cssi/SciSciGPT-SciSciNet huggingface dataset:
Reducing administrative burden through the use of IT tools.

300Background: With the increasing cost of healthcare, providers have been tasked with increasing efficiencies. While the Electronic Medical Record (EMR) is a great tool for managing the patient at...
Development of an interdisciplinary, multi-method approach to seasonal climate forecast communication at the local scale

Bridging the gap between seasonal climate forecast development and science communication best practice is a critical step towards the integration of climate information into decision-making practices for enhanced community resilience to climate variability. Recent efforts in the physical sciences have focused on the development of seasonal climate forecasts, with increased emphasis on tailoring this information to user needs at the local scale. Advances in science communication have progressed understandings of how to leverage subjective decision-making processes and trust to communicate risky, probabilistic information. Yet, seasonal climate forecasts remain underutilized in local decision-making, due to challenging divides between the physical and social sciences and the lack of an approach that combines expert knowledge across disciplines. We outline an interdisciplinary, multi-method approach to communicate local-scale predictive information by advancing a co-produced “package” that pairs a highly visual bulletin with public engagement sessions, both developed with direct user-developer engagement, leveraging existing networks and novel inclusion of uncertainty through locally relevant analogies to enhance the understanding of probabilistic information. Systematic observations revealed some level of understanding among the target audience, yet identified major processes of confusion that inhibit forecast utility. Probabilistic predictions communicated in reference to “normal” years proved to be an unintelligible comparison for individuals, given preferences for certainty in interpreting risk-related information. Our approach addresses key gaps in the literature and serves as a framework for bridging the disconnect between forecast development and science communication to advance communication and integration of climate predictions for community benefit.
GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner

The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been purported to have antidepressant-like and cognitive-enhancing effects. Many people suffering from major depressive disorder (MDD) also experience deficits in cognition. While currently approved antidepressant pharmacotherapies can alleviate the mood symptoms in some patients, they do not treat the cognitive ones. We tested whether systemic administration of a GLP-1R agonist would alter location discrimination, a cognitive task that is diminished in humans with MDD. Male and female laboratory mice (6–8 weeks old, N = 6–14/sex) were trained in a touchscreen operant task of location discrimination. Upon reaching baseline criterion, mice were administered vehicle or a GLP-1R agonist, Exendin-4, systemically prior to testing in probe trials of varying difficulty. Following GLP-1R activation, males showed modest yet non-significant performance in the location discrimination task. Females, however, showed enhanced performance during the most difficult probe tests following Exendin-4 administration. GLP-1R activation appears to enhance overall performance in the location discrimination task and does so in a sex- and difficulty-dependent manner. These preliminary yet impactful data indicate that GLP-1R agonists may be useful as an adjunctive pharmacotherapy to treat cognitive deficits associated with MDD and/or multiple neurological disorders.
Withdrawal as pregnancy prevention and associated risk factors among US high school students: findings from the 2011 National Youth Risk Behavior Survey

Abstract Purpose Withdrawal is less effective for preventing pregnancy than other contraceptive methods and offers no protection against sexually transmitted infections including HIV. Little is known from a national perspective about adolescents who primarily use withdrawal. This study describes the prevalence of withdrawal as their primary method of pregnancy prevention at last sexual intercourse among sexually active US high school students and associations with sexual risk and substance use. Methods Data from the 2011 National Youth Risk Behavior Survey were used to estimate sexually active students' most recent contraceptive method. Logistic regressions examined sexual behaviors and substance use, comparing students who used withdrawal to those who used no method, a condom and a highly effective method. Results Among 4793 currently sexually active students, 10.2% used withdrawal only, 12.4% used no method, 53.6% used a condom and 23.8% used a more effective method as their primary form of pregnancy prevention during last sexual intercourse. Students who used withdrawal were less likely than those who used no method to have had sexual intercourse before age 13 years (Adjusted Prevalence Ratio (APR) =.56) and currently use cocaine (APR=.36). Among females, students who used withdrawal were more likely to engage in risky behaviors than those who used a condom and those who used a highly effective method of pregnancy prevention in a number of ways (e.g., having multiple sex partners during the past 3 months, current alcohol use, binge drinking, current marijuana use, drank alcohol or used drugs before last sexual intercourse). Conclusions Approximately 1 in 10 sexually active students used withdrawal only, about the same percentage as those who used no method. Health care providers and others who serve adolescents may want to discuss its pros and cons with their clients and help ensure that they have information about and access to other contraceptive methods that are more effective at preventing pregnancy and sexually transmitted infections. Health care professionals should not consider young people who use withdrawal similar in risk to those that use no method.
Amnesty, Guest Workers, Fences! Oh My! Public Opinion about “Comprehensive Immigration Reform”

Prior to 2001, scholars studying public opinion about immigration policy were largely confined to analyzing the question of whether the number of immigrants allowed into the country should be increased, decreased, or kept the same. Then 2001 brought both the George W. Bush presidency and the attacks on 9/11, which led to a new discourse on immigration policy and, consequently, an entirely new range of survey questions. Americans are now regularly asked for their views on complex reform proposals, including types of guest worker programs, conditions for illegal immigrants to earn legal status, and employer sanctions. But we still know little about the dynamics of public opinion on these policy debates. Moreover, we know little about the best way to even ask people for their views on these complicated matters. The two primary goals of this paper are to document the changes in how public opinion about immigration policy has been gauged during the Bush years and to make sense of emerging patterns that the data show. The first section reviews the political climate surrounding immigration discourse from 2001 to 2008. The second section analyzes the number and nature of survey questions related to immigration policy asked during that time period. The final section examines patterns of aggregate public opinion on these new policy questions. It considers whether external events have shaped public opinion on these emerging issues, how the ways in which questions are asked shape responses, and if opinion has been stable or erratic. The results reveal a high level of stability over time, with most variation in preferences attributable to question wording. The results also show a high level of support for immigrant friendly policies, including earned legalization.
Globalization, Cropping Choices, and Profitability in American Agriculture

The paper discusses the linkages between the “globalization” of agricultural markets over recent decades and the decisions being made by individual farmers and ranchers in the United States. It is noted that technological advances lead to globalization of agricultural commodity markets and profit pressures. The continuing profit squeeze in agricultural production is having a significant effect on the cropping choices of America's farmers. When possible, acreage is being shifted out of low-revenue-generating crops and into higher-revenue-generating crops. This shift makes crop portfolios more risky over time, thus encouraging farmers to consider diversifying out of agriculture.
Design of a Planar Parallel Robot for Optimal Workspace and Dexterity

Parallel robots exhibit salient merits over their serial counterparts in applications where both accuracy and dynamic response are required. However, due to the strong dependence of geometric parameters and their performances, the corresponding design problems for the parallel robots are much more complex and the adequacy and effectiveness of the design method become more critical. In this paper, a study in the design optimization for a class of planar parallel robots is presented. The robots feature an in-parallel structure with two degrees of freedom. Dimension synthesis is performed through maximization of two key performance characteristics, addressing not only workspace but also dexterity of the robots under consideration. Optimal designs are attained using both parametric study and simplex algorithm. Results are shown by way of computer simulations aided with graphic visualizations.
Objective evaluation of differences in protein subcellular distribution.

Research on the cell and molecular biology of proteins involved in membrane traffic often requires determination of the effects of various experimental conditions on the subcellular distributions of those proteins. This is most often accomplished by acquiring fluorescence microscope images and visually comparing these images. While this approach is quite suitable for detecting major changes in distributions, it is not sensitive to small changes and does not permit a quantitative and objective analysis. We therefore describe the application of pattern analysis methods to the comparison of sets of fluorescence microscope images. This approach provides a high throughput and reproducible technique to determine whether image distributions differ within a specified statistical confidence, and is shown to resolve image sets indistinguishable by visual inspection.
Space-time metrical fluctuations induced by cosmic turbulence

For a stochastic stress-energy tensor associated with cosmic turbulence, it is observed that Einstein’s equations imply fluctuations in the space-time metric tensor. Such metrical fluctuations are shown to engender modified values for the average effective proper density and total pressure and thus to alter the solutions to the Friedman equations.
Patents vs. Statutory Exclusivities in Biological Pharmaceuticals - Do We Really Need Both?

On March 23, 2010, President Obama signed into law the Biologics Price Competition and Innovation Act (BPCIA) as part of the Patient Protection and Affordable Care Act (also known as the Healthcare Bill). BPCIA sets up a framework for the approval of generic biologics and provides for up to 12.5 years of market exclusivity for FDA approved bio-pharmaceutical products. The exclusivity is intended to run in parallel and in addition to any patents that may apply to such approved bio-pharmaceutical products, which would also grant the developers of these products monopolies in the underlying technologies on which such bio-pharmaceutical products are based. This seeming “double dipping” raises questions regarding the need and justification, if any, for such parallel, double protection of this particular class of biological products. This article seeks to address these questions. Analyzing the fundamentals and underlying assumptions of the legal regimes of patents and statutory exclusivities, this article examines their applicability to the context of bio-pharmaceuticals. Based on the conclusions reached, this article then further examines the proposition that statutory exclusivity regimes could become a blueprint for “patentless” areas of technology, replacing the traditional patent regime with a new class of incentives to invent and invest in the development of new technology.
Soft gluon exponentiation and resummation

In calculations of (semi-) inclusive events within perturbative Quantum Chromodynamics, large logarithmic corrections arise from certain kinematic regions of interest which need to be resummed. When resumming soft gluon effects one encounters quantities built out of eikonal or Wilson lines (path ordered exponentials). In this thesis we develop a simplified method to calculate higher orders of the singular coefficients of parton distribution functions which is based on the exponentiation of cross sections built out of eikonal lines. As an illustration of the method we determine the previously uncalculated fermionic contribution to the three-loop coefficient A^(3). The knowledge of these coefficients is not only important for the study of the parton distribution functions themselves, but also for the resummation of large logarithmic effects due to soft radiation in a variety of cross sections. In the second part of this thesis we study the energy flow pattern of this soft radiation in jet events. We develop the concept of event shape-energy flow correlations that suppress radiation from unobserved "minijets" outside the region of interest and are sensitive primarily to radiation from the highest-energy jets. We give analytical and numerical results at next-to-leading logarithmic order for shape/flow correlations in e+e- dijet events. We conclude by illustrating the application of our formalism to events with hadrons in the initial state, where the shape/flow correlations can be described via matrices in the space of color exchanges.
Adolescent development and the emergence of sexuality.

Adolescence is a time of significant opportunity and significant challenge. Challenges can be difficult for some adolescents, which may result in problems that are expressed as affective disturbances or by the adolescent's participation in risk-taking behaviors. This review emphasizes the changes in biopsychosocial development during adolescence. We specifically address aspects of individual change during the adolescent decade (e.g., biological, cognitive, psychosocial, and sexual development) as well as the effects of context on normal development and responses to challenges during this period. Predispositions or vulnerabilities present prior to a developmental transition may be exacerbated by the transition. Adolescents can become healthy adults with the encouragement to develop gradually by limiting the simultaneous changes they experience, where possible, and by supporting healthy development through developmentally appropriate activities and supportive relationships with adults and peers.
Computer literacy as life skills for a web 2.0 world

This paper presents an innovative computer literacy course that focuses solely on developing skills needed for life in a networked world in which one must protect oneself from identity theft, be careful posting on social networks, and use credit and debit cards wisely. The course emphasizes ethical responsibility and information literacy. Its target audience, first-year, non-computer science majors, learn what they need to know to use technology safely, effectively, efficiently, and ethically. The course is grounded in active learning, such as posting in a class wiki, and critical thinking. It is a radical alternative to a traditional software packages approach.
Hyperthermophilic Aquifex aeolicus initiates primer synthesis on a limited set of trinucleotides comprised of cytosines and guanines

The placement of the extreme thermophile Aquifex aeolicus in the bacterial phylogenetic tree has evoked much controversy. We investigated whether adaptations for growth at high temperatures would alter a key functional component of the replication machinery, specifically DnaG primase. Although the structure of bacterial primases is conserved, the trinucleotide initiation specificity for A. aeolicus was hypothesized to differ from other microbes as an adaptation to a geothermal milieu. To determine the full range of A. aeolicus primase activity, two oligonucleotides were designed that comprised all potential trinucleotide initiation sequences. One of the screening templates supported primer synthesis and the lengths of the resulting primers were used to predict possible initiation trinucleotides. Use of trinucleotide-specific templates demonstrated that the preferred initiation trinucleotide sequence for A. aeolicus primase was 5′-d(CCC)-3′. Two other sequences, 5′-d(GCC)-3′ and d(CGC)-3′, were also capable of supporting initiation, but to a much lesser degree. None of these trinucleotides were known to be recognition sequences used by other microbial primases. These results suggest that the initiation specificity of A. aeolicus primase may represent an adaptation to a thermophilic environment.
The crystal structure of Pichia pastoris lysyl oxidase.

Pichia pastoris lysyl oxidase (PPLO) is unique among the structurally characterized copper amine oxidases in being able to oxidize the side chain of lysine residues in polypeptides. Remarkably, the yeast PPLO is nearly as effective in oxidizing a mammalian tropoelastin substrate as is a true mammalian lysyl oxidase isolated from bovine aorta. Thus, PPLO is functionally related to the copper-containing lysyl oxidases despite the lack of any significant sequence similarity with these enzymes. The structure of PPLO has been determined at 1.65 A resolution. PPLO is a homodimer in which each subunit contains a Type II copper atom and a topaquinone cofactor (TPQ) formed by the posttranslational modification of a tyrosine residue. While PPLO has tertiary and quaternary topologies similar to those found in other quinone-containing copper amine oxidases, its active site is substantially more exposed and accessible. The structural elements that are responsible for the accessibility of the active site are identified...
A novel ring-opening reaction of 2,2-dimethyl-2-silabicyclo[3.1.0]hexane

Abstract The compound 2,2-dimethyl-2-silabicyclo[3.1.0]hexane reacts with hydrogen chloride in the gas phase to give a high yield of β-(chlorodimethylsilyl)ethylcyclopropane.
Stimulation of transcription by a soluble factor isolated from soybean hypocotyl by 2,4-D affinity chromatography

Abstract When crude extracts from soybean hypocotyl are passed through a column of 2,4-dichlorophenoxyacetic acid (2,4-D) substituted Sepharose, a small amount of protein is retained which can be eluted with 2 mM KOH. This KOH eluate contains a transcription factor that stimulates RNA synthesis 2–7-fold using E. coli RNA polymerase and native calf thymus DNA. Experiments using soybean multiple RNA polymerases separated by anion-exchange chromatography show that the factor stimulates the nucleolar enzyme (polymerase I), but not polymerases II and III. These results are discussed in relation to the involvement of auxin receptors in the enhancement of RNA polymerase I by auxin.
Reconciling Research, Theory, and Practice in Web-Based Teaching and Learning: The Case for Grounded Design.

WEB-BASED TEACHING AND LEARNING cannot be easily characterized. In Web-based teaching and learning, technology features are combined in a theoretically unlimited number of ways to support a multitude of requirements and preferences. We need to better understand different approaches, activities, goals and perspectives, and approaches likely to prove effective. In this paper, we review Web-based research, theory and practice, and examine the implications of different perspectives and preferences for design and implementation.
Implementing reform amidst resistance: The regulation of teacher education and work in Mexico

Abstract Influenced by worldwide globalization forces new structures of control have emerged in Mexico at the school level, and career ladders reward teachers’ compliance with testing and training schemes; nevertheless the long-standing institutions of initial teacher education continue to show a strong resistance to change. Increased accountability is necessary to improve the quality of Mexican education, but a focus on performance and testing may rest legitimacy to indigenous ways of teaching and knowing.
Myofibroblast differentiation during fibrosis: Role of NAD(P)H oxidases

Progression of fibrosis involves interstitial hypercellularity, matrix accumulation, and atrophy of epithelial structures, resulting in loss of normal function and ultimately organ failure. There is common agreement that the fibroblast/myofibroblast is the cell type most responsible for interstitial matrix accumulation and consequent structural deformations associated with fibrosis. During wound healing and progressive fibrotic events, fibroblasts transform into myofibroblasts acquiring smooth muscle features, most notably the expression of alpha-smooth muscle actin and synthesis of mesenchymal cell-related matrix proteins. In renal disease, glomerular mesangial cells also acquire a myofibroblast phenotype and synthesize the same matrix proteins. The origin of interstitial myofibroblasts during fibrosis is a matter of debate, where the cells are proposed to derive from resident fibroblasts, pericytes, perivascular adventitial, epithelial, and/or endothelial sources. Regardless of the origin of the cells, transforming growth factor-beta1 (TGF-β1) is the principal growth factor responsible for myofibroblast differentiation to a profibrotic phenotype and exerts its effects via Smad signaling pathways involving mitogen-activated protein kinase and Akt/protein kinase B. Additionally, reactive oxygen species (ROS) have important roles in progression of fibrosis. ROS are derived from a variety of enzyme sources, of which the nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase family has been identified as a major source of superoxide and hydrogen peroxide generation in the cardiovasculature and kidney during health and disease. Recent evidence indicates that the NAD(P)H oxidase homolog Nox4 is most accountable for ROS-induced fibroblast and mesangial cell activation, where it has an essential role in TGF-β1 signaling of fibroblast activation and differentiation into a profibrotic myofibroblast phenotype and matrix production. Information on the role of ROS in mesangial cell and fibroblast signaling is incomplete, and further research on myofibroblast differentiation during fibrosis is warranted.
Designing and evaluating parent educational materials.

ABSTRACTFamilies of infants in the neonatal intensive care unit (NICU) are continually seeking information about their infant. Communicating with and providing education to parents is a crucial focus for nurses, who are often challenged to provide families with culturally sensitive health informatio
Stopped for repairs

The tumor suppressor protein p53 is intimately involved in the cellular response to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45, was recently found to bind to PCNA, a component of DNA replication/repair complexes, thereby implicating Gadd45 in DNA metabolism. Using biochemical assays, a role for Gadd45 in excision repair in vitro has been demonstrated. Antisense experiments have also indicated an in vivo role for the GADD45 gene in UV-irradiation survival. These discoveries establish a link between p53 and DNA repair through Gadd45.
Influence of Pulsationless Milking on Teat Canal Keratin and Mastitis

Abstract Twenty-four Holstein cows, producing at least 21 kg of milk/d, were used in two replicate experiments to determine the effect of presence or absence of pulsation on loss of teat canal keratin during machine milking. Left quarters were milked without pulsation and right quarters were milked with pulsation. On d 0 and 10, keratin was collected from one left and from one right teat canal of each cow prior to milking and from the remaining two teat canals after milking. Milk was collected for assessment of SCC and bacteriological status on d 0 and approximately every 3 d until d 18. Quantity of keratin recovered before milking on d 10 did not differ between teats milked with or without pulsation, but loss of keratin because of milking was greater from teats milked with pulsation. By d 7, 30% (12 of 43) of quarters milked without pulsation had become infected, but no (0 of 47) quarters milked with pulsation were infected. By d 14 to 16, new infections had increased to 68% (28 of 41) of quarters milked without pulsation and 2% (1 of 43) in quarters milked with pulsation; mean SCC in pulsationless quarters increased sevenfold relative to pulsation quarters. Protein and water content of keratin did not differ because of treatment, and changes in lipid composition were minor. Histological analysis of the teats of 4 cows indicated that the mean diameter of the teat canal, within 2 h after milking, was greater without pulsation than with pulsation (680 vs. 483 μm).
Parameter discovery for stochastic biological models against temporal behavioral specifications using an SPRT based Metric for simulated annealing

Stochastic models are often used to study the behavior of biochemical systems and biomedical devices. While the structure of such models is often readily available from first principles, several quantitative features of the model are not easily determined. These quantitative features are often incorporated into the model as parameters. The algorithmic discovery of parameter values from experimentally observed facts (including extreme-scale data) remains a challenge for the computational systems biology community. In this paper, we present a new parameter discovery algorithm based on Wald's sequential probability ratio test (SPRT). Our algorithm uses a combination of simulated annealing and sequential hypothesis testing to reduce the number of samples required for parameter discovery of stochastic models. We use probabilistic bounded linear temporal logic (PBLTL) to express the desired behavioral specification of a model. We also present theoretical results on the correctness of our algorithm, and demonstrate the effectiveness of our algorithm by studying a detailed model of glucose and insulin metabolism.
Risk-Based Considerations in Developing Strategies to Ensure Pipeline Integrity—Part II: Applications

This is the second in a series of two papers generated from a recent study on risk-based analysis for developing strategies to ensure pipeline integrity. This paper focuses on the applications of the proposed deterministic and probabilistic models presented in the first paper for stochastic pipe fracture evaluations. Using these models, numerical predictions are made for line-pipe steel typically used in gas transmission pipelines and are compared with the available test data. Thereafter, the paper explores the significance of the random variables related to serviceability in pipelines subjected to flaw growth in service. The results are discussed in the light of a hydrotest-based approach to ensure pipeline integrity. It is concluded that analysis of hydrotest strategies to optimize safety for such populations (e.g., Leis and Brust, 1992) should be based on a probabilistic analysis that permits risk assessments associated with pipeline operating decisions and the type and frequency of hydrotests done to ensure continued safe operation of the line. This same probabilistic framework could be used to assess the operating and safety implications for flaw populations characterized by in-line inspection.
Type 3 Deiodinase, a Thyroid-Hormone-Inactivating Enzyme, Controls Survival and Maturation of Cone Photoreceptors

Maturation of the mammalian nervous system requires adequate provision of thyroid hormone and mechanisms that enhance tissue responses to the hormone. Here, we report that the development of cones, the photoreceptors for daylight and color vision, requires protection from thyroid hormone by type 3 deiodinase, a thyroid hormone-inactivating enzyme. Type 3 deiodinase, encoded by Dio3, is expressed in the immature mouse retina. In Dio3−/− mice, ∼80% of cones are lost through neonatal cell death. Cones that express opsin photopigments for response to both short (S) and medium-long (M) wavelength light are lost. Rod photoreceptors, which mediate dim light vision, remain essentially intact. Excessive thyroid hormone in wild-type pups also eliminates cones. Cone loss is mediated by cone-specific thyroid hormone receptor β2 (TRβ2) as deletion of TRβ2 rescues cones in Dio3−/− mice. However, rescued cones respond to short but not longer wavelength light because TRβ2 under moderate hormonal stimulation normally induces M opsin and controls the patterning of M and S opsins over the retina. The results suggest that type 3 deiodinase limits hormonal exposure of the cone to levels that safeguard both cone survival and the patterning of opsins that is required for cone function.
Existence of gaps in the spectrum of periodic dielectric structures on a lattice

We consider the finite-difference counterpart, i.e., the true lattice analog, of Maxwell's equations and equations that govern the propagation of acoustic waves in a medium with a periodic dielectric structure. In particular, the vector nature of electromagnetic waves is fully taken into account. The existence of true gaps for these lattice models is proved for a two-component medium for which the dielectric constant is everywhere real and positive, and the dielectric constant of the background is essentially larger than the one corresponding to the embedded component.
Prostaglandin E2 induces Egr-1 mRNA in MC3T3-E1 osteoblastic cells by a protein kinase C-dependent pathway

Prostaglandin E2 (PGE2) plays an important role in the regulation of osteoblast metabolism. However, the nuclear signal transduction mechanisms involved in the actions of PGE2 have not been clearly defined. One mechanism may involve induction of immediate early genes such as the transcription factor Egr-1. In the present study, we examined the effects of PGE2 on induction of Egr-1 mRNA in MC3T3-E1 osteoblasts. Time course studies with 2 μM PGE2 showed maximal induction of Egr-1 mRNA at 30 min. In cells pretreated with cycloheximide (CHX), induction of Egr-1 mRNA reached a maximum at 60 min and remained elevated for at least 240 min. Preincubation with CHX was associated with superinduction of Egr-1. Inhibition of protein kinase C activity by pretreatment with 1 μM chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) attenuated the induction of Egr-1 mRNA by 2 μM PGE2. These data indicate that in MC3T3-E1 cells, PGE2 increases Egr-1 mRNA levels via a protein kinase C-dependent pathway.
Synthesis, antiviral and contraceptive activities of nucleoside-sodium cellulose sulfate acetate and succinate conjugates.

Abstract Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2′,3′-dideoxy-3′-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT–CSA and FLT–CSA) were found to be more potent than CS and other conjugates (e.g., AZT–succinate–CS, and FLT–succinate–CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type and multidrug resistant HIV-1, the AZT–CSA conjugate displayed significant contraceptive activity in an animal model, providing the initial proof-of-concept for the design and synthesis of dual-activity compounds based on these combinations.
Novel Wnt antagonists target porcupine and Axin.

Wnt signals are seemingly ubiquitous in biology, controlling processes as diverse as bristle patterning in flies and tissue regeneration in humans. A new report describes the discovery of small molecules that inhibit Wnt signaling by two unprecedented mechanisms, paving the way for fundamental studies and perhaps improved treatment of colon cancer.
Isoforms of Kalirin, a Neuronal Dbl Family Member, Generated through Use of Different 5′- and 3′-Ends Along with an Internal Translational Initiation Site

Kalirin is a neuron-specific GDP/GTP exchange factor for Rho subfamily GTP-binding proteins. The major Kalirin transcripts in adult rat brain were identified. Most include a Sec14p-like putative lipid-binding motif followed by nine spectrin-like repeats and a Dbl homology/pleckstrin homology (DH-PH) domain. Kalirin proteins with four different NH2 termini are generated through the use of five different 5′-ends; three of the proteins differ only at the extreme NH2 terminus, and one is truncated because translation is initiated at a methionine in the 5th spectrin repeat. Four different 3′-ends yield Kalirin proteins with additional functional domains. Kalirin-7 (7-kilobase pair mRNA) terminates with a PDZ-binding motif, which in Kalirin-8 is replaced by an SH3 domain. Kalirin-9 contains another pair of DH-PH and SH3 domains. Kalirin-12 additionally encodes a putative Ser/Thr protein kinase. Antisera specific for different COOH termini established Kalirin-7 as the most abundant in cortex, with significant amounts of Kalirin-9 and Kalirin-12; Kalirin-7 was less prevalent in cerebellum and olfactory bulb. Kalirin proteins lacking the Sec14p-like domain and first four spectrin-like repeats were much less prevalent. Form-specific antisera demonstrated that different forms of Kalirin were localized to distinct subcellular regions of cultured neurons. Members of the family of Kalirin proteins may subserve different functions at these different locations.
Conducting Nanosponge Electroporation for Affordable and High-Efficiency Disinfection of Bacteria and Viruses in Water

High-efficiency, affordable, and low energy water disinfection methods are in great need to prevent diarrheal illness, which is one of the top five leading causes of death over the world. Traditional water disinfection methods have drawbacks including carcinogenic disinfection byproducts formation, energy and time intensiveness, and pathogen recovery. Here, we report an innovative method that achieves high-efficiency water disinfection by introducing nanomaterial-assisted electroporation implemented by a conducting nanosponge filtration device. The use of one-dimensional (1D) nanomaterials allows electroporation to occur at only several volts, which is 2 to 3 orders of magnitude lower than that in traditional electroporation applications. The disinfection mechanism of electroporation prevents harmful byproduct formation and ensures a fast treatment speed of 15 000 L/(h·m2), which is equal to a contact time of 1 s. The conducting nanosponge made from low-cost polyurethane sponge coated with carbon nanotube...
Mobile Web Browsing with Aural Flows: An Exploratory Study

Existing web applications force users focus their visual attention on mobile devices while browsing content and services while on the go. To support eyes-free, mobile experiences, designers can minimize interaction with a device by leveraging the auditory channel. Whereas acoustic interfaces have proven to be effective in reducing visual attention, a perplexing challenge is designing aural information architectures for the web. To address this problem, techniques to remodel existing information architectures as linear, aural flows were introduced and evaluated. Mobile web browsing with aural flows is exemplified in ANFORA News, a semiaural mobile site designed to browse large collections of news stories. An exploratory study involving frequent news readers (n = 20) investigated the usability and navigation experience with ANFORA News in a mobile setting. Initial evidence suggests that aural flows are a promising paradigm to support eyes-free mobile navigation while on the go, but users still require assis...
Magnetic properties of melt‐spun Pr‐Fe alloys

The magnetic properties of a series of amorphous Pr1−xFex alloys (.45⩽x⩽ .90) prepared by spin melting are reported. Use of high purity constituents significantly increases the range over which Roentgen amorphous alloys can be obtained by this technique. The ratio of spontaneous to saturation magnetization (at 95 kOe) indicates that, over the composition interval 0.45⩽x⩽ .75, these alloys have sperimagnetic structures in which the Fe is ferromagnetic while the Pr moments are randomly oriented. At high applied field these alloys form collinear ferromagnetic structures. At reduced temperatures (20K) coercivities of over 4800 kA/m (60 kOe) were observed. Although exhibiting the pronounced temperature dependent behavior characteristic of non S‐state rare earth‐transition metal alloys, room temperature coercivities were still appreciable; a maximum room temperature value of 224 kA/m (2.8 kOe) was found at composition x = 0.6.
Invited Commentary on Central Hypersensitivity in Patients With Subacromial Impingement Syndrome

Pain pressure threshold (PPT) measurement by handheld algometer has been validated as a tool to identify and quantitate myofascial pain sites in an individual. The average of 3 readings at a given muscle site is used, so the standard error of measurement of these devices must be considered when determining whether PPT differences between muscle sites represent true changes. This commentary discusses this issue.
Forests and Climate Change: Forcings, Feedbacks, and the Climate Benefits of Forests

The world's forests influence climate through physical, chemical, and biological processes that affect planetary energetics, the hydrologic cycle, and atmospheric composition. These complex and nonlinear forest-atmosphere interactions can dampen or amplify anthropogenic climate change. Tropical, temperate, and boreal reforestation and afforestation attenuate global warming through carbon sequestration. Biogeophysical feedbacks can enhance or diminish this negative climate forcing. Tropical forests mitigate warming through evaporative cooling, but the low albedo of boreal forests is a positive climate forcing. The evaporative effect of temperate forests is unclear. The net climate forcing from these and other processes is not known. Forests are under tremendous pressure from global change. Interdisciplinary science that integrates knowledge of the many interacting climate services of forests with the impacts of global change is necessary to identify and understand as yet unexplored feedbacks in the Earth system and the potential of forests to mitigate climate change.
Momentum transfer in 30–200 MeV 4H induced reaction with 59Co

Abstract Thick-target recoil ranges of radioactive nuclei produced in 30–200 MeV alpha-particle bombardment of 59Co have been used to deduce the longitudinal momentum transfer per projectile nucleon (p‖/A) as a function of residue mass and bombarding energy. The average value of p‖/A increases monotonically with bombarding energy and reaches a maximum value of ≈ 160 MeV/c at ≈ 23 MeV/u, and decreases thereafter. The maximum value of p‖/A is equal to the incident momentum up to ≈ 23 MeV/u and saturates at a value of ≈ 220 MeV/c beyond this energy.
HIV immune complexes prevent excitotoxicity by interaction with NMDA receptors.

Abstract Purpose Human immunodeficiency virus-1 (HIV)-associated neurocognitive disorder (HAND) is a neurodegenerative disease for which there is no available neuroprotective therapy. Viral proteins, such as Tat, have been implicated as agents of neurotoxicity via multiple mechanisms, including effects by directly binding to the NMDA receptor. We evaluated the ability of the immune response against Tat to modulate neurotoxicity at glutamate receptors. Methods Neurotoxicity was measured in primary neuronal-glial cultures and in hippocampal slice cultures. We used immunoprecipitation experiments to demonstrate interaction between Tat, NMDA receptor, and anti-Tat antibody. Using known structures of Tat and NMDA receptors, we developed a model of their interactions. Results Antibodies to Tat attenuated Tat-mediated neurotoxicity. Interestingly, Tat immune complexes also blocked neurotoxicity caused by NMDA receptor agonists but not kainate/AMPA receptor agonists. Neither Tat nor antibody alone blocked the excitotoxic effect, nor did an unrelated antigen–antibody complex. The protective effect of the Tat immune complexes was also lost when Tat was modified by nitrosylation or by using a deletion mutant of Tat. Conclusions The ability of viral immune complexes to interact with NMDA receptors and prevent excitotoxicity represents a novel host defense mechanism. Host immune responses may influence host susceptibility to various effects of viral proteins, modulating HIV complications, such as onset of HAND. These observations provide rationale for development of vaccine therapies targeting Tat for prevention of HAND.
Breast image registration by using non-linear local affine transformation

A novel breast image registration method is proposed to obtain a composite mammogram from several images with partial breast coverage, for the purpose of accurate breast density estimation. The breast percent density estimated as a fractional area occupied by fibroglandular tissue has been shown to be correlated with breast cancer risk. Some mammograms, however, do not cover the whole breast area, which makes the interpretation of breast density estimates ambiguous. One solution is to register and merge mammograms, yielding complete breast coverage. Due to elastic properties of breast tissue and differences in breast positioning and deformation during the acquisition of individual mammograms, the use of linear transformations does not seem appropriate for mammogram registration. Non-linear transformations are limited by the changes in the mammographic projections pixel intensity with different positions of the focal spot. We propose a novel method based upon non-linear local affine transformations. Initially, pairs of feature points are manually selected and used to compute the best fit affine transformation in their small neighborhood. Finally, Shepherd interpolation is employed to compute affine transformations for the rest of the image area. The pixel values in the composite image are assigned using bilinear interpolation. Preliminary results with clinical images show a good match of breast boundaries, providing an increased coverage of breast tissue. The proposed transformation is continued and can be controlled locally. Moreover, the method is converging to the ground truth deformation if the paired feature points are evenly distributed and its number large enough.
Interaction of Herpes Primase with the Sugar of a NTP

We analyzed the interaction of NTPs containing modified sugars to develop a better understanding of how DNA primase from herpes simplex virus I catalyzes primer synthesis. During the NTP binding reaction, primase tolerated a large number of modifications to the sugar ring. Altering the 2′ and 3′ carbons, and even converting the furanose sugar into an acyclic sugar, did not prevent binding. Whether or not the base on the NTP could form a correct base-pair with the template base being replicated also had minimal effects on the binding reaction, indicating that primase does not use this process to discriminate between right and wrong NTPs. Rather, the key feature that primase recognizes to bind a NTP is the 5′-γ-phosphate since converting a NTP into a NDP greatly compromised binding. During the polymerization reaction, primase tolerated substantial modification of the 2′-carbon, including the presence of either an ara or ribo hydroxyl, two hydrogens, or two fluorines. However, polymerization absolutely required that the NTP contain a 3′-hydroxyl and an intact sugar ring. Modifications at the 2′-carbon of the nucleotide at the primer 3′-terminus significantly impaired further polymerization events. Compared to a ribonucleotide, incorporation of a 2-deoxyribo- or 2′,2′-difluoro-2′-deoxyribonucleotide resulted in strong chain termination, while incorporation of an aranucleotide resulted in very strong chain termination. The implications of these data with respect to the mechanism of primase and the relationship between human and herpes primase are discussed.
Immediate posttraumatic seizures: is routine hospitalization necessary?

Objective: A recent Internet survey of pediatric neurosurgeons showed that 86% routinely admitted children with immediate posttraumatic seizures (PTS) for a brief period of observat
A New Concept in Sternal Retraction: Applications for Internal Mammary Artery Dissection and Valve Replacement Surgery

A new, unique sternal retractor that greatly facilitates exposure and dissection of the internal mammary artery is described. In addition, a built-in mechanism permits steady and adjustable retraction during valve replacement surgery.
Coordination of ad-hoc groups formed in urban environments

This paper describes a distributed framework for multi-vehicle formation ad-hoc group creation. These vehicles will determine the best possible path to desired destinations in an urban road network and use the framework to form groups of convoys with the same immediate goals. These groups will be used to provide a more efficient traffic flow through traffic lights and in the presence of non-networked vehicles. This framework allows for different low level control laws to be used depending on the situation identified by the discrete higher level control.
Peripheral Participation and the Kwakiutl Potlatch

Invited to attend a memorial potlatch in 1987 that marked his own 25–year association with the Kwakiutl people of British Columbia, the author realized how the extended time frame offered a perspective not only on a celebrated Northwest Coast tradition but also on interpersonal complexities of culture acquisition and culture change as that tradition continues into the present. This account examines the potlatch from personal dimensions, a perspective missing from the expansive literature on an otherwise well–documented activity. Jean Lave's notion of “peripheral participation” is introduced as a framework for examining how humans find their “way in” to cultural events like this without necessarily realizing the subtlety of their indoctrination.
Alcohol impairment of saccadic and smooth pursuit eye movements: impact of risk factors for alcohol dependence.

Rationale While persons at risk for alcohol dependence by virtue of heavy drinking patterns or family history (FH) of alcohol use disorders have exhibited differential alcohol responses on a variety of measures, few studies have examined alcohol's effects on eye movements in these subgroups.