cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanism Beyond Markov Models: History Information is Needed for Unbiased Pathway Reconstruction of Protein Folding

Understanding the mechanisms (pathways through configuration space) of biomolecular processes such as protein folding is a major challenge for molecular dynamics (MD) simulations. Markov state models (MSMs), which discretize simulation data by projecting onto a relatively small number of states, have become increasingly popular compact representations of the overwhelming complexity of protein configuration space and the vast quantity of trajectory data. Building on previous work showing the potential for significant bias in MSM estimates of folding and unfolding rates [Suarez et al., JCTC 2016, 12 (8), 3473], here we study MSM descriptions of (un)folding mechanisms. By comparing to independent long-time MD simulations, as well as non-Markov (NM) analyses which include history information, we find that MSMs tend to infer overly broad distributions of more equally probable pathways. By contrast, NM analyses using MSM states agree well with the narrower distributions observed in the long-time MD data. The MSMs appear to be overly permissive because they exclude the history information accounting for previous discrete states occurring in trajectories, which is necessary for an unbiased mapping of the underlying dynamics in the full configuration space to the substantially reduced discrete state space.
History, Function, and Evolutionary Biology

Science concerns itself with description of the nature and behavior of the components of the material universe. Biology in general has had occasional trouble in the past being accepted as a full-fledged science—whether because living systems were supposed to differ in some fundamental way from nonliving, physical systems [e.g., “vitalism” (Simpson, 1949, Chapter 10)] or because much of its subject matter has been seen to lie outside the canons and strictures of experimental procedure. The spectacular achievements of molecular biology, the latest phase of a century-long effort to bring biology into the laboratory, have long since removed any rational doubts, on either score, of the “scientific” status of that general area of biology that Mayr (e.g., Mayr, 1982) has called “functional” and what Simpson (e.g., Simpson, 1963) simply termed “nonhistorical.”
Astrocytes to the rescue! Glia limitans astrocytic endfeet control CNS inflammation

The blood-brain barrier (BBB) and the glia limitans serve to prevent the migration of cells and other large molecules from the blood into the CNS. Neuroinflammatory diseases are characterized by disruption of the BBB and increased leukocyte infiltration into the CNS. In this issue of the JCI, Horng and colleagues demonstrate that astrocytes of the glia limitans induce tight junction formation in response to inflammatory cues, thereby tightening the border to limit the number of activated T cells infiltrating the CNS. Moreover, preventing the formation of this inducible barrier in mice increased disease severity in models of neuroinflammation. Together, the results of this study indicate that the inducible barrier of the glia limitans should be further explored as a therapeutic target.
With great power comes great responsibility: Superhero primes and expansive poses influence prosocial behavior after a motion-controlled game task

Abstract This study examined how priming social concepts and manipulating physical poses when playing a motion-sensing flight game affected ensuing prosocial behaviors. After the experimenter “accidentally” dropped pencils, participants primed with superheroes were faster at helping compared with a control condition. Participants who controlled the game while standing and holding expansive poses helped more compared with those in the expansive pose/sitting condition. Sitting participants primed with supervillains showed decreased prosocial intention. The study expanded on previous research and addressed possible confounds by providing evidence of how social primes and physical poses affect prosocial behavior after a virtual flight task. The paper discusses theoretical implications and future directions for research interested in cognitive processes and physical mechanics in virtual experiences.
Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy?

Background and purpose Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET). Materials and methods This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location. Results Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529). Conclusion AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.
New court ruling may alter the legal landscape for gene patents.

Does permitting the patenting of genes help or hurt scientific innovation? In the traditional pharmaceutical industry, patents are widely seen as the economic cornerstone for drug development. Without them, companies argue, nothing would protect the value of their huge investments, and the incentive for progress would evaporate. Who would spend hundreds of billions of dollars to develop a product that anyone else can copy and profit from? Patent protection in the field of genetics, however, raises a number of new questions. Whereas traditional drugs are synthesized in laboratories, genes are products of nature. Genes are not created by scientists; rather, they are discovered. Do patents promote a race to discovery or a race to lock up access to natural substances that exist independently of human intervention? The patenting of genes has tremendous economic and clinical implications. Genomics likely represents the future of much of medicine. Patent protection for genes, or the lack of it, will determine the financial structure under which this new branch of biomedical science evolves. It will shape the fortunes of companies seeking to develop products, of researchers in academia and industry, and of investors. Of even greater significance, it may determine the medical benefits that patients ultimately receive. This past March, a federal court in New York issued a ruling that could dramatically change the legal landscape for gene patents. In the case of Association for Molecular Technology v. U.S. Patent and Trademark Office, Judge Robert Sweet struck down several patents for genes associated with susceptibility to breast and ovarian cancer.1 He found that they protect information, not inventions, and therefore fail to meet the criteria for patent validity. The ruling would negate most existing patents on genes and prevent the approval of future ones. The suit was brought by the American Civil Liberties Union (ACLU) along with several researchers, scientific organizations, and women who carry the genes. It targeted the patent-holders as additional defendants. These include a small biotechnology company, Myriad Genetics, Inc., and the University of Utah. The proceeding is commonly referred to as the Myriad Genetics case. The decision is certain to be appealed, and there is a good chance it will go all the way to the Supreme Court. The case will be closely watched as it proceeds. A ruling by the high court could establish the first clear legal guidelines on patents related to human genes. In the October 2009 issue of P&T, this column described the Myriad Genetics case after it had been filed.2 The outcome of the case, which is considered here, was a surprise to many. It gives new life to the movement to invalidate all patents on human genes.
Distribution Voltage Control: Current Status and Future Trends

Driven by smart distribution technologies, the widespread use of distributed energy resources (DERs), and the injection of new loads, such as electric vehicles, electric distribution systems are evolving from passive to active. The integration of DERs (including renewable distributed generation) with their uncontrollable generation variability, imposes various grid stability challenges on distribution system operation. The primary problem is significant voltage rise in the distribution feeder that forces existing voltage control devices such as onload tap-changers and line voltage regulators to operate more frequently. The consequence is the deterioration of the operating life of the voltage control mechanism. As such, a distributed active network management has to be fulfilled by taking advantage of the emerging techniques of control, monitoring, protection, and communication to assist distribution network operators in an optimal manner. This paper presents a short review of recent advancements and identifies emerging technologies and future development trends to support active management of distribution networks.
Carbon Dioxide Absorption Modeling for Off-Gas Treatment in the Nuclear Fuel Cycle

The absorption of carbon dioxide is an important process in many practical applications such as reduction of greenhouse gases, separation and purification processes in the chemical and petroleum industries, and capture of radioactive isotopes in the nuclear fuel cycle The goal of this research is to develop a dynamic model to simulate CO2 absorption by using different alkanolamines as absorption solvents. The model is based upon transient mass and energy balances for the chemical species commonly present in CO2 gas-liquid absorption. A computer code has been written to implement the proposed model. Simulation results are discussed. The reported model simulates well the response to dynamic changes in input conditions. The proposed model can be used to optimize and control the separation of carbon-14 in the form of CO2 in the nuclear industry.
How does public participation affect perceptions of public–private partnerships? A citizens’ view on push, pull, and network approaches in PPPs

In this study, we analysed US-based public opinion data to determine the influence of particular modes of participation on citizen perceptions of public–private partnerships (PPP). Our summary find...
Inductive and electrostatic effects on cobalt porphyrins for heterogeneous electrocatalytic carbon dioxide reduction

Electrochemical carbon dioxide reduction enables conversion of carbon dioxide into fuels and chemicals with renewable energy input. Cobalt-based molecular complexes have exhibited high selectivity, activity, and stability for transforming carbon dioxide into carbon monoxide. Through evaluating immobilized cobalt porphyrins functionalized with various peripheral substituents, we demonstrated that their activity is affected not only by the electronegativity of the substituents, but importantly, also by the charge of the substituents. The performance of immobilized cobalt porphyrins can be improved by introducing electron-donating and positively charged functional groups. Through kinetic studies, we were able to understand the mechanism by which electron-donating groups enhance the observed rates of carbon dioxide reduction and how cationic functionality may contribute towards electrostatic stabilization of the intermediate formed in the rate-determining step. Our methodology provides a robust and experimentally-verified method of computationally predicting the electronic effect of peripheral substitution and hence the catalytic activity of substituted porphyrins.
Fatigue Tests on Steel–Concrete Composite Beams Subjected to Sagging Moments

AbstractCurrent shear stud fatigue capacity recommended for design of shear connectors is based on experimental data from push-out tests, and there is a need to experimentally evaluate the fatigue ...
Mast cells as mediators of fibrosis and effector cell recruitment in dermal chronic graft-versus-host disease.

7050Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for patients with malignant neoplasms or inborn defects of hematopoiesis. Benefits ...
Quantifying the benefits from a care coordination program for tracheostomy placement in neonates.

Abstract Objective Value-based care models are becoming instrumental in structuring clinical care delivery in our healthcare climate. Our objective was to determine the value associated with implementation of a Family-Centered Care Coordination (FCCC) program for neonates undergoing tracheostomy. Methods A multi-disciplinary FCCC program was implemented at the Massachusetts Eye and Ear Infirmary and MassGeneral Hospital for Children in January 2013. This program is designed to ensure a safe transition out of the hospital for children undergoing tracheostomy, reduce re-admission rates, and increase caregiver quality of life (QOL). Study participants included neonates undergoing tracheostomy in 2012 and 2015. This retrospective cohort study examined length of stay (LOS), utilized time-driven activity-based costing to estimate the cost of care, assessed caregiver QOL with 1-month Pediatric Tracheostomy Health Status Instrument (PTHSI) scores, and assessed complications with 6-month Medical Complications Associated with Pediatric Tracheostomy (MCAT) scores. Results Following implementation of the FCCC program, average LOS decreased from 30.5 days (range 17–39) to 16.6 days (range 9–23). The largest process improvement (cost reduction of 61%) occurred in the discharge-planning phase. The overall cost per care cycle was reduced by 36%. A large clinically meaningful benefit was demonstrated for PTHSI (effect size 0.80) as well as MCAT scores (effect size 9.35). Conclusions We demonstrated the higher outcomes, including reductions in caregiver burden and complication rates, and the lower costs associated with implementation of the FCCC program for neonates undergoing tracheostomy.
Space launch vehicle transient particle redistribution modeling and implications for optically sensitive payloads

The performance of contamination sensitive components—such as optical components—can be degraded by particulate matter depositing on the surfaces. Particles can accumulate during manufacturing, handling and operation. For a space-based system, particles can shed from the fairing and redistribute onto sensitive surfaces during launch. An engineering modeling approach has been developed for modeling particle migration during launch. The approach involves particle detachment from the fairing, particle transport through the venting atmosphere inside the fairing, and attachment to the receiving surface. Particle size and amounts on the fairing surface can be modeled using distributions from standards, such as IEST-STDCC1246E, as well as from empirical data obtained from tape lifts. Surface interactions are modeled using theoretical as well as empirical data. Commercial computational fluid dynamics codes are used to calculate the gas flow in the fairing during depressurization during launch. This approach not only provides insight into particle redistribution during launch but also can be used to establish fairing cleanliness requirements.
Diverse cellular morphologies during lumen maturation in Anopheles gambiae larval salivary glands.

Mosquitoes are the greatest animal threat to human health, causing hundreds of millions of infections and around one million deaths each year. All mosquito-borne pathogens must traverse the salivary glands (SGs) to be transmitted to the next host, making this organ an ideal target for interventions. The adult SG develops from precursor cells located in the larval SG duct bud. Characterization of the larval SG has been limited. We sought to better understand larval SG architecture, secretion, and gene expression. We developed an optimized method for larval SG staining and surveyed hundreds of larval stage 4 (L4) SGs using fluorescence confocal microscopy. Remarkable variation in SG cell and chromatin organization differed among individuals and across the L4 stage. Lumen formation occurred during L4 stage through secretion likely involving a coincident cellular apical lipid enrichment and extracellular vesicle-like structures. Meta-analysis of microarray data showed that larval SG gene expression is divergent from adult SGs, more similar to larval gastric cecae, but different from other larval gut compartments. This work highlights the variable cell architecture of larval Anopheles gambiae SGs and provides candidate targets for genetic strategies aiming to disrupt SGs and transmission of mosquito-borne pathogens.
Comparison of DNA yield and STR profiles from the diaphysis, mid‐diaphysis, and metaphysis regions of femur and tibia long bones

DNA testing of human bones is performed for identification when there is no remaining soft tissue, which often means the samples are old or environmentally compromised. Under these circumstances, it can be difficult to obtain a STR DNA profile. It is important to recover the highest quantity and quality of DNA for STR typing. This study compared the DNA recovery and STR profiles from five anatomical locations in five femora and five tibiae. These locations include the proximal metaphysis, proximal diaphysis, mid-diaphysis, distal diaphysis, and distal metaphysis. Twenty-five femur samples and 25 tibia samples were analyzed using the Qiagen Investigator Quantiplex Pro RGQ Kit for quantitating the extracted DNA and the Qiagen Investigator 24plex QS Kit for STR DNA typing. The highest DNA recovery of the five regions tested in both the femur and the tibia was from the midshaft diaphysis. The femur samples resulted in a significantly higher DNA recovery than the tibia samples as analyzed using a Kruskal-Wallis test (P = 0.002103). The midshaft diaphysis and distal diaphysis yielded the most complete STR DNA profiles in the femora, while the distal and proximal diaphysis yielded the most complete STR DNA profiles in the tibiae. There was no correlation between the amount of DNA recovered and the completeness of the STR DNA profile produced with low template extracts in this study.
Stem cell therapies for glaucoma and optic neuropathy

Abstract Glaucoma and optic neuropathy cause permanent blindness due to loss of retinal ganglion cells (RGCs) and their axons, which are both important components of visual circuits. RGC axons neither regrow nor are they replaced after injury and death, for which cell transplant is a potential therapeutic strategy. In this review we discuss the molecular mechanisms of RGC differentiation and compare the pros and cons of stem cell–derived RGC differentiation from 2D and 3D protocols. Then, we summarize the progression of cell transplantation in rodents and its prevision in nonhuman primates. We further point out the benefits of using induced pluripotent stem cell (iPSC) for familial glaucoma, focusing on its potential as a disease model for studying an inherited genetic mutation and for drug screening.
Little Trailer Park on the Prairie: Determinants of Site Rents in Parks in the Great Plains and Rocky Mountain States

Recent research has indicated that the manufactured housing industry is highly heterogeneous, mainly because both demand conditions and zoning restrictiveness vary enormously from one locale to another. There is little formal empirical work on the industry, especially in the low population density region that encompasses the Great Plains (including Texas) and Rocky Mountain states. Using a data set with nearly 60,000 manufactured housing sales transactions for the regions, we explore the determinants of park lot rents using a GMM 3SLS model. Both park lot rent levels, their determinants, and responses to local multi-family and single-family housing conditions vary from one economic region to another.
Feeling the 2019 Hong Kong anti-ELAB movement: emotion and affect on the Lennon Walls

In this study, I discuss the affective dynamics in Hong Kong’s anti-Extradition Law Amendment Bill movement through examining the emotion and affect surrounding four Lennon Walls in various parts o...
Solid Solution Yb2-xCaxCdSb2: Structure, Thermoelectric Properties, and Quality Factor.

Solid solutions of Yb2-xAxCdSb2 (A = Ca, Sr, Eu; x ≤ 1) are of interest for their promising thermoelectric (TE) properties. Of these solid solutions, Yb2-xCaxCdSb2 has end members with different crystal structures. Yb2CdSb2 crystallizes in the polar space group Cmc21, whereas Ca2CdSb2 crystallizes in the centrosymmetric space group Pnma. Other solid solutions, Yb2-xAxCdSb2 (A = Sr, Eu), crystallize in the polar space group for x ≤ 1, and compositions with x ≥ 1 have not been reported. Both structure types are composed of corner-sharing CdSb4 tetrahedra condensed into sheets that differ by the stacking of the layers. Single crystals of the solid solution Yb2-xCaxCdSb2 (x = 0-1) were studied to elucidate the structural transition between the Yb2CdSb2 and Ca2CdSb2 structure types. For x ≤ 1, the structures remain in the polar space group Cmc21. As the Ca content is increased, a positional disorder arises in the intralayer cation sites (Yb2/Ca2) and the Cd site, resulting in inversion of the CdSb4 tetrahedral chain. This phenomenon could be indicative of an intergrowth of the opposing space group. The TE properties of polycrystalline samples of Yb2-xCaxCdSb2 (x ≤ 1) were measured from 300 to 525 K. The lattice thermal conductivity is extremely low (0.3-0.4 W/m·K) and the Seebeck coefficients are high (100-180 μV/K) across the temperature range. First-principles calculations show a minimum in the thermal conductivity for the x = 0.3 composition, in good agreement with experimental data. The low thermal conductivity stems from the acoustic branches being confined to low frequencies and a large number of phonon scattering channels provided by the localized optical branches. The TE quality factor of the Yb1.7A0.3CdSb2 (A = Ca, Sr, Eu) series has been calculated and predicts that the A = Ca and Sr solid solutions may not improve with carrier concentration optimization but that the Eu series is worthy of additional modifications. Overall, the x = 0.3 compositions provide the highest zT because they provide the best electronic properties with the lowest thermal conductivity.
Optimism/Pessimism Prediction of Twitter Messages and Users Using BERT with Soft Label Assignment

Being able to accurately predict users' outlooks on social media platforms is important for developing educational public health interventions. In this paper, utilizing the contextualized representations provided by BERT, we propose new models to predict optimism/pessimism by fine-tuning BERT. By paying attention to the negation and other syntactic patterns, the self-attention mechanism via the transformer in BERT leads to more accurate models. For example, using the commonly used dataset for optimism/pessimism prediction with the proposed Soft Label Assignment (SLA), we have achieved 100% prediction accuracy at the user level and 97.10% at the tweet message level on the test set excluding the neutral ones. Furthermore, utilizing available training sample scores, we assign labels softly, which improves the generalization of the models and therefore their performance further. We additionally analyze the attention heads to illustrate the mechanisms of our models to classify different messages and demonstrate the connections between emotions and optimism/pessimism prediction.
The use of fluorescein-conjugated Bandeiraea simplicifolia B4-isolectin as a histochemical reagent for the detection of α-d-galactopyranosyl groups: Their occurrence in basement membranes

The Bandeiraea simplicifolia B4-isolectin, which combines specifically with α-d-galactopyranosyl groups, has been conjugated with fluorescein isothiocyanate and demonstrated to be a reliable histochemical probe for the detection of these groups in normal tissues of mouse, rabbit, rat and man. Specificity of binding of the fluorescein-conjugated B. simplicifolia B4-isolectin to native cryostat tissue sections was demonstrated in two ways: 1. 1. The hapten inhibitor methyl α-d-galactopyranoside prevented the binding of the lectin to tissues whereas the non-hapten methyl α-d-glucopyranoside did not. 2. 2. Pretreatment of tissue sections with coffee bean α-galactoside abolished lectin binding whereas pretreatment with A. niger or E. coli β-galactosidase did not. The fluorescein-conjugated isolectin visualized α-d-galactopyranosyl groups in basement membranes and on the surface of certain epithelial cells of mouse, rat, rabbit, and on the surface of the TA3 murine mammary carcinoma. These studies suggest that the B. simplicifolia B4-isolectin may be of great utility in studying the family of α-d-galactosyl-containing glycoconjugates of basement membranes in pathological states accompanied by basement membrane changes, such as diabetes mellitus, and in neoplasms that secrete basement membrane.
Metalloprotein Design and Engineering

This article covers recent advances in metalloprotein design, focusing on different approaches to their design. Impressive progress has been made in designing metal-binding sites in peptides, de novo designed proteins, and native protein scaffolds. The design approach can be rational or combinatorial. Under rational design, redesigning an existing metal-binding site to a new site with dramatically different structure and function complements well the design of new metal-binding sites by revealing the role of specific residues responsible for a particular structural or functional feature of the metal-binding site of interest. To create a new metal-binding site, several approaches have been used, including design based on structural homology, by inspection, using automated computer search algorithms, or combination of the above approaches. In addition, a modular approach involving transplanting a conserved structural unit from one protein into another has also been shown to be effective. Design through combinatorial and evolutionary methods has also been successful, as it requires little prior knowledge of the protein structure. Finally, introducing unnatural amino acids or nonnative metal ions/prosthetic groups to expand the repertoires of metalloproteins has been demonstrated. Successful examples of each of the approaches are given, advantages and disadvantages of the approaches are discussed, and the outlook for future research is also presented. Keywords: metalloprotein; metallopeptide; protein design and engineering; protein redesign; de novo design; modular design; directed evolution; combinatorial design; unnatural amino acids; phage display
Researching the research process: Information‐seeking behavior, Summon, and Google Books

Purpose – This paper seeks to describe undergraduate research habits, as identified through a study at Saint Mary's College of California.Design/methodology/approach – The paper focuses on Summon, a new federated search tool produced by Serials Solutions.Findings – The paper suggests that use of library‐supplied databases may be increasing due to the ubiquity of full‐text, and the ease with which it can be associated with online indexes.Originality/value – The paper describes opposition to the Google Books settlement.
Studies of the electron transport chain of extremely halophilic bacteria. III - Mechanism of the effect of salt on menadione reductase.

Abstract Halobacterium cutirubrum extracts exhibit no menadione reductase activity in the absence of salt; activity increases with salt concentration to a maximum at 2 m or higher concentrations of sodium chloride. The enzyme activity lost at low salt concentrations can be restored by adding 2 m NaCl. In addition to this reversible loss of activity, the enzyme also exhibits a time-dependent irreversible inactivation at salt concentrations below 2 m. The effects of salt on the initial enzyme activity and on the irreversible inactivation have a reciprocal relationship to one another. A mechanism for the salt effect is proposed, on the basis of kinetic data, whereby the active, stable form of the enzyme is in a salt-dependent equilibrium with an inactive, unstable form. The effect of NaCl, according to this model, is not to prevent the irreversible denaturation of the enzyme but rather to shift the equilibrium in favor of the active, stable form. The pH dependence of the inactivation rate constant and the reversibility of the pH effect indicate that there is an acid-base equilibrium, with pK = 9.3, between a less and a more stable intermediate form of the enzyme. Low concentrations of MgCl2, CaCl2, and some polyamines also have activating and protecting effects on menadione reductase. The mode of action of these substances is shown to be unlike that of NaCl but to consist in the alteration of the intermediate form of the enzyme in such a way as to make it more stable and partially active.
The Heat and Water Budget of the Earth's Surface

Publisher Summary In the last few years, as research attention in the earth and atmospheric sciences has been turned toward the flows and storages of energy and matter in the shells of our planet, much basic knowledge has been obtained that can be organized into three frameworks, whose locus is the earth's surface, in its variegated small-scale mosaics, its continental patterns and global distributions, its solar rhythms, episodic interruptions, and modifications by man. These three frameworks are the budget of radiant energy exchange, its higher echelon neighbor the balance of energy or heat, and the balance of water as a particular form of matter. The frameworks share a common accounting procedure that expresses their continuity as special cases of the laws of conservation of mass and energy, and that provides an efficient means of organizing a large volume of information about the individual fluxes and storages at the surface, and about the surface itself in its areal differentiation over the globe. These frameworks serve earth scientists well, first, as a unifying center for physical geography, second, as a means of comparing regions, and third, as a means of evaluating the modifications on the earth's surface brought about by man. The surface of the land, augmented by the biosphere, variegated by its geology, dissected by streams, mantled with a medium that stores heat and water, plays an important role in the balances of energy and matter. The role of the surface also varies, in response to changes in its own character, which affect the reception of the incoming fluxes, the access to storage, and the release of stored energy or water. The value of the heat and water budget in presenting a coherent scheme of physical phenomena to university classes has been demonstrated in this chapter; its value in research has been shown in specific regions.
Public Locations of Cardiac Arrest Implications for Public Access Defibrillation

Background—The purpose of this study was to describe the public locations of cardiac arrest and to estimate the annual incidence of cardiac arrest per site to determine optimal placement of automatic external defibrillators (AEDs). This was a retrospective cohort study. Methods and Results—Locations of cardiac arrest were abstracted from data collected by emergency medical service programs in Seattle and King County, Washington, from January 1, 1990, through December 31, 1994. Types of commercial and civic establishments were tallied and grouped into 23 location categories consistent with Standard Industrial Codes, and the number of sites within each location category was determined. With the addition of “public outdoors” and “automobiles” as categories, there were 25 location categories. During the study period, 7185 arrests occurred, 1130 (16%) of which were in public locations. An annual incidence of cardiac arrest per site was calculated. Ten location categories with 172 sites were identified as havin...
Temperature- and light-dependent structural changes in rhodopsin-lipid membranes.

Abstract Purified, regenerable rhodopsin has been incorporated into bilayers of synthetic phospholipids. The two-dimensional distribution of rhodopsin molecules in these membranes depends on the composition and state of the hydrocarbon chains. Reversible separations of pure solid lipid and rhodopsin-rich phases have been observed in membranes with a defined composition. The distribution and phase behavior of the protein is altered by bleaching. Freeze-fracture studies of native photoreceptor membranes lend support to the notion that rhodopsin is a transmembrane protein.
Protocol to Reconstruct Historical Contaminant Loading to Large Lakes: The Lake Michigan Sediment Record of Mercury

Samples of opportunity from Pb-210 dated sediment cores collected from Lake Michigan between 1994 and 1996 were analyzed for mercury. The storage of anthropogenic and total (post-1850) mercury in the lake is calculated to be 186 and 228 t, respectively. By setting the sum of mercury stored in a representative core equal to the mercury storage within the entire lake, the time variation of annual mercury loading to the lake is calculated. The modern (1980−2002) mercury flux to the lake represented by the surface of the core at the time of collection in 1994 was 21.4 μg/m2/y. The preindustrial flux (≤1850) was 3.09 μg/m2/y, and the peak flux in 1946 was 53.3 μg/m2/y. These yield modern and peak enrichment factors of 6.92 and 17.2, respectively. Modern fluxes exceed published atmospheric deposition estimates and, therefore, include terrestrial point sources, atmospheric deposition to watersheds, and atmospheric deposition to the lake. The modern net mercury load to the lake’s sediments was 1157 kg/y in 1994. ...
Abstract 4965: Metformin has an anticancer effect by repressing TWIST/N-cadherin signaling.

Introduction and Objective. Metformin, one of the most commonly used medications for treatment of type 2 diabetes, has emerged as a potential anticancer agent. The molecular mechanisms associated with the anti-cancer effect of metformin are poorly understood. We demonstrate, for the first time, that metformin inhibits prostate cancer proliferation through suppression of TWIST/N-cadherin signaling pathway. Methods. RT–PCR, Western blot, immunofluorescence assays and confocal microscopy were applied to evaluate protein expression level. MTS assay and FACS analysis were applied to determine cellular proliferation. N-cadherin and TWIST-1 expression vectors were transfected into PC3 prostate cancer cells to establish stable cells with over-expression of N-cadherin and TWIST-1, respectively. Metformin-resistant prostate cancer cells were established by exposure to higher concentrations (10mM) of metformin over 4 weeks. Results. Treatment with metformin (5mM) inhibited proliferation in three different types of cancer cells (PC3-prostate cancer cells; T24-bladder cancer cells and 786-O- kidney cancer cells). Metformin treatment suppressed expression of N-cadherin in all cell types. Similar findings were observed by confocal microscopy. In contrast to N-cadherin, expression of E-cadherin was not affected by metformin. Metformin-mediated repression of N-cadherin was dose and time- dependent in prostate cancer cells. PC3 prostate cancer cells with stable over-expression of N-cadherin became resistant to metformin-mediated inhibition. Stable PC3 prostate cancer cells, after selection for metformin, became resistant to metformin-mediated inhibition, and the metformin-resistant cancer cells had slightly higher baseline level of N-cadherin. In addition, in the metformin-resistant cells, N-cadherin levels were unchanged after treatment with metformin. The expression of AKT and AP-1, the downstream molecules of N-cadherin, closely correlated with expression of N-cadherin after treatment with metformin. Moreover, we also found that metformin inhibited expression of TWIST-1, a transcriptional activator of N-cadherin. Similar findings were observed by confocal microscopy. PC3 prostate cancer cells with stable over-expression of TWIST-1 became resistant to metformin-mediated inhibition. Conclusions. We demonstrate that Metformin9s anti-cancer therapeutic effect may be mediated through repression of the TWIST/N-cadherin signaling pathway. Citation Format: Ge Rongbin, Zongwei Wang, Aria F. Olumi. Metformin has an anticancer effect by repressing TWIST/N-cadherin signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4965. doi:10.1158/1538-7445.AM2013-4965 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Bending Deformation Studies of Orthodontic Wires

Bending deformation has been measured for orthodontic wires ranging in diameter from .010 to .051 inch. Results establish a revised expression for Young's modulus and show that either the stiffness tester or the torque meter will yield essentially the same measured values of bending properties. The dependence of test span length in determining Young's modulus and flexural yield strength is discussed.
Divisible groups that are brauer groups

Throughour this paper G denotes an abelian divisible torsion group. It is not unreasonable to conjecture that such a G must occur as the Brauer group B(K) of some field K. Some evidence to support this conjecture is provided in [3]; it is proved there that if G is countable then G ≅ B(K) for some K algebraic over the rational field Q [3, Theorem 2]. In this note we provide still more evidence in support of htis conjecture.
Wangara, Akan and Portuguese in the fifteenth and sixteenth centuries. I. The matter of Bitu

In late medieval and early modern times West Africa was one of the principal suppliers of gold to the world bullion market. In this context the Matter of Bitu is one of much importance. Bitu lay on the frontiers of the Malian world and was one of its most flourishing gold marts. So much is clear from sixteenth- and seventeenth-century writings, both African and European. A review of this body of evidence indicates that the gold trade at Bitu was controlled by the Wangara, who played a central role in organizing trade between the Akan goldfields and the towns of the Western Sudan. It is shown that Bitu cannot be other than Bighu (Begho, Bew, etc.), the abandoned Wangara town lying on the northwestern fringes of the Akan forest country, which is known (from excavation) to have flourished in the relevant period. In the late fifteenth century the Portuguese established posts on the southern shores of the Akan country, so challenging the monopolistic position which the Wangara had hitherto enjoyed in the gold trade. The Portuguese sent envoys to Mali, presumably to negotiate trade agreements. The bid was apparently unsuccessful. The struggle for the Akan trade in the sixteenth century between Portuguese and Malian interests will be treated in the second part of this paper.
Comparison of Stress Corrosion Cracking Characteristics of CP Ti, Ti-6Al-7Nb, Ti-6Al-4V, and Ti-15Mo

The purpose of this research was to evaluate and compare the stress corrosion cracking (SCC) of Ti-15 Mo (ASTM F2066), Ti-6Al-7Nb (ASTM1295), Ti-6Al-4V ELI (ASTM F136), and Grade 4 CPTi (ASTM F67). Evaluation of alloy composition, microstructure, Vickers microhardness, and tensile properties was performed to determine compliance with the appropriate ASTM specification. For SCC testing, smooth tensile samples with a gauge length of 10 mm and a gauge diameter of 4 mm and notched samples with a notch root diameter of 4 mm (Kt=3.2) were prepared using low stress grinding procedures. Three smooth and three notched samples were tested in distilled H2O and Ringer's solution at 37°C. Testing was performed using the slow extension rate method at a stroke rate of 10−5 mm/s according to the guidelines established in ASTM G129. The ratio of the percent elongation (PER) and reduction of area (ROAR) of smooth and notched samples tested in Ringer's solution and distilled water were evaluated. The fracture surfaces of representative samples were also examined for fracture mode identification using SEM. Results showed that all alloys complied with the appropriate ASTM specification. SCC may be considered to occur in a material if the ductile properties in an aggressive media are inferior to the ductile properties in a non-aggressive media. Evaluations of the PER and ROAR ratios in smooth and notched samples for each alloy in Ringer's and distilled water showed no indication of SCC failure mechanisms. SEM examination of the fracture surfaces showed no differences in the fracture morphology regardless of the testing solution. These results were consistent with the mechanical testing data. It is therefore concluded that SCC mechanisms were not operating or contributing to the fracture of these alloys under the conditions evaluated.
Delay Generated Offset: A Direction Sensitive Pulse-Coherent Doppler Detection Technique

An offset-frequency (heterodyne) direction sensitive coherentpulsed Doppler detection method requiring a single digitally synthesized phase-shiftable oscillator and a single mixer is described. Less stringent demands are imposed on hardware in obtaining offset-frequency stability and rejection of internally generated electrical clutter, as compared with the conventional offset method employing two oscillators. Simplification of hardware and postdetector signal processing as compared with the quadrature method (two parallel homodyne detectors) is anticipated. This technique has direct application in medical ultrasonics and is generally applicable to sonar and radar systems.
Wavefront generated by reflection of a plane wave from a conic section

We use the general solution of the eikonal equation due to Stavroudis to analyze the light propagation of an incident plane wave that is reflected off-axis from a surface of revolution generated by a conic section. Specifically, a general, explicit expression for the k-function associated with reflection of a plane wave is evaluated for the geometry of the off-axis conic mirror and the resulting k-function is used, following Stavroudis and coworkers, to evaluate the reflected wavefronts and caustic surfaces. This paper presents a new application of the k-function formalism to a practical configuration, without any simplifying rotational or translational symmetry, where the wavefronts and caustics in the focal region will be analyzed.
B-tree indexes, interpolation search, and skew

Recent performance improvements in storage hardware have benefited bandwidth much more than latency. Among other implications, this trend favors large B-tree pages. Recent performance improvements in processor hardware also have benefited processing bandwidth much more than memory latency. Among other implications, this trend favors adding calculations if they save cache faults.With small calculations guiding the search directly to the desired key, interpolation search complements these trends much better than binary search. It performs well if the distribution of key values is perfectly uniform, but it can be useless and even wasteful otherwise. This paper collects and describes more than a dozen techniques for interpolation search in B-tree indexes. Most of them attempt to avoid skew or to detect skew very early and then to avoid its bad effects. Some of these methods are part of the folklore of B-tree search, whereas other techniques are new. The purpose of this survey is to encourage research into such techniques and their performance on modern hardware.
An intuitive guide to the T1 based perfusion model

We explored a number of theoretical and practical approaches used to understand and optimize contrast to noise of the versatile T1 based perfusion model. The interplay between tissue T1 and blood T1 was investigated. We also provided a succinct evaluation of the several popular T1 based methods currently applied to measure flow and flow change.
Abyssinin, a potent insect antifeedant from an african medicinal plant, bersama abyssinica

Abstract Chemical investigation of pest insect control agents from the East African Melianthaceae plants has led to the isolation and characterization of abyssinin, a compound which exhibits very strong antifeedant activity against the cotton pest insect, Heliothis zea 1 .
Flexible wide angle terahertz resonant absorber based on perfectly impedance matched metamaterials

We present the design, fabrication and characterization of a highly flexible metamaterial absorber that experimentally obtains an absorptivity of 0.96 at 1.6 THz and operates over wide angular range for transverse electric and transverse magnetic radiation.
Modeling the simulated real-world optic flow motion aftereffect

We investigated the simulated real-world optic flow motion aftereffect (MAE) (illusory sense of moving backward following adaptation to expansive optic flow). In Experiment 1, adaptation duration was either 30, 120, 240, or 480 s. Results: duration of the MAE grew with increasing adaptation duration. In Experiment 2, the MAE was measured across different combinations of values of global optical flow rate and optical edge rate. Results: the aftereffect was selective for global optical flow rate, suggesting that the aftereffect reflects gain changes at processing levels where a sense of self-motion is generated. Results were used in a computational model of this MAE, which was a modified framework by van de Grind et al. [Vision Res.44, 2269 (2004)].
Effect of IGFBP-derived peptides on incorporation of35SO4into proteoglycans

18 amino acid peptides from the C-terminal region of IGFBP-3, -5 (P3, P5), increased the incorporation of(35)SO(4)into proteoglycans in endothelial cells with greater stimulation in large vessel than microvessel cells. The homologous region of IGFBP-6 (P6) also stimulated sulfate uptake, but less potently than P3 and P5. P6 variants were synthesized with one or two amino acids changed to the basic amino acid in the equivalent position of P3. The P6 variants with one additional basic amino acid behaved similarly to P6. The P6 mutant with two altered amino acids was equipotent to P3. P3F, a scrambled version of P3 was less effective than P3. P3, P5, P6, P3F and all P6 variants all stimulated glucose uptake, which occurred only in microvessel cells. P1, P2, P4, and equimolar intact IGFBP-3 stimulated neither glucose uptake nor sulfate incorporation. Thus, C-terminal basic portions of IGFBP-3, -5 and -6 alter two specific functions of endothelial cells with sufficient differences to suggest mediation by distinct mechanisms.