cssi/SciSciGPT-SciSciNet huggingface dataset:
Unifying modeling substrate for irrigation cyber-physical systems: poster abstract

CPS's multi-domain nature is difficult to capture using existing modeling approaches, which produce compartmentalized and complex system simulation models. Unifying models of multi-domain physical phenomena and processes, and man-made artifacts into a single modeling substrate will enable enhanced design of intelligent control algorithms and analytics. Moreover, with use of known modeling abstractions, which describe the physical ordinary differential equation (ODE) relationships by introducing model components, such as those found in Electronic Design Automation (EDA) tools, models of the physical world, e.g. irrigation systems, integrated with models of cyber world, e.g. electrical circuits, can be analyzed using existing tools. This can be done by using analogies between hydraulic, electrical, mechanical, etc. (e.g Table 1). For example, we developed soil moisture transient electrical circuit model for the next generation of Irrigation CPS.
Chemoselective, enzymatic C-H bond amination catalyzed by a cytochrome P450 containing an Ir(Me)-PIX cofactor

Cytochrome P450 enzymes have been engineered to catalyze abiological C–H bond amination reactions, but the yields of these reactions have been limited by low chemoselectivity for the amination of C–H bonds over competing reduction of the azide substrate to a sulfonamide. Here we report that P450s derived from a thermophilic organism and containing an iridium porphyrin cofactor (Ir(Me)-PIX) in place of the heme catalyze enantioselective intramolecular C−H bond amination reactions of sulfonyl azides. These reactions occur with chemoselectivity for insertion of the nitrene units into C−H bonds over reduction of the azides to the sulfonamides that is higher and with substrate scope that is broader than those of enzymes containing iron porphyrins. The products from C−H amination are formed in up to 98% yield and ∼300 TON. In one case, the enantiomeric excess reaches 95:5 er, and the reactions can occur with divergent site selectivity. The chemoselectivity for C–H bond amination is greater than 20:1 in all case...
What Do We Know and Where Shall We Go

Our method in this book has been to examine social referencing in infancy within the context of a diversified and multifaceted framework, in order to see what can be learned by looking at this phenomenon from different perspectives. At this point, it seems appropriate to ask what we have discovered about referencing through this approach, and what we can suggest as to future directions in research and conceptualization. What can we say that sheds new light upon this process in which the infant (the referer) used another person’s (the referee) interpretation of an event (the referent) to make sense of that event? This chapter aims to highlight, and present in an integrated manner, the major issues that have been raised and the suggestions for future research which have been made in the chapters of this volume.
Drug delivery: Week-long diabetes therapy

A subcutaneous depot of a diabetes drug fused to a thermosensitive biopolymer leads to blood-glucose control, for over one week after a single injection, in animal models of type-2 diabetes.
Investigations of the phase relations among e1, e2 and C{\bar {\bf 1}} structures of Na-rich plagioclase feldspars: a single-crystal X-ray diffraction study.

The subsolidus phase relations of plagioclase feldspar solid solution have been puzzling mineralogists and petrologists for decades, mainly due to the complicated structures of intermediate plagioclase at low temperature. The crystal structures of 12 Na-rich plagioclase samples are investigated by single-crystal X-ray diffraction analyses. The samples studied cover a compositional range from An21 to An49 (An is anorthite, CaAl2Si2O8), as well as a wide variety of origins, from extremely slow-cooled gabbroic rocks to pegmatite and metamorphic rocks. The structures fall into three different types: C{\bar 1}, e2 and e1, with an obviously increasing trend in the ordering states of the structures. The phase transitions from C{\bar 1} to e2 and e2 to e1 are both continuous in nature, as no abrupt structure change is required for the transformation. However, the structural difference between C\bar 1 and e1 is large enough to create a miscibility gap causing the Boggild intergrowth. As the plagioclase structure becomes more and more ordered, Al-Si reorganization in the framework would occur before the ordering of Ca and Na in M sites. Dramatic variations of Na occupancy would only appear in e1 structure with density modulation. This result confirms that Al-Si ordering is the major driving force of the formation of e-plagioclase structure. The composition of the lower end of the Boggild intergrowth is precisely constrained to An44-An45, based on the structural differences between two samples from the same pegmatite crystal. The modulation periods and directions of e-plagioclase are dependent on the conditions at which e-ordering starts to happen, other than the composition of the plagioclase. However, the three components (δh, δk and δl) of the q vector show strong linear correlations among one another, indicating some crystallographic constraint on the modulation direction which might be independent from the composition. The detailed subsolidus phase relations among e1, e2 and C{\bar 1} are illustrated with a local phase diagram, and schematic free energy curves at different temperatures are provided.
Abstract 5899: Chronic Proteasome Inhibition Leads to Dilative Cardiomyopathy

Background: The proteasome is responsible for the degradation of the majority of proteins in eukaryotic cells, especially those that are damaged and/or misfolded. Hence, the proteasome is an important component of intracellular protein quality mechanisms. The significance of this proteolytic complex for cardiac function, however, remains to be determined. Methods: Female domestic pigs, 3 months of age, were randomized to a normal diet (N, n=6) or HC (daily dietary load of 2% cholesterol, 15% lard, n=6) without or with twice weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, HC+PSI, n=5). In vivo data on cardiac dimensions and function was obtained by EBCT after 11 weeks. Ex vivo tissue analyses were performed on hearts harvested after 12 weeks and included TUNEL staining for the determination of the apoptotic index (TUNEL+ cells per myocardial area) and immunoblotting for the expression of pro-apoptotic factors such as caspase 12. Results: These are as listed in Table 1[⇓][1]. Conclusions: Chronic proteasome inhibition leads to dilative cardiomyopathy along with an increase in apoptotic cells in the myocardium and stimulation of the caspase-12 proapoptotic pathways, possibly indicating induction of endoplasmic reticulum stress as the underlying pathophysiological mechanism. The current study supports a role for the proteasome in the regulation of cardiac structure and function. ![Table][2] Table 1 [1]: #T1 [2]: pending:yes
On parallelizable Markov chain Monte Carlo algorithms with waste-recycling

Parallelizable Markov chain Monte Carlo (MCMC) generates multiple proposals and parallelizes the evaluations of the likelihood function on different cores at each MCMC iteration. Inspired by Calderhead (Proc Natl Acad Sci 111(49):17408–17413, 2014), we introduce a general ‘waste-recycling’ framework for parallelizable MCMC, under which we show that using weighted samples from waste-recycling is preferable to resampling in terms of both statistical and computational efficiencies. We also provide a simple-to-use criteria, the generalized effective sample size, for evaluating efficiencies of parallelizable MCMC algorithms, which applies to both the waste-recycling and the vanilla versions. A moment estimator of the generalized effective sample size is provided and shown to be reasonably accurate by simulations.
Implementing legislative strengthening programmes: Who is in control?

Over the last few decades, international development (also known as Official Development Assistance (ODA)) has been under attack for its lack of effectiveness. Critiques reflect two conceptual challenges, the nature of expert knowledge and the centrality of local ownership of development initiatives, bounded by the practical constraint of how politically controlled resources from bilateral and international donors will be used. This article examines five implementation strategies, including their strengths and weaknesses, keyed to the level of control asserted by the donor agency. We illustrate our argument through a review of legislative strengthening projects, most of which were funded by the United States Agency for International Development (USAID) and the United Kingdom's Department for International Development (DFID) in the case of one of the models.
The Economic and Cultural Relations

As has been mentioned, one of the primary motives which led Russia to conclude the Treaty of Nerchinsk was the prospect of commercial relations with China. It was the commercial motive that led Russia to expand toward the East, and it was this motive which caused her to send so many diplomatic missions to China. Europe was then in the age of mercantilism, and the Russian Government sought to promote its China trade in line with the mercantilist doctrine. By means of a code of definite, stringent regulations Moscow set up a systematic, absolute control over the China trade. Only imperial merchants, i.e., those armed with official sanction, could participate in the trade. The route to be taken, and the commodities imported and exported, were subject to government regulations. Most missions dispatched by Russia to China, in addition to seeking free trade with China, were actually charged with trade, and therefore in many cases, we have found that the Russian Government provided the missions with government treasure for the purpose of trade. Such transactions as would bring into Russia ingots of gold and silver were especially encouraged. Custom dues were levied and collected in the form of bullion so as to obtain precious metals for the government treasury.2
Multilayers for X-Ray Optical Applications

Optical elements encompass a wide range of devices and structures all directed to the efficient manipulation of light so that specific physical ends may be achieved. Advances in several areas over the past decade have presented both the scientific and technological communities with the prospect of a new generation of optics for the x-ray and VUV. These advances have required significant technological effort resulting in a degree of microstructural control not heretofore attainable.
Right ventricular function computed by thermodilution and ventriculography. A comparison of methods.

Right ventricular ejection fractions have been difficult to estimate clinically. It has been recently suggested that right ventricular ejection fractions can be calculated by thermodilution techniques with a fast-response thermistor and computer. These studies were performed to compare right ventricular ejection fractions obtained from thermodilution and biplane ventriculography. Ten pigs were instrumented with a right ventricular angiographic, thermodilution, and systemic arterial catheter. Right ventricular ejection fractions were determined by thermodilution and ventriculography at four times: (1) baseline, (2) infusion of isoporterenol (5 μg/min), (3) 50% of baseline mean arterial pressure produced by hemorrhage, and (4) reinfusion of isoproterenol during hypovolemia. A significant correlation existed between thermodilution and ventriculographic ejection fractions (r = 0.74, p = 0.004). However, during hypovolemia, thermodilution measurements of right ventricular ejection fraction were significantly lower than ventriculographic measurements (p
History of organophosphate synthesis: the very early days

The early days of ether chemistry can be divided into two periods: before and after Williamson serendipitous discovery (1851) of a new and efficient way to produce ethers using ethyl iodide and potassium salts. In the early part of the 19th century however, before Williamson, the direct reaction between the "spirit of wine" (ethanol) and acids was the only method of generating the elusive "ethers". This brief report looks at the pharmacists-chemists involved in the quest to produce phosphoric acid ether in the pre-Williamson period (Boudet, Boullay, Lassaigne, Pelouze), paving the way for Voegeli's synthesis of triethyl phosphate (TEP) in 1848.
Beyond two worlds: Identity narratives and the aspirational futures of Alaska Native youth:

Indigenous communities across the Alaskan Arctic have experienced profound revisions of livelihood, culture, and autonomy over the past century of colonization, creating radical discontinuities between the lives of young people and those of their parents and Elders. The disrupted processes of identity development, access to livelihoods, and cross-generational mentorship associated with colonialism have created complex challenges for youth as they envision and enact viable paths forward in the context of a rapidly changing Arctic home. In this study, we consider the meanings associated with different constructions of culture and selfhood, and the ways in which these identity narratives position Inupiaq Alaskan Native youth in relation to their personal and collective futures. Through an intergenerational and participatory inquiry process, this study explores how representations of shared heritage, present-day struggles, resilience, and hope can expand possibilities for youth and thus impact individual and community health.
Thermal and cold flow properties of bio-derived rejuvenators and their impact on the properties of rejuvenated asphalt binders

Abstract Rejuvenators are widely used to improve the properties of asphalt binders particularly low temperature and fatigue cracking behavior. Rejuvenators vary significantly in terms of their physical properties and chemical composition. The nature of the interaction between the rejuvenators and the base asphalt binders is very complex and an extensive study into the chemical and thermal properties of the rejuvenators and how they impact the rheological properties of rejuvenated binders is of paramount importance. In this research, a neat PG58-28 binder is rejuvenated with three different materials produced from soybean oil at a dosage of 6% by total weight of binder. The rheological properties of the control and rejuvenated binders are assessed using performance grades showing a drop in both the critical low and high temperature grades with rejuvenation. The oxidative stability of the rejuvenators as well as the rejuvenated binders is studied using thermogravimetric analysis (TGA). The crystallization and melting points of the rejuvenators are observed using differential scanning calorimetry (DSC). DSC is also used to examine the glass transition temperatures of the control and rejuvenated binders. The TGA results showed one of the rejuvenators to be susceptible to oxidation which agreed with the rolling thin film oven (RTFO) mass loss results. The glass transition temperature of the rejuvenated binders decreased denoting improved low temperature cracking properties in line with the performance grade results.
A Clinical Review of Common Medications Used in Emergency Dermatological Situations.

BACKGROUND Medical emergencies can occur in any environment, including dermatologic and procedural surgical settings. There are many options available to dermatologic surgeons, which they should consider having easily accessible in the office in case an emergency arises. OBJECTIVE To summarize the current understanding about major medications that should be on-hand during dermatological surgeries. To review their mechanism of action, examine their general use, and dermatological use during surgical emergencies. METHODS AND MATERIALS A comprehensive review using PubMed was performed, searching for studies using these various medications in relation to cutaneous surgeries. RESULTS Distinct items such as hyaluronidase, nitroglycerin paste, aspirin, injectable epinephrine, and defibrillators are potential options to address various emergencies and should be readily accessible to dermatologic surgeons. CONCLUSION Dermatologic surgeons' knowledge of key medications and options to have in the office allow for a proper response in the event an emergency arises.
INSULIN THERAPY IN A RAT MODEL OF DIABETIC CARDIOMYOPATHY IS ASSOCIATED WITH ATTENUATION OF THE CGMP SYSTEM

Subjects with diabetes mellitus (DM) have increased risk of heart failure (HF). Despite its efficacy in maintaining euglycemia, insulin has not been shown to reduce HF risk in DM. The cyclic guanosine 3',5'-monophosphate (cGMP) system plays an important role in preserving cardiorenal function. To
„Unwertes Leben“: Herrschaftswissen im Medienzeitalter

Meinungsfreiheit ist in den modernen westlichen Gesellschaften ein hoher Wert, der nur von der „Freiheit“ der marktwirtschaftlichen Ordnung ubertroffen wird. Medien sind dabei von zentraler Bedeutung: Wer die Mittel hat, Massenmedien zu kontrollieren, kann seine Meinung einem grosen Kreis von „Empfangern“ mitteilen. Das Internet und die sozialen Medien haben die liberalistischen Prinzipien verinnerlicht. Innerhalb weniger Jahre wurde es vom Hoffnungstrager fur basisdemokratische Prozesse zur Gefahr von Meinungsvielfalt durch Tribalismus, Radikalisierung und Okonomisierung. Thema des Kapitels ist daher, in welcher Weise ethische Werthaltungen von okonomischen Prinzipien abhangen, inwieweit Medien wirtschaftliche, ideologische, extremistische und rassistische Werthaltungen vermitteln und inwiefern die modernen Medien dabei an die Medienpolitik der Nationalsozialisten anknupfen, die sich selbst als „Wertegemeinschaft“ verstanden und Propaganda in Ubereinstimmung mit den Dogmen der freien Marktwirtschaft betrieben haben.
Coerced Change-talk with Conversational Agents Promotes Confidence in Behavior Change

Motivational interviewing is a counseling technique that works, in part, by helping people talk about changing their behavior. We describe two conversational agent-based interventions to increase motivation and confidence to promote physical activity and fruit and vegetable consumption that incorporate principles from motivational interviewing. We also explore the efficacy of constraining input, so users are only allowed to express change talk in their conversation with the agent. In a within-subjects experiment we demonstrate that both interventions are effective at increasing motivation, confidence, and self-efficacy for behavior change during a single counseling session. We also demonstrate that coercing user change talk leads to significantly greater increases in confidence compared to equivalent counseling agents that allow users to express statements about not changing their behavior.
Toward a Broader Definition of Engineering Careers

Abstract The fields of science, engineering and technology have always been international. In the recent decades, the importance of global engagement has substantially increased because many emerging critical problems are trans-boundary, and optimal solutions to those require the participation of multiple stakeholders. In many cases, scientists/engineers and national/international policymakers must work together to resolve these complicated issues. Such mixed teams may be very rewarding, but also have risks and pitfalls: there is a need for great understanding and openness, which takes nontrivial effort. Increasingly, we will have to develop a new generation of engineers who would be not only comfortable, but also excited to join the policymakers in working toward resolving large, complicated, multidimensional problems. In this paper, I argue that we could inspire a cultural change by shifting from a traditional definition of engineering careers to a broader, more inclusive view, where venturing into the world of national and international policy is an acceptable and sometimes, desirable option.
Diabetes Mellitus Among Arab Americans

Diabetes is an emergent clinical and public health problem in Arab Americans, a growing segment of the US population. This chapter summarizes the current knowledge as to the prevalence of diabetes and its risk factors in this population based on available literature. Barriers to effective diabetes management and culturally adapted strategies addressing these barriers are reviewed. Special reference is made to the use of various diabetes drug therapies and a set of recommendations are presented to minimize the risks associated with fasting during Ramadan and pilgrimage for the Arab American patients with diabetes. Future representative cohort studies are critical to understanding the health needs of the Arab American patients with diabetes.
Modeling rangelands as spatially-explicit complex adaptive systems.

Abstract Rangelands cover one third of the earth's land area, provide livelihoods for one billion persons, and most have been degraded by overgrazing of domestic livestock. Recent debate about best management practices often has centered on comparison of continuous grazing and rotational grazing. Resolution to this debate may lie in viewing rangelands as complex adaptive systems. We describe a spatially-structured, individual-based model of rangelands that embodies this perspective, and simulate forage dynamics and cattle production under semi-arid rangeland conditions typical of the southern Great Plains of the USA employing both continuous and rotational grazing. Relative “success” of simulated grazing schemes depended primarily on the evaluation metric used (e.g., rangeland ecological condition, sale weight of cattle, secondary production efficiency) and the particular manage scheme employed, and neither continuous nor rotational grazing schemes were uniformly more successful. Our results demonstrate that solution of the grazing systems debate is unlikely to be found in a single group of grazing schemes, but, rather, in adaptive management of feedbacks among system components. The present work provides an example of how modeling rangelands as complex adaptive systems can aid in the evaluation of management schemes.
The Search for a Permanent Channel: Environmental Transformation of the Dagu Bar, 1897-1928:

In the late nineteenth and early twentieth centuries, the Haihe Conservancy Commission conducted a series of Western-style engineering projects to create a permanent bar channel in the Chinese city...
Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice.

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease. Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.
CityLearn: Standardizing Research in Multi-Agent Reinforcement Learning for Demand Response and Urban Energy Management.

Rapid urbanization, increasing integration of distributed renewable energy resources, energy storage, and electric vehicles introduce new challenges for the power grid. In the US, buildings represent about 70% of the total electricity demand and demand response has the potential for reducing peaks of electricity by about 20%. Unlocking this potential requires control systems that operate on distributed systems, ideally data-driven and model-free. For this, reinforcement learning (RL) algorithms have gained increased interest in the past years. However, research in RL for demand response has been lacking the level of standardization that propelled the enormous progress in RL research in the computer science community. To remedy this, we created CityLearn, an OpenAI Gym Environment which allows researchers to implement, share, replicate, and compare their implementations of RL for demand response. Here, we discuss this environment and The CityLearn Challenge, a RL competition we organized to propel further progress in this field.
Inclusive Practices and the Achievement Gap between Students with and without an Individualized Education Plan

Philosophy, ethics, legal mandates, educational theory, classroom application, and research has neither concluded nor reached scholarly saturation on the successful implementation of inclusion. This study examines inclusive practices for students with special needs by focusing on one innovative approach to narrowing the achievement gap between students on an Individual Education Plans (IEP) and students not on IEP. The innovative approach examined combined three research-based practices to create one school-wide pedagogy. The public middle school in this study integrated three educational approaches known as “Tribes,” “Integrated Thematic Instruction (ITI)”, and “MicroSocieties”. An 11-year study revealed statistically significant relationship between the innovative approach and the achievement gap between students on IEPs and students not on IEPs. Descriptive statistics and parametric testing, a linear regression, were used to make inferences in the relationship. Implications of the study continue to support existing research on individual inclusive practices, but more importantly the innovative integration of inclusive practices.
Macroinvertebrates at the source: flow duration and seasonality drive biodiversity and trait composition in rheocrene springs of the Western Allegheny Plateau, USA

Documenting flow regimes and the ecology of source headwater streams has gained considerable attention for scientific and regulatory purposes. These streams do not appear on standard maps, and local physiographic and climatologic conditions can control their origins. We investigated macroinvertebrate assemblages seasonally and in relation to flow duration, catchment and habitat variables within 14 source headwaters (< 1 ha) in the Western Allegheny Plateau over a 19-month period. We classified 6 perennial (P) and 8 intermittent (I) streams directly with continuous flow data loggers. Several biological and trait-based metrics could distinguish flow class, but few instream physical measures could. Macroinvertebrate metrics and assemblage dispersion varied seasonally and responded significantly along a gradient of total flow duration. Separate indicator species analyses generated 22 genera and 15 families with significant affinities to P streams. Richness of P-indicator taxa was also strongly correlated with flow duration gradients, and we estimated a total flow duration changepoint at 77% (3 indicator families) followed by a sharp increase in richness. Two rapid field-based flow duration methods (NC Stream Identification index and OH Headwater Habitat Evaluation index) could distinguish upstream ephemeral reaches from P and I reaches, but misclassified P as I more frequently. Our findings highlight that diverse coldwater macroinvertebrate assemblages inhabited extremely small, low-discharge springs in the region, and responded with flow duration. These source headwater habitats are susceptible to human disturbance and should be monitored as is routinely done in larger lotic systems.
A Comparison of Corporate Tax Rates in the Four Chinas: 1980–2020

This study compares the top corporate tax rates in the People’s Republic of China, Hong Kong, Macau and Taiwan from 1980-2020, using Tax Foundation data.
Management of steroid-dependent and steroid-refractory ulcerative colitis

Corticosteroids remain an effective therapy for inducing remission in patients with ulcerative colitis; however, they have not been shown to be effective for the maintenance of remission. Response to corticosteroids has been defined as the clinical improvement within 30 days of treatment with high-dose oral corticosteroids or clinical improvement within 7–10 days of treatment with high-dose intravenous corticosteroids. Patients with inflammatory bowel disease who initially respond to corticosteroids but then relapse with tapering corticosteroids or shortly after discontinuation and require reintroduction of corticosteroids to maintain control of symptoms have been defined as steroid dependent. Patients who fail to respond to corticosteroids within this time frame have been defined as steroid refractory.
Chapter 26. Recent Developments in the Therapeutics of Disorders of Bone Metabolism

Publisher Summary A variety of potent agents have become available for the treatment of such diverse skeletal disorders as Paget's bone disease, osteomalacia and rickets, and osteoporosis. Sometimes the drugs produce a definitive cure of the disorder. Suppression of disease activity occurs in patients with Paget's disease who are treated with calcitonin or disodium etidronate. In the chapter, the mode of action and pharmacological effects of selected agents are discussed in detail. Calcitonin is a 32 amino acid polypeptide hormone, whose structure shows variability among the species, in which it has been elucidated. Calcitonins of mammalian origin are less potent than those of fish origin, such as salmon and eel calcitonin, as judged by the standard bioassays of acute hypocalcemic response in the rat. Studies have been done in which the effects of single and multiple amino acid substitution in the human calcitonin molecule have been examined. Biological activity of human calcitonin could be increased, by four to five-fold, by replacing a single amino acid in position 8, 12, or 22 by the corresponding amino acid found in the dominant form of salmon calcitonin extracted from ultimobrachial glands. The mode of action of calcitonin appears to depend upon the activation of membrane-bound adenylate cyclase. The concept that calcitonin action is also dependent on membrane calcium transport has received some experimental support. Calcitonin has been used with some degree of success in the treatment of hypercalcemia. Similar detailed discussion with supporting structural diagrams done on diphosphonates and vitamin D metabolites. The diphosphonates are synthetic compounds that are structurally similar to inorganic pyrophosphate, but are resistant to enzymatic and chemical hydrolysis. After biosynthesis of cholecalciferol or ingestion of ergocalciferol, a series of hydroxylations take place in the liver and kidneys that convert some sterols to biologically active forms of vitamin D.
Comprehensive mapping of functional epitopes on dengue virus glycoprotein E DIII for binding to broadly neutralizing antibodies 4E11 and 4E5A by phage display

Here we investigated the binding of Dengue virus envelope glycoprotein domain III (DIII) by two broadly neutralizing antibodies (bNAbs), 4E11 and 4E5A. There are four serotypes of Dengue virus (DENV-1 to -4), whose DIII sequences vary by up to 49%. We used combinatorial alanine scanning mutagenesis, a phage display approach, to map functional epitopes (those residues that contribute most significantly to the energetics of antibody-antigen interaction) on these four serotypes. Our results showed that 4E11, which binds strongly to DENV-1, -2, and -3, and moderately to DENV-4, recognized a common conserved core functional epitope involving DIII residues K310, L/I387, L389, and W391. There were also unique recognition features for each serotype, suggesting that 4E11 has flexible recognition requirements. Similar scanning studies for the related bNAb 4E5A, which binds more tightly to DENV-4, identified broader functional epitopes on DENV-1. These results provide useful information for immunogen and therapeutic antibody design.
Calf Muscle Characteristics, Strength Measures, and Mortality in Peripheral Arterial Disease: A Longitudinal Study

Objectives This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD). Background Men and women with lower extremity PAD have lower calf muscle density and reduced lower extremity strength compared with individuals without PAD. Methods At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed up annually for up to 4 years. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Results Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile hazard ratio [HR]: 1.80 [95% confidence interval (CI): 1.07 to 3.03], second tertile HR: 0.91 (95% CI: 0.51 to 1.62); highest density tertile HR: 1.00; p trend = 0.020) and higher cardiovascular disease mortality (lowest density tertile HR: 2.39 [95% CI: 0.90 to 6.30], second tertile HR: 0.85 [95% CI: 0.27 to 2.71]; highest density tertile HR: 1.00; p trend = 0.047). Poorer plantar flexion strength (p trend = 0.004), lower baseline leg power (p trend = 0.046), and poorer handgrip (p trend = 0.005) were associated with higher all-cause mortality. Conclusions These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip were associated with increased mortality in these participants with PAD, independently of the ankle-brachial index and other confounders.
The role of nitric oxide in passive leg movement-induced vasodilatation with age: insight from alterations in femoral perfusion pressure.

The passive leg movement (PLM) model is a novel approach to assess vascular function. Increasing femoral perfusion pressure (FPP) by moving from the supine to the upright-seated posture augments the vasodilatory response to PLM in the young, with no effect in the old, but whether this augmented vasodilatation is nitric oxide (NO) dependent is unknown. Using an intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) to inhibit nitric oxide synthase (NOS), the posture-induced increases in the PLM responses in the young were nearly ablated, with no effect of NOS inhibition in the old. Therefore, PLM in combination with alterations in posture can be used to determine changes in NO-mediated vasodilatation with age, and thus, may be a clinically useful tool for assessing NO bioavailability across the human lifespan. We sought to better understand the contribution of nitric oxide (NO) to passive leg movement (PLM)-induced vasodilatation with age, with and without a posture-induced increase in femoral perfusion pressure (FPP). PLM was performed in eight young (24 ± 1 years) and eight old (74 ± 3 years) healthy males, with and without NO synthase inhibition via intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) into the common femoral artery in both the supine and upright-seated posture. Central and peripheral haemodynamic responses were determined second-by-second with finger photoplethysmography and Doppler ultrasound, respectively. PLM-induced increases in heart rate, stroke volume, cardiac output and reductions in mean arterial pressure were similar between age groups and conditions. In the young, L -NMMA attenuated the peak change in leg vascular conductance (ΔLVCpeak ) in both the supine (control: 7.4 ± 0.9; L -NMMA: 5.2 ± 1.1 ml min(-1) mmHg(-1) , P 0.05). Increased FPP augmented the ΔLVCpeak in the young control condition only (P 0.05). These data reveal that greater FPP increases the role of NO in PLM-induced vasodilatation in the young, but not the old, due to reduced NO bioavailability with age. Therefore, PLM involving alterations in posture may be useful to determine changes in NO bioavailability with age.
Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines

ABSTRACT Several members of the Arenaviridae family cause hemorrhagic fever disease in humans and pose serious public health problems in their geographic regions of endemicity as well as a credible biodefense threat. To date, there have been no FDA-approved arenavirus vaccines, and current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. Arenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome. Each genome segment uses an ambisense coding strategy to direct the synthesis of two viral polypeptides in opposite orientations, separated by a noncoding intergenic region. Here we have used minigenome-based approaches to evaluate expression levels of reporter genes from the nucleoprotein (NP) and glycoprotein precursor (GPC) loci within the S segment of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). We found that reporter genes are expressed to higher levels from the NP than from the GPC locus. Differences in reporter gene expression levels from the NP and GPC loci were confirmed with recombinant trisegmented LCM viruses. We then used reverse genetics to rescue a recombinant LCMV (rLCMV) containing a translocated viral S segment (rLCMV/TransS), where the viral NP and GPC open reading frames replaced one another. The rLCMV/TransS showed slower growth kinetics in cultured cells and was highly attenuated in vivo in a mouse model of lethal LCMV infection, but immunization with rLCMV/TransS conferred complete protection against a lethal challenge with wild-type LCMV. Attenuation of rLCMV/TransS was associated with reduced NP expression levels. These results open a new avenue for the development of arenavirus live attenuated vaccines based on rearrangement of their viral genome. IMPORTANCE Several arenaviruses cause severe hemorrhagic fever in humans and also pose a credible bioterrorism threat. Currently, no FDA-licensed vaccines are available to combat arenavirus infections and antiarenaviral therapy is limited to the off-label use of ribavirin, which is only partially effective and associated with side effects. Here we describe, for the first time, the generation of a recombinant LCMV where the viral protein products encoded by the S RNA segment (NP and GPC) were swapped to generate rLCMV/TransS. rLCMV/TransS exhibited reduced viral multiplication in cultured cells and was highly attenuated in vivo while conferring protection, upon a single immunization dose, against a lethal challenge with wild-type LCMV. Our studies provide a proof of concept for the rational development of safe and protective live attenuated vaccine candidates based on genome reorganization for the treatment of pathogenic arenavirus infections in humans.
The Use of Transcutaneous Electrical Nerve Stimulation (TENS) in a Major Cancer Center for the Treatment of Severe Cancer-Related Pain and Associated Disability

Background. Cancer pain is difficult to treat, often requiring a multimodal approach. While medication management remains the mainstay for the treatment of cancer pain, medications are often associated with undesired side effects. Transcutaneous electrical nerve stimulation (TENS) provides a potential adjunctive method for treating cancer pain with minimal side effects. Objective. Few studies have been performed evaluating the efficacy of TENS on cancer pain. We sought to examine the usefulness of TENS on all cancer patients and to specifically look at the use of TENS as a goal-directed therapy to improve functionality. Design. Retrospective cohort study. Methods. Since 2008, patients with chronic cancer pain and on multimodal pain regimens were trialed with TENS. Those patients who showed an improvement in pain symptoms or severity were educated about and provided with a TENS unit for use at home. Pain symptoms and scores were monitored with the visual analog scale (VAS), the numerical rating pain (NRP) scale, and Short-Form McGill Questionnaire at the start of TENS treatment and at 2 months follow-up. Results. TENS proved beneficial in 69.7% of patients over the course of 2 months. In TENS responsive patients, VAS scores decreased by 9.8 on a 0–100 mm scale ( P < 0.001), and NRP scores decreased by 0.8 on a 1–10 scale ( P < 0.001). Limitations. Lack of placebo and lack of blinding of physician and patient. Conclusions. TENS provides a beneficial adjunct for the treatment of cancer pain, especially when utilized as a goal-directed therapy.
Interning Ground Terms in XSB.

This paper presents an implementation of interning of ground terms in the XSB Tabled Prolog system. This is related to the idea of hash-consing. I describe the concept of interning atoms and discuss the issues around interning ground structured terms, motivating why tabling Prolog systems may change the cost-benefit tradeoffs from those of traditional Prolog systems. I describe the details of the implementation of interning ground terms in the XSB Tabled Prolog System and show some of its performance properties. This implementation achieves the effects of that of Zhou and Have but is tuned for XSB's representations and is arguably simpler.
Heart Failure and Tachycardia-Induced Cardiomyopathy

Congestive heart failure is a major health care concern affecting almost six million Americans and an estimated 23 million people worldwide, and its prevalence is increasing with time. Long-standing tachycardia is a well-recognized cause of heart failure and left ventricular dysfunction and has led to the nomenclature, tachycardia-induced cardiomyopathy. Tachycardia-induced cardiomyopathy is generally a reversible cardiomyopathy with effective treatment of the causative arrhythmia, either with medications, surgery, or catheter ablation. Tachycardia-induced cardiomyopathy remains poorly understood and is likely under-diagnosed. A better understanding of tachycardia-induced cardiomyopathy and improved recognition of its presence in clinical practice is vital to the health of patients with this disorder. The goal of this review is to discuss the pathogenesis and clinical manifestations of tachycardia-induced cardiomyopathy, as well as approaches to its diagnosis and treatment.
Short-latency auditory evoked potentials in the monkey. I. Wave shape and surface topography.

Abstract The components and topography of the short-latency auditory evoked potentials (SLAEPs) in the monkey were analyzed using a combination of surface and epidural electrodes. Nine positive peaks, and a slow negativity following wave 7, are identified in the SLAEP recorded at the vertex referred to the mastoid ipsilateral to a monaural stimulus. Subcomponents of waves 1 and 3 are consistently observed, and other waves are probably compound as well. Barbiturate anesthesia results in latency prolongations which are cumulative across components but does not alter the component sequence. With binaural stimulation there is simple summation of the monaural responses for the components preceding wave 7, but a binaural interaction for wave 7. The polarity and clarity of the various components depend on the recording configuration selected. No single configuration is optimal for the demonstration of all components, and the use of montages with multiple electrodes may increase the information gained from clinical SLAEP recordings in man. The monkey SLAEP components can be grouped based on similarities of their surface topographies, which suggest similar anatomic orientations of their underlying generators. Probable homologues between the components of the simian and human SLAEP, based on temporal sequence, topography, and the effects of variation of the stimulus parameters, are: Jewett's waves I through VII correspond to monkey waves 1, 3, and 5 through 9. Due to differences in the size and shape of the heads, the monkey waves 2 and 4 correspond to negativities in the human SLAEP, labeled IN and IIN after the components which they follow. Another peak, with latency between waves 7 and 8 in the monkey and V and VI in man, is only clearly seen in the mastoid-to-mastoid linkage, contralateral negative.
Why ozonolysis may not increase the hydrophilicity of particles

Abstract It is commonly assumed that atmospheric oxidation of hydrocarbon particles or hydrocarbon coatings on particles leads to polar products and increased water uptake, altering atmospheric visibility and increasing the likelihood they will act as cloud condensation nuclei (CCN). We show here through laboratory experiments that increased water uptake depends on the 3-dimensional structure of the particles. Laboratory studies of particles formed during ozonolysis of surface-bound alkenes, present as terminally unsaturated self-assembled monolayers (C8= SAM) on a silica substrate, were carried out at room temperature and 1 atm pressure. SAMs were exposed to ∼10 13 O 3 molecules cm −3 for 40 min and resultant particles were analyzed using single particle Fourier transform infrared micro-spectroscopy (micro-FTIR) and secondary ion mass spectroscopy (SIMS). Spectroscopy results show that –COOH and other polar groups are formed but are buried inside a hydrophobic shell, consistent with earlier observations ( McIntire et al., 2005; Moussa et al., 2009 ) that water uptake does not increase after reaction of the terminal alkene with O 3 . These insights into the 3-D structure of particles formed on oxidation have important implications for the ability of secondary organic aerosols to act as CCN. In addition, the nature of the surface of the particles is expected to determine their uptake into biological systems such as the surface of the lungs.
Phantoms For The Accurate Simulation Of Energy-Dependent Patient/X-Ray Beam Interactions

Many quality control procedures in diagnostic radiology require the accurate simulation of the x-ray spectrum transmitted by the patient. Measurements of the contrast produced by mammographic imaging systems and the adjustment of phototimers used with rare earth screens are examples of such procedures. An analytical method for designing two-component phantoms which accurately simulate not only the narrow-beam attenuation but also the scattering properties of specified thicknesses of given tissue compositions is presented. As an example, a mammography phantom composition which matches both the narrow-beam attenuation and the scattering of 50% adipose/50% glandular breast tissue to better than ±0.5% at x-ray energies from 10 to 75 keV is described. An extension of the method to the design of three-component materials with improved simulation properties (±0.1%) is also described. These materials are suitable for tissue simulation in computed tomography (CT) applications.© (1981) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.