cssi/SciSciGPT-SciSciNet huggingface dataset:
When to Conduct a Renal Impairment Study During Drug Development: US Food and Drug Administration Perspective

To optimize drug therapy for individuals, it is critical to understand how various intrinsic (e.g., age, gender, race, genetics, organ impairment) and extrinsic factors (e.g., diet, smoking, concomitantly administered drugs) affect drug exposure and response.(1) Up to now, it has been far easier to discover effects on exposure caused by these factors, and the US Food and Drug Administration (FDA) has published several guidance documents with recommendations on how to evaluate these factors during drug development.
Heats of adsorption of carbon monoxide on bone mineral and on thorium oxide by gas-solid chromatography.

Isosteric heats of adsorption qst have been measured by both pulse and continuous flow chromatography for carbon monoxide on bone mineral and on thorium oxide. Pretreatment of the solids consisted of vacuum outgassing at 500°C. Previous work has shown that the first small increments of water (θ < 0.10) are bound to the pretreated surface with a heat of adsorption of 20 kcals/mole for the bone mineral but 30–40 kcals/mole for the thorium oxide. The qst values for CO at low coverage (say θ = 0.002) are if anything slightly less on the thoria surface. This indicates that in spite of its considerably stronger attraction for chemisorbed water the thoria surface has no greater polarizing power for CO than has the bone mineral surface. The qst values obtained by the pulse and continuous flow methods support the conclusion of an earlier publication from this laboratory that the pulse method gives results which are somewhat in error in cases where the isotherms at low coverage fail to conform to Henry's law.
Addressing Suicidality in Primary Care Settings

By design or by default, primary care providers (PCPs)are frequently the vanguard in the fight against suicide. Recent studies have highlighted programs to improve screening and prevention of suicidality in the medical home, particularly among high-risk patients, such as adolescents, the elderly, and veterans. Increasing efforts are also being paid to improving the PCP’s skill in assessing for suicidality. However, it is becoming increasingly apparent that screening alone will not significantly lower suicide rates until it occurs within a well-integrated system that facilitates timely referral to more intensive mental health services for those patients who need them. Unfortunately, such systems are sorely lacking in many, if not most, areas of the USA.
Electrochemical investigations of platinum-methyluracil-blue and the related binuclear complex [(NH3)2Pt(MeU)2Pt(NH3)2](NO3)2

Abstract The redox behavior of the head-to-head bis(μ- (1-methyluracilato- N 3 , O 2 )-bis( cis -diammine platinum(II)) dinitrate, PtMeU, and platinum 1-methyluracil blue, PtMeUB, was studied by cyclic voltammetry (CV), rotating disk voltammetry (RDV), and controlled-potential coulometry (CPC). Redox titrimetry, electrochemistry/electron paramagnetic resonance spectroscopy (EPR), and liquid chromatography (LC) served as complementary techniques. The former reactant exhibits two-step electro-oxidation, consistent with the formation of a mixed-valence Pt(II, III) state en route to Pt(III, III). The latter also appears to oxidize to a uniform Pt(III) state. Although the oxidative-reductive electrochemistry of both reactants exhibits chemical reversibility, the heterogeneous electron-transfer kinetics are notably sluggish. The latter appears to be associated with the formation of an inhibiting film on the electrode surface. A slow conversion of PtMeU to a PtMeUB-like state was revealed by CV and LC. The complex, oligomeric nature of PtMeUB was revealed by means of gradient LC examination. Comparing oxidative and reductive electrolysis curves for PtMeUB yielded an average platinum oxidation state of 2.08. All observed behavior for PtMeUB, as well as for PtMeU, is accounted for by invoking +2 and +3 oxidation states for platinum; redox titrimetry using Ce(IV) revealed inconsequential oxidation of both of these systems beyond the III state. An estimate of molecular weight for the platinum blue was made by employing RDV in conjunction with the Einstein-Stokes equation.
Dapsone-Induced Sulfone Syndrome:

OBJECTIVE:To report a patient with dapsone-induced sulfone syndrome.CASE SUMMARY:A 42-year-old HIV-infected African American man developed fever, lymphadenopathy, exfoliative dermatitis, hepatitis, and methemoglobinemia 4 weeks after starting dapsone. Complete resolution of symptoms and laboratory abnormalities occurred with cessation of dapsone therapy.DISCUSSION:Sulfone syndrome is not a well-known sequela of dapsone therapy. It is not dose-related, usually occurs in doses of 50–300 mg/d, all cases occur within 2 months of starting dapsone, all patients have fever, and most patients will develop rash and evidence of hepatic injury. The temporal relationship between dapsone therapy and onset of clinical symptoms and objective data led us to believe that dapsone caused sulfone syndrome in our patient. An objective causality assessment revealed that the adverse drug event was probable.CONCLUSIONS:Although sulfone syndrome appears to be relatively uncommon, healthcare practitioners must be aware of the pote...
Deworming the world.

Worms or helminths have historically infected more than half the world's population, but were largely neglected by medical science and public health interventions because they were considered non-fatal and of minimal clinical significance. During the 1980s, several oral drugs that were originally developed for veterinary use were discovered to cure, in a single dose, most human helminth infections. This allowed the first systematic population-based studies of the morbid sequelae of chronic worm infection and their potential reversibility after treatment. Based on these studies, we now know that almost all infected children and many adults, particularly pregnant and lactating women, suffer adverse effects from worms, including growth stunting, anemia, decreased cognitive development, and poor birth outcomes as well as poor school and work performance. Worm-infected people also respond less well to vaccinations and are more susceptible to several co-conditions such as HIV and cirrhosis. Based on these findings, several vertically organized national control programs were initiated in developing countries against schistosomiasis and the soil-transmitted helminths (hookworm, ascariasis, and whipworm). In 2005, the impact of helminth infections was redefined in terms of disability-adjusted life years (DALYs). All worm infections amenable to population-based mass chemotherapy are thought today to cause 30 million DALYs worldwide or very close to the worldwide impact of tuberculosis (TB) or malaria. In addition, almost all worm-induced DALYs are potentially reversible or preventable with periodic treatment. In 2001, the World Health Assembly advocated for mass deworming to reach 75% of the at-risk school-aged children of the world, but by 2011 only 13% had been reached. The recent large donations of anti-helminth drugs by major pharmaceutical companies linked to the inclusion of the “neglected tropical diseases” into current priorities for AIDS/TB and malaria now represent the best hope for closing this gap.
Exterior vs. interior rotors in robotic brushless motors

Many robotic actuators must generate high torques and accelerations. Exterior-rotor brushless motors seem better suited for these tasks than conventional interior-rotor brushless motors. Models of these two motor types were used to calculate benchmarks and evaluate motor performance in simulated tasks for different motor geometries. Exterior-rotor motors had higher motor constants and efficiency, but lower rated power compared with interior-rotor motors. They required less energy to perform typical robotic tasks. Four exterior-rotor motors were fabricated and compared with manufacturing data from the best existing brushless DC motors. The exterior-rotor motors had more than a 250% increase in stall torque density compared with the best known brushless DC motor (RoboDrive) and more than a 740% increase in stall torque density compared with more common motors such as those produced by MicroMo and Maxon. These exterior-rotor motors appear promising for robotic applications.
Big Data in Accounting: An Overview

SYNOPSIS: This paper discusses an overall framework of Big Data in accounting, setting the stage for the ensuing collection of essays that presents the ongoing evolution of corporate data into Big ...
Notes on the superposition scandal

Attention is focused on continuous-space shift-invariant systems with continuous system maps and inputs and outputs that are elements of L∞(Rd). It is shown that infinite superposition can fail in this important setting. It is also shown that continuous shift-invariant linear mappings need not commute with the operation of integration (even when the two composite operations are well defined).
The skinny on SIRT1 regulation

SIRT1 (sirtuin 1), the mammalian orthologue of yeast Sir2, is a highly conserved NAD+-dependant deacetylase that is emerging as an important regulator of aging and metabolic disease. SIRT1 and its family members promote longevity in different model organisms, including yeast, worms, flies and mice.
Significant Bronchodilator Responsiveness and "Reversibility" in a Population Sample

Chronic Obstructive Pulmonary Disease (COPD) is defined by being “not fully reversible”, most guidelines recommend measurement of lung function after the administration of a bronchodilator. The objective of this study was to compare bronchodilator responsiveness (significant improvement in the FEV1 or FVC) to full-, partial- or “inverse”’ reversibility in obstruction status in a population-based sample in Southeastern Kentucky. The study population was selected using random digit dialing of an adult population in Southeastern Kentucky as part of the Burden of Lung disease (BOLD) project. Lung function was assessed using spirometry pre- and post-bronchodilation. Subjects presence and severity of COPD was classified using modified Global Obstructive Lung Disease (GOLD) criteria. We examined the relation between changes in “obstruction” status (based on the FEV1/ FVC of 0.7) and the presence of “significant bronchodilator responsiveness” (based on ≥ 12% improvement in the FEV1 or the FVC). The final population with acceptable pre- and post-bronchodilator spirometry included 440 participants. 32/440 subjects (7.3%) changed from obstructed to unobstructed (fullreversibility), 19/440 (4.3%) changed from unobstructed to obstructed (“inverse”-reversibility), 389/440 (88.4%) had either no-change or partial-reversibility, and 65/440 (14.8%) had bronchodilator responsiveness. Among those with full-reversibility, only 9/32 (28.1%) had bronchodilator responsiveness, whereas among subjects with “inverse”-reversibility, 10/19 (52.6%) had bronchodilator responsiveness. Among all subjects with bronchodilator responsiveness, only 19/65 (29.2%) changed categories. Our findings suggest that significant bronchodilator responsiveness is not the same as “reversibility” of “obstruction”, even though these terms are often used interchangeably. BACKGROUND COPD is a chronic disease of the lungs and is characterized by irreversible airflow limitation, and is currently the fourthleading cause of death in the United States (1, 2). GOLD defines COPD as a preventable and treatable disease with airflow limitation that is usually progressive and associated with an abnormal
Analysis of memory referencing behavior for design of local memories

Memory referencing behavior is analyzed via the study of traces for the purpose of developing new local memory structures and management techniques. A novel trace processing technique called flattening reduces the dependence of the results on the underlying compiler and architecture on which the trace was generated, and partitions each memory location into its constituent values. The referencing patterns of each value in the resulting trace is described via statistics such as interreference time, lifetime, etc. The referencing patterns of the entire trace are described via histograms showing the distributions of the statistics for the individual values. The results of this analysis indicate the use of a program controlled cache to efficiently reduce the traffic from the cache to main memory. By using program control, the future knowledge of the compiler can be imparted to the cache, allowing the rejection of dead values and early replacement of values with long interreference times.
Cure Cycle Design for Thermosetting-Matrix Composites Fabrication under Uncertainty

Design of the optimal cure temperature cycle is imperative for low-cost of manufacturing thermosetting-matrix composites. Uncertainties exist in several material and process parameters, which lead to variability in the process performance and product quality. This paper addresses the problem of determining the optimal cure temperature cycles under uncertainty. A stochastic model is developed, in which the parameter uncertainties are represented as probability density functions, and deterministic numerical process simulations based on the governing process physics are used to determine the distributions quantifying the output parameter variability. A combined Nelder–Mead Simplex method and the simulated annealing algorithm is used in conjunction with the stochastic model to obtain time-optimal cure cycles, subject to constraints on parameters influencing the product quality. Results are presented to illustrate the effects of a degree of parameter uncertainty, constraint values, and material kinetics on the optimal cycles. The studies are used to identify a critical degree of uncertainty in practice above which a rigorous analysis and design under uncertainty is warranted; below this critical value, a deterministic optimal cure cycle may be used with reasonable confidence.
Quantitative Modeling of Complex Environments

There are many formal approaches to specifying how the mental state of an agent entails the particular actions it will perform. These approaches put the agent at the center of analysis. For some questions and purposes, it is more realistic and convenient for the center of analysis to be the task environment, domain or society of which agents will be a part. This paper presents such a task environment-oriented modeling framework that can work hand in hand with more agent-centered approaches. Our approach features careful attention to the quantitative computational interrelationships between tasks, to what information is available and when to update an agent's mental state and to the general structure of the task environment rather than single-instance examples. A task environment model can be used for both analysis and simulation, it avoids the methodological problems of relying solely on single-instance examples and provides concrete, meaningful characterizations with which to state general theories. This paper is organized around an example model of co-operative problem solving in a distributed sensor network.
Evolution of a unique mitotype-specific protein-coding extension of the cytochrome c oxidase II gene in freshwater mussels (Bivalvia: Unionoida).

A unique mode of mitochondrial DNA inheritance, designated doubly-uniparental inheritance (DUI), occurs in three bivalve subclasses (Pteriomorpha: Mytiloida, Palaeoheterodonta: Unionoida, Heterodonta: Veneroida), indicating that DUI may be a widespread phenomenon among bivalves. In mytiloids, breakdown of this pattern of inheritance (gender-switching) is observed in natural populations and in a phylogenetic context. In contrast, gender-switching has not occurred during the evolutionary history of unionoids. Here we present sequences for the male (M) and female (F) mitotypes from an additional 8 species of Unionoida. Consistent with previous observations, the M and F mitotypes of all species form reciprocally monophyletic clades supporting the hypothesis of taxon-specific rates of gender-switching. Coinciding with the absence of gender-switching is an ≈185 codon extension of the cytochrome c oxidase II (MTCO2) locus in the male genome. The extension is present in all 12 unionoid species examined, including a representative of the family Margaritiferidae, indicating that this protein-coding polymorphism originated ≥ 200 MYBP. Although the extension is well conserved in length among 11 of the 12 species, one taxon has a significantly shortened extension. Lastly, examination of the rates and patterns of substitution indicate that the extension is evolving under relaxed purging selection, a pattern inconsistent with the conserved nature of MTCO2 or any cytochrome c oxidase locus.
Family- and population-based designs identify different rare causal variants

Both family- and population-based samples are used to identify genetic variants associated with phenotypes. Each strategy has demonstrated advantages, but their ability to identify rare variants and genes containing rare variants is unclear. To compare these two study designs in the identification of rare causal variants, we applied various methods to the population- and family-based data simulated by the Genetic Analysis Workshop 17 with knowledge of the simulated model. Our results suggest that different variants can be identified by different study designs. Family-based and population-based study designs can be complementary in the identification of rare causal variants and should be considered in future studies.
The Function of Phenomenal States: Supramodular Interaction Theory.

Discovering the function of phenomenal states remains a formidable scientific challenge. Research on consciously penetrable conflicts (e.g., “pain-for-gain” scenarios) and impenetrable conflicts (as in the pupillary reflex, ventriloquism, and the McGurk effect [H. McGurk & J. MacDonald, 1976]) reveals that these states integrate diverse kinds of information to yield adaptive action. Supramodular interaction theory proposes that phenomenal states play an essential role in permitting interactions among supramodular response systems—agentic, independent, multimodal, information-processing structures defined by their concerns (e.g., instrumental action vs. certain bodily needs). Unlike unconscious processes (e.g., pupillary reflex), these processes may conflict with skeletal muscle plans, as described by the principle of parallel responses into skeletal muscle (PRISM). Without phenomenal states, these systems would be encapsulated and incapable of collectively influencing skeletomotor action.
Parainfluenza virus infection associated with posterior reversible encephalopathy syndrome: a case report

Posterior reversible encephalopathy syndrome is a clinical and radiological entity. The most accepted theory of posterior reversible encephalopathy syndrome is a loss of autoregulation in cerebral blood flow with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema. In infection-associated posterior reversible encephalopathy syndrome, a clinical pattern consistent with systemic inflammatory response syndrome develops. Parainfluenza virus has not been reported in the medical literature to be associated with posterior reversible encephalopathy syndrome. We report herein the case of a 54-year-old Caucasian woman with posterior reversible encephalopathy syndrome associated with parainfluenza virus infection who presented with generalized headache, blurring of vision, new-onset seizure and flu-like symptoms. Infection-associated posterior reversible encephalopathy syndrome as well as hypertension-associated posterior reversible encephalopathy syndrome favor the contribution of endothelial dysfunction to the pathophysiology of this clinicoradiological syndrome. In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of posterior reversible encephalopathy syndrome in patients presenting with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in posterior reversible encephalopathy syndrome is paramount.
New Institutional Economics and the Failure of Sustainable Forestry in Ghana

This article explores reasons for the failure of sustainable forestry in Ghana. Its contribution to the debate examines the problem of increased timber logging from an institutionalist point of view. Drawing on New Institutional Economics methodologies, the article sets out hitherto unexamined rationales for the failure to reverse deforestation in Ghana. The focus is on key actors and institutions in the timber market and the state bureaucracy. The article challenges the assumption that legislation on sustainable forestry is motivated solely by the public interest. The article concludes by suggesting a raft of approaches to dealing with deforestation in Ghana.
Detection of hormone-sensitive lipase in various tissues. II. Regulation in the rat testis by human chorionic gonadotropin.

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase found in a variety of tissues, primarily in adipose and steroidogenic tissues, that hydrolyzes triglycerides and cholesteryl esters. In the rat testis steady-state levels of HSL mRNA increase dramatically during sexual maturation. In ad- dition, HSL-like immunoreactive proteins of 84, -89, and - 102 kD have been observed in sexually immature rats with ad- ditional - 113 and - 127 kD immunoreactive proteins expressed in mature animals. In the present studies the ability of human chorionic gonadotropin (hCG) to regulate the expression of HSL and HSL-like immunoreactive proteins in rat testes has been examined. Treatment of sexually immature rats with daily injections of hCG caused a gradual increase in HSL activity that reached an 80% rise (P < 0.01) after 5 days. This was paralleled by a 3-fold increase (P < 0.01) in the 84 kD protein representing the active HSL enzyme. The - 89 kD immunoreactive protein was also increased -5-fold (P < 0.01) in parallel to the 84 kD protein and HSL activity. The -102 kD immunoreactive pro- tein was increased by hCG treatment (P < 0.01); however, its expression did not follow changes in HSL activity or in the 84 and -89 kD immunoreactive proteins, peaking within 12 h and declining thereafter. The -113 and -127 kD immunoreactive proteins did not appear during the 5 days of hCG treatment. Steady-state levels of HSL mRNA increased 60-100% (P < 0.02) in parallel to the changes in HSL activity and in the 84 and - 89 kD immunoreactive proteins. Thus, hCG increases the activity of HSL in the rat testis by increasing HSL mRNA levels and the amount of HSL protein. Although the -102 kD HSL-like immunoreactive protein is increased by hCG treat- ment, it appears that it might be a functionally unique but im- munologically related protein.- Kraemer, F. B., S. Patel, A. Singh-Bist, S. S. Gholami, M. S. Saedi, and C. Sztalryd. Detection of hormone-sensitive lipase in various tissues. XI. Regulation in the rat testis by human chorionic gonadotropin. J. Lipid Res. 1993. 34: 609-616.
Inferring door locations from a teammate's trajectory in stealth human-robot team operations

Robot perception is generally viewed as the interpretation of data from various types of sensors such as cameras. In this paper, we study indirect perception where a robot can perceive new information by making inferences from non-visual observations of human teammates. As a proof-of-concept study, we specifically focus on a door detection problem in a stealth mission setting where a team operation must not be exposed to the visibility of the team's opponents. We use a special type of the Noisy-OR model known as BN2O model of Bayesian inference network to represent the inter-visibility and to infer the locations of the doors, i.e., potential locations of the opponents. Experimental results on both synthetic data and real person tracking data achieve an F-measure of over .9 on average, suggesting further investigation on the use of non-visual perception in human-robot team operations.
Pyridoxine deficient diet and desoxypyridoxine in the therapy of lymphosarcoma and acute leukemia in man.

Three patients with disseminated lymphosarcoma and 3 cases of acute leukemia were placed on a pyridoxine deficient diet together with desoxypyridoxine for periods of four to fourteen days. Although there was evidence of malnutrition in the form of weight loss and weakness, none of the signs of specific pyridoxine deficiency described in animals was observed in the human. There was no unequivocal evidence of depression of hemopoiesis, no significant atrophy of lymphoid tissue, no signs of demyelinization of nerves, and no abnormality of tryptophane metabolism determined by urinary xanthurenic acid excretion. The possibility that the dietary restriction of pyridoxine was too brief for the development of a deficiency syndrome was considered, but it was pointed out that the rigors of the procedure were too great to justify more protracted periods of observation. Two patients had acute toxic manifestations following the administration of large doses of desoxypyridoxine. These were characterized by transient epileptiform convulsions. There were no sequelae and no recurrence of the symptoms when the dose of the drug was reduced. There was no evidence that the restriction of pyridoxine in the diet together with desoxypyridoxine for periods up to two weeks had any therapeutic effect in lymphosarcoma or acute leukemia. Also, no potentiation of the cytotoxic effect of nitrogen mustard was observed in the patients with lymphosarcoma when chemotherapy was given after the completion of the pyridoxine deficient regimen. It is to be emphasized that this does not absolutely exclude the possibility that pyridoxine deficiency may adversely affect lymphosarcoma in man. The short duration of the experiment and the well known refractoriness to any form of therapy of the tumors in these patients are factors which may have militated against a satisfactory outcome of the regimen.
Strategic Cultures and Foreign Policy Decision-Making: The Case of India and its Ties with Israel

The influence of the domestic in foreign policy decision-making has tended to be one of the prime concerns in international relations and several scholarly works have investigated the role and impact of political parties, coalition politics, bureaucracy, lobbies and diaspora on foreign policy choices of countries. Equally intriguing has been the literature on the influence of strategic culture on external policies of states. This approach, which could be traced to the writings of Sun Tzu, Thucydides and Clausewitz on national character and to Jack Snyder's 1977 account of the nature of the Soviet state, considers strategic culture of countries to change rather slowly if at all. The case of the Indian strategic culture manifests a similar - semipermanence. Rooted in the politico-strategic thought of Nehru, the country's first prime minister, Indian strategic culture has been characterized by a conspicuous restraint in undertaking conventional realist actions in international politics - a trend more or less unchanged over time. Such a restraint can be identified in the country's policy of nuclear minimalism, its military modernization and in its bilateral strategic relationship with the state of Israel. It is the third phenomenon, that this paper seeks to elaborate. Despite its strong ties with Israel, there is an astonishing lack of publicization of the the relationship, an incessant inclination of the Indian political establishment to pay lip service to the Palestinian cause and an identifiable unwillingness to use the relationship to advance direct military strategic interests- demonstrated for example, in India's refusal to accept Israel's offer of help during the 26/11 terrorist sabotage in Mumbai. The paper therefore, seeks to demonstrate the influence of the prevailing strategic culture of a country on its foreign policy behaviour, using the Indian example as a case in point.
Marketable Securities: Storage or Investment?

Corporate liquidity demand models view investments in marketable securities as a relatively simple store of excess liquidity (the storage view). However, compared to excess cash, marketable securities have more in common with investment and payout. For firms with repatriation tax exposure, constrained to a limited payout and permanent foreign real-investment plans, the average coefficient difference between excess cash and market investment regressions is zero. For all firms, the difference is 12%. The findings suggest that market investment is no longer a passive store of excess liquidity. Rather, market investment is associated with general investment and liability-driven investment.
Shape Memory Polymers from Blends of Elastomers and Small Molecule Additives

Summary Shape memory polymers are useful stimuli-responsive functional materials. This article reviews the fabrication of shape memory polymers through the blending of elastomers and small molecule additives. A comprehensive overview of this area is provided with an emphasis on the unique properties and advantages of specific material systems.
A Machine Learning Approach to Linking FOAF Instances

The friend of a friend (FOAF) vocabulary is widely used on the Web to describe individual people and their properties. Since FOAF does not require a unique ID for a person, it is not clear when two FOAF agents should be linked as coreferent, i.e., denote the same person in the world. One approach is to use the presence of inverse functional properties (e.g., foaf:mbox) as evidence that two individuals are the same. Another applies heuristics based on the string similarity of values of FOAF properties such as name and school as evidence for or against co-reference. Performance is limited, however, by many factors: non-semantic string matching, noise, changes in the world, and the lack of more sophisticated graph analytics. We describe a supervised machine learning approach that uses features defined over pairs of FOAF individuals to produce a classifier for identifying co-referent FOAF instances. We present initial results using data collected from Swoogle and other sources and describe plans for additional analysis.
Promoting Medication Adherence in Older Adults Through Early Diagnosis of Neurocognitive Disorders

Objective: Community-dwelling older adults with neurocognitive disorders experience high risk of and often suffer severe consequences from medication nonadherence. Due to the important role of informal caregivers in the care of patients with neurocognitive disorders, medication management involves both patients and families. A formal diagnosis of a neurocognitive disorder may improve both provider-patient and provider-family communications and resulting regimen adherence, yet many with signs of neurocognitive disorders remain undiagnosed. The goal of this study was to examine the differences in medication management behaviors for family caregivers of mildly impaired older adults with or without a formal neurocognitive disorder diagnosis. Method: The study included 112 women who provided at least 2 forms of medication assistance for a mildly cognitively impaired older adult with (n = 38, 34%) or without (n = 75, 66%) a reported neurocognitive disorder diagnosis and who completed online self-assessments of medication adherence and self-efficacy for medication management from May 2012 to May 2013. Cases were selected for analyses based on analog Clinical Dementia Rating scores between 0.5 and 1, indicating mild cognitive impairment in the older adult. Results: Compared to families unaware of a neurocognitive disorder diagnosis, caregivers reporting knowledge of a neurocognitive disorder diagnosis in their older family member endorsed higher medication management self-efficacy and increased levels of adherence-related behaviors. Step-wise logistic regression analyses demonstrated statistical significance in using these adherence and self-efficacy variables to differentiate between the presence or absence of a known neurocognitive disorder diagnosis (N = 112, χ26 = 22.84, P < .05). Conclusions: A formally charted and communicated neurocognitive disorder diagnosis is associated with improved medication management behaviors and medication-related self-efficacy in neurocognitive disorder family caregivers.
Human brains teach us a surprising lesson

The unique cognitive abilities of humans have long captured the imagination of philosophers and neuroscientists alike. But which features of the human brain set us apart from other mammals? Most likely, our intellectual advantages result from a relative expansion of cortical regions responsible for associative and executive function ( 1 ). However, the question of how this cortical expansion is achieved during human development has remained unresolved. A major clue came from the elucidation of neurogenic events taking place during the later phases of embryonic human brain development. This began with the recognition that the human cortical subventricular zone is greatly expanded relative to that of lower mammals. This evolutionary innovation allowed for the marked expansion of associative cortex, especially the frontal lobes. Subsequently, a thorough investigation of the fetal human cortex revealed the existence of a number of distinct excitatory neuronal progenitor types (e.g., outer radial glia) that were identified as key to driving a remarkable burst of late neurogenesis ( 2 ). However, the cortex is able to function only when excitatory and inhibitory activities in the brain are balanced. On page 81 of this issue, Paredes et al. ( 3 ) identify a population of interneurons that migrate to the cortex during infancy to establish inhibitory circuits.
Abstract 1780: Targeted inactivation of CRL4-CDT2 E3 ubiquitin ligase as a novel therapeutic strategy for malignant melanoma

The CRL4CDT2 E3 ubiquitin ligase is emerging as a critical regulator cell cycle progression, primarily through the targeted ubiquitylation and degradation of critical cell cycle regulators including CDT1, p21 and SET8 via the 26S proteasome. CDT2, the substrate receptor of the CRL4CDT2 E3 ligase is overexpressed or amplified in several human malignancies, but its role in the development or progression of these cancers remains elusive. We show that CDT2 is overexpressed in primary and metastatic melanoma. Targeted depletion of CDT2 by si-RNA or its pharmacological inhibition by MLN4924, a selective NEDD8-activating enzyme (NAE) inhibitor, suppressed the proliferation of melanoma cancer cells in vitro and inhibited tumor growth of human melanoma xenografts in mice, irrespective of the BRAF mutation status. Inhibition of CRL4CDT2 in melanoma cells with various genetic backgrounds, but not in immortalized human melanocytes, resulted in robust p21- and SET8-dependent rereplication. These results identify the CRL4CDT2 E3 ubiquitin ligase as a promising new therapeutic target for cutaneous melanoma, and demonstrate the efficacy of MLN4924 as a promising anti-melanoma agent. Citation Format: Mouadh Benamar, Fadila Guessous, Patrick Corbett, Craig L. Slingluff, Tarek Abbas. Targeted inactivation of CRL4-CDT2 E3 ubiquitin ligase as a novel therapeutic strategy for malignant melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1780. doi:10.1158/1538-7445.AM2015-1780
A Potpourri of Research and Opinions

The articles in this issue feature a potpourri of writings that discuss issues facing two-year college libraries. From information literacy instruction to the new phenomenon of librarians working t...
MULTIMODALITY INTRAVASCULAR IMAGING TO EVALUATE PLAQUE CHARACTERISTICS IN PATIENTS WITH DIABETES MELLITUS

Background: The aim of this study was to assess the plaque characteristics of obstructive lesions in diabetes mellitus (DM) patients presenting with stable coronary artery disease (CAD) at the time of percutaneous coronary intervention, using multimodality intravascular imaging registry. Methods: A
Effect of dietary palmitic and stearic acids on sucrose motivation and hypothalamic and striatal cell signals in the rat

We have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4–6 wk. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM...
SES, Heart Failure, and N-terminal Pro-b-type Natriuretic Peptide: The Atherosclerosis Risk in Communities Study.

Introduction Compared with coronary heart disease and stroke, the association between SES and the risk of heart failure is less well understood. Methods In 12,646 participants of the Atherosclerosis Risk in Communities Study cohort free of heart failure history at baseline (1987–1989), the association of income, educational attainment, and area deprivation index with subsequent heart failure–related hospitalization or death was examined while accounting for cardiovascular disease risk factors and healthcare access. Because SES may affect threshold of identifying heart failure and admitting for heart failure management, secondarily the association between SES and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, a marker reflecting cardiac overload, was investigated. Analysis was conducted in 2016. Results During a median follow-up of 24.3 years, a total of 2,249 participants developed heart failure. In a demographically adjusted model, the lowest-SES group had 2.2- to 2.5-fold higher risk of heart failure compared with the highest SES group for income, education, and area deprivation. With further adjustment for time-varying cardiovascular disease risk factors and healthcare access, these associations were attenuated but remained statistically significant (e.g., hazard ratio=1.92, 95% CI=1.69, 2.19 for the lowest versus highest income), with no racial interaction (p>0.05 for all SES measures). Similarly, compared with high SES, low SES was associated with both higher baseline level of NT-proBNP in a multivariable adjusted model (15% higher, p Conclusions SES was associated with clinical heart failure as well as NT-proBNP levels inversely and independently of traditional cardiovascular disease factors and healthcare access.
Childhood Obesity and the Regulation of Growth, Thyroid Function, Sexual Development, and Calcium Homeostasis

Certain endocrine and metabolic disorders cause mild to moderate weight gain and fat deposition. Excess fat storage in turn can have profound effects on intermediary metabolism and endocrine function. We begin this section with a brief discussion of endocrine disorders that promote excess weight gain. We then review the effects of obesity on linear growth and bone maturation, thyroid function, sexual development, adrenal function, and calcium homeostasis and bone mineralization. Subsequent chapters in this volume discuss the implications of obesity for insulin production and action and the regulation of glucose tolerance, blood pressure, lipid metabolism and atherogenesis, sleep hygiene, and hepatic function.
Source Characteristics and Contaminant Plume Evolution

This study investigated how features of mass distribution within a source area control the pattern of contaminant plume evolution. A series of numerical trials was conducted which simulated contaminant migration in a three-dimensional saturated porous media with multiple source patches representing zones of contamination. Results showed that the extent of mixing near the source was greatly affected by both advection and dispersive mixing processes. The factors affecting the concentration distribution in the dissolved plume were size and distribution of source patches, dispersivity values, and the ratio of total patch area to the source area. The influence of dispersive mixing increased as the size of source patches decreased. However, dispersion was less important when patches were clustered or the ratio of total patch area to the source area increased. The variations in concentration values near the source, which were caused by differences in sizes and distribution of patches, diminished as the contaminant traveled further from the source. This result implies that detailed information on source characteristics generally would not be required beyond a certain travel distance. The exception in this regard is the ratio of total patch area to the source area, i.e., a zero-difference point. However, the location of this zero-difference point cannot be predicted easily because the location was affected by several source characteristics.
The WFIRST coronagraph instrument: technology demonstration and science potential (Conference Presentation)

The Wide Field Infrared Survey Telescope (WFIRST), which is entering Phase B for a launch in 2026, is NASA’s next large space observatory after the James Webb Space Telescope. In addition to the primary science carried out by The Wide Field Instrument (WFI), which is designed to carry out surveys of galaxies in the near infrared, explore the properties of dark energy and dark matter, and carry out a microlensing survey to complete the census of exoplanets, there will be a technology demonstration of a Coronagraph Instrument (CGI) for very high-contrast imaging and spectroscopy of nearby exoplanets. The CGI will incorporate two coronagraph types and demonstrate low- and high-order wavefront correction for the first time on a space telescope. Operating in the visible, it will consist of a direct imaging camera and a lenslet based integral field spectrograph, both using electron-multiplying CCDs in the focal plane, as well as polarizers allowing direct imaging in separate polarization states. Written by the lead science and engineering team, supported by two science investigation teams (SITs – https://wfirst.gsfc.nasa.gov/science/fswg/scienceteam.html), this paper presents an overview of the technology requirements on the instrument, the instrument design, and the operational plans to demonstrate exoplanet imaging and spectroscopic capability. Also described is how CGI will advance algorithms for extracting planet images from the background and retrieving spectra from a space IFS. Once the core performance is successfully demonstrated, CGI will also be used in the latter part of the mission for a dedicated science and Guest Observer (GO) program. This paper thus also describes the potentially revolutionary science that will be enabled through direct imaging and spectroscopy of known radial velocity planets and debris disks as seen in reflected light.
Correlates of shelter use among young adults experiencing homelessness

Abstract Rates of shelter use among young adults (ages 18–24) experiencing homelessness are disproportionally low, compared to youth or older adults experiencing homelessness. The high unsheltered rate exposes these young adults to significant short- and long-term risks, while shelter use is associated with positive and improved outcomes, including increased access to other supportive services. Few studies have focused on factors related to low rates of shelter use among young adults or on the relative importance of such factors. The present study examines a series of background and contextual factors that are associated with shelter use among young adults experiencing homelessness. Using survey data (n = 338) collected in Houston, Texas, this study employs multiple logistic regression to examine correlates of shelter use and to assess the relative importance of each factor. Results indicate several significant characteristics were positively associated with shelter use, including being female, being non-white, using other types of services, and Internet use. We highlight research, practice, and policy implications around understanding differences in shelter and drop-in center use and ensuring young adults can find and access shelters with services geared toward their age group.
Monster truck FERMIAC

After World War II, Los Alamos was anxious for its own computer. While on a walk along the river during a picnic with their families, Enrico Fermi outlined to L.D.P. King a plan for an analog compu...
A Phytochemical Investigation of Nectandra membranacea from Monteverde, Costa Rica:

Bioactivity screening of Nectandra membranacea from Monteverde, Costa Rica, revealed that the crude bark extract has in-vitro cytotoxic activity against the Hep G2 and MDA-MB-231 human tumor cell l...
Immunogenetic polymorphism of lipoproteins in swine: 2. Five new allotypic specificities (Lpp6, Lpp11, Lpp12, Lpp13, and Lpp14) in the Lpp system

Five new antigenic markers (allotypes) of swine serum lipoproteins are described. Specific antiallotype reagents were obtained from alloimmune precipitating sera. Identification studies and genetic analysis indicate that the five serum alloantigens—designated Lpp6, Lpp11, Lpp12, Lpp13, and Lpp14—are markers of low-density lipoproteins (LDL),d 1.002–1.075 g/ml, and are members of a previously described Lpp system. The Lpp6 allotype belongs to the group of individual markers and is determined by a new codominant allelic gene,Lpp6, whereas the remaining four antigens—Lpp11, Lpp12, Lpp13, and Lpp 14—named common specificities, behave as alternative variants to Lpp1, Lpp2, Lpp3, and Lpp4, respectively, forming pairs of mutually exclusive alloantigens. Each Lpp gene in a heterozygous animal expresses itself independently on separate molecules and each haplotype carries one individual and at least four common specificities. The relationship between common and individual specificities, together with their number in the complex haplotypes, seems to shed some light on evolution of Lpp genes. It is proposed in this concept that the original gene for low-density lipoproteins in swine, and also in rhesus monkeys and the human, consisted of genetic information for common specificities only, the individual specificities evolving later as a result of point mutations.
Too Close to the Flame: Duplicated ICARUS Genes and Growth at Higher Temperatures

Plants can adjust their growth and reproduction cycles according to the local climate they experience, but how will they respond when ambient temperatures rise? Most Arabidopsis ( Arabidopsis thaliana ) accessions respond by increasing cell elongation and accelerated flowering, but some cannot cope
Biofabricated tumor microenvironments for studying colorectal cancer in vitro and in vivo.

e14689Background: Microenvironmental mechanics have a tremendous effect on the progression, phenotype, and therapeutic response of cancer cells positioning it as a high-potential target for novel t...
Communicatively Navigating Identities, Silence, and Social Protest

Social protests in the United States of America (U.S.) are increasing in frequency, including the Dakota Access pipeline protests, the Women’s March in 2017 and 2018, and March for our Lives. Thous...
Pattern of recurrence after curative resection of stage I-III duodenal adenocarcinoma.

794Background: Duodenal adenocarcinoma (DA) is a rare cancer with limited data regarding the pattern of disease recurrence following resection. Methods: A retrospective review of 115 patients with ...
Quantification and Propagation of Uncertainty in the Magnetic Characteristic of Steel and Permanent Magnets of a Synchronous Machine Drive

The numerical calculation of the electromagnetic fields within a permanent magnet synchronous machine (PMSM) is sensitive to the magnetic characteristic of steel and permanent magnets. The objective of this work is to quantify the impact of magnetization curve uncertainties on the performance of a PMSM and its drive system. Our approach is as follows. First, we construct stochastic models that reflect the uncertainties in B–H curves and PM remanent flux density. Second, to overcome the computational limitations of finite element analysis, we replace it with surrogate models based on Gaussian process regression. Third, we perform uncertainty propagation studies to assess the combined effect of steel and PM uncertainties on the maximum average torque vs. speed characteristics and the minimum dc-link voltage.