cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene regulation and genetics in neurochemistry, past to future.

Ask any neuroscientist to name the most profound discoveries in the field in the past 60 years, and at or near the top of the list will be a phenomenon or technique related to genes and their expression. Indeed, our understanding of genetics and gene regulation has ushered in whole new systems of knowledge and new empirical approaches, many of which could not have even been imagined prior to the molecular biology boon of recent decades. Neurochemistry, in the classic sense, intersects with these concepts in the manifestation of neuropeptides, obviously dependent upon the central dogma (the established rules by which DNA sequence is eventually converted into protein primary structure) not only for their conformation but also for their levels and locales of expression. But, expanding these considerations to non-peptide neurotransmitters illustrates how gene regulatory events impact neurochemistry in a much broader sense, extending beyond the neurochemicals that translate electrical signals into chemical ones in the synapse, to also include every aspect of neural development, structure, function, and pathology. From the beginning, the mutability – yet relative stability – of genes and their expression patterns were recognized as potential substrates for some of the most intriguing phenomena in neurobiology – those instances of plasticity required for learning and memory. Near-heretical speculation was offered in the idea that perhaps the very sequence of the genome was altered to encode memories. A fascinating component of the intervening progress includes evidence that the central dogma is not nearly as rigid and consistent as we once thought. And this mutability extends to the potential to manipulate that code for both experimental and clinical purposes. Astonishing progress has been made in the molecular biology of neurochemistry during the 60 years since this journal debuted. Many of the gains in conceptual understanding have been driven by methodological progress, from automated high-throughput sequencing instruments to recombinant-DNA vectors that can convey color-coded genetic modifications in the chromosomes of live adult animals. This review covers the highlights of these advances, both theoretical and technological, along with a brief window into the promising science ahead. This article is part of the 60th Anniversary special issue.
Where are you organizationally situated? Views from here

We reflect personally and historically on some of the institutions that have nurtured and shaped conversations at the intersections of sociology and religious studies, particularly professional associations. Our argument is simple. The ways different scholars understand the relationship between the sociology of religion and religious studies have a lot to do with the institutions that nurtured us and through which we engage in the conversation. We push back on simple black and white distinctions that paint their approaches in oppositions: more historical vs. more contemporary, more qualitative vs. more quantitative, more concerned with normative concerns vs. more “objective”—in favor of a more nuanced view. We keep in mind the Christian origins of the main professional organizations at these intersections and call for deeper dialogue not just between sociologists and scholars in religious studies but with colleagues involved with a range of other groups.
The Material Culture of Mormonism: A Review

The study of Mormon religious material culture, or the purposeful shaping of human and natural environments through “[religiously] dictated plans” (Deetz 1997, 7), has a long, rich history, and has...
Retinopathy of prematurity: screening and treatment in Costa Rica

Aim To determine the recent demographic data, risk factors and results of retinopathy of prematurity (ROP) screening and treatment in Costa Rica. Methods The medical records of all preterm infants meeting ROP screening criteria (≤34 weeks’ gestational age (GA) or birth weight (BW) ≤1750g, and those determined at risk by neonatologists) in the national healthcare system, Costa Rica, January 2010–December 2014, were retrospectively reviewed. The numbers and percentages of infants with ROP, risk factors, percentage of patients treated and treatment outcomes were determined. Comparison is made with screening criteria and literature reports of ROP incidence in other countries. Results The study population included 3018 preterm infants. Overall, 585 patients (585/3018, 19.4%) were found to have ROP. Of these, 15.4% (90 patients) required laser treatment, and 53% of those requiring treatment had BW Conclusion We provide comprehensive data of ROP care in Costa Rica allowing assessment and comparison of screening criteria and protocol.
Deep Networks for Decoding Natural Images from Retinal Signals

Decoding sensory stimuli from neural signals can be used to reveal how we sense our physical environment, and is critical for the design of brain-machine interfaces. However, existing linear techniques for neural decoding may not fully reveal or exploit the fidelity of the neural signal. Here we develop a new approximate Bayesian method for decoding natural images from the spiking activity of populations of retinal ganglion cells (RGCs). We sidestep known computational challenges with Bayesian inference by exploiting “amortized inference” via artificial neural networks developed for computer vision, which enables nonlinear decoding that incorporates natural scene statistics implicitly. We use a decoder architecture that first linearly reconstructs an image from RGC spikes, then applies a convolutional autoencoder to enhance the image. The resulting decoder, trained on natural images, significantly outperforms state-of-the-art linear decoding, as well as simple point-wise nonlinear decoding. Additionally, the decoder trained on natural images performs nearly as accurately on a subset of natural stimuli (faces) as a decoder trained specifically for the subset, a feature not observed with a linear decoder. These results provide a tool for the assessment and optimization of retinal prosthesis technologies, and reveal that the neural output of the retina may provide a more accurate representation of the visual scene than previously appreciated.
Nonlinear characterization of two dimensional materials (Conference Presentation)

Two-dimensional materials have attracted significant interest recently for their unique optical properties compared to their bulk counterparts. Specifically, the family of transition metal dichalcogenides (TMD), such as MoS2 and WS2, have large second order nonlinear susceptibility. Extraordinary second harmonic generation and sum frequency generation have been observed. Here we investigate the second order nonlinearity of 2D materials, including TMD layered materials with dopants and defects. Experimental results and preliminary theoretical analysis will be discussed.
Upregulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma and other malignancies

5143 Here we describe a novel pharmacologically-induced death pathway in tumor cells involving c-Jun upregulation and caspase-dependent c-Abl cleavage using the tyrophostin adaphostin (NSC680410) as a tool compound. Adaphostin has been previously studied as a bcr-abl inhibitor in CML. However its role in MM is unknown. After demonstrating its anti-myeloma cytotoxicity, expression profiling of adaphostin-treated MM cells was carried out to identify its molecular targets. Surprisingly, c-Jun was the most upregulated gene even at the earliest point of analysis (2 hours). Subsequently, adaphostin-induced c-Abl cleavage was observed in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-Abl fragment or wild type c-Jun, as well as knockdown of c-Abl and c-Jun expression by siRNA, confirmed that adaphostin-induced c-Jun upregulation triggers downstream caspase-mediated c-Abl cleavage, inhibition of MM cell growth, and induction of apoptosis. Moreover, our data suggest that this mechanism may not be restricted to MM, but may also be important in a broad range of malignancies, including erythroleukemia and solid tumors. Finally, given our results suggesting that c-Jun upregulation induced cell growth inhibition and apoptosis in a variety of tumor cells, we performed Oncomine analysis of 13 tumor datasets representing a broad spectrum of tumor types. Nine of these tumors, including Diffuse Large B-Cell Lymphoma, demonstrated significantly lower levels of c-Jun expression in tumor cells versus cellular counterparts. Therefore these data indicate that c-Jun upregulation and subsequent c-Abl cleavage may not only be drug-induced, but also represent a physiologic defense mechanism of normal cells against malignant transformation.
Frequency of First-Year Student Interactions With Advisors

Although acknowledged that academic advising helps students adjust to and deal with the challenges of college, little is known about students' frequency of interactions with advisors. Using data from 52,546 full-time, first-year students at 209 diverse institutions, we examined the frequency with which students met with academic advisors and the way these interactions vary by student and institutional characteristics. We found that the typical first-year student met with an advisor 1 to 3 times during his or her first college year; however, the number of meetings varied across student subpopulations and institutional types.
Take Flight : the evolution of an Orton Gillingham-based curriculum

Thirty years ago in this journal, Aylett Royall Cox reported on the development of Alphabetic Phonics, a revision of the existing Orton Gillingham treatment for children with dyslexia. This paper continues that discussion and reports on the evolution of that curriculum as it is represented in a comprehensive dyslexia treatment program informed by intervention research. The paper describes the curriculum and reports data from a hospital-based learning disabilities clinic that provides qualified support for treatment efficacy and the value of added comprehension instruction. The results are then discussed in the context of current and future issues in dyslexia intervention.
Biofeedback Treatment for Headaches

Classic medical treatment of migraine and tension-type headaches is an ongoing struggle and challenge for the medical practitioner. Pharmacologic treatment does not cure these common conditions and...
Evaluation of RTOT algorithm: A first implementation of OBSS_PD-based SR method for IEEE 802.11ax

The main goal of the IEEE 802.11ax project is to improve the network efficiency of IEEE 802.11 systems in dense deployments. There are currently several methods under consideration in the IEEE 802.11ax task group to achieve the aforementioned goal, including Multi-User Multiple Input Multiple Output (MU-MIMO), Multiple Packet Data Unit-aggregation, channel bonding, in addition to several Spatial Reuse (SR) improvements strategies. In this paper, we focus on the SR improvements methods and more specifically on one of the proposed solution at IEEE to improve SR for 802.11ax: Overlap Basic Service Set Physical Detection (OBSS_PD)-based SR. This solution combines adjusting the power transmission and Carrier Sense Threshold (CST) in order to increase the number of successful concurrent transmissions in dense networks. In this article, we propose and evaluate the RSSI To OBSS Threshold (RTOT) algorithm which is, to the best of our knowledge, the first algorithm to implement OBSS_PD-based SR technique. RTOT uses the beacon Received Signal Strenght Indicator (RSSI) to dynamically compute the CST, and derive afterwards the transmission power to use. We evaluate RTOT algorithm by simulation in a dense scenario. We show that the overall system throughput can be improved up to 80 % compared to IEEE 802.11 legacy networks. We highlight that the overall throughput improvement comes at the expense of per-station throughput degradation, and thus the fairness among stations is severely compromised. A trade-off must be considered between maximizing the overall throughout and maintaining an acceptable per-station throughput.
Closed yet open DRAM: achieving low latency and high performance in DRAM memory systems

DRAM memory access is a critical performance bottleneck. To access one cache block, an entire row needs to be sensed and amplified, data restored into the bitcells and the bitlines precharged, incurring high latency. Isolating the bitlines and sense amplifiers after activation enables reads and precharges to happen in parallel. However, there are challenges in achieving this isolation. We tackle these challenges and propose an effective scheme, simultaneous read and precharge (SRP), to isolate the sense amplifiers and bitlines and serve reads and precharges in parallel. Our detailed architecture and circuit simulations demonstrate that our simultaneous read and precharge (SRP) mechanism is able to achieve an 8.6% performance benefit over baseline, while reducing sense amplifier idle power by 30%, as compared to prior work, over a wide range of workloads.
Correlated pairing theory of liquid 3 He

A variational calculation of the ground-state energy of liquid /sup 3/He is presented. The trial wave functions investigated are correlated pairing functions. By including pairing, we are able to investigate the possibility that the ground state of liquid /sup 3/He is pair condensed. The correlation permits us to apply the theory to a realistic model of the /sup 3/He interactions, including the strong short-range repulsion. The energy of a normal-state trial function is compared at several densities to the energy of singlet s-wave pair condensed state (BCS pairing) and the isotropic triplet pair condensed state (Balian-Werthamer pairing). Within the approximations used, the lowest-energy state from this class of trial functions is the normal state. We briefly discuss possible reasons for the failure of this calculation to exhibit the experimentally observed superfluid state.
Simplification. Conservation and Adaptivity in the Front Tracking Method

The front tracking method was first introduced by Richtmyer for the numerical solution of hyperbolic equations. The solution of hyperbolic equations contains discontinuities such as contact discontinuities and shocks. The former exist even in linear equations when the initial condition is discontinuous. The latter are associated with the nonlinearity of the hyperbolic system. Finite difference and finite volume methods give a satisfactory numerical approximation and convergence rate in the region where the solution is smooth. However they fail to deliver physically correct solutions at discontinuities, especially when the equation of state across the discontinuity is sharply different. By separating the smooth regions at the discontinuity through an interface, the front tracking method overcomes this numerical difficulty by applying finite difference solvers to each smooth subdomain while treating the discontinuity with special care and propagating the front using the exact solution of the Riemann problem.
Treatment with Cl-amidine, a peptidyl arginine deiminase (PAD) inhibitor, significantly reduces collagen-induced arthritis (CIA) (50.6)

Antibodies to citrullinated protein antigens (ACPA) are specific for rheumatoid arthritis (RA). Post-translational citrullination of epitopes to which ACPA are directed is catalyzed by PADs. We have previously shown that ACPA develop in CIA and contribute to joint damage. In this study we used Cl-amidine, a small molecule that specifically inhibits all PAD enzymes, to determine whether limiting PAD activity can modify CIA. CIA and collagen antibody-induced arthritis (CAIA, a model of the antibody-mediated effector pathway of CIA) were induced in DBA/1j mice using standard methods. Mice received either no treatment, vehicle alone (PBS), or 1, 10 or 50 mg/kg/day Cl-amidine by daily IP injection. Cl-amidine reduced CIA disease activity scores by 42%, 53% and 55% in the respective treatment groups (1, 10, 50 mg/kg/day) as well as C3 deposition, IgG1 and IgG2a anti-mouse CII Abs and epitope spreading to citrullinated epitopes. Conversely, Cl-amidine treatment had no effect on the development of CAIA. These results suggest that PADs are essential components in the development of inflammatory arthritis. This work was funded by an ACR REF WOR Grant.
Methods of Study

In this chapter, a brief survey will be given of the most common routine methods to study the microscopic structure of cells, tissues, and organs.
Clinical experience with wearable cardioverter defibrillators at a tertiary electrophysiology program.

Background A wearable cardioverter defibrillator (WCD) is an alternative for patients who are not immediate candidates for an implantable cardioverter defibrillator (ICD). Methods Retrospective analysis of 242 patients prescribed a WCD from January 2014 through March 2015 with 1-year follow-up. Results A WCD was prescribed to 242 patients during the 15-month period. Forty-one patients were excluded due to lack of complete follow-up. The remaining 201 patients received a WCD for primary or secondary prevention of SCD. Seventy-nine percent of WCDs were prescribed by nonelectrophysiologists. Underlying etiologies for the WCD prescription included: 38% nonischemic cardiomyopathy, 25% recent myocardial infarction, 16% newly diagnosed ischemic cardiomyopathy, 12% documented ventricular arrhythmia, 6% ICD lead extraction, and 3% had high risk conditions for sudden cardiac death. During 1-year follow-up, 96 patients (48%) received an ICD and five patients (2.5%) received appropriate shocks and one patient (0.5 %) received an inappropriate shock. Other 105 (52%) patients subsequently did not require an ICD due to either improvement in ejection fraction, refusal of ICD therapy, or death. Conclusions About half of patients prescribed a WCD subsequently receive an ICD and the rate of appropriate shock therapy from the WCD is 2.5%.
Belonging in Black and White: Race, Photography, and the Allure of Heimat in West German Gay Magazines from the 1950s

Physique photography played an important role in conditioning erotic subjectivity for gay male readers of West Germany’s 1950s homophile magazines. To date, scholars of the period have focused on t...
Exercise training promotes a GDF15-associated reduction in fat mass in older adults with obesity.

Obesity is a major risk factor for metabolic disease. Growth differentiation factor 15 (GDF15) has shown promise as a weight loss agent for obesity in animal studies. In healthy lean humans, fastin...
Race and the Criminal Justice System Response to Sexual Assault: A Systematic Review

Prior research has consistently documented that the vast majority of sexual assault cases do not progress through the criminal justice system. However, there is less agreement in prior work on how race influences case progression, resulting in a literature frequently described as "inconsistent." This systematic review examines all prior research that has included race as an independent variable in predicting the criminal justice system response to sexual assault (N = 34) in an effort to provide insight into seemingly disparate findings. We assess each study for the degree to which race was a focal point of interest, if and what theory was used to inform the investigation of race, how samples were drawn, and how and whose race was measured. Results illustrate that findings in prior research are not inconsistent, but rather unite to tell a nuanced story of the role of race in the criminal justice system response to sexual assault. The review demonstrates how decisions made by researchers throughout the research process can have significant impacts on reported findings, and how such findings may be used to influence policy and practice.
Current State of Wind Turbine's Health Monitoring

Harvesting energy on a global, sustainable, and economic scale is one of the major challenges of this century. However, long-term economic sustainability of wind energy is still to be achieved. Wind turbines are heavy, complex machines with large flexible structures working under turbulent, unpredictable environmental conditions. Their efficiency, cost effectiveness, reliability and availability are also highly dependent on their structural health. This paper provides an overview of existing health monitoring approaches. Their merits and drawbacks are discussed. Future research directions are also examined.
Factors associated with students’ attitude change in online peer assessment – a mixed methods study in a graduate-level course

Positive student attitude towards peer assessment can be demonstrated through high-quality peer assessment activities. Research findings on students’ attitudes before and after such activities were...
Aluminizing of steel to improve high temperature corrosion resistance

The aluminizing process is described in detail with a focus on pack cementation. Following an introduction to pack cementation, the thermodynamics and kinetics of the aluminizing process are discussed. Experimental examples from the aluminizing of austenitic stainless steels are presented with appropriate analyses of the microstructural aspects of the coated steels. Applications for this type of coating are also discussed.
Neural networks for faster optical alignment

A technique for providing neural network-coached alignment of optical systems is described in detail. The goal is to increase the speed of convergence to an aligned optical system. The neural network model is trained with the wavefront errors (WFEs) of thousands of randomly misaligned instances of the lens system that are modeled in Zemax OpticStudio®. The optical specialist measures the WFE of the misaligned system, then a neural network suggests specific adjustments to be made to the alignment fixturing (which adjuster, which direction, and by what amount). The technique has been developed into a MATLAB®-based tool called rapid optical system alignment with neural network assist that is shown to analytically and experimentally increase the speed of alignment. It is capable of achieving WFEs that are within a few percent of the nominally aligned condition. The ultimate goal is to deploy such a tool to enable an optical specialist to more quickly align challenging optical systems employing freeform or segmented surfaces. Analytical and experimental results for spherically symmetric systems are shown along with an outline of future work.
Mcrs1 interacts with Six1 to influence early craniofacial and otic development

The Six1 transcription factor plays a major role in craniofacial development. Mutations in SIX1 and its co-factor, EYA1, are causative for about 50% of Branchio-otic/Branchio-oto-renal syndrome (BOR) patients, who are characterized by variable craniofacial, otic and renal malformations. We previously screened for other proteins that might interact with Six1 to identify additional genes that may play a role in BOR, and herein characterize the developmental role of one of them, Microspherule protein 1 (Mcrs1). We found that in cultured cells, Mcrs1 bound to Six1 and in both cultured cells and embryonic ectoderm reduced Six1-Eya1 transcriptional activation. Knock-down of Mcrs1 in embryos caused an expansion of the domains of neural plate genes and two genes expressed in both the neural plate and neural crest (zic1, zic2). In contrast, two other genes expressed in pre-migratory neural crest (foxd3, sox9) were primarily reduced. Cranial placode genes showed a mixture of expanded and diminished expression domains. At larval stages, loss of Mcrs1 resulted in a significant reduction of otic vesicle gene expression concomitant with a smaller otic vesicle volume. Experimentally increasing Mcrs1 above endogenous levels favored the expansion of neural border and neural crest gene domains over cranial placode genes; it also reduced otic vesicle gene expression but not otic vesicle volume. Co-expression of Mcrs1 and Six1 as well as double knock-down and rescue experiments establish a functional interaction between Mcrs1 and Six1 in the embryo, and demonstrate that this interaction has an important role in the development of craniofacial tissues including the otic vesicle.
Interleaved Difference-Frequency-Generation for Mid-Infrared Microcomb Spectral Densification

Generation of mid-infrared combs (3.3 micron band) with GigaHertz line spacing is demonstrated by interleaved difference-frequency-generation. The method, applied to a 22 GHz repetition-rate microcomb, is useful for spectral densification of sparse micro-comb spectra.
Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience.

Background Invasive fungal disease (IFD) is a serious complication among the immunocompromised population. Isavuconazole is a newer broad-spectrum antifungal agent with promising efficacy and safety. However, there remains limited data to favor its use over current first-line agents. Objectives We aimed to evaluate isavuconazole use and describe rates of associated breakthrough invasive fungal disease (bIFD). Methods A single-center, retrospective study was conducted to evaluate patients receiving isavuconazole for prophylaxis or treatment of IFD between July 1, 2017 and December 31, 2018. Patient-related and outcomes data were extracted from electronic medical records. Descriptive statistics were used to analyze our findings. Results A total of 54 patients received 61 isavuconazole courses. Isavuconazole was most commonly prescribed for primary prophylaxis in the acute myeloid leukemia (AML) and allogeneic hematopoietic stem cell transplant (HSCT) population along with treatment for possible invasive fungal disease. The primary reasons for choosing isavuconazole included QTc shortening effects, decreased risk of acute kidney injury, broader spectrum of activity, and concern for breakthrough invasive fungal disease on a different prophylactic agent. We found a breakthrough rate of 8.5% for patients and 7.8% for courses. Conclusions Isavuconazole appears to be a promising alternative for prophylaxis and treatment of invasive fungal disease. We observed similar bIFD rates and improved tolerability when compared to historical data for posaconazole and voriconazole.
Childhood ADHD Symptoms in Relation to Trauma Exposure and PTSD Symptoms among College Students: Attending to and Accommodating Trauma.

Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are highly comorbid among children and adolescents with a history of maltreatment and trauma. This comorbidi...
The Paradox of Extreme Close-Up Gaze.

If somebody gazes at your left eye, you perceive them as looking straight at you. They switch their gaze with a single saccade to your right eye. You see their eyes move, yet they paradoxically end...
One-pot synthesis of enzyme@metal–organic material (MOM) biocomposites for enzyme biocatalysis

Metal–organic frameworks/materials (MOFs/MOMs) are advanced enzyme immobilization platforms that improve biocatalysis, materials science, and protein biophysics. A unique way to immobilize enzymes is co-crystallization/co-precipitation, which removes the limitation on enzyme/substrate size. Thus far, most enzyme@MOF composites rely on the use of non-sustainable chemicals and, in certain cases, heavy metals, which not only creates concerns regarding environmental conservation but also limits their applications in nutrition and biomedicine. Here, we show that a dimeric compound derived from lignin, 5,5′-dehydrodivanillate (DDVA), co-precipitates with enzymes and low-toxicity metals, Ca2+ and Zn2+, and forms stable enzyme@Ca/Zn–MOM composites. We demonstrated this strategy on four enzymes with different isoelectric points (IEPs), molecular weights, and substrate sizes. Furthermore, we found that all enzymes displayed slightly different but reasonable catalytic efficiencies upon immobilization in the Ca–DDVA and Zn–DDVA MOMs, as well as reasonable reusability in both composites. We then probed the structural basis of such differences using a representative enzyme and found enhanced restriction of enzymes in Zn–DDVA than in Ca–DDVA, which might have caused the activity difference. To the best of our knowledge, this is the first aqueous-phase, one-pot synthesis of a lignin-derived “green” enzyme@MOF/MOM platform that can host enzymes without any limitations on enzyme IEP, molecular weight, and substrate size. The different morphologies and crystallinities of the composites formed by Ca–DDVA and Zn–DDVA MOMs broaden their applications depending on the problem of interest. Our approach of enzyme immobilization not only improves the sustainability/reusability of almost all enzymes but also reduces/eliminates the use of non-sustainable resources. This synthesis method has a negligible environmental impact while the products are non-toxic to living things and the environment. The biocompatibility also makes it possible to carry out enzyme delivery/release for nutritional or biomedical applications via our “green” biocomposites.
Theoricae novae planetarum Georgii Peurbachii dans l'histoire de l'astronomie Essay Review of Michela Malpangotto, Theoricae novae planetarum Georgii Peurbachii dans l'histoire de l'astronomie. Sources, edition critique, avec traduction française, commentaire technique, diffussion du XVe au XVIIe Siècle. Paris: CNRS Éditions, 2020. 751pp. 65.00 €. ISBN-10: 2271134587, ISBN-13: 978-2271134585.

Georg Peurbach’s Theoricae novae planetarum has a unique history inseparable from the very beginning of scientific printing, so we shall begin with that history. In the spring of 1471, Johannes Reg...
Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward

Background Certain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude) and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking. Methods We examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, age: 42.40±12.22) and its relationship to drug reward. Rest-activity rhythms were assessed by one-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride Positron Emission Tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed. Results We found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or 'social jet lag', whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate. Conclusion These findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders. Trial registration ClinicalTrials.gov: NCT03190954FUNDING. This work was accomplished with support from the National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).
Pretreatment Nutrition-Inflammation Biomarkers Correlated with Differential Cytokine Profiles in Taiwanese Patients with Colorectal Cancer.

Systemic inflammation plays a pivotal role in colorectal cancer (CRC) development. Two hallmarks reflect the severity of inflammation-circulating cytokines and nutrition-inflammation biomarkers (NIBs); however, their interplay has not been fully investigated. In total, 128 CRC patients were included. Ten circulating cytokines (TNF-α, TGF-β, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) and NIBs were analyzed. The relationship between cytokines, NIBs, clinicopathological variables, and overall survival (OS) was assessed using univariate and multivariate analyses. Three NIBs (CRP-to-albumin ratio [CAR]), neutrophil-to-lymphocyte ratio [NLR]), and prognostic nutritional index [PNI]) were associated with OS in univariate analysis; however, CAR was better for OS prediction in multivariate analysis (P = 0.015). None of the serum cytokines analyzed showed a significant association with OS. High CAR (≥0.25) and high IL-10 (≥76.6 pg/mL), high NLR (≥8.2) and high IL-23 (≥51.2 pg/mL), and high PNI (≥42.4) and high IL-1β (≥14.3 pg/mL) values were correlated. CAR, NLR, and PNI were not correlated with each other, whereas circulating cytokines were closely interrelated. High CAR was an independent predictor of poor OS in patients with CRC. Different NIBs have unique cytokine profiles, but show no correlation with each other. There is a close association among the circulating cytokines.
Homo Aestheticus: The Invention of Taste in the Democratic Age

Can subjective, individual taste be reconciled with an objective, universal standard? Luc Ferry argues that this problem of aesthetic theory is fundamentally related to the political problem of democratic individualism. Ferry begins in the mid 1600s with the simultaneous invention of the notions of taste (the essence of art as subjective pleasure) and modern democracy (the idea of the State as a consensus among individuals). He explores the differences between subjectivity and individuality by examining aesthetic theory as developed first by Kant's predecessors and then by Kant, Hegel, Nietzsche, and proponents of the avant-garde. Ferry discerns two "moments" of the avant-garde aesthetic: the hyperindividualistic iconoclasm of creating something new, and the hyperrealistic striving to achieve an extraordinary truth. The tension between these preserves an essential element of the Enlightenment concern for reconciling the subjective and the objective - a problem at once aesthetic, ethical, and political. Rejecting "postmodern" proposals for either a radical break with or return to tradition, Ferry embraces a postmodernism that recasts enlightenment notions of value as a new intersubjectivity. His original analysis of the growth and decline of the modern avant-garde movement illuminates the connections between aesthetics, ethics, and political theory.
Preschoolers’ inferences about pointers and labelers: The modality matters

Abstract Preschoolers seek out and endorse new labels from informants who have previously provided accurate labels over those who have previously provided inaccurate labels (e.g., Koenig et al., 2004). In Study 1, we show that 4-year-olds also prefer a previously accurate pointer over a previously inaccurate one as a source of information about newly hidden objects. In Study 2, we show that they do not expect that a previously accurate pointer will necessarily be a good labeler, though they do expect a previously accurate labeler will be a good pointer. This asymmetry suggests that the scope of inferences children draw about the knowledge of informants can be influenced by the modality in which they communicate. By sharing semantic information (e.g., object names), labelers demonstrate generalizable knowledge; by sharing episodic information (e.g., an object’s location), pointers demonstrate more limited knowledge.
Civil-Military Jurisdiction with Respect to United States Military Forces in the Philippines 1898–1947

The criminal jurisdictional arrangements established between the Philippines and the United States after World War II were influenced by a background of practice that developed over the fifty years following American occupation of Manila in 1898.1 This period afforded a variety of situations capable of generating conflicts of jurisdiction between civil and military authorities. These situations included war and insurrection, colonialism, and the peace time stationing in one independent nation of military forces of another independent nation. Under each of these diverse conditions some form of criminal jurisdictional arrangement was established.
The Rise of Planning in Industrial America, 1865-1914

Introduction: The Tripod of Power Part 1: Islands of Conscious Power 1. Organizing Production 2. Planning 3. Contracts in Performance. Interlude: Choosing the Future Part 2: Redwoods in the Garden 4. Taylor's Bargain 5. Antitrusts 6. Deciding for Bigness 7. Contracts at Liberty. Epilogue: 'War is the Health of the State'
Salad and Simile: A Defense of Cultivation

Sydney Lea Before you, spinach green as lucre. You dream of opportunity?perhaps a lucky letter. But hearts of iceberg lettuce yellow like junk mail. Disappointment in early June, a season of legumes, new roots and leaves. Time will pass: the fern of the asparagus turn to feathers, as for sweeping woe like dust that settles, needing re-arrangement. Your mind has wandered from the bowl like a woodchuck from his burrow to devour odd weeds. Sitting, my Candide, conning greens like tea-dregs, you conjure bleak perspectives. But why not a possible beneficence? You are what you eat: conversely, though, what you eat is you? the pear tomato centers in the dish not like a jaundiced hope but like the sun you wished for months ago when deep ice sealed the ever-anxious tubers (parsnip, rutabaga, turnip) and the cover crop of vetch. "Good salads may be prologues to bad suppers": so a proverb has it. Thus your salad was a simile before it grew. Why not toss it? Assume these bitter herbs and shoots you chew
Identification of the MAP2- and P75-binding domain in the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase. Cloning and expression of the cDNA for bovine brain RII beta.

cDNA clones coding for the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase were isolated from a bovine brain cDNA expression library in lambda gt11. The cDNA codes for a protein of 418 amino acids which is 98% homologous to the rat and human RII beta proteins. A series of expression vectors coding for truncated RII beta proteins were constructed in pATH plasmids and fusion proteins were expressed in Escherichia coli. Polyclonal and monoclonal antibodies made against purified bovine brain RII were immunoreactive with the fusion proteins on Western blots. The expressed RII beta-fusion proteins were used in overlay assays to identify the region in RII beta which binds to microtubule-associated protein 2 (MAP2) and to the 75,000-dalton calmodulin-binding protein (P75) (Sarkar, D., Erlichman, J., and Rubin, C.S. (1984) J. Biol. Chem. 259, 9844-9846) in bovine brain. Fusion protein containing amino acids 1-50 of the RII beta NH2 terminus (RII beta(1-50)] bound to both MAP2 and P75 immobilized on nitrocellulose filters. A pATH11-directed fusion protein containing the 31 amino acid RII-binding site of the human MAP2 protein (MAP2(31)) (Rubino, H.M., Dammerman, M., Shafit-Zagardo, B., and Erlichman, J. (1989) Neuron 3, 631-638) also bound RII beta-fusion proteins containing RII beta amino acids 1-50. Three fusion proteins, RII beta(1-25), RII beta(25-96), and RII beta(1-265,25-96 deleted) did not bind to MAP2(31) nor P75. The results showed that the binding domain for MAP2 and P75 was located within the NH2-terminal 50 amino acids of RII beta. Preincubation of bovine heart protein kinase II alpha and RII beta(1-50) with MAP2(31) prevented their binding to both P75 and MAP2(31) that were immobilized on nitrocellulose, suggesting that the binding sites for MAP2 and P75 are located near each other or that the same site on RII was binding to both proteins.
Consolidation Under Time-Dependent Loading

In analyzing consolidation settlements caused by time dependent loading, the engineer typically replaces the actual load-time curve with a series of step loads and applies the theory for instantaneous loading. For the case of one-dimensional vertical flow and simple ramp loading, the time-settlement curve may be approximated using a graphical construction orginiated by Terzaghi or curves presented by Schiffman. However, the method is reviewed and suitable design curves are presented. For one-dimensional vertical flow all of the assumptions of Terzaghi.s basis theory are retained except the assumption of instantaneous loading. For the sand drain case, solutions are obtained for purely radial flow and for combined vertical and radial flow.
Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes

Superior cell culture models for hepatitis B virus (HBV) will help advance insights into host-virus interactions. To identify mechanisms regulating HBV replication, this study used cultured human HepG2 cells and adult or fetal hepatocytes transduced with adenoviral vector to express HBV upstream of green fluorescent protein. The vector efficiently transduced all cell types. In HepG2 cells, replicative viral intermediates, nucleocapsid-associated HBcAg, and HBsAg were expressed. However, in fetal or adult hepatocytes, pregenomic HBV RNA and viral RNAs were expressed, but nucleocapsid-associated HBcAg in cells or HBsAg in culture medium were absent, indicating interruptions in viral replication due to possible microRNA-related interference. MicroRNA profiling demonstrated that a large number of microRNAs with antiviral potential were differentially expressed in hepatocytes after culture. In transfection assays using HepG2 cells, candidate antiviral microRNAs, e.g., hsa-miR-24 or hsa-miR-638 decreased the levels of HBV transcripts or HBV gene products. Since candidate microRNAs could have targeted interferon response genes as an alternative explanation interferon signaling was examined. However, HBV replication in cultured hepatocytes was not restored despite successful inhibition of JAK1/2-STAT signaling by the inhibitor, ruxolitinib. Therefore, HBV was unable to complete replication in cultured hepatocytes due to expression of multiple antiviral microRNAs. This mechanism should help understand restrictions in HBV replication for developing HBV models in cultured cells while providing frameworks for pathophysiological studies of HBV replication in subsets of hepatocytes or stem/progenitor cells during hepatitis.
Direct study of DNA-protein interactions in repressed and active chromatin in living cells.

Abstract Current methods for analysis of chromatin architecture are invasive, utilizing chemicals or nucleases that damage DNA, making detection of labile constituents and conclusions about true in vivo structure problematic. We describe a sensitive assay of chromatin structure which is performed in intact, living yeast. The approach utilizes expression of SssI DNA methyltransferase (MTase) in Saccharomyces cerevisiae to provide an order-of-magnitude increase in resolution over previously introduced MTases. Combining this resolution increase with the novel application of a PCR-based, positive chemical display of modified cytosines provides a significant advance in the direct study of DNA-protein interactions in growing cells that enables quantitative footprinting. The validity and efficacy of the strategy are demonstrated in mini-chromosomes, where positioned nucleosomes and a labile, operator-bound repressor are detected. Also, using a heterologous system to study gene activation, we show that in vivo hormone occupancy of the estrogen receptor is required for maximal site-specific DNA binding, whereas, at very high receptor-expression levels, hormone-independent partial occupancy of an estrogen-responsive element was observed. Receptor binding to a palindromic estrogen-responsive element leads to a footprint with strand-specific asymmetry, which is explicable by known structural information.
Revitalizing electromagnetics education with the flipped classroom

We report results of a flipped classroom approach to teaching electromagnetics that was undertaken at the Georgia Institute of Technology. In a flipped classroom, students read or watch videos prior to class. In class, students build on that basic knowledge by participating in active learning, including group problem solving, demos and labs, and design activities.
M theory and topological strings. 2.

It is shown how the topological string amplitudes encode the BPS structure of wrapped M2 branes in M-theory compactification on Calabi-Yau threefolds. This in turn is related to a twisted supersymmetric index in 5 dimensions which receives contribution only from BPS states. The spin dependence of BPS states in 5 dimensions is captured by the string coupling constant dependence of topological string amplitudes.
AI: what simulationists really need to know

The authors discuss aspects of the application of artificial intelligence (AI) to simulation. The topics covered are: the place of AI techniques and an AI philosophy for simulation; expanding the bounds of simulation; what simulationists need to know about their problems; AI and simulation-some lessons learned; and AI contributions to simulation. >
The “Not-So-Final Remark” The Journey to Becoming White Allies

This project examines white student learning in the Intergroup People of Color-White People Dialogues (POC-WHITE) and Intragroup White Racial Identity Dialogues (IWRID) at a small liberal arts coll...
Auralization i: vortex sound synthesis

Auralization is the process of extracting and displaying meaningful information in the form of sound from data. Through not only visualization but also auralization, users may have better understandings of the data, especially when it is visually complicated. In this work, a field auralization technique is introduced, which objective is at the sound synthesis from field information represented as 3D time-varying volume data. Our technique takes a hybrid approach between parameter mapping and direct simulation. During preprocessing, acoustic strengths are computed at each vertex at each time step of volume data. During interaction, users navigate within the volume space and audio frames are computed by integrating the radiations from the sources. A number of problems inherent in this problem and our solutions are discussed.
Recent developments in the pharmacological treatment of advanced pancreatic cancer.

Metastatic pancreatic cancer is one of the leading causes of cancer-related death in North America and Europe. The high mortality rate associated with pancreatic cancer is related to the fact that the vast majority of patients develop incurable, metastatic disease. Such patients have, in the past, had few treatment options. In recent years, however, the systemic administration of gemcitabine has been accepted as a standard first-line treatment for patients with advanced pancreatic cancer. While treatment with gemcitabine has been shown to result in both clinical benefit and in prolongation of survival, objective tumour responses following therapy with gemcitabine are relatively uncommon and median survival times remain short. Current efforts have, therefore, focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Several such combinations appear to be associated with higher objective response rates than single-agent gemcitabine and have been well-tolerat...
Partial Bi-Sr-Cu-O subsolidus diagram at 800°C with and without lithium carbonate

Solid-phase relationships have been determined for the Bi2O3–SrO–CuO system at 800°C in air with and without Li2CO3 mineralizer. Two ternary compounds were detected with Bi:Sr:Cu ratios of approximately 2:2:1 and a solid-solution phase 11−;x:9+x:5 with 0x0.4. The solid-solution phase is a 9 K super-conductor at x=0.4. Two additional compounds with Bi:Sr:Cu ratios of approximately 4:9:1 and 2:7:2 are apparently stabilized by the presence of Li2CO3, but do not form without it. X-ray crystallographic data are provided for each compound. Ramifications for quaternary Bi:Sr:Ca:Cu-O superconductors are discussed.