cssi/SciSciGPT-SciSciNet huggingface dataset:
Sleep and Suicide in Older Adults: An Opportunity for Intervention

Whether as a standalone disorder or as a symptom associated with existing pathology, the prevalence of sleep disturbance increases with age. Older adults also experience a myriad of risk factors for suicide, including depression, and have elevated rates of suicide. There is now significant evidence linking sleep disturbances to suicidal thoughts and behaviors. The use of pharmacologic means to treat insomnia (e.g., sedative hypnotics) is also commonplace among older cohorts and has been associated with suicide. Behavioral treatment of insomnia represents an efficacious alternative to pharmacotherapy among older adults, which while improving sleep, may concurrently reduce depressive symptomatology. Implications and clinical recommendations of the sleep-suicide relationship are discussed.
PEP-19 modulates calcium binding to calmodulin by electrostatic steering.

PEP-19 is a small protein that increases the rates of Ca2+ binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca2+ binding and to sensitize HeLa cells to ATP-induced Ca2+ release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher’s mitt near Ca2+ binding loop III of CaM. The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca2+ binding to the C-domain of CaM by ‘catching’ and electrostatically steering Ca2+ to site III. The protein PEP-19 increases the rates of calcium binding to calmodulin. Here, the authors report the structure of PEP-19 bound to the C-terminal domain of calmodulin, and are able to propose a mechanism for the observed increased calcium association rate.
Ideological obstacles to effective climate policy: The greening of markets, technology, and growth:

In light of the 2015 Paris Climate Agreement, this project synthesizes and advances critiques of the possibility of a sustainable capitalism by adopting an explicit ‘negative’ theory of ideology, u...
Advancing LGBT Health Care Policies and Clinical Care Within a Large Academic Health Care System: A Case Study

Culturally competent health care is especially important among sexual and gender minority patients because poor cultural competence contributes to health disparities. There is a need to understand how to improve health care quality and delivery for lesbian, gay, bisexual, and transgender (LGBT) veterans in particular, because they have unique physical and mental health needs as both LGBT individuals and veterans. The following article is a case study that focuses on the policy and clinical care practices related to LGBT clinical competency, professional training, and ethical provision of care for veteran patients in the VA Boston Healthcare System. We apply Betancourt et al.'s (2003) cultural competence framework to outline the steps that VA Boston Healthcare System took to increase cultural competency at the organizational, structural, and clinical level. By sharing our experiences, we aim to provide a model and steps for other health care systems and programs, including other VA health care systems, large academic health care systems, community health care systems, and mental health care systems, interested in developing LGBT health initiatives.
A distributed approach for DG integration and power quality management in railway power systems

Currently, railway systems are electrified to meet the rising demand for faster speed, more stable operation and more passenger traffic. Although special electrical traction systems are utilized to provide power for railway load consumption, major power quality challenges are present. This paper addresses the Volt/VAR control problem in railway power systems (RPS) considering distributed generations (DGs) interconnected to the system via smart inverters. An economic Volt/VAR sensitivity analysis approach is developed to obtain ideal reactive power injected from DG units. An adaptive energy reserve method is presented, which routes the surplus energy available to the energy storage system (ESS) to be utilized eventually. The problem of decreasing system losses, and maintaining a good voltage profile is formulated as a multi-objective optimization problem. A six-bus system is used for control architecture validation. Simulation results indicate reduction in the technical losses and the stress on automatic voltage regulators. Easy to implement model, without hard to design parameters and high efficiency, highlights the potential aspects for real-life applications.
Aromaticity and its chemical manifestations

Summary Aromaticity may be considered as the stabilization of a molecule that results from π-electron delocalization in a closed shell system. It has a number of chemical manifestations such as an endothermic first hydrogenation energy, a tendency toward bond length equalization, enhanced diamagnetic susceptibilities and characteristic nmr chemical shifts. However, as noted above, none of these are really unique. Polycyclic aromatic compounds having significant π-electron stabilization often have a variety of bond lengths. Linear aromatic systems cannot have special magnetic properties since such properties result from cyclic delocalized systems. In discussing resonance, Pauling stated “The theory of resonance in chemistry is essentially a qualitative theory, which like the classical structural theory, depends for its successful application largely upon a chemical feeling that is developed through practice.” The same is true with aromaticity.
Rib Fracture Associated with Bordetella pertussis Infection

Rib Fracture Associated with B. pertussis Infection A 66-year-old woman presented with a 2-week history of cough as well as bruising and pain across the right flank. Nasopharyngeal culture confirmed infection with Bordetella pertussis, and imaging revealed a rib with a displaced fracture that had resulted from coughing.
Race, class, and space: an intersectional approach to environmental justice in New York City

The present study contributes to the environmental justice (EJ) literature by quantitatively examining spatial location within a city through an intersectional lens. Specifically, we develop the li...
Balthasar Bekker and the Spirit Debate

Father Perreaud had been away from his home in Macon for five days, but because this was nothing unusual his maid continued her daily chores in expectation of his return. On the evening of September 14th, 1623, as the maid and another young lady were asleep in the same room, the young lady was awakened by a series of pulls on the curtain of her bed. Furniture in the room was suddenly thrown down, and when the lady tried to leave the room the door seemed to be held shut from the other side. When she later asked the maid why she had done these things to frighten her, the maid said that she had done nothing, but that perhaps the boy sleeping in the antechamber was responsible.
Operation ARIES!: A Computerized Game for Teaching Scientific Inquiry

ARIES (Acquiring Research Investigative and Evaluative Skills) is a computerized educational game in which players attempt to stop extraterrestrials from implicitly stunting scientific progress on Earth by publishing bad research in a variety of fields. Players progress through three modules: 1) read and be tested on an on-line science text, 2) evaluate potentially flawed research articles, and 3) learn question-asking skills. ARIES incorporates multiple learning principles, such as testing effects, generation effects, and formative feedback.
Imagination, Play and Becoming The Text

A child’s greatest achievements are possible in play. In play a child always behaves beyond his average age, above his daily behavior; in play it is as though he were a head taller than himself (Vygotsky, 1978, p. 102).
Design and Operation of a Sensible Heat Peaking Unit for Small Modular Reactors

Approximately 19% of the electricity produced in the United States comes from nuclear power plants. Traditionally, nuclear power plants, as well as larger coal-fired plants, operate in a baseload m...
Determining the Complex Refractive Index of Neat CdSe/CdS Quantum Dot Films

Understanding how structural and synthetic factors influence the complex refractive index of quantum dot (QD) solids is crucial to tailoring the light–matter interactions of QD-containing photonic and optoelectronic devices. However, neat QD films are challenging to accurately model as they are a mixture of inorganic core/shell materials and surrounding organic ligands. Furthermore, both the QD film morphology and the complex refractive index vary due to particle size, ligand chain length, and the deposition process. Here, we study the complex refractive index of neat CdSe/CdS core/shell QD films by using variable-angle spectroscopic ellipsometry to derive the effective complex refractive index using Kramers–Kronig consistent dispersion models. We use this information in conjunction with intrinsic refractive index data of CdSe and CdSe/CdS QDs extracted from solution-state absorption data and effective medium approximations (EMA) to describe neat QD films. We find that EMAs can successfully be used as a t...
Abstract WP174: Factors Associated With Medication Knowledge Among Stroke Survivors

Introduction: Adequate medication knowledge among stroke patients has been shown to be associated with a reduction in vascular risk factors and recurrent stroke. Yet, limited research has investiga...
Sound Practice: Evaluating DACS Compliance in Archival Description of Music Recordings

Standardization of descriptive practice supports improved access to archival collections with sound recordings of music. However, description of music sound recordings is complicated because of the unique characteristics of both music and sound recordings. Unfortunately, the standard for archival description in the United States, Describing Archives: A Content Standard (DACS), does not supply specific rules for music sound recordings, although it does recommend that archivists consult The International Association of Sound and Audiovisual Archives (IASA) Cataloguing Rules: A Manual for Description of Sound Recordings and Related Audiovisual Media for guidance. Given the wide range of descriptive options available via this recommendation, this study evaluates the extent to which finding aids for music collections with sound recordings successfully adhere to DACS, both in the application of IASA’s Rules as well as overall compliance with the standard in description of music sound recordings. Using document analysis methodology, this study finds low compliance with DACS and shows that finding aids commonly fail to apply IASA’s Rules correctly in description of music sound recordings. More research is needed to determine the reason(s) for this noncompliance. Possible solutions to improve standardization could include updating and clarifying the instructions in DACS, or using a different standard that provides specific instructions for description of archival sound recordings.
A Rapid Synthesis of Hydroxymethylacylfulvene (HMAF) Using the Allenic Pauson−Khand Reaction. A Synthetic Approach to Either Enantiomer of This Illudane Structure

An allenic Pauson−Khand reaction has been employed in the preparation of (±)-hydroxymethylacylfulvene (HMAF), an anticancer agent that is currently in Phase II clinical trials for a variety of solid tumor types. The synthesis is effected in 11 steps from commercially available starting materials. In addition, an asymmetric route to the title compound has been established by intersecting the racemic synthesis with an enantiomerically pure intermediate. The preparation of the enantiomerically pure intermediate involved the Sharpless asymmetric dihydroxylation (AD) of a trisubstituted olefin of an enyne system. This approach provides access to both enantiomers of HMAF simply by changing the ligands in the Sharpless AD reaction. Optimized conditions for the stereospecific synthesis of E or Z trisubstituted enynes from an aliphatic ketone using either Peterson olefination or Horner−Wadsworth−Emmons protocols are reported. Finally, a better understanding of the stereoelectronic requirements of the allenic P−K r...
Connecting motivations to outcomes: A study of park visitors’ outcome attainment

Abstract Assessing the visitor experience for management in park and protected areas has long been the research focus of social scientists working in concert with park managers. One approach to protected area management—outcomes focused management—examines either the motivations that guide the behavior of recreationists or the outcomes that are attained through outdoor recreation experiences as a means of better meeting visitor expectations. Though longstanding calls have been made to integrate motivations and outcomes, they remain separated—as researchers select one or the other as measures of either the drivers of or the actual visitor experience. This study is an attempt to connect motivations to outcomes with the goal of understanding their relationship and developing an outcome-based means of measuring the quality of experiences in a heavily visited area of Grand Teton National Park, Wyoming. Using a pre- and post-experience survey approach, researchers first asked visitors what outcomes they were seeking from the area and then examined to what degree they attained the outcomes that drove their visitation. Results of a structural equation model suggest that visitors were able to attain the outcomes they were seeking from their experience, with the exception of escaping society. The use of outcome attainment as a possible measure of quality is subsequently discussed.
A stomatal model of anatomical tradeoffs between photosynthesis and pathogen defense

Stomatal pores control both leaf gas exchange and are an entry for many plant pathogens, setting up the potential for tradeoffs between photosynthesis and defense. To prevent colonization and limit infection, plants close their stomata after recognizing pathogens. In addition to closing stomata, anatmoical shifts to lower stomatal density and/or size may also limit pathogen colonization, but such developmental changes would permanently reduce the gas exchange capacity for the life of the leaf. I developed and analyzed a spatially explicit model of pathogen colonization on the leaf as a function of stomatal size and density, anatomical traits which determine maximum rates of gas exchange. The model predicts greater stomatal size or density increases colonization, but the effect is most pronounced when stomatal cover is low. I also derived scaling relationships between stomatal size and density that preserves a given probability of colonization. These scaling relationships set up a potential conflict between maximizing defense and minimizing stomatal cover. To my knowledge, this is the first mathematical model connecting gas exchange and pathogen defense via stomatal anatomy. It makes predictions that can be tested with experiments and may explain variation in stomatal anatomy among plants. The model is generalizable to many types of pathogens, but lacks significant biological realism that may be needed for accurate predictions.
Modifiable mediators associated with the relationship between adiposity and leukocyte telomere length in US adults: The National Health and Nutrition Examination Survey.

Abstract Obesity is associated with age-related health conditions and telomere attrition – a marker of cellular aging. Obesity is attributable to adverse modifiable lifestyle factors. Little is known about the mediation effect of lifestyle factors associated with the relationship between obesity and telomere length. Our objective was to examine this association in the US. Pack years smoked, drinking level per day, physical activity (PA) per week and diet based on Healthy Eating Index (HEI) were assessed as mediators associated with the relationship between adiposity measures and leukocyte telomere length (LTL); adiposity measures included body mass index (BMI), % total body fat (TBF) and waist circumference (WC). Separate adjusted linear regressions and mediation analysis were conducted on a total of 4919 respondents aged 20–84 years using cross-sectional 1999–2002 data from the US National Health and Nutrition Examination Survey. Inadequate PA correlated with 1.28% shorter LTL and was a factor accounting for 35% of the relationship between BMI and LTL (β = −0.0128, 95% CI = 0.0259, 0.0004, p = .05). Smoking 30–≥59 pack years correlated with 4% shorter LTL and accounted for 21% of the relationship between %TBF and LTL (β = −0.0386, 95% CI = −0.0742, −0.0030, p = .03). Improvement in diet correlated with 0.11% longer LTL and contributed 25% of the association between %TBF and LTL (β = 0.0011, 95%CI =0.0004, 0.0018, p = .01). Diet correlated with 0.11% longer LTL and correspond to 28% of the relationship between WC and LTL (β = 0.0011, 95%CI = 0.0004, 0.0018, p = .03). Interventions to improve modifiable behaviors may ameliorate cellular aging and aging related health conditions due to obesity among US adults.
Integrative Network Analysis of Predicted miRNA-Targets Regulating Expression of Immune Response Genes in Bovine Coronavirus Infection

Bovine coronavirus (BCoV) infection that causes disease outbreaks among farm animals, resulting in significant economic losses particularly in the cattle industry, has the potential to become zoonotic. miRNAs, which are short non-coding segments of RNA that inhibits the expression of their target genes, have been identified as potential biomarkers and drug targets, though this potential in BCoV remains largely unknown. We hypothesize that certain miRNAs could simultaneously target multiple genes, are significantly conserved across many species, thereby demonstrating the potential to serve as diagnostic or therapeutic tools for bovine coronavirus infection. To this end, we utilized different existing and publicly available computational tools to conduct system analysis predicting important miRNAs that could affect BCoV pathogenesis. Eleven genes including CEBPD, IRF1, TLR9, SRC, and RHOA, significantly indicated in immune-related pathways, were identified to be associated with BCoV, and implicated in other coronaviruses. Of the 70 miRNAs predicted to target the identified genes, four concomitant miRNAs (bta-miR-11975, bta-miR-11976, bta-miR-22-3p, and bta-miR-2325c) were found. Examining the gene interaction network suggests IL-6, IRF1, and TP53 as key drivers. Phylogenetic analysis revealed that miR-22 was completely conserved across all 14 species it was searched against, suggesting a shared and important functional role. Functional annotation and associated pathways of target genes, such as positive regulation of cytokine production, IL-6 signaling pathway, and regulation of leukocyte differentiation, indicate the miRNAs are major participants in multiple aspects of both innate and adaptive immune response. Examination of variants evinced a potentially deleterious SNP in bta-miR-22-3p and an advantageous SNP in bta-miR-2325c. Conclusively, this study provides new insight into miRNAs regulating genes responding to BCoV infection, with bta-miR-22-3p particularly indicated as a potential drug target or diagnostic marker for bovine coronavirus.
A Series of Unfortunate Strokes (1425)

Objective: Thrombotic thrombocytopenic purpura (TTP) is a disease that, if untreated, carries a mortality as high as 90%. As such, prompt recognition is paramount. TTP is typically associated with small vessel occlusions, but large vessel occlusions have rarely been reported. We present a case of congenital TTP, known as Upshaw-Shulman syndrome, in a young woman with recurrent TIAs and subsequent left M1 occlusion with left Middle Cerebral Artery syndrome. Background: A 16-year-old girl presented to our institution with multiple episodes of transient focal neurologic deficits, each associated with a new punctate infarct. Standard workup was unrevealing, and cerebral angiogram confirmed a non-specific vasculopathy. The patient was diagnosed with primary CNS angiitis by an outside institution, and initiated on cyclophosphamide and prednisone. Despite this treatment, recurrent TIAs continued. Findings of low serum platelets yielded further workup with reduced ADAMTS13 activity of 6%. Standard treatment with fresh frozen plasma (FFP) was followed unexpectedly by a left M1 occlusion, that was not amenable to mechanical thrombectomy. Nevertheless, treatment with plasma exchange followed by biweekly serial FFP has led to complete disease remission. Design/Methods: NA Results: NA Conclusions: We present a case of adolescent onset recurrent TIAs diagnosed elsewhere as CNS angiitis. As treatments were deemed ineffective, workup revealed antibody-negative reduced ADAMTS13 activity. Genetic testing revealed two heterozygous mutations on separate exons, one representing a pathogenic mutation and one representing a variant of unknown significance. We postulate that the latter is in fact a pathogenic variant and mutations were in trans configuration, allowing for an autosomal recessive disease to manifest pathogenicity. Also known as Upshaw-Shulman syndrome, congenital TTP typically presents in infancy. Our case is remarkable for the late age of onset, and unexpected large vessel occlusion following standard treatment. TTP should be a consideration for all cases of pediatric onset stroke. Disclosure: Dr. Bibu has nothing to disclose. Dr. Bhise has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen.
Human Consequences of Multiple Nuclear Detonations in New Delhi (India): Interdisciplinary Requirements in Triage Management

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system with significant innovation in interdisciplinary disaster management applicable generally to urban nuclear detonation medical response. Model estimates of nuclear war casualties employed ESRI’s ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency’s WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency’s (DTRA’s) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory’s LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kt detonations and a single 1 mt (1000 kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims. Of particular importance is the interdisciplinary cooperation necessary for such a large-scale emergency response event, which would be exemplified by efforts such as the application of a Nuclear Global Health Workforce.
Silicon Carbide Semiconductors with Wide Bandgap for Electric Vehicles

Sales of electric vehicles are rising steadily. However, a major shortcoming is currently still the range of the vehicles in purely electric operation. To minimize losses in the transmission of electrical energy and thus increase the range of the vehicles, United Silicon Carbide has developed silicon carbide semiconductors that can be used to realize more efficient electrical drivetrains and power components.
Characterization of non-Fickian moisture absorption in thermosetting polymers

A recently developed moisture absorption model for thermosetting polymers that combines the non-Fickian, diffusion hindrance effects and three-dimensional anisotropy is introduced. The hindered diffusion model is shown to predict both short term Fickian and long term anomalous moisture absorption behavior often observed in thermosetting polymers and their composites. The salient characteristics of long term moisture uptake such as the equilibrium moisture content and the effect of non-Fickian phenomena are presented. Anomalous moisture concentration profiles predicted by the two-dimensional solution of hindered diffusion model are demonstrated for various cases, including the through-the-thickness moisture profile of a 40-ply, quartz/bismaleimide (BMI) composite laminate. The effects of diffusion hindrance and anisotropy on the two-dimensional, through-the-thickness concentration profiles are illustrated. The moisture absorption parameters for an EPON 862 epoxy laminate are recovered from the experimental moisture absorption data. The hindered diffusion model is shown to accurately predict the moisture uptake of EPON 862 over the complete absorption time period. The non-Fickian effects governed by the hindrance coefficient are identified for both EPON 862 and quartz/BMI composite laminate. It is shown that the quartz/BMI laminate displays significant non-Fickian behavior compared to EPON 862 epoxy resin.
O2(b1Σg+, υ = 0, 1) relative yields in O(1D) + O2 energy transfer

Energy transfer from O(1D) to O2 is the main source of O2(b1Σg+) in vibrational levels υ = 0 and 1 in the Earth's thermosphere. Knowledge of the relative yields for O2(b1Σg+) production in υ = 0 and 1 is essential for a reliable interpretation and modeling of the O2 atmospheric band emissions (b1Σg+–XΣg−3) from these two vibrational levels. We report laboratory measurements of the relative yields at room temperature. In the experiments, O2(b1Σg+, υ = 0, 1) is generated by O(1D) + O2 collisions following partial photodissociation of O2 at 157.6 nm. O2(b1Σg+, υ = 0, 1) emission detection is used to monitor the temporal evolution of the vibrational level populations. The measured fractional yield for υ = 1 is 0.8 ± 0.1, in contrast with the results of previous studies that indicated dominant O2(b1Σg+, υ = 0) production. A revision is warranted of the values used for these relative yields in atmospheric models.
Esophageal Peristaltic Dysfunction in Peptic Esophagitis

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.
Cloud droplet nucleation and its connection to aerosol properties

Publisher Summary Anthropogenic aerosols influence the Earth's radiation balance and climate directly, by scattering shortwave (solar) radiation in cloud-free conditions and indirectly, by increasing concentrations of cloud droplets thereby, enhancing cloud shortwave reflectivity. These effects are thought to be significant in the context of changes in the earth radiation budget over the industrial period, exerting a radiative forcing that is of comparable magnitude to that of increased concentrations of greenhouse gases over this period but opposite in sign. However, the magnitudes of both the direct and indirect aerosol effects are quite uncertain. Much of the uncertainty of the indirect effect arises from incomplete ability to describe changes in cloud properties arising from anthropogenic aerosols. This chapter examines recent studies pertaining to the influence of anthropogenic aerosols on loading and properties of aerosols affecting their cloud nucleating properties and indicative of substantial anthropogenic influence on aerosol and cloud properties over the North Atlantic.
New Developments in Plane-Wave Based ab initio Calculations

New developments in plane-wave based ab initio calculations are reviewed. First, a general framework for electrostatic calculations is presented that allows 3-dimensional periodic systems (solids, liquids), 2-dimensional periodic systems (surfaces), and non-periodic systems (clusters) to be treated properly and easily (J. Chem. Phys. 110, 2810–2821 (1999) and J. Chem. Phys. 115, 3531 (2001)). Second, a general method for describing systems in which the electrons are assumed to be localized in a single small region of space embedded within a large chemically inert bath, is discussed (J. Chem. Phys. 116 5351 (2002)) that significantly enhances the ability of plane-wave based techniques to study reactions in biological systems.
Strategies for investigation and control of process- and degradation-related impurities

Publisher Summary This chapter discusses the strategies for investigation and control of process- and degradation-related impurities. The chapter describes strategies for the investigation of process-related and degradation-related impurities in drug substances and drug products. Particular emphasis is given to a chemistry-guided approach and the iterative nature of investigations as knowledge is gained. The delineation of impurity type and source used is presented in the chapter. Considerations for investigating and controlling crystal forms, residual solvents, and microbiological impurities have been addressed in International Conference on Harmonization (ICH) guidelines. One strategy for impurity investigation might be termed as the “technique-oriented approach.” The main feature of this approach is to use as many techniques as possible to search for impurities. This would include various types of chromatographic techniques with multiple detection schemes. Duloxetine hydrochloride is a secondary amine that is a potent inhibitor of both serotonin and norepinephrine reuptake. Because the drug is unstable in acid, oral dosing requires encapsulation within an enteric coating that consists of hydroxypropylmethylcellulose (HPMC) and HPMC acetate succinate (HPMCAS).
Second Language Acquisition: Research and Applied Linguistics.

The purpose of this chapter is to provide an overview of second language acquisition (SLA) research over the past several decades and to highlight the ways in which it has retained its original applied and linguistic interests, and enhanced them by addressing questions about acquisition processes. As the chapter will illustrate, SLA research has become increasingly bidirectional and multifaceted in its applications. As new theories and research have emerged on language, and even more so, on learning, their application to the study of SLA has been fruitful. It has led to long-needed explanations about developmental regularities and persistent difﬁculties and has opened up new lines of research on the processes and sequences of second language (L2) development.
Correlated X-ray and Optical Variability in X-ray Binaries

It has long been known that X-ray and optical/UV variability in active X-ray binaries is sometimes correlated. The expectation has been that this arises from rapid reprocessing of X-rays into longer wavelength photons, and hence that the lags between the bandpasses can be used to reconstruct an echo-map of the binary, revealing the geometry and spatial scale of reprocessing sites. I will review how this can be done, what can be learned, and what progress has been made with real data. In addition, an interesting twist to the story has emerged in the form of correlated variability that does not seem associated with reprocessing. This extends to very short timescales, includes quasi-periodic behavior, and may be associated with optical synchrotron emission from a jet. Finally, contrary to expectations we have recently discovered that similar correlations are seen even in an ostensibly `quiescent' object allowing similar analyses of reprocessing effects.
H+-ATPase activity of Escherichia coli F1F0 is blocked after reaction of dicyclohexylcarbodiimide with a single proteolipid (subunit c) of the F0 complex.

Abstract Dicyclohexylcarbodiimide (DCCD) specifically inhibits the F1F0-H+-ATP synthase complex of Escherichia coli by covalently modifying a proteolipid subunit that is embedded in the membrane. Multiple copies of the DCCD-reactive protein, also known as subunit c, are found in the F1F0 complex. In order to determine the minimum stoichiometry of reaction, we have treated E. coli membranes with DCCD, at varying concentrations and for varying times, and correlated inhibition of ATPase activity with the degree of modification of subunit c. Subunit c was purified from the membrane, and the degree of modification was determined by two methods. In the "specific radioactivity" method, the moles of [14C]DCCD per total mole of subunit c was calculated from the radioactivity incorporated per mg of protein, and conversion of mg of protein to mol of protein based upon amino acid analysis. In the "high performance liquid chromatography (HPLC) peak area" method, the DCCD-modified subunit c was separated from unmodified subunit c on an anion exchange AX300 HPLC column, and the areas of the peaks from the chromatogram quantitated. The shape of the modification versus inhibition curve indicated that modification of a single subunit c per F0 was sufficient to abolish ATPase activity. The titration data were fit by nonlinear regression analysis to a single hit mathematical model, A = Un(1 - r) + r, where A is the relative activity, U is the ratio of unmodified/total subunit c, n is the number of subunit c per F0, and r is a residual fraction of ATPase activity that was resistant to inhibition by DCCD. The two methods gave values for n equal to 10 by the specific radioactivity method and 14 by the HPLC peak area method, and values for r of 0.28 and 0.30, respectively. Most of the r value was accounted for by the observed dissociation of 15-20% of the F1-ATPase from the membrane under ATPase assay conditions. When the minimal, experimentally justified value of r = 0.15 was used in the equation above, the calculated values of n were reduced to 8 and 11, respectively. The value of n determined here, with a probable range of uncertainty of 8-14, is consistent with, and provides an independent type of experimental support for, the suggested stoichiometry of 10 +/- 1 subunit c per F1F0, which was determined by a more precise radiolabeling method (Foster, D. L., and Fillingame, R. H. (1982) J. Biol. Chem. 257, 2009-2015).
Immunocompetent cells in the chicken: II. Synergism between thymus cells and either bursa or bone marrow cells in the humoral immune response to sheep erythrocytes☆

Newly hatched F1 hybrid chicks isogenic for the strong B histocompatibility locus were rendered immunologically incompetent by cyclophosphamide treatment and x-irradiation. They were then injected intravenously with thymus, bone marrow, or bursa cells together with sheep erythrocytes (SE) and received another iv injection of SE 3 days later. Splenic plaque-forming cells (PFC) and serum hemagglutinins were assayed 7 days after transfer. At donor ages of 14–26 days, cells from thymus (T) and bone marrow (BM) showed synergism when injected together, as indicated by a significantly higher geometric mean of PFC per recipient spleen in the BM + T group than in the BM group. The response of the T group was extremely low. With thymus and bursa cells from 6- to 28-day-old donors, significant synergism was demonstrated in 3 of 9 individual experiments. However, almost all the other 6 experiments showed marked differences in the same direction, and the combined probability for all experiments was < 0.001. The most striking demonstration of thymus + bursa synergism was made in 2 experiments using 1-week-old donors. Bone marrow cells from 1-week-old donors failed to cooperate with thymus, as did BM cells from older bursectomized agammaglobulinemic donors. This suggests that B cells from bone marrow originate in the bursa. Thymus-bursa cooperation was somewhat difficult to demonstrate in individual experiments using donors over 1 week of age, owing to the occurrence of some responses with bursal cells alone and to variability of response within bursa or bursa + thymus recipient groups. Synergism between thymus and bursa cells was more consistently demonstrable when irradiated normal spleen or low doses of bone marrow cells were added. These additions led to an increased response and a lowered coefficient of variation in the thymus + bursa recipient groups. The ‘third’ cell type needed for optimal response by the thymus and bursa cells together was tentatively identified as a macrophage.
Quantum Interference in Macroscopic Crystals of Nonmetallic Bi 2 Se 3

Photoemission experiments have shown that Bi2Se3 is a topological insulator. By controlled doping, we have obtained crystals of Bi2Se3 with nonmetallic conduction. At low temperatures, we uncover a novel type of magnetofingerprint signal which involves the spin degrees of freedom. Given the mm-sized crystals, the observed amplitude is 200-500x larger than expected from universal conductance fluctuations. The results point to very long phase-breaking lengths in an unusual conductance channel in these nonmetallic samples. We discuss the nature of the in-gap conducting states and their relation to the topological surface states.
Abnormal lipopolysaccharide binding protein as marker of gastrointestinal inflammation in Parkinson disease.

Objective: To evaluate whether lipopolysaccharide binding protein (LBP) can be used to distinguish PD subjects from control subjects and to assess whether LBP levels correlate with PD disease severity. Methods: We measured plasma LBP (ng/ml) using an ELISA kit in 94 PD subjects of various stages and 97 control subjects. Disease severity was assessed using the UPDRS and Hoehn and Yahr staging. The LBP level between the PD and control groups was compared using analysis of covariance. Spearman correlation was used to explore the relationship between LBP level and disease severity. Results: The mean LBP level in PD subjects (n=94) was significantly different from control subjects (n=95, p=0.018). In PD subjects, we did not find a correlation between mean LBP level and disease severity. Conclusions: Our data suggests that LBP is one GI biomarker related to LPS induced neurotoxicity. However, there was significant variability in LBP levels within the PD and control groups, limiting its utility as a stand-alone biomarker. This study supports the role of LPS induced neurotoxicity in PD and further exploration of this pathway may be useful in developing sensitive and specific biomarkers for PD.
Training Models in Clinical Psychology

There are three major training models in American clinical psychology, all of which require a doctoral degree: the scientist–practitioner model (Boulder conference, 1949), the scholar–practitioner model (Vail conference, 1973), and the clinical scientist model (Bloomington conference, 1994). Elsewhere in the world, there is a distinctive British model, approved in 1987, requiring a doctor of clinical psychology degree, and EuroPsy, the generic model approved by the European Federation of Psychologists' Associations, requiring the equivalent of a research-based master's degree plus a year supervised postgraduate professional experience. Keywords: Kelly, George; practice in clinical psychology; behavior therapy; cognitive behavior therapy; psychoanalysis
Redundancy revisited [CMOS combinational circuits]

This paper shows that when it comes to CMOS designs undetectability does not necessarily imply redundancy. The definition of redundancy is extended to account for the special behavior encountered in CMOS designs. The accuracy of the new redundancy definition has been tested on several CMOS chips and has been found to be correct.
Modeling of pressure generation by lasers in melanosomes: how to avoid stress confinement and blow up a melanosome

We have made a detailed theoretical investigation of the pressure generated in melanosomes upon absorption of laser energy. Our model treats the melanosome as a homogeneous absorber surrounded by a transparent water medium. The mechanical impedance mismatch between the absorbing melanosome and the surrounding medium is taken into account and has important ramifications. We have calculated the pressure profiles for pulses of microsecond duration down to picosecond duration. We show that the concept of stress confinement is not valid for this system. Though pressure amplitudes generated at the surface do reach a limit as the pulse duration is shortened below a nanosecond, no such pressure confinement occurs at the center of the absorber. As the pulse duration is shortened below a nanosecond, the tensile pressure at the center continues to rise without limit. This implies that explosive fracturing of the melanosome can occur due to the large tensile stresses, and accomplishing this fracturing requires smaller fluences as the pulse duration is shortened. We present quantitative results exhibiting how the core's tensile stress increases as the pulse duration is shortened.
Aspects of the tetrahedral neutrino mass matrix

The four-parameter tetrahedral neutrino mass matrix introduced earlier by the author is studied in two specific limits, both having only two parameters and resulting in {theta}{sub 13}=0, {theta}{sub 23}={pi}/4, and tan{sup 2}{theta}{sub 12}=1/2. One limit corresponds to a recent proposal which predicts a normal ordering of neutrino masses; the other is new and allows both inverted and normal ordering.
Incentive pay: Productivity, sorting, and adjacent rents

Abstract I model and empirically test the hypothesis that higher-quality workers prefer performance pay to time-rate based pay because they realize rent upon two different dimensions: Explicit and implicit rents. First, higher-quality workers are outright more productive than their lower-quality counterparts, earning them explicit rent ( Curme and Stefanec, 2007 ). Second, these same factors of production facilitate the unobserved heterogeneity for incentive workers, earning them implicit rent because they can produce a given level of output with less effort. I find strong empirical evidence to confirm that these implicit rents exist and I measure them at 1.5–3.4 percent of average real hourly earnings.
Measuring granule phase volume distributions using X-ray microtomography

Abstract Although granule microstructure has been shown to have a significant influence on granule performance, e.g., impact attrition resistance, dissolution rate, and granule strength, there has been a lack of research on methods to identify granule components in 3D space to describe granule microstructural properties. This paper presents techniques to non-destructively identify and describe spatial distributions of particle, binder, and air volumes within wet-granulated granules using X-ray microtomography (XRμT). Ten granules were produced from glass ballotini particles and aqueous PVP binder and were imaged using XRμT. Particle and binder volumes were identified from the output images by using a combination of gray intensity value thresholds and image processing techniques. A new technique, utilizing the intersection of convex hulls defined along the granule's three principal planes, was developed to distinguish between the intra-granular and extra-granular air space. Segmented glass ballotini masses were accurate and insensitive to the gray value thresholds. Segmented PVP mass was sensitive to both the lower gray value threshold and the elimination of particle partial voxels. Therefore, the effect that the segmentation method had on image measurements was investigated. Identified internal air volumes gave good agreement when compared to the powder bed porosity and to the predicted average particle coordination number. The spatial distributions of the phases are described both radially from the granule's center of mass and with planes starting from the top of each granule. While phase volume fractions are uniformly distributed in the radial direction, axial distributions show that the binder volume fractions at the top of the granules are approximately 3% larger than at the bottom of the granules. This localization of binder was found to be consistent regardless of the binder identification method and is the first quantitative proof of intra-granular binder segregation for granules formed with a binder solution.
SECULAR AND RELIGIOUS MEMORY IN EGYPT: RECALLING NASSERIST CIVICS

L'A. montre comment un certain nombre d'Egyptiens ont repondu a l'influence croissante des islamistes en se tournant vers l'heritage nasserien. En effet, ce dernier met en avant le sens civique et l'unite nationale sur le mode seculier. L'Egypte reste une societe ou la tradition nasserienne domine et ceci parce que dans une large mesure, le parti au pouvoir, un avatar de l'ideologie du parti unique nasserien, a reussi a capturer les institutions. Ainsi, certains Egyptiens cherchent a se reapproprier une memoire publique et a affirmer une culture civique seculiere
In-Plane Deformation Measurements Using Digital Image Correlation of Ultrasonic C-Scan Images

The extension of digital image correlation method to ultrasonic C-scan acoustical speckle images of the bulk is presented in this paper. The approach discussed in this paper is ideally suited to composite materials such as particulate composites, fiber-reinforced plastics, and laminated composites. It can also be effectively employed for critical surfaces that are not within view, such as interfaces and back surfaces. Images taken prior to and after deformation are analyzed to estimate a deformation profile from changes in the image. The aim of the method is to find the displacements and strains of small subsets from the second image relative to the first one. This is accomplished by comparing the intensity levels of the subsets in the images. The speed and accuracy of the system is enhanced by the genetic algorithms(GAs) which are used to optimize correlation of images. An ultrasonic C-scan system was used to obtain the intensity images of the front or back surface of an isotropic or composite material. Three experimental tests were conducted to illustrate the application of Ultrasonic C-scan digital image correlation method. These tests include: 1) uniform translation, 2) small angle rotation, and 3) uniform deformation. A laminated carbon/epoxy composite panel (305×305×8 mm) was used for uniform translation and small angle rotation tests. A rubber specimen was used to perform the uniform axial deformation test. The results of correlated displacements (angles) are compared to the actual displacements (angles). The accuracy and applied limitation of the three experiments are also illustrated in this paper.Copyright © 2003 by ASME