cssi/SciSciGPT-SciSciNet huggingface dataset:
A Prototype Immersive, Multi-user 3D Virtual Learning Environment for Individuals with Autism to Learn Social and Life Skills: A Virtuoso DBR Update

The specific aim of this session is to discuss the early design of a collaborative, immersive learning intervention for youth with Autism Spectrum Disorders (ASD), named Virtuoso. Building on our presentation at AECT 2016, this session will describe design and development progress to date, share our design narrative, explicate underlying theoretical and design principles, provide session participants an overview of the Virtuoso system, and present a timeline of ongoing research and development.
Current Information Technology Issues and Moral Intensity Influences

This study presents a review and analysis of how common information technology (IT) unethical actions are viewed by a sample of students, faculty, and practitioners and what moral intensity variables influenced their decision. The findings reveal that all the questionable moral situations were judged with varying levels of opposition. Gender, age, and student status all affected ethical decisions. It was also found that different moral intensity variables had varying influences on moral decisions. Practitioners can use these findings to tailor moral education and training activities. Researchers can further explore the initial findings and refine the varying impact and influences.
Contortions of Memory

This chapter focuses on important themes related to place and memory that emerge when the element of conflict exerts additional forces on place-based memories. Which functions and manifestations of memory are of increased importance when conflict, trauma, migration, or exile disrupt the normal relationship between peoples and the places they have called home? I shape my discussion with examples from a number of cities, including Berlin, Jerusalem, and Lhasa. This discussion is organized under the themes of: intergenerational memory, cultivated memory, urban mythologies, image, and absence.
Investigating the impact of Sense of Place on site visit frequency with non-motorized travel modes

Abstract This paper examines the relationships between: (i) Sense of Place (SOP); (ii) non-motorized travel; and (iii) the use of information and communication technologies (ICT). A guiding principle in built environment design for sustainability and livability is a latent construct termed Sense of Place (SOP), which leads visitors to perceive and associate a strong identity or character with a particular location. We hypothesize that visitors' SOP affects their access of sites via walking/biking or other non-motorized travel modes. Furthermore, we also hypothesize their ICT use shapes their SOP. In an information era, mobile ICT provide ubiquitous information and communication across multiple geographies, expanding interaction with locations to include both the physical and virtual. Visitors can engage with a location pre and post-trip through online reviews or virtual visualizations, such as Google Street View. To investigate these interrelationships, we conduct a visitor intercept survey and analyze the responses to investigate the direction and magnitude SOP impacts on non-motorized site visit frequency. The estimation results indicate that SOP statistically impacts non-motorized visits; ICT use for learning about the site was found to positively impact visitors' estimated SOP.
Low-Computational Complexity Intrusion Detection System for Jamming Attacks in Smart Grids

Transformation of the traditional power grid into a smart grid hosts an array of vulnerabilities associated with communication networks. Furthermore, wireless mediums used throughout the smart grid promote an environment where Denial of Service (DoS) attacks are very effective. In wireless mediums, jamming is the typical DoS attack technique employed to diminish system operations thus affecting smart grid stability. In this study, an intrusion detection system (IDS) is proposed to detect jamming attacks in the smart grid. This IDS algorithm analyzes received signal strength indicator (RSSI) and packet loss rate (PLR) of 802.11 network traffic in smart grid communication systems to detect jamming attacks. Experimental results corroborate theoretical analysis.
Electromagnetic Interference (EMI)

Radiated emissions in high-speed DSP systems are caused by fastswitching currents and voltages propagating through printed circuit board traces. As DSP speed increases, printed circuit board traces are becoming more effective antennas, and these antennas are radiating unwanted energies that interfere with other circuitry and with other systems located nearby. This section outlines different ways to design for low EMI and find the root cause of EMI problems when they occur. It only covers the electrical design aspects of EMI even though shielding, cabling and other mechanical fixes can also be used to help reduce the emissions below the maximum allowable limits. In general, mechanical solutions are very expensive for high volume designs. Even worse, the mechanical solutions may have to change when the DSP speed increases.
Keratinocyte growth factor-induced motility of breast cancer cells.

Endogenous growth factors and cytokines are known to have a major influence on the progression, motility and invasiveness of tumor cells. We have reported previously that conditioned media from mouse fibroblasts increases the motility of breast cancer cells. Further, we determined that keratinocyte growth factor (KGF) was an active factor from mouse fibroblasts responsible for most of the motility response in breast cancer cells. The present study examined the effect of human KGF on the motility of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines in culture using time-lapse videomicroscopy to quantify cell motility. In the present study we observed that recombinant human KGF enhanced several parameters of cellular motility in ER-positive cells but not in ER-negative cell lines. Further, we observed that the level of KGF receptor (KGFR) expression in ER-positive cells was much greater than in the ER-negative cell lines. The motility response to KGF was found to be both dose-and time-dependent. Of the three ER-positive breast cancer cell lines tested, MCF-7 cells were the most responsive to KGF stimulation. Finally, MCF-7 cells grown in estrogen-depleted media did not respond to KGF. These results suggest that KGF from stromal tissue surrounding a primary tumor mass can enhance tumor cell motility and may be an early signal in the progression of breast cancer cells to a more motile and metastatic phenotype. Thus, KGF, KGFR and/or the KGF signaling pathway may be important therapeutic targets for the treatment or prevention of breast cancer metastasis.
Assessing the Impact of Diversity, Corporate Governance and Management Demographics on Firm Performance

Assembling the right management team is a challenging and complex process in today’s global economy. The recent worldwide financial meltdown has simply underscored the importance of a far-sighted and balanced management organisation. The characteristics and composition of the management team along with effective corporate governance policies can also play a role in addressing these challenges. The purpose of this paper is to illustrate how analytical modeling can be used in helping shape organisational teams. A panel data analysis of S&P 1500 firms for the period 2004 to 2007 was performed. The results from the analysis show that management team diversity and commitment to good corporate governance both have a positive impact on firm performance as measured by Tobin’s Q.
Résultats du traitement des fractures de l’humérus distal. Que mesurons-nous ?

Abstract Introduction We evaluate the most common outcome measures used in distal humerus fracture studies in order to suggest standardization for future research. Materials and methods A systematic review identified articles assessing the outcomes of acute distal humerus fractures from 2006 to 2016 from PubMed and Web of Science databases. The inclusion criterion was studies reporting on the outcomes of treatment of acute distal humerus fractures. Review articles, meta-analyses, studies with Results One hundred and nine of 2158 articles met inclusion criteria. The median number of fractures per study was 35. Mean patient age was 55.0 years. Average follow-up was 35 months. Range of motion and strength measurements were reported in 90 % and 17 % of studies, respectively. Twenty patient reported outcome instruments were used. The most commonly reported measures were MEPS, DASH, VAS pain, and Quick DASH scores. An average of 1.9 outcome measures were reported per study. A journal impact factor of ≥ 1.5 was associated with more reported outcome measures. Articles including elbow arthroplasty were associated with higher impact factor journals, more outcome measures, and longer follow-up. Level of evidence was not associated with the number of reported outcome measures. Discussion The current distal humerus fracture literature inconsistently reports outcome measures. More outcome measures were reported in higher impact journals. Future distal humerus fracture studies should include MEPS, DASH or Quick DASH, and VAS Pain scores to allow for appropriate cross-study comparison. Level of evidence IV, systematic review.
A guide to maximizing the therapeutic potential of protein-polymer conjugates by rational design.

Proteins are an important class of therapeutics that have advantages including high target specificity, but challenges to their use include rapid clearance and low physical stability. Conjugation of synthetic polymers is an effective approach to address the drawbacks and enhance other properties such as solubility. In this review, we present various considerations in synthesizing protein–polymer conjugates for therapeutic applications with a focus on the choice of polymer, protein, and conjugation method, as well as characterization and evaluation of the resulting conjugate in order to maximize the therapeutic potential of the protein drug.
Intermediate pressure optimization for two-stage air-source heat pump with flash tank cycle vapor injection via extremum seeking

Abstract The flash-tank-cycle vapor injection technique has been developed for heat pump operation under cold climate, however, lack of effective control strategy has limited its practical acceptance. This paper presents a novel control strategy for a two-stage air source heat pump water heater with flank-tank-cycle vapor injection. The intermediate pressure setpoint for the injection loop is regulated by the upper electronic expansion valve. Then, a real-time optimization or optimal control framework adjusts the intermediate pressure setpoint to minimize the total power consumption, with the compressor capacity used to satisfy the load demand via an inner-loop controller. In particular, the extremum seeking controller is applied as a model-free real-time optimization strategy for such purpose. To evaluate the proposed control strategy, a Modelica based dynamic simulation model is developed for such system. Simulations under fixed, staircase and realistic ambient temperature profiles validate the effectiveness of the proposed control strategy. Besides real-time optimization of system efficiency, a major merit of this strategy is to retain the use of saturated vapor for the injection line, instead of levitating the superheat. The inherent efficiency of the flash tank cycle is thus maintained without additional devices, and the liquid level can be maintained in a proper range.
Direct inference and the sleeping beauty problem

This article is an attempt to use the insights of objective probability theory to solve the Sleeping Beauty problem. The approach is to develop a partial theory of direct inference and then apply that partial theory to the problem. One of the crucial components of the partial theory is the thesis that expected indefinite probabilities provide a reliable basis for direct inference. The article relies heavily on recent work by Paul D. Thorn to defend that thesis. The article’s primary conclusion is that Beauty (the perfectly rational agent of the Sleeping Beauty story) can by way of a justifiable direct inference from a statement of expected indefinite probability reach the conclusion that the epistemic probability that the relevant coin toss lands heads is 1/3. The article also provides an account of why the self-locating information that Beauty acquires on Monday is evidentially relevant to the question of whether the coin toss lands heads or tails.
Optimal-Frequency Critical Soft Switching Method of Synchronous DC/DC Converter Based on Model Predictive Control

To improve power density and efficiency, a critical soft switching principle with optimal-frequency model predictive control method is proposed in this paper for DC/DC power converter. Firstly, this paper analyzes the boundary constraints of critical soft switching that are derived with the key parameters of the interlock time and threshold current for typical SiC and GaN devices. Then, according to the derived critical soft switching constraints, two optimal-frequency control methods are proposed based on model predictive control (MPC) to eliminate the turn-on losses especially during the transient period. Compared to the traditional PI controller, the efficiency can be further improved during the reference variation period, because of the fast response of MPC. Finally, the test results verify the theoretical analysis.
Four-dimensional analysis of human brain tumor spheroid invasion into fetal rat brain aggregates using confocal scanning laser microscopy

The advent of confocal microscopy and fluorescence probes has made possible the routine visualization of the complex three-dimensional structures of thick fixed or live specimens. Four-dimensional (4-D) imaging of biological specimens (three-dimensional image reconstruction of the same living sample at different time points), remains a seldom-used application of confocal microscopy. In the present study we used 4-D imaging techniques to quantitate the invasion of human brain tumor spheroids into fetal rat brain aggregates (FRBAs), using the vital fluorescence membrane dyes, 3,3′-Dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) as visualization probes. We found invasion patterns similar to the in vivo behavior of these tumors in the brain. Glioblastoma spheroids showed diffuse and circumscribed infiltration accompanied by cystic degeneration or necrosis of FRBAs. Spheroids from cerebral metastasis, however, showed a sharp delimitation of the invasive margin, and did not penetrate the FRBA beyond a depth of 55 µm. Measured rates of glioblastoma invasion varied with the tumor specimens examined. The slopes of the mid-portions of plots of % infiltration vs. time (hours) for four glioblastoma cell lines were 1.7 ± 0.21 (SD), 0.67 ± 0.11, 1.4 ± 0.22 and 1.3 ± 0.18. We conclude that confocal microscopy with vital fluorescence probes is a practical method that allows for close monitoring and quantitation of the process of invasion in live tissue preparations, and may be used for assessing the in vitro effects of various tumor treatments.
Fitness after Fifty

(1976). Fitness after Fifty. Journal of Physical Education and Recreation: Vol. 47, No. 4, pp. 47-51.
A New Look at the Hartogs Extension Phenomenon

We give a new proof of the classical Hartogs extension phenomenon in several complex variables. This proof works equally well for meromorphic functions. We further related the Hartogs extension phenomenon to the $$\overline{\partial }$$ problem in a new way. Finally, we interpret the Hartogs extension phenomenon in the lanuage of automorphism group accumulation points.
Rb3InCl6: A Monoclinic Double Perovskite Derivative with Bright Sb3+-Activated Photoluminescence.

Here, we present the synthesis and crystal structure of Rb3InCl6 prepared from air stable reagents via a two-step process that proceeds through the intermediate Rb2InCl5·H2O. Rb3InCl6 crystallizes ...
The role of hyoid muscles in biotremor production in Chamaeleo calyptratus.

ABSTRACT The production of biotremors has been described in veiled chameleons (Chamaeleo calyptratus), but the mechanism by which they are produced is unknown. We gathered muscle activation data via electromyography (EMG), with simultaneous recordings of biotremors using an accelerometer, to test for the role of hyoid muscles in biotremor production. We recorded a mean biotremor frequency of 150.87 Hz for females and 136.01 Hz for males. The durations of activity and the latencies to onset and offset for the M. sternohyoideus profundus (SP), M. sternohyoideus superficialis (SS), Mm. mandibulohyoideus (MH) and M. levator scapulae (LS) were all significantly correlated with biotremor durations and biotremor onset and offset, respectively. Linear mixed-effect regression model comparisons of biotremor duration indicated that models containing either the MH and/or the SP and LS account for the most variation in biotremor duration. Twitch times for the SP (100 ms) and the SS (132 ms) at field active body temperature, however, were individually too slow to produce the biotremors at the observed frequency without alteration after production by other anatomical structures. These results implicate the SP, SS, MH and LS in the production of biotremors, but the exact mechanism of production requires further study.
Haptics with Input: Back-EMF in Linear Resonant Actuators to Enable Touch, Pressure and Environmental Awareness

Today's wearable and mobile devices typically use separate hardware components for sensing and actuation. In this work, we introduce new opportunities for the Linear Resonant Actuator (LRA), which is ubiquitous in such devices due to its capability for providing rich haptic feedback. By leveraging strategies to enable active and passive sensing capabilities with LRAs, we demonstrate their benefits and potential as self-contained I/O devices. Specifically, we use the back-EMF voltage to classify if the LRA is tapped, touched, as well as how much pressure is being applied. The back-EMF sensing is already integrated into many motor and LRA drivers. We developed a passive low-power tap sensing method that uses just 37.7 uA. Furthermore, we developed active touch and pressure sensing, which is low-power, quiet (2 dB), and minimizes vibration. The sensing method works with many types of LRAs. We show applications, such as pressure-sensing side-buttons on a mobile phone. We have also implemented our technique directly on an existing mobile phone's LRA to detect if the phone is handheld or placed on a soft or hard surface. Finally, we show that this method can be used for haptic devices to determine if the LRA makes good contact with the skin. Our approach can add rich sensing capabilities to the ubiquitous LRA actuators without requiring additional sensors or hardware.
Caring for the Uninsured

With a large uninsured population, the United States continues to depend heavily on health care safety net providers for ensuring access to essential services, in particular, vaccination services. The Consolidated Appropriations Act of 2021 provides modest funding to support health care for the uninsured, but the American Rescue Plan offered by the Biden administration promises both dramatic expansion as well as an approach to implementation that promotes equitable access to care. This paper was prepared as part of the COVID-19 Policy Playbook: Legal Recommendations for a Safer, More Equitable Future, a comprehensive report published by Public Health Law Watch in partnership with the de Beaumont Foundation and the American Public Health Association.
Cancer disparities among patients with advanced metastatic breast cancer.

e18566Background: We previously elucidated sociodemographic factors associated with risk-of-death, in a subgroup of patients with Stage IV human epidermal growth factor 2 (HER)+ breast cancer. To f...
Graph skeletonization of high-dimensional point cloud data via topological method

Geometric graphs form an important family of hidden structures behind data. In this paper, we develop an efficient and robust algorithm to infer a graph skeleton behind a point cloud data (PCD)embedded in high dimensional space. Previously, there has been much work to recover a hidden graph from a low-dimensional density field, or from a relatively clean high-dimensional PCD (in the sense that the input points are within a small bounded distance to a true hidden graph). Our proposed approach builds upon the recent line of work on using a persistence-guided discrete Morse (DM) theory based approach to reconstruct a geometric graph from a density field defined over a triangulation of low-dimensional Euclidean domain. In particular, we first give a very simple generalization of this DM-based algorithm from a density-function perspective to a general filtration perspective. On the theoretical front, we show that the output of the generalized algorithm contains a so-called lexicographic-optimal persistent cycle basis w.r.t the input filtration, justifying that the output is indeed meaningful. On the algorithmic front, this generalization allows us to use the idea of sparsified weighted Rips filtration (developed by Buchet etal) to develop a new graph reconstruction algorithm for noisy point cloud data (PCD) (which do not need to be embedded). The new algorithm is robust to background noise and non-uniform distribution of input points. We provide various experimental results to show the efficiency and effectiveness of our new graph reconstruction algorithm for PCDs.
HMO/PPO Directory. Gottlieb, Richard, editor.

With the national spotlight focused on the provision of health care in the United States, the directory provides useful insurance statistics and directory listings of HMO/PPO (Health Maintenance Or...
PET/CT Imaging of Inflammation and Calcification

The biological processes within atherosclerotic plaques are known to be critically important to the progression and rupture of plaques. Among them inflammation is thought to be a key participant in all stages of atherosclerosis, from plaque initiation to progression and atherothrombosis. Accordingly, imaging of inflammation may provide important insights into the atherosclerotic milieu.
Holtzman J: Uncertain Tastes: Memory, Ambivalence, and the Politics of Eating in Samburu, Northern Kenya

This book unexpectedly frustrated me and at the same time delighted me which is not unlike what the author, Jon Holtzman, wants to convey about Samburu food, that is, its ambivalence and contradictions. The book is a compendium of several years of research in Samburu, and some of the materials have been taken from journal articles, reassembled into a book. Those interested in understanding more about pastoral diet intake and nutritional status will be disappointed however. This book is not about that, though there is a short mention to it in Chapters 2 and 9 (without references). Rather, this book is about the Samburu way of viewing their world as seen through food. We see broad cultural patterns and changes in those patterns through the mundane daily experience of food and eating. For those people who are food insecure, food is perhaps an excellent metaphor for life as Samburu becomes socialized into their culture of hunger. The book is thus about the cultural significance surrounding food and how people of various ages and gender socially manipulate its production (livestock and the superiority of a diet of milk, meat, and blood), its processing (raw versus cooked), its consumption (who consumes what types of food), and its changes. Food possesses values, practices, and social relations and reveals cultural changes, and Holtzman nicely navigates this realm of understanding.
A Total Quality Management Approach To Assurance Of Learning In The Accounting Classroom: An Empirical Study

The research presented in this paper seeks to discern which combination of pedagogical tools most positively impact student learning of the introductory Accounting curriculum in the Principles of Accounting courses in a 4-year U.S. public college. This research topic is relevant because it helps address a quandary many instructors experience: how to teach quantifiable courses in a way that resonates with and reaches undergraduate business students. The significance is underscored by concerns that U.S.-educated students lack quantitative ability needed in the 21 st century workplace, and is heightened all the more by uncertainties in the current economic climate that would seem to make quantitative competencies all the more vital. Toward that end, student perceptions of course delivery methods were analyzed at the conclusion of the first of a two-course sequenced introductory Accounting course. The results were used to redesign the second half of the course, after which measured perceptions were compared with actual outcomes. Results and proscriptions for advancing Principles of Accounting course pedagogy are presented.
Compact fuzzy rule base generation methods for computer vision

Rule-based approaches are commonly used in vision systems to solve complex problems. The rules are usually elaborated by experts. The authors propose a method to generate such rules automatically from training data. The proposed approach achieves this in four stages: estimation of class membership functions, elimination of redundant features, estimation of the membership functions of linguistic labels that best describe the nonredundant features, and generation of rules. Redundancy detection and rule base generation stages are achieved by training appropriate fuzzy connective-based aggregation networks. >
Armstrong on thespatio-temporality of universals 1

Provocatively, David Armstrong's properties are supposed to be both universals and spatio-temporal. What does this amount to? I consider four of Armstrong's views, in order of ascending plausibility: (1) the exemplification account, on which universals are exemplified by space-times; (2) the location account, on which universals are located at space-times; (3) the first constituent account, on which spatio-temporal relations are elements of what I call the form of time; and, the true view, (4) the second constituent account, on which universals are spatio-temporal only ‘derivatively’ by being constituents of states of affairs which are so ‘primarily’. The first two accounts are rejected because they entail that space-times must be substantival. In making plausible the second constituent account, I distinguish primitive and derivative spatio-temporality. Something is primitively spatio-temporal when it is at a space-time, or stands in spatio-temporal relations. Something is derivatively spatio-temporal whe...
On the incorporation of thymidine in the cytoplasm of Amoeba proteus

Resume L'incorporation de la thymidine tritiee par le cytoplasme a ete etudiee dans plusieurs souches differentes d' Amoeba proteus . La majeure partie sinon la totalite du materiel radioactif non soluble dans les acides est localisee dans une molecule similaire a celle de l'ADN, comme l'indiquent les resultats de l'incubation de preparations fixees, en presence de ribonuclease ou de desoxyribonuclease. L'incorporation dans le cytoplasme a lieu aussi bien en presence qu'en absence du noyau et est relativement independante de la nutrition prealable des cellules. L'aspect de l'image autoradiographique des cellules anuclees ainsi que des cellules intactes soumises a un jeune prolonge suggere que la materiel sensible a la DNase est associe a un constituant cytoplasmique particulaire dont la distribution se modifie au cours du jeune et en l'absence du noyau. Rien ne permet de preciser le role physiologique eventuel de ce materiel qui ne peut etre caracterise jusqu'a present que par sa sensibilite a l'action de la DNase et son insensibilite a l'action de la RNase. Des etudes preliminaires au microscope electronique ne permettent pas d'attribuer l'incorporation d'isotopes a la presence de corps etrangers dans le cytoplasme amibien. A titre d'hypothese, on peut imaginer que dans les conditions de ces experiences, des desoxyribonucleotides s'accumulent et se polymerisent dans le cytoplasme alors que normalement ils le feraient dans le noyau.
Molecular characterization of the receptor-ligand complex for parathyroid hormone.

Molecular models for the interaction of parathyroid hormone (PTH) with its G-protein-coupled receptors (PTH1 and PTH2) have been developed. The proposed ligand−receptor complex is based on experimental data from spectroscopic investigations of the hormone and receptor fragments as well as theoretical structure predictions based on homology analysis with proteins of known structure. From the insight afforded by the models, biochemical and pharmacological observations can be correlated with specific molecular or atomic interactions. The ligand selectivity of PTH2, specifically the lack of binding of His5-containing analogues, can be ascribed to unfavorable steric interactions (the binding pocket is markedly smaller in PTH2 than PTH1) as well as repulsive Coulombic forces between amino acids of like-charge (a positively charged H384 is located in the binding pocket in PTH2). The model of PTH1 suggests that the constitutive activity observed from the incorporation of a positively charged amino acid at positio...
Photosynthetically active radiation use efficiency of Dactylis glomerata and Schedonorus phoenix along a hardwood tree-induced light gradient

Photosynthetically active radiation use efficiency (PARUE) of orchardgrass (Dactylis glomerata L.) and tall fescue (Schedonorus phoenix (Scop.) Holub) was determined. Leaf mass was harvested for canopies at different shade levels when each reached 20 cm height with 5 cm residue for regrowth to simulate grazing. Total incident PAR at each site was summed for the growth period (S-PAR). Values for PARUE were calculated from dried leaf mass divided by S-PAR. The more highly shaded plants reached 20 cm at lower S-PAR. While overall leaf mass decreased linearly with shade induced decreases in S-PAR, PARUE increased exponentially. The coefficients for the equations representing this exponential increase vary for forage species and may represent a useful index for characterizing forage response to silvopastoral systems.
Effects of chemical treatment on immunochemical properties of human growth hormone and sheep interstitial cell-stimulating hormone.

Abstract Complement fixation has been compared with quantitative precipitin tests for the investigation of the immunochemical activity of HGH and S-ICSH as well as of chemical derivatives of these hormones. Contents of HGH and S-ICSH in the pituitary gland have been determined by these two immnnochemical techniques. Modification of HGH by oxidation with performic acid or partial hydrolysis with proteolytic enzymes resulted in decreased immunochemical activity. S-ICSH oxidized with performic acid did not combine with antibody to the native S-ICSH, but S-ICSH oxidized with periodate manifested a complete reaction with the antibody.
Electrophilic PPARγ ligands inhibit corneal fibroblast to myofibroblast differentiation in vitro: a potentially novel therapy for corneal scarring.

Abstract A critical component of corneal scarring is the TGFβ-induced differentiation of corneal keratocytes into myofibroblasts. Inhibitors of this differentiation are potentially therapeutic for corneal scarring. In this study, we tested the relative effectiveness and mechanisms of action of two electrophilic peroxisome proliferator-activated receptor gamma (PPARγ) ligands: cyano-3,12-dioxolean-1,9-dien-28-oic acid-methyl ester (CDDO-Me) and 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) for inhibiting TGFβ-induced myofibroblast differentiation in vitro. TGFβ was used to induce myofibroblast differentiation in cultured, primary human corneal fibroblasts. CDDO-Me and 15d-PGJ2 were added to cultures to test their ability to inhibit this process. Myofibroblast differentiation was assessed by measuring the expression of myofibroblast-specific proteins (αSMA, collagen I, and fibronectin) and mRNA (αSMA and collagen III). The role of PPARγ in the inhibition of myofibroblast differentiation by these agents was tested in genetically and pharmacologically manipulated cells. Finally, we assayed the importance of electrophilicity in the actions of these agents on TGFβ-induced αSMA expression via Western blotting and immunofluorescence. Both electrophilic PPARγ ligands (CDDO-Me and 15d-PGJ2) potently inhibited TGFβ-induced myofibroblast differentiation, but PPARγ was only partially required for inhibition of myofibroblast differentiation by either agent. Electrophilic PPARγ ligands were able to inhibit myofibroblast differentiation more potently than non-electrophilic PPARγ ligands, suggesting an important role of electrophilicity in this process. CDDO-Me and 15d-PGJ2 are strong inhibitors of TGFβ-induced corneal fibroblast to myofibroblast differentiation in vitro, suggesting this class of agents as potential novel therapies for corneal scarring warranting further study in pre-clinical animal models.
CD-SEM calibration with TEM to reduce CD measurement error

In this paper, we will describe why the calibration process between CD-SEM and transmission electron microscopy (TEM) was performed. TEM is considered to be a unique solution such that we could obtain CD and sidewall angle accurately. TEM has the merit of having good resolution, but the measurement is performed over small segments of device features. The CD measurement error related to line edge roughness (LER) was also investigated in order to avoid the degradation in the accuracy of TEM measurement of CD. Many efforts were performed to reduce the uncertainty in TEM measurement of CD. The amount of the uncertainty related to TEM CD measurement was approximately 5 nm. We could obtain the linear relationship between CD-SEM and TEM measurements of CD Of logic gate lines ranging form 0.12 micrometers to 0.20 micrometers . The average CD measured using TEM was 15 nm lower than the CD measured with CD-SEM at poly silicon etched profile which had the sidewall angle of 86 degrees. Such difference is unacceptable in the CD measurement. The CD measurement error could be compensated with the modification of the measurement algorithms. The reproducibility of CD measurement for various algorithms was also investigated. It was shown that TEM measurement of CD could be applicable for the calibration with CD-SEM measurement to control various processes with different sidewall angles.
Form finds function.

Assigning function to uncharacterized enzymes discovered through genome projects has provided a great challenge to the fields of informatics, enzymology and structural biology. Docking potential ligands into flexible models of protein structures and docking potential high-energy intermediates, rather than substrates, into known structures are two new computational approaches that have provided a much-needed boost to the field.
Cytotoxicity and Selectivity in Skin Cancer by SapC-DOPS Nanovesicles

Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4% by volume tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.
Structural Consequences of Divalent Metal Binding by the Adenylyl Cyclase Toxin of Bordetella pertussis

Abstract Adenylyl cyclase toxin of Bordetella pertussis has been shown by several investigators to require Ca 2+ for its actions on target cells, but little is known about the nature and specificity of divalent metal binding to this novel toxin. Calcium is the preferred divalent metal since toxic actions are markedly reduced in the presence of divalent species other than calcium. Mn 2+ EPR was used to quantitate and characterize divalent metal binding and revealed that the toxin contains approximately 40 divalent metal sites, consisting of at least one class of high-affinity sites that bind Mn 2+ with a K D of 0.05 to 0.35 μM and one or more classes of lower affinity sites. Water proton relaxation data indicate that approximately 30 of these sites are completely inaccessible to bulk solvent. Our observations, together with the sequence homology between adenylyl cyclase toxin and the alkaline protease of Pseudomonas aeruginosa, indicate that the formation of five β-sheet helices within the repeat domain of the toxin upon binding Ca 2+ is required for cell intoxication.
Optically Induced Analytical Error in Glow Discharge Optical Emission Spectrometry

It is shown that the common practice of imaging the plasma directly onto the spectrometer entrance slit in analytical glow discharge optical emission spectrometry (GDOES) may induce analytical error when used with samples which are chemically heterogeneous. An alternative method for transferring the source emission to the entrance slit is demonstrated to eliminate the potential error, suggesting its routine use in analytical GDOES.
Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-β and TNF-α in 3D culture

Chemokines act as important secondary inflammatory mediators which are released by cells in response to a variety of stimuli. Chemokines bind to cell surface receptors and act as second-order cytokines with specialized functions in inflammation. The role of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) (also called CCL5 (chemokine (C-C motif) ligand 5)) has received little attention to date in disc tissue. Microarray analyses of lumbar disc annulus tissue revealed that RANTES expression was significantly upregulated in more degenerated Thompson grades IV and V discs compared to expression levels in grades I, II and III discs (p=0.032). Immunolocalization confirmed the presence of RANTES in the annulus and nucleus of the disc, and localized the RANTES receptors CCR1, CCR3 and CCR5 to cells in the disc. In vitro studies with IL-1-β and TNF-α challenges, both proinflammatory cytokines resulted in elevated levels of RANTES in conditioned media (p<0.01); TNF-α exposure, however, produced significantly greater levels than did IL-1alpha (p<0.0001), suggesting a differential regulation by TNF-α. Local production of RANTES in vivo by annulus and nucleus cells, and in vitro induction of RANTES by proinflammatory cytokines suggest that disc cells are primary effector cells as well as target cells, and thus can mediate physiological immune-related processes during disc degeneration by both autocrine and paracrine signaling.
High-throughput sequence determination of cyclic peptide library members by partial Edman degradation/mass spectrometry.

Cyclic peptides provide attractive lead compounds for drug discovery and excellent molecular probes in biomedical research. Large combinatorial libraries of cyclic peptides can now be routinely synthesized by the split-and-pool method and screened against biological targets. However, post-screening sequence determination of hit peptides has been problematic. In this report, a high-throughput method for the sequence determination of cyclic peptide library members has been developed. TentaGel microbeads (90 μm) were spatially segregated into outer and inner layers; cyclic peptides were displayed on the bead surface, whereas the inner core of each bead contained the corresponding linear peptide as the encoding sequence. After screening of the cyclic peptide library against a macromolecular target, the identity of hit peptides was determined by sequencing the linear encoding peptides inside the bead using a partial Edman degradation/mass spectrometry method. On-bead screening of an octapeptide library (theore...
Acoustic phonon instabilities and structural phase transitions

Structural phase transitions are considered in which the order parameter is a homogeneous deformation of the crystal. The fluctuations at these transitions are the acoustic modes, and it is shown that an effective Hamiltonian may be constructed describing the homogeneous deformations and their fluctuations. There are three cases which result, those in which there are no fluctuations with wavelengths less than the crystal dimensions, those in which the acoustic modes have strongly temperature-dependent velocities for wave vectors on particular lines of reciprocal space, and those for which the velocities are temperature dependent for wave vectors within planes in reciprocal space. In many cases, the transitions are expected to be first order because of the presence of cubic invariants in the effective Hamiltonian. In those which may be continuous, the behavior is shown by use of renormalization-group theory to be that of classical Landau theory, with the possibility of logarithmic corrections in one particular instance. Unfortunately, we are unaware of any examples of this case, but in the other cases, the results are in accord with experimental results.
Valuing natural heritage: park visitors' values related to World Heritage sites in the USA

The World Heritage Convention rests on the assumption that World Heritage sites hold value for people globally and that these values promote protection of sites. This study focuses on natural sites, selected for environmental significance. All World Heritage sites are also supposed to be of ‘outstanding universal value’, with a variety of values attributed to them in World Heritage and other documents, including aesthetic, cultural and spiritual values. This study investigates via a survey whether such values are recognized by visitors to natural sites in the USA, and how useful they are for generating support for sites. Most visitors appreciated sites primarily for their environmental importance; a minority recognized other values listed in World Heritage documents, even though most visitors had little understanding of the Convention itself. In general, recognition of World Heritage status did not translate into greater protection or support for sites beyond what they already receive as national parks, e...
The migration of a compound drop due to thermocapillarity

The quasistatic thermocapillary motion of a compound drop in an unbounded fluid possessing a uniform temperature gradient is analyzed. For completeness, gravitational effects are included in the treatment. The general model is formulated, and the equations for the concentric case are solved using spherical polar coordinates, while the eccentric case is handled using bispherical coordinates. Results are given for the velocity of the drop as well as that of the droplet with respect to the drop, along with useful approximations. Illustrative results are presented graphically for the thermocapillary migration of a compound drop in the special case when the droplet is a gas bubble. In addition to the velocities of the drop and the bubble, representative isotherms and streamlines also are presented which display interesting qualitative features.
Vacuum metallurgy in the United States

Abstract The author discusses the various forms of vacuum processing existent in the metallurgical industry today. Detailed attention is given to all aspects of vacuum induction melting, such as furnace design, pumping plant, refractories employed, typical reactions leading to the purification of the processed material and properties of the product. Similar information is given on the consumable electrode melting method. Present-day U.S. plant capacity for the former process is estimated at an annual throughput of 5,000 tons and for the latter process at 12,000 tons. The article concludes with a brief mention of vacuum sintering and the Bochumer Verein process.
Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3β

The stabilization of endothelial cell (EC) barrier function within newly formed capillaries is a critical feature of angiogenesis. We examined human lung EC barrier regulation elicited by hepatocyte growth factor (HGF), a recognized angiogenic factor and EC chemoattractant. HGF rapidly and dose-dependently elevated transendothelial electrical resistance (TER) of EC monolayers (>50% increase at 100 ng/ml), with immunofluorescence microscopic evidence of both cytoplasmic actin stress fiber dissolution and strong augmentation of the cortical actin ring. HGF rapidly stimulated phosphatidylinositol 3′-kinase, ERK, p38 mitogen-activated protein kinase, and protein kinase C activities. Pharmacological inhibitor studies demonstrated each pathway to be intimately involved in HGF-induced increases in TER, cortical actin thickening, and phosphorylation of the Ser/Thr glycogen synthase kinase-3β (GSK-3β), a potential target for the HGF barrier-promoting response. GSK-3β phosphorylation was strongly correlated with re...
Variation in soil phosphorus, sulfur, and iron pools among south Florida wetlands

To determine relationships between soil nutrient status and known gradients in primary production, we collected and analyzed soils from 17 LTER sampling sites along two transects through south Florida wetland ecosystems. Through upstream freshwater marsh, a middle reach including the oligohaline marsh/mangrove ecotone, and downstream estuarine habitats, we observed systematic variation in soil bulk density, organic content, and pools of phosphorus (P), inorganic sulfur, and extractable iron. Consistent with observed differences in wetland productivity known to be limited by P availability, total P averaged ~200 μg g dw−1 in soils from the eastern Taylor Slough/Panhandle and was on average three times higher in soils from the western Shark River Slough. Along both transects, the largest pool of phosphorus was the inorganic, carbonate-bound fraction, comprising 35–44% of total P. Greater than 90% of the total inorganic sulfur pool in these south Florida wetland soils was extracted as pyrite. Freshwater marsh sites typically were lower in pyrite sulfur (0.2–0.8 mg g dw−1) relative to marsh/mangrove ecotone and downstream estuary sites (0.5–2.9 mg g dw−1). Extractable iron in freshwater marsh soils was significantly higher from the Taylor Slough/Panhandle transect (3.2 mg g dw−1) relative to the western Shark River Slough transect (1.1 mg g dw−1), suggesting spatial variation in sources and/or depositional environments for iron. Further, these soil characteristics represent the collective, integrated signal of ecosystem structure, so any long-term changes in factors like water flow or water quality may be reflected in changes in bulk soil properties. Since the objective of current Everglades restoration initiatives is the enhancement and re-distribution of freshwater flows through the south Florida landscape, the antecedent soil conditions reported here provide a baseline against which future, post-restoration measurements can be compared.