cssi/SciSciGPT-SciSciNet huggingface dataset:
All-Electron Path Integral Monte Carlo Simulations of Small Atoms and Molecules

Imaginary-time Feynman path integrals describe quantum mechanics at finite temperatures. Monte Carlo simulations using path integrals have many applications to nanoscale physics. Fermions introduce negative terms in the partition function, which we remove with a fixed-node approximation. In this article, we give an introduction to path integral Monte Carlo simulations. We focus on a difficult problem: the direct application of fermion path integrals to light atoms and molecules. Work on this problem illustrates the technical challenges facing path integral simulations, and may lead to new ab initio methods. To appear as pages 181–195 of Computer Simulations Studies in Condensed Matter Physics XVII, edited by D. P. Landau, S. P. Lewis, and H. B. Schtter, (Springer Verlag, Heidelberg, Berlin, 2006).
Forest Urban Construction Planning of Taohua Town,Putuo District in Zhoushan City

Features and advantages of Taohua Town,Putuo District in Zhoushan City were analyzed. The guiding ideology and principle of planning of forest urban construction were introduced. Forest urban greening landscape ecological system including ′A heart,an area,a gallery′ were put forward,so as to provide the reference for the forest urban construction planning of Taohua Town,Putuo District in Zhoushan City.
A Split GFP Barrel with an Internal Cavity that Binds the Chromophore

GFP chromophores are formed post-translationally from amino acids and are thus covalently attached to the interior of the beta-barrel. The chromophore analog 4-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) is non-fluorescent in solution but has been used to visualize proteins [1] and RNAs [2] by binding in vivo by suppressing non-radiative decay by cis-trans isomerization. Here we report a method to reconstitute the model chromophore HBDI with its original environment, the GFP beta-barrel (apoGFP). This construct can be alternatively viewed as a split GFP similar to those developed in our lab [3] but split at the site of the chromophore. When this construct is refolded in the presence of HBDI, a novel protein whose absorption and fluorescence are very similar to the natural protein is formed, despite the absence of any covalent connection. This suggests a very unusual protein topology in which the C- and N-termini of the protein are buried, and evidence concerning this will be described. This new semi-synthetic technique enables us to further explore the photophysics of fluorescent proteins and expand the opportunities for incorporating synthetic chromophores not limited to natural or unnatural amino acids [4].[1] Walker, C. L. et al., Curr. Opin. Chem. Biol.2015, 27, 64-74.[2] You, M.; Jaffrey, S. R. Annu. Rev. Biophys.2015, 44, 187-206.[3] Kent. K. P.; Oltrogge, L. M.; Boxer, S. G. J. Am. Chem. Soc.2009, 131, 15988-15989.[4] Oltrogge, L. M.; Boxer, S. G. ACS Cent. Sci., 2015, 1, 148-156.
CHOLESTEROL LEVELS IN YOUNG ADULTS : SCREEN AND INTERVENE ?

Early intervention is cost-effective over the long term: The cost of cholesterol-lowering drugs is easily offset by savings in the treatment of cardiovascular disease. Besides, most interventions are dietary, not pharmacologic.
Psychobiology of Personality: Temperament and Personality: Trait Structure and Persistence

As in the 1991 first edition of this book, I begin with a discussion of temperament and personality and their basic dimensions. This is a necessary first step in a top-down approach because one cannot begin a levels analysis of psychobiology without a classification of traits at the top level. It would be like a science of astronomy without distinctions between planetary bodies such as asteroids, planets, stars, and galaxies; geology as a science of “rocks” sorted by size; or biology that makes distinctions only between two-legged and four-legged creatures – putting humans and chickens in the same category. Classification of phenomena is basic to any science. Without it, all is chaos. There is a difference, however, between the classification of behavioral traits and other types of scientific classification. We are not defining “types” in the sense of clear-cut assortment of individuals. The concept of continuous, normally distributed trait dimensions is not widely understood outside of psychology. I purposely use the labels “high” and “low” sensation seekers, rather than type terms, such as “Big-T” and “Little-t,” to define persons falling near the extreme ends of the continuum on this trait. Types, however, may be defined from a combination of independent dimensions as particular combinations of high or low scores on these dimensions in the same way that syndromes of psychopathology are defined by particular combinations of symptoms. In the earlier volume, I discussed certain issues about traits that preoccupied personality researchers in the 1970s.
Recent security issues on cognitive radio networks: A survey

Cognitive radio networks are a method for improving wireless communications with radios that can adapt their operating parameters to cope with changes in their environment. This flexibility enables radios to perform with greater throughput, robustness, and field updatability than traditional wireless communication devices; unfortunately, it also presents several security challenges unique to cognitive radio networks and new angles for traditional attacks. These threats can be classified into radio configurability and cognitive radio behavioral vulnerabilities. In this paper we explore specific threats to cognitive radio networks and their countermeasures from literature. With this paper, readers can have a thorough understanding of cognitive radio network security and the research trends in this area.
Near-Field Enhanced Negative Luminescent Refrigeration

Under negative bias, a semiconductor's $r\phantom{\rule{0}{0ex}}a\phantom{\rule{0}{0ex}}d\phantom{\rule{0}{0ex}}i\phantom{\rule{0}{0ex}}a\phantom{\rule{0}{0ex}}n\phantom{\rule{0}{0ex}}t$ temperature can drop significantly below its $t\phantom{\rule{0}{0ex}}h\phantom{\rule{0}{0ex}}e\phantom{\rule{0}{0ex}}r\phantom{\rule{0}{0ex}}m\phantom{\rule{0}{0ex}}o\phantom{\rule{0}{0ex}}d\phantom{\rule{0}{0ex}}y\phantom{\rule{0}{0ex}}n\phantom{\rule{0}{0ex}}a\phantom{\rule{0}{0ex}}m\phantom{\rule{0}{0ex}}i\phantom{\rule{0}{0ex}}c$ temperature, and it can be used to cool another body via radiative exchange. The technique has never taken off, though, due to limited power density, and the weak performance of nonideal real-world materials. This study presents a near-field refrigeration system with high cooling power density and efficiency, and supporting fast temperature modulation. Ideally, this device can operate close to the Carnot limit---and it continues to perform well even in the presence of strong nonidealities.
Assembly of the Limonoid Architecture by a Divergent Approach: Total Synthesis of (±)-Andirolide N via (±)-8α-Hydroxycarapin

We report the first total synthesis of the limonoid andirolide N using a 12-step sequence from commercially available materials. The final step of this route demonstrates the chemical feasibility of our biosynthetic proposal that andirolide N arises from 8α-hydroxycarapin. The strategic use of a degraded limonoid as a platform for the synthesis of more structurally complex congeners may be a general approach to obtain limonoids with diverse functional properties.
Hematopoiesis: Reconciling Historic Controversies about the Niche

The niche, as first conceptualized, was in conflict with the prevailing wisdom that stem cells have internal logic. The niche hypothesis has been indisputably confirmed. Yet, recent findings indicate little plasticity of epigenetically scripted hematopoietic stem/progenitors. Reconciling this conflict requires re-envisioning the niche as an enabler, not designer, of cell fate.
Queerly Remembered: Rhetorics for Representing the GLBTQ Past, Thomas R. Dunn

In Thomas R. Dunn’s view, GLBTQ advocates have “represented and contested” past and present GLBTQ histories in order to “influence or persuade the judgments by dominant, apparently heterosexual cit...
Application Modernization at LLNL and the Sierra Center of Excellence

In 2014, Lawrence Livermore National Laboratory began acquisition of Sierra, a pre-exascale system from IBM and Nvidia. It marks a significant shift in direction for LLNL by introducing the concept of heterogeneous computing via GPUs. LLNL’s mission requires application teams to prepare for this paradigm shift. Thus, the Sierra procurement required a proposed Center of Excellence that would align the expertise of the chosen vendors with laboratory personnel that represent the application developers, system software, and tool providers in a concentrated effort to prepare the laboratory’s codes in advance of the system transitioning to production in 2018. This article presents LLNL’s overall application strategy, with a focus on how LLNL is collaborating with IBM and Nvidia to ensure a successful transition of its mission-oriented applications into the exascale era.
Show Me the Money: "Dark Money" and the Informational Benefit of Campaign Finance Disclosure

Campaign finance compliance and transparency reveal important non-policy attributes that voters care about. They may signal how the candidate would govern if elected. Using vignette and conjoint survey experiments, I show that voters in primary elections base their candidate selection on transparency considerations, even where the candidate shares the respondents’ preferred policy positions. The findings bring campaign finance compliance into the scholarly conversation about candidate valence, and they explain why some primary candidates discourage dark money support only to embrace it in the general election.
Not Just Skin Deep: Systemic Disease Involvement in Patients With Cutaneous Lupus

Cutaneous lupus erythematosus, specifically discoid lupus erythematosus, disproportionately affects those with skin of color and may result in greater dyspigmentation and scarring in darker skin types. In this article, we review investigations relevant to cutaneous lupus patients with skin of color at University of Texas Southwestern Medical Center, associations and risk of progression to systemic lupus, and recommendations for monitoring for systemic disease spread. Between 5% and 25% of patients with cutaneous lupus can develop systemic lupus. If they progress to systemic disease, patients often develop mild systemic disease with primarily mucocutaneous and musculoskeletal manifestations. Patients with cutaneous lupus should be followed up closely to monitor for systemic disease involvement. The University of Texas Southwestern Cutaneous Lupus Erythematosus Registry, of which almost two thirds of participants are those with skin of color, is a part of an ongoing effort to better understand the pathophysiologic mechanisms of CLE and to identify prognostic indicators of risk of progression to systemic lupus.
Autophagy and the tumor microenvironment

Malignant cells do not act as separate entities; they exist in the context of an emergent microenvironment that they create in concert with the host over several years of intimate interaction. The tumor microenvironment (TME) is composed of inflammatory/immune cells, endothelial cells, fibroblasts, cytokines, chemokines, growth factors and the extracellular matrix. The TME has been implicated in the regulation of tumor initiation and progression, determining metastatic potential, and impacting the response to therapy. The TME is highly dynamic and contains subpopulations of cancer cells with temporally varying gradients of cellular metabolism, O2 content, pH, genomic stability and a propensity for aggressive behavior. The stressors present within the TME, include hypoxia, low nutrient availability, immune infiltrates, inflammatory factors and unscheduled cell death associated with release of endogenous damage associated molecular pattern (DAMP) molecules. DAMPs, including the chromatin-binding protein high mobility group box 1 (HMGB1), alert the host of tissue damage or injury by triggering immune responses and activating stress mechanisms such as autophagy through their interaction with pattern recognition receptors. Autophagy, a conserved lysosomal degradation pathway, is a cell maintenance program that is operative at basal levels in all cells, extinguishing during traversion of the cell cycle. It is invoked at higher levels as a survival mechanism in response to environmental and cellular stress. The role of autophagy in cancer including the TME is complex and may differ depending on tumor type or context. In this chapter, recent advances in our understanding of autophagic molecular mechanisms and functions in the TME are reviewed.
Complementary and Alternative Medicine in Hospice and Palliative Care: A Systematic Review.

Abstract Context The aim of palliative care is to improve quality of life for patients with serious illnesses by treating their symptoms and adverse effects. Hospice care also aims for this for patients with a life expectancy of six months or less. When conventional therapies do not provide adequate symptom management or produce their own adverse effects, patients, families, and caregivers may prefer complementary or alternative approaches in their care. Objectives The objectives of this study were to evaluate the available evidence on the use of complementary or alternative medicine (CAM) in hospice and palliative care and to summarize their potential benefits. Methods A defined search strategy was used in reviewing literature from major databases. Searches were conducted using base terms and the symptom in question. Symptoms included anxiety, pain, dyspnea, cough, fatigue, insomnia, nausea, and vomiting. Studies were selected for further evaluation based on relevancy and study type. References of systematic reviews were also assessed. After evaluation using quality assessment tools, findings were summarized and the review was structured based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Out of 4682 studies, 17 were identified for further evaluation. Therapies included acupressure, acupuncture, aromatherapy massage, breathing, hypnotherapy, massage, meditation, music therapy, reflexology, and reiki. Many studies demonstrated a short-term benefit in symptom improvement from baseline with CAM, although a significant benefit was not found between groups. Conclusion CAM may provide a limited short-term benefit in patients with symptom burden. Additional studies are needed to clarify the potential value of CAM in the hospice or palliative setting.
Coordination chemistry of lanthanides in a AOT-CMPO solvent extraction system: UV-Vis and XAFS studies.

The extractability and coordination chemistry for lanthanides in a binary extraction system containing aerosol OT (AOT) and a phosphine oxide (CMPO) have been investigated by means of UV-Vis and X-ray absorption fine structure (XAFS) techniques over a range of extractant concentrations. In addition to the Fourier transform EXAFS analysis, the application of wavelet transform (WT) to the Fourier transform was adapted to the Ho L-III edge to provide a better contrast between the heavier and lighter backscattering atoms at higher coordination shells in the mixed extractant system. Through the variation of the ratio of AOT and CMPO and the acid concentration of the aqueous phase, a synergistic effect appeared at a 1 : 1 ratio of AOT and CMPO using a moderate acid concentration (0.5 M HNO3). It was also found that CMPO itself is directly coordinated with the metal ions by forming the bond with PO and CO, while AOT extracts the lanthanide as a hydrated form through reverse micelle formation. However, the complex of CMPO (CO–M and PO–M) to metal becomes weaker as it is mixed with AOT. Our results indicate that complexation from the CMPO is aiding the control of water extraction through reverse micelles from AOT, which results in the cooperative effect of certain mixtures of AOT–CMPO. The information from this coordination environment offers insight into the role of reverse micelle formation in a mixed-extractant solvent extraction system.
The effects of oral nicotine administration and abstinence on sleep in male C57BL/6J mice

Sleep disturbances are common in smoking cessation attempts and are predictive of relapse. Despite this knowledge, there is no established animal model to study the effect of nicotine abstinence on sleep and EEG parameters. The present study was conducted to characterize sleep and wakefulness in male C57BL/6J mice during periods of oral nicotine administration and abstinence. Male C57BL/6J mice were implanted with EEG/EMG recording devices. EEG/EMG data were recorded continuously for a period of 4 weeks. At the beginning of week 2, 200 μg/ml of nicotine was added to the 0.2% saccharin vehicle drinking solution. Following a 2-week period of oral nicotine administration, abstinence was initiated by excluding the nicotine from the 0.2% saccharin vehicle drinking solution. EEG/EMG were analyzed at pre-nicotine baseline, during nicotine administration, and on days 1, 2, and 5 of abstinence from nicotine. Oral nicotine administration decreased total sleep time during the active phase, consistent with the stimulant actions of nicotine. In contrast, NREM sleep quantity was increased during the active phase on nicotine abstinence day 1 and REM sleep was decreased during days 2 and 5 of abstinence. Further, sleep fragmentation was increased during the inactive phase on all days of abstinence. Oral nicotine administration and abstinence from nicotine also altered EEG relative power frequencies during the inactive and active phase. Both oral nicotine administration and abstinence lead to sleep disturbances in mice. Similarities between this model and human reports on the effect of nicotine/nicotine withdrawal on sleep support its utility in examining the molecular mechanisms that modulate the relationship between sleep, nicotine, and nicotine abstinence/withdrawal.
Patient satisfaction reporting for patellofemoral arthroplasty is significantly lacking: a systematic review

ABSTRACTBackground: Patellofemoral Arthroplasty (PFA) has been shown to be successful in restoring knee function and quality of life in patients with the isolated patellofemoral disease. Patient sa...
A pilot study to implement an artificial intelligence (AI) system for gastrointestinal cancer clinical trial matching

Abstract Background Clinical trials improve our knowledge of diseases and treatments while providing patients access to investigational agents. However, approximately 3% of newly diagnosed cancer patients are enrolled in clinical trials in the United States. Identifying an appropriate trial for a patient is time-consuming and cumbersome in the busy clinical practice. The Watson for Clinical Trial Matching (CTM) cognitive system uses AI to derive patient and cancer-related attributes from structured and unstructured text found in the electronic health record. These attributes are matched to complex eligibility criteria in clinical trial protocols. Methods In April 2019, a pilot study was launched to test the feasibility of implementing CTM in Gastrointestinal (GI) oncology at Mayo Clinic in Rochester, MN. Two clinical research coordinators (CRCs) screened patients for potential clinical trials prior to their clinic visits using both CTM and the traditional manual screening method. To avoid bias, each CRC screened a separate set of patients by both methods alternating which methodology was used first. The clinical trial match results were blinded to both CRCs. For each method, time to complete the screen and number of potential clinical trial matches were recorded. Results A total of 35 GI cancer patients with new diagnosis, recent resection or restaging scans were analyzed. Patients were evaluated against 50 GI-specific drug therapy and multi-disease phase I clinical trials. Clinical trial matching using CTM took an average of 10.1 minutes (Range: 4 to 20 min) per patient compared to an average of 30.5 minutes (Range: 5 to 75 min) per patient (p Conclusions Implementation of Watson for CTM system with a CRC team may enable high volume patient screening for a large number of clinical trials in an efficient manner and promote awareness of clinical trial opportunities within the GI oncology practice. Further analysis to evaluate CTM accuracy and impact on enrollment is warranted and currently underway. Legal entity responsible for the study The authors. Funding Mayo Clinic. Disclosure T. Haddad: Advisory / Consultancy: TerSera Therapeautics; Research grant / Funding (self): Takeda. S. Coverdill: Full / Part-time employment: IBM Watson Health; Shareholder / Stockholder / Stock options: IBM. M. Rammage: Full / Part-time employment: IBM Watson Health; Licensing / Royalties: IBM. All other authors have declared no conflicts of interest.
The pore structural evolution of the Marcellus and Mahantango shales, Appalachian Basin

Abstract The generation and primary migration of hydrocarbons in organic-rich shale leaves void space in organic matter, which is the porosity associated with organic matter commonly observed under scanning electron microscope (SEM). In this study, Middle Devonian black shale core samples were collected from three wells penetrating the organic-rich Marcellus Shale and the organic-lean Mahantango Formation in Pennsylvania and West Virginia. Pyrolysis, ion milled SEM and low-pressure nitrogen adsorption analysis were conducted to investigate the organic richness and the properties of the pore system. Vitrinite reflectance (Ro) values in the range of 1.36%–2.89% represent a maturity spectrum covering the wet-gas to post-mature zones. In general, the pore system is composed of organic matter-hosted pores and mineral-hosted pores. However, the dominant pore types and pore sizes vary stratigraphically across lithology and abundance of organic matter. All the organic matter observed in this study shows an amorphous occurrence. Pore space between mineral grains (both silt-size and clay-size) can be filled by organic matter, which contains secondary porosity generated by thermal cracking of kerogen. Mineral-hosted pores are concentrated in organic-lean samples in which secondary organic matter could not fill most of the primary pore space. The destruction of primary mineral-hosted pores and the generation of secondary organic matter-hosted pores were observed. TOC values show positive correlations with the porosity, specific surface area, and the abundance of micropores. Increasing thermal maturity correlates with a significant decrease of pore volume and surface area, primarily through diminishing or vanishing of micropores. The richness and thermal maturity of organic matter in organic-rich Devonian shale can be effective parameters for evaluation of reservoir quality and upscaling the appraisal.
A Comparative Study of the Immune Reaction in Germfree and Conventional Mice

In recent years considerable attention has been devoted to the germinal centers of lymphatic tissue, particularly as these structures relate to the immune reaction (see reviews by Thorbecke and Hurlimann, 1965, and Congdon and Hanna, 1967). Results of various studies have demonstrated 1) that an antigen-stimulated proliferation of large pyroninophilic cells occurs in germinal centers (Hanna, 1964; Cottier et al., 1967), and this proliferation is antigen dose dependent (Hanna et al., 1966); 2) that the sensitized immune cell compartment develops first in lymphatic nodules at the time of germinal center hyperplasia (Thorbecke et al., 1964); and 3) that during the course of an immune reaction, antigen is localized and retained extracellularly in plasma membrane infoldings of specialized reticular cells which constitute the fixed stroma of the germinal center (Szakal and Hanna, 1968, Nossal et al. , 1968).
Another Spinal Mishap

An anesthesia resident is anesthetizing the skin with 1% plain lidocaine prior to performing a spinal anesthetic for an elective cesarean delivery. Using the 25 gauge cutting needle provided on the tray (the “skin wheal needle”), he first anesthetizes the skin and subcutaneous tissue and then generously injects local anesthetic into the interspinous ligament in various places—but does not always draw back on the syringe before each injection (L-1). For his last injection—deep into the interspinous ligament, he thinks—he inserts the 25 gauge needle all the way to the hub, injects about 1 mL of 1% lidocaine, and then draws back on the syringe (L-2). He obtains the free flow of clear fluid, presumably CSF. There had been no paresthesia with the needle insertion, and the anesthesia attending who is supervising him tells the resident to simply inject his correct and intended intrathecal dose through the “skin wheal” needle (L-3). The resident complies and immediately tells the patient what happened, reassuring her that the minor mistake should not cause any problems (L-4). The cesarean delivery proceeds smoothly and the spinal resolves routinely, but the day following delivery the nurses on the postpartum ward inform the anesthesia team that the patient is complaining of a headache every time she sits up.
Phenotype and Natural History of Inflammatory Bowel Disease in Patients With Concomitant Eosinophilic Esophagitis.

BACKGROUND The co-occurrence of autoimmune diseases is well recognized. Though studies have suggested that eosinophilic esophagitis (EoE) is more common in patients with inflammatory bowel diseases (IBD), whether co-occurrence of EoE modifies natural history of IBD is unknown. METHODS This was a retrospective case-control study at a referral center. Cases consisted of patients with IBD and EoE, with both diseases diagnosed using established criteria. Controls comprised patients with IBD without concomitant EoE. Two controls were selected per case and were matched for duration of IBD. Relevant covariates regarding disease presentation and natural history were extracted from the medical record and compared between the 2 groups. RESULTS A total of 95 IBD-EoE cases and 190 IBD controls were included in our study. The IBD-EoE group was diagnosed with IBD at a younger age than those with IBD alone (22.3 years vs 29.0 years; P < 0.001) and were more likely to be male (80.0% vs 45.8%; P < 0.001). There were no differences in medical or surgical therapy for IBD between the 2 groups. Among those with IBD-EoE, patients for whom IBD was diagnosed first presented more commonly with dysphagia (50.8% vs 26.9%; P = 0.04) and endoscopically had evidence of esophageal rings (50.0% vs 23.1%; P = 0.02) when compared with those where EoE was diagnosed first. CONCLUSION Patients with concurrent IBD-EoE are diagnosed at a younger age and more likely to be males but have similar natural history as those without EoE. There were differences in EoE phenotype based on whether the EoE or IBD was diagnosed first.
Reconfigurable Integrated Optical Interferometer Network-Based Physically Unclonable Function

In this article we describe the characteristics of a large integrated linear optical device containing Mach–Zehnder interferometers and describe its potential use as a physically unclonable function. We propose that any tunable interferometric device of practical scale will be intrinsically unclonable and will possess an inherent randomness that can be useful for many practical applications. The device under test has the additional use-case as a general-purpose photonic manipulation tool, with various applications based on the experimental results of our prototype. Once our tunable interferometric device is set to work as a physically unclonable function, we find that there are approximately $\mathbf {6.85\times 10^{35}}$ challenge-response pairs, where each challenge can be quickly reconfigured by tuning the interferometer array for subsequent challenges.
Understanding General Aviation Accidents in Terms of Safety Systems

This research provides a new, data-driven method that could be used to estimate the impact of integrating an automated safety system into a target class of general aviation aircraft. General Aviation (GA), that is, air travel apart from scheduled air carriers, is still more dangerous than automobile travel by several metrics. This fact should drive research to understand which safety systems might make significant improvements in GA aircraft safety. Pre-existing accident classification schemes are often very general and do not necessarily provide the insight necessary to judge the impact of a given safety technology. This paper attempts to use machine learning methods, applied to a novel transformation of the publicly available NTSB accident database, to create a model based on a set of pre-scored accident records that can be used to provide a notional estimate of the impact of an automatic ground collision avoidance system (Auto GCAS) in terms of fatal events that might have been prevented had such a system been installed. This study found that the number of fatality accidents that were predicted to be prevented by Auto GCAS was significant. The events that were thus predicted by the model spanned multiple CICTT Occurrence Categories, indicating that attempting to categorize the impact of the Auto GCAS system in terms of controlled flight into terrain (CFIT) alone, for example, would under-represent the potential benefit by not including saves cutting across the low altitude operations (LALT), unintended flight into instrument meteorological conditions (UIMC), and loss of control in-flight (LOC-I) categories.
Regulation of Dopamine D1 Receptor Signaling at the Golgi Apparatus by a Low Affinity Dopamine Transporter

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors expressed in humans. It has been traditionally thought that GPCRs can only signal on the plasma membrane, where receptors are activated upon binding of external cues. However, recent work has demonstrated that, in several cases, subcellularly-localized GPCRs are also activated upon the presence of external cues resulting in downstream signaling pathways. Whether subcellular activation of GPCRs is limited to subsets of GPCRs or is a general aspect of GPCR signaling is not known. Additionally, establishing GPCR signaling from subcellular compartments is the first step in unraveling the physiological consequences of compartmentalized signaling for each GPCR family member. Here, using novel nanobody-based biosensors, we demonstrate that dopamine D1 receptor (D1DR), the primary mediator of dopaminergic signaling in the brain and kidney, is activated at both the plasma membrane and the Golgi apparatus upon the presence of its ligand. Interestingly, we found that activation of the Golgi pools of D1DRs is dependent on Organic Cation Transporter 2 (OCT2), a low affinity dopamine transporter, providing an explanation for how dopamine, a membrane impermeant ligand, accesses subcellular pools of D1DR. We also show that Golgi-localized D1DRs regulate local cAMP production and mediate protein kinase A activation at the Golgi membranes. Together, our data suggest that spatially compartmentalized signaling hubs are previously unappreciated regulatory aspects of D1DR signaling. Our data also provide further evidence for the role of transporters in regulating subcellular GPCR activity.
Negotiation of Czech Ethnic Identity through Folk Costume in the Midwest

Folk costumes operate as a language to communicate distinctive group and individual identities such as ethnic identity, and previous researchers found that wearing folk costumes is one way that Czech ethnic identity is celebrated in the United States. Large numbers of Czechs emigrated to America in the 1870s-1920s, but eventually a generation was born that had no contact with immigrant ancestors. The purpose of our research was to examine what role folk costume plays in the negotiation of Czech ethnic identity and how meaning is constructed and communicated through Czech folk costumes. We conducted 12 in-depth, semi-structured interviews with the descendants of Czech immigrants in a previously unexplored Czech population of the Midwest. We identified three major themes: feelings of connectedness, sense of pride, and the importance of being authentic. Through our work, we contribute to the historical and cultural preservation and documentation of modern-day Czech traditions.
The Berlin Premiere of Gluck’s Iphigénie en Aulide in 1809: An Opera to Restore the Monarchy and the Nation

After devastatingly defeating Prussian forces in 1806, Emperor Napoleon’s forces occupied Berlin, reduced Prussia’s territories, and forced King Friedrich Wilhelm III into exile. When the king retu...
The Consequences of Prematurity: Understanding and Therapy

The birth of an infant before the completion of the normal 40-week gestational period has been postulated to represent a perinatal trauma with detrimental effects upon the health of both the infant and its mother, and upon their social interaction as well. There has been a long history of concern with the intellectual consequences of prematurity. In more recent times, additional concerns have been raised by studies finding that prematurely born children are more frequently abused by their parents than other children (Klein and Stern, 1971). As our understanding of the processes of psychological development has advanced, we have been better able to appreciate the social context for both of these consequences of premature birth and to begin programs for the alteration of both the intellectual and social deficits associated with prematurity.
Corrections and Criminalistics: Pragmatism, Principles, and Policy

A survey and analysis was conducted regarding the use of forensic science services in a correctional setting. Within the broader context of issues affecting involvement of police and prosecutions in custodial criminality, we have considered (a) whether existing forensic science services meet the needs of those who live and work in prisons and (b) the likely benefits of making specially tailored and easily accessible forensic services available. Investigative policies were reviewed for three correctional institutions including federal, state, and county jurisdictions. Also examined were types of cases, investigative effort, and relationships with outside investigative bodies. This study found a surprising underutilization of forensic science matters. The potential benefits of such services are considered from the view of the forensic scientist, the prison investigator, and society. In the light of these benefits, policy options are discussed.
Resistance to Computer‐based Technology in the Workplace

There are many instances of documented resistance to computer‐based technology. Presents the two most important causes for resistance. Moreover, also presents solutions/techniques to reduce resistance. The first important cause for resistance is based on the notion that, even though technical barriers have fallen, some features of computer‐based technology are difficult for end‐users to learn. The other is based on a personality profile of the end‐user. Offers suggestions to alleviate both of these sources of resistance.
America's Tweak to the Loser Pays Rule: A Board-Insulating Mechanism?

In May 2014 the Delaware Supreme Court upheld a corporate by-law provision that shifts the cost of unsuccessful shareholder derivative suits to the plaintiff shareholders. But unlike the “loser pays” rule prevalent in the United Kingdom, whereby the losing party pays the litigation costs of the winner, the version upheld in Delaware is one-sided — the plaintiffs are liable for legal costs if they lose, but do not recover legal costs if they win. Not surprisingly, more than 20 corporations have adopted similar bylaws since the May 2014 decision. In “America’s Tweak to the Loser Pays Rule: A Board-Insulating Mechanism?” I explain the so-called “tweaked loser pays rule” and explore its ramifications.
Electromyographic Evaluation of Operation of a Railroad Hand Brake

Ten male subjects performed four methods of setting a vertical boxcar hand brake. Muscle activity was recorded in arm, leg, and back muscles. Each method was rated in terms of adherence to principles of work design and rated by subjects in order of comfort. Maximum braking force was recorded for each method and the subjects were videotaped to analyze postures. Biographical and strength data were recorded. The study found that as equipment arrangements allowed the operator to assume a more upright posture, braking force tended to increase, comfort ratings improved, EMG signals tended to decrease, and the task adhered to more principles of physiologically sound work design. Strength of the left arm was the major predictor of braking force, and back muscle activity tended to increase as braking force increased.
The Debate Regarding the Freedman's Bureau: Is Equality of Process Sufficient for Equality of Results?

Historians and political theorists have delineated the concept of equality into two categories: the competitive individualist notion of equality of process and the egalitarian ideal of equality of results. The former is concerned with providing a level playing field for all, while the latter focuses on a just distribution resulting from the process. In other words, the egalitarian spirit was not absent from American history, but Americans believed that justice would best be served through competition.
Is Language the Key to Human Intelligence

What factors make humans unique? Spoken language? Recursion? In his Perspective, Premack uses a recent study showing that tamarin monkeys can acquire nonrecursive but not recursive grammar ( Fitch et al.) as a springboard to discuss various aspects of human uniqueness.
A CMOS variable gain amplifier for a wideband wireless receiver

The variable gain amplifier (VGA) embedded in an automatic gain control (AGC) loop is an essential component of a linear receiver. The AGC builds up the received signal to some specified peak output so that it fully loads the fixed full-scale of, say, an A/D converter in the IF section. The VGA described here is for use in a low-IF wideband receiver. An active analog filter with programmable bandwidth selects the channel of interest. Active filters suffer from a high input noise level, which can easily dominate the receiver noise figure. The VGA must therefore amplify the received signal enough to overcome filter noise. The circuit reported here is designed to give a continuously variable gain from 0 to 70 dB. Unlike the GSM receiver, the high-order QAM modulation being detected in this receiver cannot tolerate discrete gain jumps. It is more of a challenge to design an amplifier with continuously variable gain, than one whose gain changes in steps. Furthermore, as the VGA bandwidth is fixed at 20 MHz, it must be able to handle much larger signals in adjacent channels before they are removed by the filter. To obtain the best overall performance, the AGC assigns gain to one VGA placed before the filter and possibly another one after it. A good gain assignment algorithm is essential to useful AGC design.
Design Features of Drug–Drug Interaction Trials Between Antivirals and Oral Contraceptives

The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs.
May the Best Molecule Win: Competition ESI Mass Spectrometry

Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences.
Strategic alliances and networks in supply chains: knowledge management, learning and performance measurement

This manuscript defines and analyses the concept of a strategic alliance as one specialized collaborative agreement among vertically-allied firms in the supply chain. Vertical relationships and alliances coagulate among upstream and downstream firms in an effort to form networks that are synergistic and add value beyond what an individual firm may be able to achieve. One driver to form a strategic alliance is intellectual property that serves as a base for maximizing value added within a supply chain. Multiple diverse organizations that collaborate within a supply chain compose a network. Knowledge management is introduced in the analysis of strategic alliances. Knowledge management logic helps in understanding the information-sharing aspects of a strategic alliance. Ambiguity plays a role in the extent to which information is shared. Thus, knowledge management provides novel insight into the foundations of a strategic alliance. The potential of a strategic alliance creating a real option for managers is examined along with the characteristics of networks that are organized around constant learning. Strategic-alliance performance evaluation also is addressed. Sometimes it is not appropriate to evaluate the strategic alliance based on conventional means such as profit and return on investment. Strategic alliances may involve objectives such as entering new markets, learning and obtaining new skills, and/or sharing risks and resources. When a profit centre is not part of the object of cooperation the alliance presents challenges to managers in terms of evaluation. Performance evaluation of alliances is suggested based on a certain-to-fuzzy continuum of inputs and outputs.
T Cell Recognition of Human Pre-Proinsulin Peptides Depends on the Polymorphism at HLA DQ Locus: A Study Using HLA DQ8 and DQ6 Transgenic Mice

Abstract ABSTRACT: HLA DQ8 (DQ A1∗0301/DQB1∗0302) molecule is implicated in the susceptibility to insulin dependent diabetes mellitus whereas, HLA DQ6 (DQ A1∗0103/DQB1∗0601) molecule may have a protective effect. In this study we used mice transgenic to HLA DQ8 and HLA-DQ6 to elucidate the T cell determinants on a putative islet cell target antigen, insulin. These mice do not express endogenous mouse class II heterodimers on cell surface. Using overlapping synthetic peptides spanning the complete sequence of human pre-proinsulin, we identified the sequences recognized by T cells in DQ8 transgenic mice and compared these to those in DQ6 transgenic mice. We observed a differential pattern of recognition of epitopes on human pre-proinsulin (HPI) polypeptide presented by the HLA DQ8 allele as compared to HLA DQ6. The sequences 1-24 and 44-63 were immunodominant in DQ8 transgenic mice while DQ6 transgenic mice primarily recognized sequences 14-33 and 74-93 of HPI. We found that the immune response generated in HLA DQ8 transgenic mice against HPI 1-24 cross-reacted to the mouse pre-proinsulin sequence 1-24. The T cell response were specifically inhibited using anti- CD4 and anti-DQ8 monoclonal antibodies. This cross-recognition of self sequences raises the possibility of modulation of experimental diabetes using this peptide.
Tyrosine Phosphorylation of c-ErbB-2 Is Regulated by the Cellular Form of Prostatic Acid Phosphatase in Human Prostate Cancer Cells

Abstract Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. In prostate carcinomas, the cellular PAcP is decreased. We investigated its functional role in these cells. Several lines of evidence support the hypothesis that cellular PAcP functions as a neutral protein-tyrosine phosphatase and is involved in regulating prostate cell growth. In this study, we identify its in vivo substrate. Our results demonstrated that, in different human prostate cancer cell lines, the phosphotyrosine (Tyr(P)) level of a 185-kDa phosphoprotein (pp185) inversely correlates with the cellular activity of PAcP. On SDS-PAGE, this pp185 co-migrates with the c-ErbB-2 oncoprotein. Immunodepletion experiments revealed that c-ErbB-2 protein is the major pp185 in cells. Results from subclones of LNCaP cells indicated the lower the cellular PAcP activity, the higher the Tyr(P) levels of c-ErbB-2. This inverse correlation was further observed in PAcP cDNA-transfected cells. In clone 33 LNCaP cells, l-(+)-tartrate suppresses the cellular PAcP activity and causes an elevated Tyr(P) level of c-ErbB-2 protein. Epidermal growth factor stimulates the proliferation of LNCaP cells, which concurs with a decreased cellular PAcP activity as well as an increased Tyr(P) level of c-ErbB-2. Biochemically, PAcP dephosphorylates c-ErbB-2 at pH 7.0. The results thus suggest that cellular PAcP down-regulates prostate cell growth by dephosphorylating Tyr(P) on c-ErbB-2 oncoprotein in those cells.
The Distribution of Environmental Equity: Exploring Spatial Nonstationarity in Multivariate Models of Air Toxic Releases

Abstract Conventional multivariate regression can hide important local variations in the relationships among independent and dependent variables in models of environmental equity. Geographically weighted regression (GWR), in combination with choropleth mapping, can reveal this spatial nonstationarity and shed light on its form. We use GWR, in combination with conventional univariate and multivariate statistics, to model the density of air toxic releases in New Jersey, as listed in the U.S. Environmental Protection Agency's Toxic Release Inventory (TRI). The GWR analysis shows that the relationships among race, class, employment, urban concentration, and land use with air toxic release density in New Jersey vary significantly over space. Generally, there is a positively significant relationship of minorities with air toxic releases over a large swath of urban and suburban New Jersey, although this pattern is not evident for all urban areas. Northeast New Jersey, the most densely populated part of the state...