cssi/SciSciGPT-SciSciNet huggingface dataset:
Mathematical modeling and analysis of spinal circuits involved in locomotor pattern generation and frequency-dependent left-right coordination

Coordination between left and right neural activities in the spinal cord during locomotion is controlled by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Talpalar et al. [1] recently reported that genetic elimination of the V0 CINs caused switching from a normal left-right alternating pattern of motor activity to a left-right synchronized “hopping” pattern. Furthermore, ablation of only the inhibitory V0 neurons (V0D subtype) resulted in a lack of left-right alternation at low locomotor frequencies and maintaining this alternation at high frequencies, whereas selective ablation of the excitatory V0 neurons (V0V subtype) maintained the left–right alternation at low locomotor frequencies and switched the motor output to a left-right synchronized ("hopping") pattern at high frequencies. To analyze and explain the above findings, we developed a simplified mathematical model of neural circuits consisted of four pacemaker neurons representing left (LF) and right (RF) flexor and left (LE) and right (RE) extensor half-centers interacting via commissural pathways representing V3, V0D, and V0V CINs (Fig. ​(Fig.1).1). The “locomotor” frequency in the model was controlled by a parameter defining the excitability of neurons (via the leak reversal potentials) and commissural pathways, whose changes represented the corresponding changes induced by changing the concentration of N-methyl-D-aspartate (NMDA) applied to control the locomotor frequency in the isolated rodent spinal cord preparations [1]. Figure 1 Model schematic. The model demonstrated: (1) a typical left-right alternating pattern under control conditions; (2) switching to a synchronized hopping activity at any frequency after removing commissural connections representing both V0 (V0D and V0V) neurons; (3) a synchronized left-right pattern at low frequencies and left-right alternation of activity at high frequencies after removing the commissural connections representing V0D neurons; (4) an alternating left-right pattern at low frequencies with synchronized hopping at high frequencies after removing the commissural connections representing V0V neurons. We used the bifurcation and fast–slow decomposition methods to analyze the behavior of this network in the four above states/regimes and transitions between them. The model was able to reproduce and provide explanation to several important experimental phenomena and generated predictions that can be tested experimentally.
Association of Periodontitis With Rheumatoid Arthritis: A Pilot Study

Background: Similarities exist in the epidemiology and immunopathogenesis of periodontitis and rheumatoid arthritis (RA), but the associations between their respective disease activities and severities are less well documented. We evaluated the prevalence and severity of periodontitis in United States (U.S.) veterans with RA and their relationship to RA disease activity and severity.Methods: Patients with RA from an outpatient rheumatology clinic were eligible, and patients with osteoarthritis (OA) served as controls. Dentists, masked to the rheumatologic diagnoses, performed periodontal probing and examined dental panoramic radiographs to assess the presence and severity of periodontitis. Associations of periodontitis with RA were examined using multivariate regression, whereas the association of periodontitis with disease-severity measures in RA was examined using the χ2 test.Results: Sixty-nine patients with RA (57 males and 12 females) and 35 patients with OA (30 males and five females) were studied. ...
Hydrophobicity and Hydrophilicity of Steroid Binding Sites

It has been amply demonstrated over the years that the binding of steroids to albumin is predominantly hydrophobic in nature (Vol. I. Ch. VII. 1). This follows from the validity of the polarity rule which says that entrance of polar, i.e., hydrophilic groups into a steroid molecule decreases, entrance of hydrophobic groups increases, its protein binding affinity. This rule, therefore, is an expression of a hydrophobic character of binding. A similar binding behavior has been observed for α1-acid glycoprotein (Vol. I, Ch. XIII.4) and beta-lactoglobulin (Vol. I, Ch. VII. 1). On the other hand, the polarity rule does not apply to the binding of steroids to CBGs from various species. This is especially evident for steroid interaction with guinea pig CBG (Table V-16) which binds steroids with increasing number of hydroxy groups more and more strongly. It is also apparent for binding of steroids to human CBG (Table V-23) which shows that the relatively hydrophobic progesterone associates with lower affinity than its hydroxylated derivatives.
The effect of presenting complaint on the risk of developing ventilator-associated pneumonia for patients intubated in an academic emergency department

Ventilator associated pneumonia (VAP) is a complication of mechanical ventilation that increased ICU length of stay and mortality. Eckert found 26% of trauma patients intubated in the ED develop VAP as compared to 6.5% of those intubated in the ICU. Green demonstrated that 70% of critically ill patients were intubated pre-hospital or in the ED and 18.2% remained in the ED for more than 4 hours.
Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth

Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344-52. ©2016 AACR.
The contribution of foreign direct investment to exports: An empirical study of 23 LDCs

Insufficient capital and foreign exchange have often been portrayed as key constraints to the growth and development of less developed countries. These economies have thus come to rely on foreign direct investment as a means of increasing their capital base and foreign exchange reserves and, via the operation of foreign subsidiary firms, as a strategy for increasing the production not only of locally consumed commodities but also of exports. This article focuses on the latter aspect.
Canons for objectivist interpretation

L'A. determine la legitimite des theories objectivistes de E. D. Hirsch, H. G. Gadamer et M. C. Beardsley, concernant la conception de regles valides garantissant l'objectivite de l'interpretation, selon le modele de l'hermeneutique romantique et de la Nouvelle Critique
Effects of Temperature and Wind Speed on Pink Boll worm (Lepidoptera: Gelechiidae) Moth Captures During Spring Emergence

Numbers of pink bollworm moths, Pectinophora gossypiella (Saunders), captured daily in California’s Palo Verde Valley during spring emergence were recorded in 6 data sets: 1985 emergence cages; 1986, 1987, and 1989 pheromone traps in cotton fields; and 1986 and 1989 valley wide pheromone survey traps. For 5 of the 6 data sets, numbers of moths were positively correlated with mean temperature for the interval 1800-2200 hours and minimum temperature for the interval 1800-0600 hours, and negatively correlated with mean wind speed for the interval 1800-2200 hours and the time at which wind speed fell below and stayed 22°C. Although temperature and wind affect dispersion of the pheromone plume, there appears to be a direct effect on the moths themselves because regression model parameters were similar in nonpheromone-baited emergence cages and in pheromone traps.
Course Builder Skill Maps

In this paper, we present a new set of features introduced in Course Builder that allow instructors to add skill maps to their courses. We show how skill maps can be used to provide up-to-date and actionable information on students' learning behavior and performance.
Assessment on Inter-laboratory Comparison of Analytical Capacity on Halohydrocarbons in Household Drinking Water

[Objective]To determine and validate the capacity of performing analysis of the laboratories in the disease prevention and control channel by effectively evaluating and monitoring their proficiency of detection techniques via intercomparison of these labs.[Methods]The quantitative analysis of seven constituents of halohydrocarbons in household tap water was selected as the indices for this test.Two water samples for comparison,A and B,were analyzed by the participating labs separately. The results were statistically processed according to the intercomparison procedures specified in the National Standards:"Standard detection method for household drinking water:Specifications of organics"(GB/T 5750.8—2006 )as well as the "Proficiency testing by interlaboratory comparisons——Part 1:Development and operation of proficiency testing schemes"(GB/T 15483.1- 1999 )and "Proficiency testing by interlaboratory comparisons——Part 2:Selection and use of proficiency testing schemes by laboratory accreditation bodies"(GB/T 15483.2-1999 ).[Results]Among the fifty one participating laboratories,fifty of them accomplished inter-laboratory comparison of results on seven analytes while one laboratory analyzed two analytes only,namely chloroform and carbon tetrachloride.The statistical results of this inter-laboratory comparison on analysis of halohydrocarbons in water samples showed that most robust coefficients of variance were below 10%and the average rate of satisfaction of the results was 77.3%(|Z|≤2 results were satisfactory ),while the average rate of unsatisfaction was 9.4%(2|Z|3 results were questionable ).Among the seven constituents of halohydrocarbons analyzed,carbon tetrachloride had the highest rate(84.3%)of satisfaction,and dibromochloromethane had the lowest rate(70.0%) of satisfaction;whereas monobromo-dichloro-methane had the highest rate(22.0%) of unsatisfaction,and trichloroethylene had the lowest rate(6.0%) of unsatisfaction.[Conclusion]The intercomparison results of the analysis of halohydrocarbons in household drinking water by the participating labs demonstrated that the analysis capacities of these labs are basically controllable and comparable.
Topological optimization on the deformation mechanism of flexible trailing edge of certain pilot-less aircraft

Taking the airfoil trailing edge of certain concrete typed aircraft as the background of study,a kind of flexible trailing edge mechanism was designed so as to achieve the goal of lightening the masses and realizing its self-adaptive deformation.Taking the deviation between the actual displacement and the target displacement as the objective function,and use the distribution loading received by its surface as the constraint to establish the optimization model of topological mechanism by means of SIMP(density rigidity interpolation) method,and to solve the model by the use of OC(Optimization Criterion) method.Carrying out optimization calculation by adopting the Matlab,and then using the Pro/E to let the optimization result be transformed into a 3D entity model.And this model was leaded into ANSYS for carrying out a verified analysis.The flexible trailing edge mechanism that can achieve the 0~10.8°deformation was obtained,which could satisfy the requirements for the pilot-less aircraft to make changes from the initial state to the highest state of aerodynamic efficiency.
Value of Tongyin's Unpublished Literature and Versions in Russian

Tongyin was the most popular book complied by Xixia people at that moment,which has two versions,Yichang version and re-proofreading version. Unpublished literature and version deepened the study of it,as well as the holistic cognition of literature of Heishui City.
Full Scale Evaluation of How Task-Based Overview Displays Impact Operator Workload and Situation Awareness When in Emergency Procedure Space

Control room modernization is critical to extending the life of the 99 operating commercial nuclear power plants (NPP) within the United States. However, due to the lack of evidence demonstrating the efficiency and effectiveness of recent candidate technologies, current NPP control rooms operate without the benefit of various newer technologies now available. As nuclear power plants begin to extend their licenses to continue operating for another 20 years, there is increased interest in modernizing the control room and supplementing the existing control boards with advanced technologies. As part of a series of studies investigating the benefits of advanced control room technologies, the researchers conducted an experimental study to observe the effect of Task-Based Overview Displays (TODs) on operator workload and situation awareness (SA) while completing typical operating scenarios. Researchers employed the Situation Awareness Rating Technique (SART) and the NASA Task Load Index (TLX) as construct measures.
An Improved Algorithm for Real‐Time S‐Wave Picking with Application to the (Augmented) ANZA Network in Southern California

Abstract We develop an automatic shear‐wave picking algorithm suitable for real‐time applications as well as with existing databases. The method can scan through packets of continuous waveforms and make picks without prior knowledge of whether earthquakes have occurred. This makes the algorithm suitable for detecting earthquakes at the same time. Expanding upon and improving the method of Ross and Ben‐Zion (2014a), the algorithm first uses polarization filters to remove P ‐wave energy from the seismogram. Then, short‐term average/long‐term average and kurtosis detectors are applied to the data in tandem to lock in on the phase arrival. The method is tested by applying it to a full month of continuous waveform data recorded by a regional network at 123 stations and comparing the resulting automatic picks with 11,353 handmade picks. The automatic picks are found to be within 0.16 s of the analyst picks 75% of the time, and S picks are successful 92% of the time that a P ‐wave pick is made. The algorithm is then applied to an entire year of continuous data and detects 11,197 earthquakes. The hypocenters of these earthquakes are, on average, improved by more than 1 km when compared with the regional network’s automated catalog.
User-side Wi-Fi evil twin attack detection using random wireless channel monitoring

Free open wireless Internet access is a complimentary Wi-Fi service offered by most coffee shops, fast food restaurants and airports to their customers. For ease of access, these Wi-Fi networks are inherently insecure where no authentication/ encryption is used to protect customers wireless data. An attacker can easily deceive a wireless customer (WC) by setting up a rogue access point (RAP) impersonating the legitimate access point (LAP). The WC connecting to the RAP becomes an easy target to the Man-In-the-Middle Attack (MIMA) and data traffic snooping. In this paper, we present a real-time client-side detection scheme to detect evil twin attack (ETA) when the attacker relies on the LAP to direct WC data to the Internet. The WC can detect ETA by monitoring multiple Wi-Fi channels in a random order looking for specific data packets sent by a dedicated sever on the Internet. Once an ETA is detected, our scheme can clearly identify whether a specific AP is a LAP or a RAP. The effectiveness of the proposed detection method was mathematically modeled, prototyped and evaluated in real life environment with a detection rate approximates to 100%.
Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

Background: To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Methods: Twenty-six PA patients treated with RT from 2011–2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Results: Median age was 69 y (range, 46–86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation ( Conclusions: Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.
Towards practical incremental recomputation for scientists: an implementation for the Python language

Computational scientists often prototype data analysis scripts using high-level languages like Python. To speed up execution times, they manually refactor their scripts into stages (separate functions) and write extra code to save intermediate results to disk in order to avoid recomputing them in subsequent runs. To eliminate this burden, we enhanced the Python interpreter to automatically memoize (save) the results of long-running function executions to disk, manage dependencies between code edits and saved results, and re-use memoized results rather than re-executing those functions when guaranteed safe to do so. There is a ∼20% run-time slowdown during the initial run, but subsequent runs can speed up by several orders of magnitude. Using our enhanced interpreter, scientists can write simple and maintainable code that also runs fast after minor edits, without having to learn any new programming languages or constructs.
Neurotransmitter Modulation by the Gut Microbiota

The gut microbiota - the trillions of bacteria that reside within the gastrointestinal tract - has been found to not only be an essential component immune and metabolic health, but also seems to influence development and diseases of the enteric and central nervous system, including motility disorders, behavioral disorders, neurodegenerative disease, cerebrovascular accidents, and neuroimmune-mediated disorders. By leveraging animal models, several different pathways of communication have been identified along the "gut-brain-axis" including those driven by the immune system, the vagus nerve, or by modulation of neuroactive compounds by the microbiota. Of the latter, bacteria have been shown to produce and/or consume a wide range of mammalian neurotransmitters, including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA). Accumulating evidence in animals suggests that manipulation of these neurotransmitters by bacteria may have an impact in host physiology, and preliminary human studies are showing that microbiota-based interventions can also alter neurotransmitter levels. Nonetheless, substantially more work is required to determine whether microbiota-mediated manipulation of human neurotransmission has any physiological implications, and if so, how it may be leveraged therapeutically. In this review this exciting route of communication along the gut-brain-axis, and accompanying data, are discussed.
Gated Communities: Global South

Gated communities are private, low-density housing developments usually located beyond the urban core. Globalisation, urban growth, deindustrialisation, heightened fear of urban crime, and shrinking states are behind their expansion in the global South. Urban sprawl, expanded urban land markets, deep social polarisation, and new service jobs on urban peripheries are some of its consequences. Notoriously, as gated communities of developing countries located amidst poor suburban settlements, they furthered social contrasts in the suburbs. Ironically, for gated communities’ dwellers, it is the visibility of these contrasts that feeds the narrative of urban crime and justifies the gates that surround them.
Quantifying heterogeneity of expression data based on principal components.

MOTIVATION The diversity of biological omics data provides richness of information, but also presents an analytic challenge. While there has been much methodological and theoretical development on the statistical handling of large volumes of biological data, far less attention has been devoted to characterizing their veracity and variability. RESULTS We propose a method of statistically quantifying heterogeneity among multiple groups of datasets, derived from different omics modalities over various experimental and/or disease conditions. It draws upon strategies from analysis of variance and principal component analysis in order to reduce dimensionality of the variability across multiple data groups. The resulting hypothesis-based inference procedure is demonstrated with synthetic and real data from a cell line study of growth factor responsiveness based on a factorial experimental design. AVAILABILITY AND IMPLEMENTATION Source code and datasets are freely available at https://github.com/yangzi4/gPCA. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Untargeted adductomics of Cys34 modifications to human serum albumin in newborn dried blood spots.

Metabolism of chemicals from the diet, exposures to xenobiotics, the microbiome, and lifestyle factors (e.g., smoking, alcohol intake) produce electrophiles that react with nucleophilic sites in circulating proteins, notably Cys34 of human serum albumin (HSA). To discover potential risk factors resulting from in utero exposures, we are investigating HSA-Cys34 adducts in archived newborn dried blood spots (DBS) that reflect systemic exposures during the last month of gestation. The workflow includes extraction of proteins from DBS, measurement of hemoglobin (Hb) to normalize for blood volume, addition of methanol to enrich HSA by precipitation of Hb and other interfering proteins, digestion with trypsin, and detection of HSA-Cys34 adducts via nanoflow liquid chromatography-high-resolution mass spectrometry. As proof-of-principle, we applied the method to 49 archived DBS collected from newborns whose mothers either actively smoked during pregnancy or were nonsmokers. Twenty-six HSA-Cys34 adducts were detected, including Cys34 oxidation products, mixed disulfides with low molecular weight thiols (e.g., cysteine, homocysteine, glutathione, cysteinylglycine), and other modifications. Data were normalized with a novel method (“scone”) to remove unwanted technical variation arising from HSA digestion, blood volume, DBS age, mass spectrometry analysis, and batch effects. Using an ensemble of linear and nonlinear models, the Cys34 adduct of cyanide was found to consistently discriminate between newborns of smoking and nonsmoking mothers with a mean fold change (smoking/nonsmoking) of 1.31. These results indicate that DBS adductomics is suitable for investigating in utero exposures to reactive chemicals and metabolites that may influence disease risks later in life.
WHEN A ZEBRA CHANGES ITS STRIPES: GENOMIC RECLASSIFICATION OF A RARE CAUSE OF RESTRICTIVE CARDIOMYOPATHY

This case will illustrate the role of genetic testing in a rare restrictive cardiomyopathy through identification of a novel gene mutation. A 38 year old woman was diagnosed with a restrictive cardiomyopathy. She has a history of short stature, mildly dysphormic facial features, scoliosis, and
Myelin membrane structure at 10 A resolution.

Electron density profiles of three types of myelin have been determined directly by comparison of their X-ray patterns with 10 A spacing. The asymmetry detected within the lipid hydrocarbon region indicates that cholesterol is concentrated at the external side of the membrane bilayer.
THU0155 PATIENT ADHERENCE WITH A SMARTPHONE APP FOR DISEASE MONITORING IN RHEUMATOID ARTHRITIS

Background: Patients increasingly are asking for tools to improve self-management. Electronic patient reported outcomes (ePROs) transmitted digitally allow patients to both communicate with their clinicians between visits and help track their own disease activity. While several tools have been developed in rheumatology, few data have been reported regarding patient adherence. Objectives: To examine patient adherence to a smartphone app for rheumatoid arthritis (RAapp). Methods: We developed a smartphone app to deliver daily disease assessments to patients with RA (RAapp). The app was tested as part of a randomized controlled trial examining the potential clinical benefits of RAapp compared to a wait-list control. These analyses focus only on the adherence of patients who received RAapp and completed the 6-month trial. We recruited RA patients from the rheumatology practice at a large academic medical center in the US. Patients with at least 6weeks of stable DMARD use who were at least 18years of age were required to give written informed consent, be fluent in English, and have a smartphone with an iOS or android operating system. RAapp was downloaded by patients through a password protected link on to the patient’s phone after consent. Patient’s received daily notifications regarding disease assessments, including disease activity (RADAI), function (MDHAQ), pain (PROMIS), fatigue (PROMIS), sleep (PROMIS), and depression (PROMIS). The current set of analyses focused on adherence to RAapp, overall, by scale, and over the 6 months of the trial. We examined adherence to RAapp over the duration of the study and examined factors related to adherence using mixed regression models. Factors tested included patient age, sex, educational attainment, and baseline CDAI. Results: 75 patients received RAapp and have data included in these analyses (5 patients are in the last month of follow-up). 60 (80%) were female; age breakdown was 24% Conclusion: We developed and tested an ePRO app for RA (RAapp). Among a large group of patients, adherence to the app was good but declined slightly over time. There was no substantial variation in adherence with different ePRO scales. Older age was the only significant predictor of adherence. Disclosure of Interests: Daniel Solomon Grant/research support from: Abbvie, Amgen, Genentech, Janssen, and Pfizer, Fengxin Lu Grant/research support from: Pfizer, Chang Xu Grant/research support from: Pfizer, Joshua Colls Grant/research support from: Pfizer, Dong Hyun Suh Grant/research support from: Pfizer, Meredith Murray Grant/research support from: Pfizer, Cassandra Corrigan Grant/research support from: Pfizer, Yvonne Lee Shareholder of: Express Scripts, Grant/research support from: Pfizer
Seasonally sympatric songbirds that differ in migratory strategy also differ in neuroendocrine measures.

Abstract Seasonally breeding animals initiate gonadal recrudescence when mechanisms that suppress reproduction give way to mechanisms that stimulate it. However, knowledge of mechanistic changes in hormonal regulation during this transition is limited. Further, most studies of reproductive timing have focused on males, despite the critical role of females in determining breeding phenology. Closely related populations that live in the same environment but differ in reproductive timing provide an opportunity to examine differences in mechanisms during the transition from the pre-reproductive to reproductive state. We studied closely related migrant and resident populations of dark-eyed juncos (Junco hyemalis) that reside in the same environment in spring but differ in breeding phenology. Residents initiate breeding earlier than migrants, which do not breed until after they have migrated. To directly study differences in the hypothalamic mechanisms of reproduction, we captured 16 migrant and 13 resident females from the field on March 25-April 11. We quantified expression of mRNA transcripts and show that resident females had higher abundance of gonadotropin-releasing hormone transcripts than migrant females, indicating greater reproductive development in resident than migrant females living in the same environment. We also found higher transcript abundance of estrogen receptor and androgen receptor in migrant than resident females, suggesting that negative feedback may delay reproductive development in migrant females until after they migrate. These differences in hypothalamic mechanisms may help to explain differences in reproductive timing in populations that differ in migratory strategy.
Regulatory Oversight and Benefit-Cost Analysis: A Historical Perspective

The Office of Information and Regulatory Affairs (OIRA) in the Executive Office of the President coordinates the federal government’s regulatory agenda, reviews executive branch agencies’ draft regulations, and oversees government-wide information quality, peer review, privacy, and statistical policies. Remarkably, its regulatory oversight functions, and the benefit-cost framework underlying them, have not changed significantly through six very different presidential administrations. This article examines the evolution of executive regulatory oversight and analysis from the 1970s to today, exploring the reasons for its durability and whether the current imposition of a regulatory budget challenges the bipartisan nature of regulatory practice.
Calming Neurons with a Microglial Touch

In vivo two-photon imaging of microglia in the intact brain has revealed that microglia constantly survey neuronal soma. Research over the past decade and a recent paper by Cserep et al. published in Science are now uncovering the nature, mechanisms, and consequences of these interactions in health and injury.
Implementing Population Medicine in a Pain Management Practice.

PURPOSE To document and improve the quality of our chronic pain management using population management methods. METHODS An analytic registry was developed, and all new patients were enrolled for 12 months. Patient demographics, standardized pain and function measures, and treatments were recorded. Usual care was provided. The registry was used to organize care and analyze management and outcomes. RESULTS Of 454 total patients, only 154 (34%) completed a 6-month cycle of care. High no-show rates were documented for follow-up appointments for several reasons. The majority of 6-month completers showed improved pain levels. DISCUSSION This quality improvement project identified assessment and care gaps and led to improvements. An ongoing need to improve measures of pain and function was documented.
Gene regulation gravitates towards either addition or multiplication when combining the effects of two signals

Abstract Signals often ultimately affect the transcription of genes, and often, two different signals can affect the transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. Mechanistic models can predict a range of combined responses, with the most commonly applied models predicting additive or multiplicative responses, but systematic genome-wide evaluation of these predictions are not available. Here, we performed a comprehensive analysis of the transcriptional response of human MCF-7 cells to two different signals (retinoic acid and TGF-β), applied individually and in combination. We found that the combined responses exhibited a range of behaviors, but clearly favored both additive and multiplicative combined transcriptional responses. We also performed paired chromatin accessibility measurements to measure putative transcription factor occupancy at regulatory elements near these genes. We found that increases in chromatin accessibility were largely additive, meaning that the combined accessibility response was the sum of the accessibility responses to each signal individually. We found some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors.
Phosphodiesterase-probes show distinct defects in rd mice and Irish setter dog disorders.

The phosphodiesterase from the visual cells of rd mice and affected Irish setter dogs has been analyzed, using biochemical, biophysical, and immunological techniques. The authors' findings demonstrate that the mechanisms that cause a deficiency in phosphodiesterase activity in rd mice and Irish setter dogs are distinctly different. Apparently, the phosphodiesterase complex is normal in affected Irish setter dogs but is abnormal in rd mice. The criteria used for determining the normalcy of the phosphodiesterase complex were sedimentation characteristics, immuno-cross-reactivity, and histone-activation, which is shown to be a unique characteristic of the visual cell enzyme. According to these criteria, the phosphodiesterase complex in the visual cells of rd mice is either absent or abnormal from the onset of visual cell differentiation until degeneration, because (1) it exhibits no cross-reactivity with antibody to phosphodiesterase; (2) it is not activated by histone; and (3), if present, it exhibits abnormal sedimentation characteristics and perhaps subunit structure. On the other hand, phosphodiesterase from the visual cells of affected Irish setter dogs is normal by the same criteria, because (1) it cross-reacts with antibody against phosphodiesterase; (2) it is activated by histone; and (3) it exhibits normal sedimentation and electrophoretic patterns. It is proposed that depressed levels of phosphodiesterase activity in affected setter photoreceptors are due, perhaps, to a defect in the light-initiated cascade which activates the enzyme normally, in situ. Invest Ophthalmol Vis Sci 26:1569-1579, 1985 Guanosine cyclic 3',5'-monophosphate (cyclic GMP) is a natural constituent of rod photoreceptor cells which appears to be associated with the visual process. Its metabolism is altered by light, with photon capture initiating a series of biochemical reactions that culminate in the activated hydrolysis of cyclic GMP by the enzyme, phosphodiesterase (PDE). 1 " 6 The exact role that cyclic GMP or cyclic GMP hydrolysis plays in visual cell function has yet to be resolved, but evidence suggests that cyclic GMP participates in visual transduction or in the mechanisms of visual adaptation. Whatever the ultimate resolution of this issue, cyclic GMP appears to play a role that is essential for the maintenance of visual cell viability. In the inherited disorders of rd (retinal degeneration) mice and affected Irish setter dogs, an abnormality in
On the Failure of Economists to Grasp the Difference between the Calculus (Instantaneous Change) Model Used by Keynes in the General Theory to Define the Mathematical Theory of the Multiplier in His Model and the Actual Dynamic or Process Multiplier that Occurs in Historical Time That Was Not in His Model

The mathematical(logical), technical, theoretical exposition of the multiplier given in chapter 10 of the General Theory by Keynes is identical to the exposition given by Keynes in chapter 26 of the A Treatise on Probability in footnote 1 on page 315. The mathematical theory requires that the limit be taken of an infinite, declining, geometric series of numbers. This instantaneous multiplier result, which is derived by an application of the differential calculus, has nothing to do with a dynamic multiplier or of any type of actual, period analysis or income spending process occurring in actual or historical time. The confusion among economists since 1936 stems from economists taking seriously the claims made by two mathematically illiterate, confused, and inept economists, Joan Robinson and Dennis Robertson, who had no idea about how to use simple algebra, much less differential calculus, in an economic application. This confusion between a theoretical, mathematical, economics model and the actual real world process it has been used to model through simplification, lies at the heart of the exchanges between A. Cottrell and Basil Moore in 1994. Once this is exposed, their exchanges over the multiplier show that they have nothing to do with what Keynes wrote on pages 122-123 and the General Theory.
Spatial Variation of Cell-Types, Cellular Colocalization, and Intercellular Communication Delineates Brain Tissue Architecture Beyond Morphological Layers

Spatial organization of cell-types, their colocalization patterns, and intercellular communication mechanisms are critical aspects of brain architecture and function. Understanding these aspects requires integrating data from single-cell RNA-Seq (scRNA-seq) and spatial transcriptomics (ST),the two cutting edge technologies that offer complementary insights into tissue architecture and function. Integrating these data types is non-trivial since they differ widely in the number of profiled genes and often do not share marker genes for given cell-types. We developed STANN, a neural network model that overcomes these methodological challenges for single-cell resolution ST data. We applied STANN to assign cell-types in a recent ST dataset (seqFISH+) of mouse olfactory bulb (MOB). Our analysis of STANN’s assigned cell-types revealed principles of MOB architecture and intercellular communication in unprecedented detail and beyond the conventional morphological layer-based description. We find that the proportions of cell-types are consistent within individual morphological layers of MOB, but vary widely between the layers. Surprisingly, even within a morphological layer, we find high spatial variation in cellular colocalization patterns and intercellular communication mechanisms. These observations imply the formation of spatially localized gene regulatory networks, and suggest that spatially localized receptor-ligand usage refines subtypes of major cell-types and play an important role in determining their colocalization patterns.
Imaging diagnosis of bronchogenic carcinoma (the forgotten disease) during times of COVID-19 pandemic: Current and future perspectives

Patients with bronchogenic carcinoma comprise a high-risk group for coronavirus disease 2019 (COVID-19), pneumonia and related complications. Symptoms of COVID-19 related pulmonary syndrome may be similar to deteriorating symptoms encountered during bronchogenic carcinoma progression. These resemblances add further complexity for imaging assessment of bronchogenic carcinoma. Similarities between clinical and imaging findings can pose a major challenge to clinicians in distinguishing COVID-19 super-infection from evolving bronchogenic carcinoma, as the above-mentioned entities require very different therapeutic approaches. However, the goal of bronchogenic carcinoma management during the pandemic is to minimize the risk of exposing patients to COVID-19, whilst still managing all life-threatening events related to bronchogenic carcinoma. The current pandemic has forced all healthcare stakeholders to prioritize per value resources and reorganize therapeutic strategies for timely management of patients with COVID-19 related pulmonary syndrome. Processing of radiographic and computed tomography images by means of artificial intelligence techniques can facilitate triage of patients. Modified and newer therapeutic strategies for patients with bronchogenic carcinoma have been adopted by oncologists around the world for providing uncompromised care within the accepted standards and new guidelines.
Cross-partisanship and the vulnerability democracy: how civility and nonpartisanship undermined civil society in interwar Germany

Exclusionary nationalist movements’ rise in recent years challenges liberal democracy’s trust in political institutions’ ability to neutralize and incorporate extremism. The crisis of liberal democ...
In situ x-ray diffraction of high density polyethylene during dynamic drive: Polymer chain compression and decomposition

Polymers are widely implemented materials often used for safety and security in our daily lives. However, we do not have a thorough understanding of the phase transformations of these materials when exposed to extreme condition, high strain rate events. To study polymers in these severe environments, we performed plate impact experiments that impart a one-dimensional shockwave, at high pressures and temperatures, to observe the materials response. Generally, velocimetry is the experimental diagnostic used to capture the movement of high velocity interfaces to then calculate the mechanical variables associated with shock compression. However, when a material undergoes a phase transition, such as between two crystalline phases or melting to decomposition during shock compression, velocimetry does not explicitly indicate what structural change occurred. At the Dynamic Compression Sector at the Advanced Photon Source, gas gun driven compression has been paired with x-ray diffraction, providing the ability to study both the shock parameters and structural changes concurrently. We explored high density polyethylene (HDPE) both on its reactants Hugoniot ( <10.12 GPa) and within its transition region (24.3 GPa) where HDPE is hypothesized to decompose from reactants to products. With x-ray diffraction, we observed both polymer chain compression and crystal structure reorientation from orthorhombic to monoclinic above 6 GPa as well as either a possible phase change or chemical decomposition at 24.3 GPa. With these experiments, we were able to determine the crystalline and amorphous Hugoniot loci at pressures below the polymer transition region.
Proximity, Contact, and Play Interactions of Zoo-Living Juvenile and Adult Orangutans, with Focus on the Adult Male

The behavioral development of young apes is influenced by their physical and social environments. Deficient or limited environments can result in reproductive insufficiencies (see Beck and Power, 1988) and behavioral deficits, such as Stereotypic movements (see Puleo, et al., 1983; Meder, 1989). The role of the environment in behavioral deficits is evident from studies where stereotypies were reduced or eliminated when the physical or social environments were enhanced (Clarke, et al., 1982; Puleo, et al., 1983; Meder, 1989). The mere presence of conspecifics, however, does not guarantee the development of species-typical behavior, even in complex social groups. For example, a young orangutan reared in a social group containing only adults is limited in its opportunities for social play (Zucker, et al., 1986; see Baldwin, 1986, for more about social and ecological constraints on play). Although adult orangutans of both sexes do play, the rate of adult play is much lower than that of immature orangutans (Zucker, et al., 1986), and in playing with immature orangutans, the style of play of adult females differs from that of adult males (Zucker, et al., 1978). Nursery-reared apes are at risk for behavioral deficits as their social and physical environments usually are less complex than their respective natural environments, although nursery environments and rearing protocols can be made relatively complex and stimulating.
The Politics of “The Least Dangerous Branch”: The Court, the Constitution, and Constitutional Politics Since 1945

This essay, written for a broad scholarly audience, surveys the history and scholarship on the U.S. Constitution and the courts from 1945 to the end of the twentieth century. The essay focuses on iconic moments that have influenced constitutional theory in the second half of the twentieth century, particularly Brown v. Board of Education, Roe v. Wade, and the memory of the New Deal era. It briefly surveys important lines of argument about the courts, including the countermajoritarian difficulty, the question of whether courts offer a "hollow hope" of social change, and the scholarly reaction to Bush v. Gore. The essay appears in a collection on a broad range of issues in post-1945 U.S. history, featuring the work of important U.S. historians, including Ellen Schrecker, Kevin Gaines, Nelson Lichtenstein and Linda Gordon. As an introduction to the rich history of the constitution and the courts since 1945, the essay may be of greatest interest to scholars in fields other than law, academics from other countries who are interested in America law, and graduate students.
Pathogenesis of Atherosclerosis

Atherosclerotic vascular disease is a leading cause of death and disability throughout the USA and other industrialized nations and consumes enormous fiscal resources. Atherosclerosis involves the development of a plaque composed of variable amounts of atherogenic lipoproteins, extracellular matrix (collagen, proteoglycans, glycosaminoglycans), calcium, vascular smooth muscle cells, inflammatory and immune cells (chiefly monocyte-derived macrophages, T lymphocytes, mast cells, dendritic cells), and new blood vessels. Atherosclerosis represents a chronic inflammatory response to vascular injury triggered by a variety of risk factors that injure endothelium and promote lipoprotein infiltration, retention, and modification, combined with leukocyte entry, retention, proliferation, and activation. Atherosclerosis predisposes to arterial thrombosis and acute arterial occlusion when plaque disruption leads to activation of the clotting cascade in the vasculature. Ultimately, most lethal and significant occlusive cardiovascular events result from plaque disruption leading to thrombosis. Disruption of plaques is believed to result from inflammation and immune activation in the plaque leading to matrix degradation and inadequate repair. Inflammation plays a crucial role in the initiation, progression, and eventual destabilization of atherosclerotic plaques. Disruption-prone plaques generally contain large necrotic lipid core with adventitial remodeling, plaque cap inflammation, increased neovascularity, and intraplaque hemorrhage.