to proliferate, express 3sHSD and sequester lipid droplets. In the co-cultures, the adrenocortical cells are smaller, form larger clusters and show denser 3sHSD staining than the adrenocortical cells alone. The presence of the sym...
Onboard Knowledge Systems in Vehicles

Texas Instruments has been heavily involved with building knowledge systems of various types for many different kinds of applications from factory schedulers to diagnostic systems for complex equipment to pilots' aids in military aircraft. We have also broadcast a series of television programs on applications of knowledge systems. The author was asked to write about onboard knowledge systems in automobiles, but that was one of the kinds of application for which we have not yet built knowledge systems. Few references can be found in the literature for knowledge systems that have been completed for onboard use. As a result, this paper is a speculation, based on the experience of building and using knowledge systems in other domains. It is also intended to be something of an analogy ... based on other experience, where will the opportunities and problems lie with onboard knowledge systems?
Interaction of Lead and Bacterial Lipids

Studies on the interaction of lead with lipid components indicate that individual lipids do not provide specific stable binding sites for lead, but that natural membrane lipid mixtures may simply provide an environment suitable for nucleation of lead.
Abl kinase constructs expressed in bacteria: facilitation of structural and functional studies including segmental labeling by expressed protein ligation

A great portion of tyrosine kinases are involved in cell development and their structural alteration is intimately involved in associated pathologies of development and oncology. These kinases are one of the major groups of targets under investigation for molecular therapeutics. To carry out biochemical and structural biological studies on these kinases, economical production of their purified forms is highly desirable. However over-expressing tyrosine kinases as recombinant forms in bacterial systems and their purification is a significant challenge. Abelson kinase (Abl) has previously been expressed on a large scale to facilitate X-ray crystallography and NMR structure studies mainly in baculovirus infected insect cells. Even though success has been achieved in expression of soluble tyrosine kinases in E. coli with chaperones to improve correct folding, low expression levels of kinases are intrinsic in such systems because of diversion of resources to produce chaperones. Here we present a straightforward method to express and purify isolated Abl kinase domain and SH3–SH2–kinase multi-domain structures. The expressed Abl protein retains its correct folding and biological function. The yield of soluble protein is in a several mg L−1 range in minimal media. Furthermore we demonstrate that segmental isotopic labelling using expressed protein ligation can be achieved using bacterial expressed Abl kinase domain constructs, which is especially useful in NMR structure–activity studies.
Antagonism of 5-hydroxytryptamine by benzquinamide

Abstract Benzquinamide protected mice from tremors induced by 5-HTP and nialamide; it blocked the pulmonary vasoconstrictor effects of 5-HT in dog open chest preparations, reduced 5-HT-induced contractions of cat nictitating membrane and protected rats from antidiuretic and nephrotoxic effects of 5-HT.
Mobile robot navigation with vision-based neural networks

Mobile robot technology is spreading its use in the development of advance manufacturing systems. Methods of multi-sensory fusion data with vision, sonar and limit switches have been developed as the most flexible, but expensive approaches. Other approaches are more common such as buried wire AGV's. They decrease the cost of the mobile robot, but degrade the flexibility of the navigation system as well. This paper uses neural networks (NNs) with only one camera to obtain similar flexibility as the high cost approaches, but in a cost-efficient way. The NNs use translation and perspective information of features in images to determine the proper alignment and position of the mobile robot.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Electrophoresis in one buffer at two pH values

A theory for discontinuous electrophoresis in a polyacrylamide gel is presented for one buffer at two pH values. It is shown that polyions stack between identical leading and trailing ions, and resolve in a gel of constant polyacrylamide concentration. The theory is illustrated by the separation of serum protein polyions in a Tris-glycinate buffer of pH 8.19 in the well-forming gel, and pH 9.16 in the resolving gel. The selected concentrations and electrolyte ionization degrees of Tris and glycine have values at which the serum protein polyions stack between the resolving and electrode buffers, followed by separation in the resolving gel.
Calcium homeostasis in rat septal neurons in tissue culture

Abstract Septal neutons from embryonic rats were grown in tissue culture. Microfluorimetric and electrophysiological techniques were used to study Ca2+ homeostasis in these neurons. The estimated basal intracellular free ionized calcium concentration ([Ca2+]i) in the neurons was low (50–100 nM). Depolarization of the neurons with 50 mM K+ resulted in rapid elevation of [Ca2+]i to 500–1,000 nM showing recovery to baseline [Ca2+]i over several minutes. The increases in [Ca2+]i caused by K+ depolarization were completely abolished by the removal of extracellular [Ca2+], and were reduced by ∼80% by the ‘L-type’ Ca2+ channel blocker, nimodipine (1 μM). [Ca2+]i was also increased by the excitatory amino and l -glutamate, quisqualate, AMPA and kainate. Responses to AMPA and kainate were blocked by CNOX and DNOX. In the absence of extracellular Mg2+, large fluctuations in [Ca2+]i were observed that were blocked by removal of extracellular Ca2+, by tetrodotoxin (TTX), or by antagonists ofN-methyl d -aspartate (NMDA) such as 2-amino 5-phosphonovalerate (APV). In zero Mg2+ and TTX, NMDA caused dose-dependent increases in [Ca2+]i that were blocked by APV. Caffeine (10 mM) caused transient increases in [Ca2+]i in the absence of extracellular Ca2+, which were prevented by thapsigargin, suggesting the existence of caffeine-sensitive ATP-dependent intracellular Ca2+ stores. Thapsigargin (2 μM) had little effect on [Ca2+]i, or on the recovery from K+ depolarization. Removal of extracellular Na+ had little effect on basal [Ca2+]i or on responses to high K+, suggesting that Na+/Ca2+ exchange mechanisms do not play a significant role in the short-term control of [Ca2+]i in septal neurons. The mitochondrial uncoupler, CCCP, caused a slowly developing increase in basal [Ca2+]i; however, [Ca2+]i recovered as normal from high K+ stimulation in the presence of CCCP, which suggests that the mitochondria are not involved in the rapid buffering of moderate increases in [Ca2+]i. In simultaneous electrophysiological and microfluorimetric recordings, the increase in [Ca2+]i associated with action potential activity was measured. The amplitude of the [Ca2+]i increase induced by a train of action potentials increased with the duration of the train, and with the frequency of firing, over a range of frequencies between 5 and 200 Hz. Recovery of [Ca2+]i from the modest Ca2+ loads imposed on the neuron by action potential trains follows a simple exponential decay (τ = 3–5s).
Role of TATA Box Sequence and Orientation in Determining RNA Polymerase II/III Transcription Specificity

Work from a number of laboratories has indicated that the TATA box sequence can act as a basal promoter element not only for RNA polymerase II (RNAP II) transcription, but also for transcription by RNA polymerase III (RNAP III). We previously reported that, in the absence of other cis-acting elements, the canonical TATA sequence TATAAAAA specifically supported transcription by RNAP II in an unfractionated Drosophila nuclear extract, whereas the sequence TTTTTATA (the same sequence in reverse orientation) directed RNAP III transcription. We have now examined a variety of other TATA box sequences with regard to RNA polymerase selectivity and their ability to support RNAP III transcription. The results have allowed us to rank these TATA box sequences with respect to their relative strengths as RNAP III promoter elements in unfractionated Drosophila extracts. Further, the data indicate that T residues at positions 2 and 4 of the TATA box appear to be important determinants of RNAP III selectivity in this system, whereas A residues at these positions favor RNAP II transcription. Finally, the data suggest that transcription factors TFIID and TFIIIB, although both capable of binding a variety of TATA elements, have distinct sequence preferences for recognizing the TATA box and possibly the surrounding DNA.
Sporocarp Ulrastructure and Development in the Protostelid Cavostelium apophysatum1

Ultrastructural observations on the sporocarp of the protostelid Cavostelium apophysatum are presented, including information about the mechanism of sporocarp development. The onset of sporogenesis is marked by cessation of trophic activity and the secretion of a protective sheath. The protoplast gradually molds itself into two distinct zones approximating the shape of the final sporocarp–a hyaloplasmic pre-stalk zone and a globose incipient spore zone. The protoplast in the stalk zone deposits a fibrillar and amorphous stalk acropetally as the stalk protoplast moves into the incipient spore region. The last portion of the stalk to be deposited is the apophysis, a hollow cup-like structure at the stalk apex. Spore wall deposition begins as the stalk nears completion. The wall consists of a single electron-dense layer ornamented with hollow cones and solid projections. The mechanism of sporocarp development in C. apophysatum is compared to the developmental patterns of the protostelids Planoprotostelium aurantium and Schizoplasmodiopsis amoeboidea.
Dissecting Requirements for Auto-inhibition of Actin Nucleation by the Formin, mDia1

The mammalian formin, mDia1, is an actin nucleation factor. Experiments in cells and in vitro show that the N-terminal region potently inhibits nucleation by the formin homology 2 (FH2) domain-containing C terminus and that RhoA binding to the N terminus partially relieves this inhibition. Cellular experiments suggest that potent inhibition depends upon the presence of the diaphanous auto-regulatory domain (DAD) C-terminal to FH2. In this study, we examine in detail the N-terminal and C-terminal regions required for this inhibition and for RhoA relief. Limited proteolysis of an N-terminal construct from residues 1-548 identifies two stable truncations: 129-548 and 129-369. Analytical ultracentrifugation suggests that 1-548 and 129-548 are dimers, whereas 129-369 is monomeric. All three N-terminal constructs inhibit nucleation by the full C terminus. Although inhibition by 1-548 is partially relieved by RhoA, inhibition by 129-548 or 129-369 is RhoA-resistant. At the C terminus, DAD deletion does not affect nucleation but decreases inhibitory potency of 1-548 by 20,000-fold. Synthetic DAD peptide binds both 1-548 and 129-548 with similar affinity and partially relieves nucleation inhibition. C-terminal constructs are stable dimers. Our conclusions are as follows: 1) DAD is an affinity-enhancing motif for auto-inhibition; 2) an N-terminal domain spanning residues 129-369 (called DID for diaphanous inhibitory domain) is sufficient for auto-inhibition; 3) a dimerization region C-terminal to DID increases the inhibitory ability of DID; and 4) DID alone is not sufficient for RhoA relief of auto-inhibition, suggesting that sequences N-terminal to DID are important to RhoA binding. An additional finding is that FH2 domain-containing constructs of mDia1 and mDia2 lose >75% nucleation activity upon freeze-thaw.
From implementation to theory in product synthesis

Future software development will rely on product synthesis, i.e., the synthesis of code and non-code artifacts for a target component or application. Prior work on feature-based product synthesis can be understood and generalized using elementary ideas from category theory. Doing so reveals (a) practical and previously unrecognized properties that product synthesis tools must satisfy, and (b) non-obvious generalizations of current techniques that will guide future research efforts in automated product development.