cssi/SciSciGPT-SciSciNet huggingface dataset:
Neurophysin expression is stimulated by dopamine D1 agonist in dispersed hypothalamic cultures

We have exposed primary dispersed hypothalamic cultures from 14-day-old fetal Sprague-Dawley rats to substances known to either elevate adenosine 3',5'-cyclic monophosphate (cAMP) levels or increase vasopressin (VP) secretion. The levels of VP in the medium collected from the cultures were determined by radioimmunoassay, and the number of neurophysin (NP)-positive cells after immunohistochemistry was counted. cAMP-elevating agents, 3-isobutyl-1-methylxanthine (200 microM) and forskolin (25 microM), in combination (I-F) maintained NP synthesis and VP secretion in 19-day cultures. I-F replacement by K+ (28 mM), isoproterenol (10 microM), glutamate (10 microM), or bicuculline (10 microM) during the last week of culture resulted in maintenance of NP expression and transient stimulation of VP secretion, but these agents did not induce NP expression independently of I-F treatment. In contrast, exposure to the dopamine D1 agonist SKF-38393 (10 microM) significantly increased NP expression independently and after replacement of I-F. Dopamine D1A receptors were detected by immunofluorescence on NP-expressing cells, providing a morphological basis for this response. These results suggest a role for D1A receptors in the regulation of VP gene expression.
The dedicated volunteers of JOSA A: editorial.

JOSA A is home to work ranging from the psychophysics of vision to the propagation of plasmons, from computational imaging to non-line-of-sight communications. Covering such a broad intellectual swath presents challenges that we meet through extraordinary voluntary service from those in the community we serve. The team of topical editors at JOSA A is drawn from a broad array of fields, careers, and cultures, and even at the individual level they bring the strength of diverse intellectual perspective. They commit many hours of their time and immeasurable mental energy every month to produce a journal we are very proud of. I am profoundly grateful to the dedicated people who serve on our team of topical editors. In this editorial, I would like to give our readers a more in-depth introduction to our team.
Our Experience with User Experience: Exploring Staffing Configurations to Conduct UX in an Academic Library

ABSTRACTA research project was undertaken by a university library system to develop a sustainable user experience strategy. A task force was convened to conduct a pilot project with members from both libraries in the system to assess staffing responsibilities, guidelines, processes, and data-gathering procedures. The team tested an electronic resources list common to both libraries. In describing the methods employed by the task force in their research, this article outlines the benefits and drawbacks of staffing configurations to initiate user experience practices in an academic library setting.
An auxiliary sensor processor to provide real time fuel delivery feedback for a microprocessor based diesel engine controller

Commande par microprocesseur d'un moteur diesel. Utilisation d'un deuxieme microprocesseur auxiliaire pour traiter les donnees provenant des capteurs, et fournir en temps reel les donnees concernant l'injection de carburant dans la boucle de contre-reaction
3′-Phosphoadenosine 5′-Phosphosulfate Allosterically Regulates Sulfotransferase Turnover

Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of small molecules-metabolites, drugs, and other xenobiotics-via the transfer of the sulfuryl moiety (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyls and primary amines of acceptors. SULT1A1 is the most abundant SULT in liver and has the broadest substrate spectrum of any SULT. Here we present the discovery of a new form of SULT1A1 allosteric regulation that modulates the catalytic efficiency of the enzyme over a 130-fold dynamic range. The molecular basis of the regulation is explored in detail and is shown to be rooted in an energetic coupling between the active-site caps of adjacent subunits in the SULT1A1 dimer. The first nucleotide to bind causes closure of the cap to which it is bound and at the same time stabilizes the cap in the adjacent subunit in the open position. Binding of the second nucleotide causes both caps to open. Cap closure sterically controls active-site access of the nucleotide and acceptor; consequently, the structural changes in the cap that occur as a function of nucleotide occupancy lead to changes in the substrate affinities and turnover of the enzyme. PAPS levels in tissues from a variety of organs suggest that the catalytic efficiency of the enzyme varies across tissues over the full 130-fold range and that efficiency is greatest in those tissues that experience the greatest xenobiotic "load".
Interpersonal Communication in Marketing: An Overview:

Interpersonal communication in marketing is approached from a perspective that focuses on communication signs. A classification scheme is presented and relevant literature surveyed. Directions for ...
An Energy-Dispersive X-Ray Fluorescence Analysis of Two Late Paleoindian Allen-Frederick Obsidian Point Bases from The Estancia Basin, Central New Mexico

www.escholarship.org/uc/item/58w2f2nr LETTER REPORT Department of Anthropology 232 Kroeber Hall University of California Berkeley, CA 94720-3710 AN ENERGY-DISPERSIVE X-RAY FLUORESCENCE ANALYSIS OF TWO LATE PALEOINDIAN ALLEN-FREDERICK OBSIDIAN POINT BASES FROM THE ESTANCIA BASIN, CENTRAL NEW MEXICO 18 February 2011 Dr. Bruce Huckell Maxwell Museum of Anthropology University of New Mexico Albuquerque, NM 87131 Dear Bruce, Both these artifacts were produced from Valles Rhyolite (Cerro del Medio), Jemez Mountains, northern New Mexico. While some Valles Rhyolite obsidian has entered the Rio Grande alluvium as a result of two minor pyroclastic events of Cerro del Medio, it is very rare and appears only to have reached as far south as Tijera Wash, and only in nodules less than 20 mm in diameter (Broxton et al. 2006; Shackley 2005, 2010). These relatively large projectile points could not be produced from Valles Rhyolite secondary deposits. The samples were analyzed using a Thermo Scientific Quant’X EDXRF spectrometer in the Archaeological XRF Laboratory, El Cerrito, California. Instrumental methods can be found at http://www.swxrflab.net/anlysis.htm. Analysis of the USGS RGM-1 standard indicates high machine precision for the elements of interest (Govindaraju 1994; Table 1 here). Sincerely, M. Steven Shackley Professor and Director VOICE: (510) 642-2533 INTERNET: shackley@berkeley.edu http://www.swxrflab.net/
Mass Screening for Genetic Disease

Automation has already brought our screening capability to the point where the same specimen can be used to detect a number of hereditary aminoacidurias in addition to PKU. Yet application falls far behind: only six laboratories in the U. S. now do such automated multiple testing. Regionalizing the effort could close this gap—and involve practically no increase in cost over that of screening for PKU alone.
Multifocal Intrahepatic Artery Aneurysm with FDG-avid Thrombosis Simulating Metastasis: Report of a Rare Case

Hepatic artery aneurysm (HAA), although rare, represents a serious diagnostic and therapeutic challenge due to high rupture rate and associated mortality. Early detection and accurate diagnosis are essential for successful management. Here, we present an extremely rare case of multi-focal intrahepatic HAA with confined intrahepatic rupture and hypermetabolic activity at PET imaging, simulating metastasis of melanoma. A retrospective review found only two other HAA at our institution between 2000 and 2015, both of which involved the extrahepatic artery. This report highlights the importance of clinical, radiological, and pathological correlation in the management of this rare condition.
Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners

Background: Multiple sclerosis (MS) is a chronic neurologic disease associated with gait impairment that adversely affects quality of life (QOL). Data are lacking on the impact of these impairments from the perspectives of people with MS and care partners of a person with MS, defined as individuals caring for a friend or family member with MS.
Superior Outcome Using Cyclosporin A Alone Versus Cyclosporin A Plus Methotrexate for Post-Transplant Immunosuppression In Children with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Abstract 4502 Graft-versus-host disease (GVHD) is a major complication and one of the main causes of death after hematopoietic stem cell transplantation (HSCT). The GVHD prophylaxis influences the incidence of GVHD, relapse rate, and patient's survival. GVHD is associated with graft-versus-leukemia effect, which is mediated by donor T lymphocytes and decreases the risk of relapse. Therefore, a reduced post-transplant immunosuppression might have a positive impact on patient's survival. The outcome of different immunosuppressive prophylaxis regimen for adult patients has been studied extensively, whereas the effect on children has yet to be determined. Therefore, we performed a retrospective study analyzing 62 children (median age, 11 years) with acute lymphoblastic leukemia (n=35) or acute myeloid leukemia (n=27) who underwent bone marrow (n=56), peripheral blood stem cell (n=4), or umbilical cord blood (n=2) transplantation in a single center between November 1984 and July 2008. All respective donors were HLA-identical siblings. The patients received an immunosuppressive prophylaxis consisting of cyclosporin A (CSA) plus methotrexate (MTX) (n=43) or cyclosporin A alone (n=19). Patients in the CSA+MTX arm received CSA at a total dose of 10 mg/kg/day on day -1, 5mg/kg/day on days 0 to 4, and 3 mg/kg/day starting on day 5, and in addition MTX at a dosage of 10 mg/m2 on days 1, 3, 6, and 11. The 19 patients in the CSA arm received CSA at a total dose of 3 mg/kg/day starting on day -1. Concerning the patient's gender, age, diagnosis, and state of remission prior to transplantation, the two groups did not differ significantly. Patients who received CSA alone as post-transplant immunosuppression had a significantly reduced cumulative incidence of relapse (5% versus 40%; p=0,002), a significantly increased 5-year event-free survival (84% versus 35%; p=0.001), and a significantly increased 5-year overall survival (84% versus 42%; p=0.004). Interestingly, the incidence of acute GVHD grade II-IV in patients in the CSA arm was equivalent to the CSA+MTX arm (26% versus 19%; p=0.440). In addition, we did not observe a significant difference in the cumulative incidence of chronic GVHD (32% in the CSA arm versus 23% in the CSA+MTX arm; p=0.428). There was also no significant difference in the cumulative incidence of treatment related mortality after 1 year (10% in the CSA arm versus 23% in the CSA+MTX arm; p=0.165). In conclusion, CSA alone for post-transplant immunosuppression allows a stronger graft-versus-leukemia effect and thereby reduces the relapse rate and the number of patients dying of leukemia effectively without increase of acute and chronic GVHD. Post-transplant immunosuppression consisting of CSA alone leads to a superior outcome and should be preferred in children with a HLA-identical sibling as donor. Disclosures: No relevant conflicts of interest to declare.
Corporate environmental responsibility and global online cross-sector alliance network: a cross-national study

With the rise of global environmental issues and the emerging trend of corporate social responsibility (CSR) and corporation–non-governmental organization (NGO) alliances, organizations are develop...
Observations on the Effect of Environment on Schizophrenic Behavior in the Psychiatric Hospital.

(1966). Observations on the Effect of Environment on Schizophrenic Behavior in the Psychiatric Hospital. Psychiatry: Vol. 29, No. 4, pp. 412-421.
Abstract 598: Circulating peptides for predicting subsequent cardiotoxicity in cancer patients with chemotherapies

In recent years with the development of new anticancer therapies, cardiotoxicity has been a known adverse event resulting from direct myocyte damage, and leads to increased treatment-associated mortality. However, the effective approach of early diagnosis and monitoring treatment-induced cardiac dysfunction is not available because its underlying mechanism is still unclear. Traditional screening that relied on left ventricular ejection fraction (LVEF) is lack of sensitivity to early detect subclinical changes or predict the subsequent declines in cardiac functions with treatment. A more noninvasive approach to early diagnose and monitor treatment-induced cardiotoxicity is in an urgent need. Our group has developed nanoporous silica thin films (Nanotraps) for peptide enrichment prior to mass spectrometry (MS) analysis as a robust technology platform for accurate and reproducible peptide biomarkers detection. Cancer patients with chemotherapies were split into three groups, non-toxicity (NT, n = 36), slight cardiotoxicity (SCT, n = 26) and cardiotoxicity (CT, n = 23). After statistical analysis and sequencing by LC-MS/MS, two peptides candidates (a fragment from serum amyloid A-1525 (SAA-1525)) and Hepcidin-25) were identified with significant up-regulation in cardiotoxic groups (with the cut off ratio of 1.5-fold and p-value ≤ 0.01 among cohorts). The area under curve (AUC) values of SAA-1525 and hepcidin-25 are 0.929 and 0.844 for distinguishing CT from NT, respectively (95% CI = 0.839-1.000 and 0.696-0.993); if combining two peptides as a biomarker pattern, the AUC value can be increased to 0.942 (95% CI = 0.864-1.00). SCT patients could also be classified by this two-marker pattern (AUC = 0.771, 95%CI = 0.606-0.936). In addition, we investigated the proteolytic process analysis of cathepsin B, which was identified as the key protease to generate SAA-1525. SAA-1525 was detected in the mixture of recombinant SAA1 full protein and purified cathepsin B, and its expression level increased with reaction time and enzyme amount. Both cathepsin B inhibitors, E64 and ALLM, could stop the generation of SAA-1525. Our study provides strong evidence to support the application of circulating peptides as minimally invasive way for predicting/monitoring chemotherapy-induced cardiotoxicity. Citation Format: Jia Fan, Qing H. Meng, Christopher Bone, Stephen Igo, Ye Hu. Circulating peptides for predicting subsequent cardiotoxicity in cancer patients with chemotherapies. [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 598. doi:10.1158/1538-7445.AM2015-598
China, Too, Is Fighting to Defend a Way of Life

The issue at stake, as far as the Western world and the Western civilization are concerned, is, therefore, despotism versus democracy: it is freedom versus oppression and peace versus the lust for conquest by brute force.
Time, Narrative, and Maternity in Augustine’s Confessions

In this chapter Rose recounts Augustine’s struggle to escape the transitory conditions of history and time that generate his autobiographical narration and explores his desire to pass into the non-narratable permanence of timelessness and eternity. Augustine associates his struggle with his tumultuous relationship with his magnetic mother Monica, whose interventions both enable and impede his destiny. He achieves his desired destiny in the form of fully embraced faith, symbolized by baptism in the Catholic Church that occurs at the precise textual moment of his mother’s death. The chapter demonstrates that Augustine rhetorically exploits the cultural paradigm of the dead mother plot as the vehicle of significance with impeccable narrative brilliance.
HIV-1 Tat Primes and Activates Microglial NLRP3 Inflammasome-Mediated Neuroinflammation

Neuroinflammation associated with HIV-1 infection is a problem affecting ∼50% of HIV-infected individuals. NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Because HIV-1 Transactivator of Transcription (Tat) protein continues to be present despite antiretroviral therapy and activates NF-kB, we hypothesized that Tat could prime the NLRP3 inflammasome. We found a dose- and time-dependent induction of NLRP3 expression in microglia exposed to Tat compared with control. Tat exposure also time-dependently increased the mature caspase-1 and IL-1β levels and enhanced the IL-1β secretion. These in vitro findings were validated in archival brain tissues from Simian Immunodeficiency Virus (SIV)-infected and uninfected rhesus macaques. Further validation of NLRP3 priming in vivo involved administration of lipopolysaccharide (LPS) to HIV transgenic (Tg) rats followed by assessment of IL-1β mRNA expression and inflammasome activation (ASC oligomers and mature IL-1β). Intriguingly, LPS potentiated upregulation of IL-1β mRNA and inflammasome activation in HIV-Tg rats compared with the wild-type controls. Interestingly, we found an inverse relationship in the expression of NLRP3 and its negative regulator, miR-223, suggesting a miR-223-mediated mechanism for Tat-induced NLRP3 priming. Furthermore, blockade of NLRP3 resulted in decreased IL-1β secretion. Collectively, these findings suggest a novel role of Tat in priming and activating the NLRP3 inflammasome. Therefore, NLRP3 can be envisioned as a therapeutic target for ameliorating Tat-mediated neuroinflammation.SIGNIFICANCE STATEMENT Despite successful suppression of viremia with increased longevity in the era of combined antiretroviral therapy, chronic inflammation with underlying neurocognitive impairment continues to afflict almost 50% of infected individuals. Viral, bacterial, and cellular products have all been implicated in promoting the chronic inflammation found in these individuals. Understanding the molecular mechanism(s) by which viral proteins such as HIV-1 Transactivator of Transcription (Tat) protein can activate microglia is thus of paramount importance. Herein, we demonstrate a novel role of Tat in priming and activating NLR family pyrin domain containing 3 (NLRP3) inflammasomes in microglial cells and in HIV-Tg rats administered lipopolysaccharide. Targeting NLRP3 inflammasome pathway mediators could thus be developed as therapeutic interventions to alleviate or prevent neuroinflammation and subsequent cognitive impairment in HIV-positive patients.
The Use of Primary Prevention Statin Therapy in Those Predisposed to Atherosclerosis

Many guidelines exist for the use of statins in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Few have focused on disease specific states that predispose to ASCVD. This review is intended to focus on the recommendations and evidence in inflammatory diseases that predispose to an increased risk of ASCVD beyond what conventional cardiac risk scores would predict. Certain autoimmune inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), and psoriasis/psoriatic arthritis have all been shown to increase the risk of ASCVD. Other diseases such as human immunodeficiency virus (HIV) and mediastinal radiation have also been correlated with increased ASCVD. In RA and HIV, the evidence suggests a benefit to added statin therapy and society guidelines favor early initiation. The evidence for statin therapy in RA is limited to observational studies with small secondary analysis. In HIV, there is a large ongoing clinical trial to assess efficacy. In those with psoriasis and psoriatic arthritis, there is limited evidence for or against statin therapy independent of a calculated cardiac risk score. Finally, in SLE and in those with exposure to mediastinal radiation, cardiac events remain high, but evidence is limited on the beneficial effects of statin therapy. There are many individuals who have an increased risk for ASCVD above what is predicted from a cardiac risk score. It would be beneficial to create risk prediction models with statin therapy recommendations that are tailored to those predisposed to accelerated atherosclerosis.
Biomass supply contract pricing and environmental policy analysis: A simulation approach

Abstract This paper proposes an agent-based simulation model to study the biomass supply contract pricing and policy making in the biofuel industry. In the proposed model, the agents include farmers and a biofuel producer. Farmers' decision-making is assumed to be profit driven, which is formulated as a mixed-integer optimization model, and the biofuel producer's pricing decision is represented with a linear equation with an objective to maximize profits. A case study based on Iowa has been developed to analyze the interactions between the stakeholders and assist determination of the optimal pricing equation for the biofuel producer. Simulation results show that under such a pricing strategy, the biofuel producer can achieve higher profitability than using a fixed price. The impact of government environmental regulations on farmers' decision-making and biomass supply has also been analyzed, and managerial insights have been derived.
Abstract 13925: Association of Ankle-Brachial Index With Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: A normal ankle-brachial index (ABI) is defined as 1.0 to 1.4; abnormal ABI is defined as ≤0.90 whereas >0.9 to 1.40 indicates noncompressible arteries. Although peripheral arterial disease has been shown to be associated with incident AF, it is unclear whether borderline ABI or noncompressible arteries are associated with incident AF. We aimed to evaluate this association of borderline ABI and ABI >1.4 in the ARIC study, a population-based prospective cohort study. Methods: We included 14,794 participants (age, 54.2 ± 5.8 yrs, 55% women, 26% blacks) who attended the baseline exam (1987-89) and without prevalent AF. Incident AF was identified from hospital discharge records, death certificates, and ECGs. We used Cox proportional hazard models to evaluate the association between ABI categories and incident AF. Results: During a mean follow-up of 19.8 years, there were 2288 incident AF cases. After full adjustment in Model 2, compared with ABI 1.0-1.4, the hazards ratio (HR) (95% CI) of ABI 0.9 to 1.4 was associated with an increased risk of AF (Table). Conclusions: This study is the first to show that borderline ABI is independently associated with AF further supporting that borderline ABI is not benign. Our findings also suggest that detection of preclinical and early clinical atherosclerosis may identify individuals at increased risk of AF.
Charles T. Jackson and William T.G. Morton Patented the “Ethereal Solution of Opium” of Elton Romeo Smilie

Abstract The Jackson-Morton 1846 patent for surgical insensibility by means of sulphuric ether states that opiates can be added to the ether and co-administered by inhalation. The erroneous concept that ether could carry opiates in its vapor phase at room temperature was proposed in Boston in 1846 by Elton Romeo Smilie (1819-1889), who believed that the opiates were more important than the ether vehicle.
Key Design Considerations When Calculating Cost Savings for Population Health Management Programs in an Observational Setting.

OBJECTIVE To illustrate the impact of key quasi-experimental design elements on cost savings measurement for population health management (PHM) programs. DATA SOURCES Population health management program records and Medicaid claims and enrollment data from December 2011 through March 2016. STUDY DESIGN The study uses a difference-in-difference design to compare changes in cost and utilization outcomes between program participants and propensity score-matched nonparticipants. Comparisons of measured savings are made based on (1) stable versus dynamic population enrollment and (2) all eligible versus enrolled-only participant definitions. Options for the operationalization of time are also discussed. DATA COLLECTION/EXTRACTION METHODS Individual-level Medicaid administrative and claims data and PHM program records are used to match study groups on baseline risk factors and assess changes in costs and utilization. PRINCIPAL FINDINGS Savings estimates are statistically similar but smaller in magnitude when eliminating variability based on duration of population enrollment and when evaluating program impact on the entire target population. Measurement in calendar time, when possible, simplifies interpretability. CONCLUSION Program evaluation design elements, including population stability and participant definitions, can influence the estimated magnitude of program savings for the payer and should be considered carefully. Time specifications can also affect interpretability and usefulness.
Gaze-based interaction: A 30 year retrospective

Abstract Gaze-based interaction is reviewed, categorized within a taxonomy that splits interaction into four forms, namely diagnostic (off-line measurement), active (selection, look to shoot), passive (foveated rendering, a.k.a. gaze-contingent displays), and expressive (gaze synthesis). Diagnostic interaction is the mainstay of eye-tracked applications, including training or assessment of expertise, and is possibly the longest standing use of gaze due to its mainly offline requirements. Diagnostic analysis of gaze is still very much in demand, especially in training situations such as flight or surgery training. Active interaction is rooted in the desire to use the eyes to point and click, with gaze gestures growing in popularity. Passive interaction is the manipulation of scene elements in response to gaze direction, e.g., to improve frame rate. Expressive eye movement is drawn from its synthesis, which can make use of a procedural (stochastic) model of eye motion driven by goal-oriented tasks such as reading. In discussing each form of interaction, seminal results and recent advancements are reviewed, highlighting outstanding research problems. The survey paper extends an invited proceedings contribution to VS-Games 2017.
Patients with hippocampal amnesia successfully integrate gesture and speech

During conversation, people integrate information from co-speech hand gestures with information in spoken language. For example, after hearing the sentence, "A piece of the log flew up and hit Carl in the face" while viewing a gesture directed at the nose, people tend to later report that the log hit Carl in the nose (information only in gesture) rather than in the face (information in speech). The cognitive and neural mechanisms that support the integration of gesture with speech are unclear. One possibility is that the hippocampus - known for its role in relational memory and information integration - is necessary for integrating gesture and speech. To test this possibility, we examined how patients with hippocampal amnesia and healthy and brain-damaged comparison participants express information from gesture in a narrative retelling task. Participants watched videos of an experimenter telling narratives that included hand gestures that contained supplementary information. Participants were asked to retell the narratives and their spoken retellings were assessed for the presence of information from gesture. For features that had been accompanied by supplementary gesture, patients with amnesia retold fewer of these features overall and fewer retellings that matched the speech from the narrative. Yet their retellings included features that contained information that had been present uniquely in gesture in amounts that were not reliably different from comparison groups. Thus, a functioning hippocampus is not necessary for gesture-speech integration over short timescales. Providing unique information in gesture may enhance communication for individuals with declarative memory impairment, possibly via non-declarative memory mechanisms.
Some Estimates for a System of Multiple Reactions

Various studies of a certain system of autocatalytic reactions in a spatially uniform environment have shown the importance of the concentration of the pool chemical in determining the frequency of oscillation of the concentration of the autocatalytic intermediates. Here we give bounds on this important variable in the more general spatially distributed case.
Microtubules and Microtubular Protein

Microtubules are among the most numerous “organelles” in the ultra-structure of neurons and are universally present in eukaryotes (1, 2). They occur in the mitotic spindle of dividing cells, cilia, flagella, sperm tails, and are abundant in neuronal axons and dendrites. Representative electron micrographs showing the abundance and morphology of microtubules in crayfish ventral nerve cord are presented in Figs. 1–3. In a few cases, direct counts of the number of microtubules have been made and the results indicate that they are more numerous in nonmyelinated than myelinated axons (3, 4). They are also more abundant in the axons of immature animals than in mature animals (5). An extensive survey of microtubules in rabbit vagus nerve nonmyelinated axons and in crayfish ventral cord axons revealed a considerable numerical variation among axons, even from the same animal. The average number per square micron is 40 in rabbit vagus and 26 in crayfish ventral cord (3).
PLASTICITY | Seizure-Related Changes in Dendritic Spine Structure

Seizures cause brain injury via various mechanisms, including neuronal death and ‘non-lethal’ effects on neuronal structure and function. Dendritic spines receive most cortical excitatory synaptic inputs and are implicated in synaptic plasticity and learning. Previous histopathological studies of human epilepsy and animal models demonstrate abnormalities in dendritic structure, including spine loss. Our laboratory has used modern in vivo multiphoton imaging techniques to directly view acute dendritic injury in living mice during seizures, and has studied the actin-mediated mechanisms implicated in causing these dendritic changes. Selective stabilization of dendritic actin networks may represent a novel therapeutic strategy for preventing seizure-induced brain injury.
An Active Learning In-Class Demonstration of Good Experimental Design

This article presents an active learning demonstration available on the Internet using Java applets to show a poorly designed experiment and then subsequently a well-designed experiment. The activi...
Pineal Gland and Melatonin

This article succinctly summarizes what is known about the pineal gland and its secretory product melatonin. The pineal gland, a small dorsal outgrowth of the brain stem, is an end organ of the visual system; its function is determined by light and darkness as perceived by the retinas. The neural connections between the eyes and the pineal gland involve the peripheral sympathetic nervous system and an important synaptic relay in the suprachiasmatic nuclei, the biological clock. During darkness at night, the pineal gland, in response to norepinephrine released onto pineal cells by postganglionic sympathetic nerve fibers, produces melatonin and discharges it into the blood; as a consequence, blood levels of melatonin are elevated at night. The 24 h cycle of blood melatonin functions in the regulation of circadian rhythms and in promoting nighttime sleep. In addition, melatonin inhibits growth of some tumors, has modulatory effects on the immune system, and functions as a direct free-radical scavenger and as an indirect antioxidant. Some of melatonin’s actions are mediated via specific receptors while others are receptor independent.
Translating evidence into action: An intervention for increasing vitamin D supplementation in a deficient rehabilitation population

Introduction/Background Inadequate vitamin D is highly prevalent, affecting approximately 42-77% of the general United States population. Vitamin D deficiency (VDD) increases the risk of osteoporosis, falls, and fractures. Acute inpatient rehabilitation patients have several risk factors for VDD, and the adverse effects of VDD may hinder long-term functional gain. Material and method Prospective cohort study, evaluating patients admitted before and after a screening intervention as part of a quality improvement initiative at an academic, freestanding acute inpatient rehabilitation hospital. This study included a convenience sample of patients admitted two months pre-intervention (n = 128), and patients admitted two months post-intervention (n = 129). Providers obtained a routine serum vitamin D level on admission (universal screening), then utilized a standard supplementation protocol. Vitamin D insufficiency (VDI) was defined as a 25-hydroxyvitamin D (25(OH)D) level of 20–29.9 ng/mL, and VDD as Results Pre-intervention, 10.2% of patients were screened for VDD, with 23.1% found to be VDI and 46.2% VDD. Post-intervention, 89.9% of patients were screened, with 31.9% found to be VDI and 47.4% VDD. Pre-intervention, 88.9% of all screened patients were on vitamin D supplementation at discharge versus 75.0% post-intervention. In both uni- and multivariate analyses, we found increased risk of VDD was significantly associated with African American race (OR 7.3, 95% CI, 1.56–34.2, P = 0.12) and age younger than 65 (OR 13.6, 95% CI, 2.5–73.8, P = 0.002). Diagnoses in the “other neurologic” category were associated with decreased risk of VDD (OR 0.01, 95% CI, 0.001–0.193, P = 0.002). Conclusion Given the high prevalence of VDD in an acute inpatient rehabilitation hospital, a routine screening and standardized supplementation protocol may be a good practice to improve quality of care.
CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFβ and BMP through SMAD signaling

Summary Objective Upregulation of calcium/calmodulin-dependent kinase II (CaMKII) is implicated in the pathogenesis of osteoarthritis (OA) and reactivation of articular cartilage hypertrophy. However, direct inhibition of CaMKII unexpectedly augmented symptoms of OA in animal models. The role of CaMKII in OA remains unclear and requires further investigation. Methods Analysis of CaMKII expression was performed in normal human and OA articular chondrocytes, and signaling mechanisms were assessed in articular, fetal and Pluripotent Stem Cell (PSC)-derived human chondrocytes using pharmacological (KN93), peptide (AC3-I) and small interfering RNA (siRNA) inhibitors of CaMKII. Results Expression levels of phospho-CaMKII (pCaMKII) were significantly and consistently increased in human OA specimens. BMP2/4 activated expression of pCaMKII as well as COLII and COLX in human adult articular chondrocytes, and also increased the levels and nuclear localization of SMADs1/5/8, while TGFβ1 showed minimal or no activation of the chondrogenic program in adult chondrocytes. Targeted blockade of CaMKII with specific siRNAs decreased levels of pSMADs, COLII, COLX and proteoglycans in normal and OA adult articular chondrocytes in the presence of both BMP4 and TGFβ1. Both human fetal and PSC-derived chondrocytes also demonstrated a decrease of chondrogenic differentiation in the presence of small molecule and peptide inhibitors of CaMKII. Furthermore, immunoprecipitation for SMADs1/5/8 or 2/3 followed by western blotting for pCaMKII showed direct interaction between SMADs and pCaMKII in primary chondrocytes. Conclusion Current study demonstrates a direct role for CaMKII in TGF-β and BMP-mediated responses in primary and PSC-derived chondrocytes. These findings have direct implications for tissue engineering of cartilage tissue from stem cells and therapeutic management of OA.
IOMiner: Large-Scale Analytics Framework for Gaining Knowledge from I/O Logs

Modern HPC systems are collecting large amounts of I/O performance data. The massive volume and heterogeneity of this data, however, have made timely performance of in-depth integrated analysis difficult. To overcome this difficulty and to allow users to identify the root causes of poor application I/O performance, we present IOMiner, an I/O log analytics framework. IOMiner provides an easy-to-use interface for analyzing instrumentation data, a unified storage schema that hides the heterogeneity of the raw instrumentation data, and a sweep-line-based algorithm for root cause analysis of poor application I/O performance. IOMiner is implemented atop Spark to facilitate efficient, interactive, parallel analysis. We demonstrate the capabilities of IOMiner by using it to analyze logs collected on a large-scale production HPC system. Our analysis techniques not only uncover the root cause of poor I/O performance in key application case studies but also provide new insight into HPC I/O workload characterization.
Pulmonary Hypertension Care Centers: Hope for the Future From a Patient's and Caregiver's Perspectives

In 1987, after three years of being treated aggressively for asthma and then a prolapsed mitral valve, I was finally diagnosed with primary pulmonary hypertension (PPH). I was told I would be lucky...
Response to commentaries on Powell/Scarffe feature article

We are grateful for the thoughtful attention the commentators and editors have given our paper. They raise many substantive points that warrant a response, but for reasons of journal space our reply must be brief. In our paper, we argue for an amended hybrid account of ‘disease’ in human medicine that takes normative ethics seriously, guards against pernicious classifications of disease and reconnects the concept with the goals of healthcare institutions in which disease diagnosis is embedded. Carel and Tekin, in their respective pieces, raise issues about the objectivity and effective operationalisation of our account, Agar makes an ‘evolutionary’ case for disease concept eliminativism in mental health, and Wakefield and Conrad contend that our proposed modification to the harmful dysfunction account is unnecessary and undesirable. We will respond to each in turn. The rational moral justification component of our account raises difficult moral epistemological questions regarding which reasons are the weightiest ones and who should be allowed to participate in the rational justification process (though so too, we would note, does much bioethical inquiry). Carel suggests that inevitable disagreement on this point undermines the alleged objectivity of our proposal. We agree with Tekin, however, that this is a feature of our account rather than a bug. What constitutes a good reason in moral deliberation is a question that goes to the very philosophical foundation of ethics (see1 for a recent discussion); but disagreement over which reasons are the weightiest ones does not prevent ethicists and policy makers from objectively assessing the strength of moral arguments by evaluating their empirical adequacy and logical structure, and this can take us a long way toward adjudication. The fact that rational justification has been used to support immoral practices and institutions does not warrant abandoning a reason-based approach to ethics any more than …
Effects of different attention tasks on concurrent speech in adults who stutter and fluent controls

Abstract Purpose : Motor theories indicate that focusing attention on well-practiced movements interferes with skilled performance; however, specific forms of attention (alerting vs. orienting vs. executive control) associated with this effect are not well understood. The present study explored this question in relation to stuttering, and examined whether dual task conditions that engaged sustained attention or working memory (WM) affected speech fluency in different ways. We also considered whether fluency changes were associated with changes in speech rate and language. Methods : Nineteen adults who stutter (AWS) and 20 controls produced spontaneous speech under a baseline condition and two dual task conditions: one involving a sustained attention task, the other involving WM demands. Results : Both groups produced fewer stutter-like disfluencies under dual task relative to baseline conditions and this reduction did not differ between the two dual tasks (attention vs. WM). Speech rate and language variables, which were potentially influenced by attention conditions, were not affected by dual tasks in the same way as disfluencies, and appeared to be unassociated with fluency results. Conclusions : Findings indicate that atypical disfluencies decrease when attention is divided, even when secondary task demands are minimal, as they were in the sustained attention task. For simple secondary tasks, fluency changes do not appear to be a byproduct of slowed rate and are not accompanied by observable changes in language. These results demonstrate that simple manipulations of attention can induce measurable effects on aspects of speech production, and may be a useful tool for facilitating fluency in clinical intervention.
Pirfenidone inhibits epithelial-mesenchymal transition in keloid keratinocytes.

Background Keloids are benign fibroproliferative skin lesions that are difficult to treat and become a lifetime predicament for patients. Several treatment modalities have been put forth, but as yet no satisfactory approach to the prevention or treatment of keloids has been identified. The process of epithelial-to-mesenchymal transition (EMT) has been implicated in keloid scarring, as keloid keratinocytes display an EMT-like phenotype. This study investigated the potential of pirfenidone, an antifibrotic agent, to counteract EMT-like alterations in keloid keratinocytes, including gene expression, cell migratory and proliferative functions. Methods Normal and keloid keratinocytes were isolated from discarded normal skin tissues and from resected keloid tissues, respectively. Cells were quiesced for 24 h without epidermal growth factor DS-Qi1MCDigital and were exposed to transforming growth factor-beta1 (TGF-β1; 10 ng/mL), with or without pirfenidone (400 μg/mL), for an additional 24 h. The effects of pirfenidone on cytotoxicity, cell migration, cell proliferation, and on expression of genes and proteins involved in EMT were assayed. Statistical significance was determined by two-way ANOVA using Sigma Plot. Results We found that pirfenidone did not elicit any cytotoxic effect at concentrations up to 1000 μg/mL. A statistically significant dose-dependent decrease in basal cell proliferation rate was noted in both normal and keloid keratinocytes when exposed to pirfenidone at concentrations ranging from 200 to 1000 μg/mL. Pirfenidone significantly decreased basal cell migration in both normal and keloid keratinocytes, but a significant decrease in TGF-β1-induced cell migration was seen only in keloid keratinocytes. Significant inhibition of the expression of TGF-β1-induced core EMT genes, namely hyaluronan synthase 2, vimentin, cadherin-11, and wingless-type MMTV integration site family, member 5A along with fibronectin-1, was observed in both normal and keloid keratinocytes treated with pirfenidone. In addition, the protein levels of vimentin and fibronectin were significantly reduced by pirfenidone (400 μg/mL) in both normal and keloid keratinocytes. Conclusions For the first time, this study shows the efficacy of pirfenidone in inhibiting the EMT-like phenotype in keratinocytes derived from keloids, suggesting that pirfenidone may counteract a critical contributor of keloid progression and recurrence.
What Context Matters and at What Level? A Test of Racial/Ethnic Threat, Symbolic Threat, and Structural Inequality Perspectives in Juvenile Court Decision-Making:

Do traditional theories of conflict influence juvenile court decision-making and explain racial/ethnic disparities? Racial/ethnic threat, symbolic threat, and structural inequality perspectives pur...
Glutathione Improves the Antioxidant Activity of Vitamin C in Human Lens and Retinal Epithelial Cells: Implications for Vitreous Substitutes.

Tissues in the eye are particularly susceptible to oxidative damage due to light exposure. While vitamin C (ascorbic acid) has been noted as a vital antioxidant in the vitreous humor, its physiolog...
Treatment of Post-Hypoxic Myoclonus using Pallidal Deep Brain Stimulation Placed Using Interventional MRI Methods

Background: Post-hypoxic myoclonus (PHM) is characterized by generalized myoclonus after hypoxic brain injury. Myoclonus is often functionally impairing and refractory to medical therapies. Deep brain stimulation (DBS) has been used to treat myoclonus-dystonia, but few cases of PHM have been described. Case report: A 33-year-old woman developed severe, refractory generalized myoclonus after cardiopulmonary arrest from drowning. We performed MRI-guided asleep bilateral pallidal DBS placement, resulting in improvement in action myoclonus at one year. Discussion: Our case contributes to growing evidence for DBS for PHM. Interventional MRI guided DBS technique can be used for safe and accurate lead placement. Highlights: We report a case of a patient who developed post-hypoxic myoclonus after cardiopulmonary arrest from drowning, who later underwent deep brain stimulation to treat refractory myoclonus. This is the first case to describe asleep, interventional MRI-guided technique for implanting DBS leads in post-hypoxic myoclonus.
Prognostic Role of Hepatorenal Function Indexes in Patients With Ebstein Anomaly.

Abstract Background Hepatorenal dysfunction is a risk factor for mortality in patients with chronic tricuspid regurgitation due to acquired heart disease. Ebstein anomaly is the most common cause of primary tricuspid regurgitation in adults with congenital heart disease, but the prevalence and prognostic implications of hepatorenal dysfunction are unknown in this population. Objectives The purpose of this study was to determine the risk factors and prognostic implications of hepatorenal dysfunction, as measured primarily by the use of model for end-stage liver disease excluding international normalized ratio (MELD-XI score), as well as looking at other associated factors. Methods This was a retrospective study of adults with Ebstein anomaly who received care at Mayo Clinic from 2003 to 2018. Results Of 692 patients, the median MELD-XI score was 10.2 (interquartile range: 9.4 to 13.3); 53 (8%) died and 3 (0.4%) underwent heart transplant. MELD-XI was an independent predictor of death/transplant (hazard ratio: 1.32; 95% confidence interval: 1.11 to 2.06; p Conclusions Hepatorenal dysfunction is a predictor of mortality in Ebstein anomaly, and RA dysfunction and hypertension are hemodynamic biomarkers that can identify patients at risk for deterioration in hepatorenal function and mortality. These data highlight the prognostic importance of noncardiac organ-system dysfunction, and provide complementary clinical risk stratification metrics for management of these patients.
Problem-based learning case studies: Delivery of an educational method and perceptions at two schools of pharmacy in Italy.

Abstract Background and purpose Problem-based learning (PBL) case studies are not currently offered in the pharmacy school curriculum in Italy. This study sought to assess the perceptions of a PBL case study activity delivered at two pharmacy schools in Italy. Educational activity and setting A total of 64 pharmacy students and three pharmacy faculty from Italy participated in the live PBL activity. They collaborated on teams with pharmacy students from the United States to discuss a patient case and prepare drug therapy recommendations. A cross-sectional survey was performed to assess the Italian participants' perceptions before and after partaking in the PBL activity. Findings Results from the survey utilizing a five-point Likert-type scale (1 = strongly disagree to 5 = strongly agree) demonstrated that students and faculty from both pharmacy schools in Italy perceived the value in applying information learned in PBL to their current or future practices (4.48 ± 0.79) and in collaborating with a team to improve patient care (4.66 ± 0.79). In addition, the vast majority (93%) of participants agreed or strongly agreed that they would be interested in continuing to participate in PBL in the future. Summary Students and faculty at two pharmacy schools in Italy found the delivery of a PBL exercise to be beneficial for their professional development. This may suggest an opportunity for pharmacy schools in Italy to add the PBL case-based teaching method into their curriculum.