cssi/SciSciGPT-SciSciNet huggingface dataset:
Activated retinoid receptors are required for the migration and fate maintenance of subsets of cortical neurons

Layer-specific cortical neurons are essential components of local, intracortical and subcortical circuits and are specified by complex signaling pathways acting on cortical progenitors. However, whether extrinsic signals contribute to postmitotic cortical neuronal development is unclear. Here we show in mice that retinoic acid (RA) receptors are activated in newly born migrating cortical neurons indicative of endogenous RA in the cortex. Disruption of RA signaling in postmitotic neurons by dominant-negative retinoid receptor RAR403 expression specifically delays late-born cortical neuron migration in vivo. Moreover, prospective layer V-III neurons that express RAR403 fail to maintain their fates and instead acquire characteristics of layer II neurons. This latter phenotype is rescued by active forms of β-catenin at central and caudal but not rostral cortical regions. Taken together, these observations suggest that RA signaling pathways operate postmitotically to regulate the onset of radial migration and to consolidate regional differences in cortical neuronal identity.
Redox signaling in the growth and development of colonial hydroids

SUMMARY Redox signaling provides a quick and efficient mechanism for clonal or colonial organisms to adapt their growth and development to aspects of the environment, e.g. the food supply. A `signature9 of mitochondrial redox signaling, particularly as mediated by reactive oxygen species (ROS), can be elucidated by experimental manipulation of the electron transport chain. The major sites of ROS formation are found at NADH dehydrogenase of complex I and at the interface between coenzyme Q and complex III. Inhibitors of complex III should thus upregulate ROS from both sites; inhibitors of complex I should upregulate ROS from the first but not the second site, while uncouplers of oxidative phosphorylation should downregulate ROS from both sites. To investigate the possibility of such redox signaling, perturbations of colony growth and development were carried out using the hydroid Podocoryna carnea. Oxygen uptake of colonies was measured to determine comparable physiological doses of antimycin A1 (an inhibitor of complex III), rotenone (an inhibitor of complex I) and carbonyl cyanide m-chlorophenylhydrazone (CCCP; an uncoupler of oxidative phosphorylation). Using these doses, clear effects on colony growth and development were obtained. Treatment with antimycin A1 results in `runner-like9 colony growth, with widely spaced polyps and stolon branches, while treatment with CCCP results in `sheet-like9 growth, with closely spaced polyps and stolon branches. Parallel results have been obtained previously with azide, an inhibitor of complex IV, and dinitrophenol, another uncoupler of oxidative phosphorylation. Perhaps surprisingly, rotenone produced effects on colony development similar to those of CCCP. Assays of peroxides using 2′,7′-dichlorofluorescin diacetate and fluorescent microscopy suggest a moderate difference in ROS formation between the antimycin and rotenone treatments. The second site of ROS formation (the interface between coenzyme Q and complex III) may thus predominate in the signaling that regulates colony development. The fat-rich, brine shrimp diet of these hydroids may be relevant in this context. Acyl CoA dehydrogenase, which catalyzes the first step in the mitochondrial β-oxidation of fatty acids, carries electrons to coenzyme Q, thus bypassing complex I. These results support a role for redox signaling, mediated by ROS, in colony development. Nevertheless, other redox sensors between complexes I and III may yet be found.
A Review of “The Librarian's Nitty-Gritty Guide to Social Media”

Whenever author Laura Solomon's IT department rolled out a change or update, it was her job as the library Web master to notify staff. Solomon's notification e-mails typically contained two section...
Prediction of 1-octanol solubilities using data from the Open Notebook Science Challenge.

1-Octanol solubility is important in a variety of applications involving pharmacology and environmental chemistry. Current models are linear in nature and often require foreknowledge of either melting point or aqueous solubility. Here we extend the range of applicability of 1-octanol solubility models by creating a random forest model that can predict 1-octanol solubilities directly from structure. We created a random forest model using CDK descriptors that has an out-of-bag (OOB) R2 value of 0.66 and an OOB mean squared error of 0.34. The model has been deployed for general use as a Shiny application. The 1-octanol solubility model provides reasonably accurate predictions of the 1-octanol solubility of organic solutes directly from structure. The model was developed under Open Notebook Science conditions which makes it open, reproducible, and as useful as possible.
Effect of high glucose and high sucrose diets on glucose tolerance of normal men

The control diet was a 3,025-kcal, solid diet containing 40% of calories as carbohydrate, 43% fat, and 17% protein fed in four meals daily. The glucose and sucrose diets were liquid diets supplemented with vitamins and minerals which were fed in four equal feedings. The glucose diets contained 3,000 kcal with 15% of calories as calcium caseinate; 20, 40, 60, or 80% as glucose; and the remaining calories as corn oil. The sucrose diets contained 2,800 kcal, and minor adjustments in total calories were made to maintain body weight. These diets contained 15% of calories as sodium caseinate, 40 or 80% as sucrose, and 45 or 5% as corn oil.
Homogeneous charge compression ignition technology implemented in a hybrid electric vehicle: System optimal design and benefit analysis for a power-split architecture

Homogeneous charge compression ignition technology can improve fuel economy by providing increased efficiency at low-load operation. This article examines the implementation of this technology in hybrid propulsion systems. To assess the benefits, a physics-based model for a spark ignition–homogeneous charge compression ignition dual-operation engine is developed, together with system and component models, and is used to optimize a crossover sport utility van with a power-split hybrid powertrain. Comparison of optimal designs for the pure spark ignition and dual homogeneous charge compression ignition cases indicates the reduction in the fuel consumption based on our modeling assumptions to be in the range 2.5–5%, depending on the test cycle. These benefits increase substantially when the acceleration performance requirements increase. An analysis method is presented to show how such engine-level changes affect the entire powertrain characteristics, and mode maps are developed to indicate when the benefits...
Parametric Study of the Stochastic Seismic Response of Simple Nonlinear Structures

In the present study, time-dependent autoregressive - moving average (ARMA) models are used for stochastic modeling of earthquake ground motions. In a first stage, the earthquake models are checked against the real seismic data from which they have been identified. In a second stage, these models are used to simulate the stochastic seismic response of idealized linear and nonlinear structures. By varying the earthquake model parameters and the structural model parameters, a sensitivity study of the stochastic seismic response of these structural models is performed. A brief description of the developed methodology and some significant results obtained are presented in the sequel.
Team Personality: A Dynamic, Contextualized View

Abstract. Team personality has received much attention as organizations increasingly organize work around teams. Yet the concept of team personality in the current literature has not been well developed; typically it is considered as an extrapolation of individual personality traits to team. In the present paper, we address team personality by considering recent advances in personality theories and in teams. We argue team personality is a reasonable construct, but it needs to be viewed directly at the team level and from a contextualized perspective. Furthermore, we identify critical contextual conditions under which team personality is embedded and suggest ways in which team personality can be measured taking contextual issues into account.
Cyproheptadine stimulated prolactin release in the young turkey (Meleagris gallopavo).

Abstract Cyproheptadine (CHD) at doses of .1 to 10.0 mg/kg body weight produced a dose-related elevation in prolactin (PRL) and no change in luteinizing hormone (LH) levels. Cyproheptadine pretreatment failed to depress the quipazine (serotonin agonist)-induced PRL rise. Rather than inhibiting the serotonergic induction of PRL release in the young turkey, CHD exerted a stimulatory influence on PRL release through another mechanism.
Shopping orientation segments: exploring differences in store patronage and attitudes toward retail store environments among female apparel consumers

The purpose of this study was to identify shopping orientation segments for US female consumers. The sample included 151 women, aged 18 years and over. This research examined differences in the segments relative to store patronage preferences (i.e. department, discount, specialty), attitude toward the environment of the store selected as first choice when shopping for a specific apparel item (i.e. a dress), and demographic characteristics. Cluster analysis revealed that four shopping segments described the female consumers. The segments were named Decisive Apparel Shopper, Confident Apparel Shopper, Highly Involved Apparel Shopper, and Extremely Involved Apparel Shopper, based on several shopping factors. Differences were found among the shopping orientation segments for store of first choice, attitude and household income. Implications and future research directions are discussed.
ALEXANDER VON HUMBOLDT'S LEGACY IN VENEZUELA

After nearly one hundred years since Humboldt's return to Europe from the Americas, there is little about the famous traveler and naturalist that has not been written on already. A close scrutiny of his scientific legacy, however, reveals important scientific findings of his travels that had not been fully analysed in the past, namely his contributions to the study of palms and his influence on explorers and naturalists who followed his path in the American tropics. In the following essay, I explore in particular Humboldt's contributions to the knowledge of the peach palm (Bactris gasipaes H.B.K.) and his relationship with the French chemist Jean Batiste Boussingault, who visited Venezuela in 1822–1823.
Racial discrimination, mood disorders, and cardiovascular disease among black americans.

Purpose To examine associations between racial discrimination, mood disorders, and cardiovascular disease (CVD) among Black Americans. Methods Weighted logistic regression analyses were performed on a nationally representative sample of Black Americans (n = 5022) in the National Survey of American Life (NSAL; 2001–2003). Racial discrimination and CVD were assessed via self-report. Mood disorder was measured with the World Health Organization Composite International Diagnostic Interview. Results Model-adjusted risk ratios (RRs) revealed that participants with a history of mood disorder had greater risk of CVD (RR, 1.28; 95% confidence interval (CI), 1.12–1.45). This relationship was found specifically among those younger than 50 years of age (RR, 1.56; 95% CI, 1.27–1.91). There was a significant interaction between racial discrimination and mood disorder in predicting CVD in the total (F = 2.86, 3 df, p = .047) and younger sample (F = 2.98, 3 df, p = .047). Participants with a history of mood disorder who reported high levels of racial discrimination had the greatest risk of CVD. Conclusions The association between racial discrimination and CVD is moderated by history of mood disorder. Future studies may examine pathways through which racial discrimination and mood disorders impact CVD risk among Black Americans.
Perioperative Management of Carotid Endarterectomy: A Survey of Clinicians' Backgrounds and Practices

Objective To examine current trends in anesthetic practice for management of carotid endarterectomy (CEA) and how practice may differ by groups of practitioners. Design An online survey was sent to the Society of Cardiovascular Anesthesiologists and Society of Neuroscience, Anesthesiology, and Critical Care e-mail list servers. Responses were voluntary. Setting Academic medical centers and community-based hospitals providing perioperative care for a CEA in the United States and abroad. Participants Anesthesiologists who provide perioperative care for patients undergoing a CEA. Interventions None Measurements and Main Results Of 664 responders (13% response rate), most (66%) had subspecialty training in cardiovascular anesthesiology, had been in practice more than 10 years (68%), and practiced in the United States (US, 81%). About 75% of responders considered general anesthesia as a preferable technique for CA, and about 89% of responders provided it in real life, independent of subspecialty training. The most preferable intraoperative neuromonitoring was cerebral oximetry (28%), followed by EEG (24%), and having an awake patient (23%). Neuroprotection was not considered by 33% of responders, and upon conclusion of a case, 59% preferred an awake patient for extubation, while 15% preferred a deep extubation. Neuroanesthesiologists and non-US responders more often risk stratify patients for perioperative cerebral hyperperfusion syndrome, compared with cardiac anesthesiologists and US responders (p = 0.004 and p Conclusions Although there are areas of perioperative management in which there seems to be agreement for the CEA, there are also areas of divergent practice that could represent potential for improvement in overall outcomes. There are many potential reasons to explain divergence in practice by location or subspecialty training, but it remains unclear what the “best practice” may be. Future studies examining outcomes after carotid endarterectomy should include perioperative anesthetic management strategies to help delineate “best practice.”
Genius in Science

The present chapter borrows its title from a paper by Michael Polanyi that has already been published three times (in English), and which, no doubt, will deservedly be published more. The present discussion has, indeed, developed out of comments on that paper by Polanyi — both were read in the Boston Colloquium for the Philosophy of Science, 7 April 1970. Yet it is not necessary to add the subtitle ‘Comments on Polanyi’s paper’ because it might just as well read, ‘Comments on the whole literature on the topic’.
No peace without injustice: Hobbes and Locke on the ethics of peacemaking

Is the demand for justice likelier to cause or to prevent war? Hobbes expresses sympathy for the former view and Locke for the latter. However, they both reason their way toward an intermediate position, symbolized by the impartial judge in Locke's theory and the arbitrator in Hobbes's theory. Peace is possible when we create a process that resolves disputes according to widely intuitive principles of equality and reciprocity. This requires, however, that we refrain from imposing our particular interpretations of justice, and that we tolerate the possibility of unjust outcomes. Hobbes and Locke's reasoning shows us why international institutions are needed to serve as an impartial judge for the resolution of civil and international conflicts. They rebut persistent skepticism about the fitness of international institutions to promote peace and justice. Recent scholarship on ethno-political conflict confirms the wisdom of their analysis.
Physician-assisted suicide and public policy

Soulevant la question du droit d'euthanasie et de son institutionnalisation dans les hopitaux, l'A. etudie le probleme de la legalisation du suicide medicalement assiste au regard de la politique publique. Examinant l'asymetrie entre le droit du patient de refuser un traitement et la decision du medecin a mettre fin a la vie, l'A. mesure l'abime qui separe la loi ideale de la situation reelle, d'une part, et etablit une nouvelle distinction entre la signfication symbolique et la signification pratique du suicide medicalise
Characterization of the CW starter plasma RF matching network for operating the SNS H- ion source with lower H2 flows

The Spallation Neutron Source H− ion source is operated with a pulsed 2-MHz RF (50-60 kW) to produce the 1-ms long, ∼50 mA H− beams at 60 Hz. A continuous low power (∼300 W) 13.56-MHz RF plasma, which is initially ignited with a H2 pressure bump, serves as starter plasma for the pulsed high power 2-MHz RF discharges. To reduce the risk of plasma outages at lower H2 flow rates which is desired for improved performance of the following radio frequency quadrupole, the 13.56-MHz RF matching network was characterized over a broad range of its two tuning capacitors. The H-α line intensity of the 13.56-MHz RF plasma and the reflected power of the 13.56-MHz RF were mapped against the capacitor settings. Optimal tunes for the maximum H-α intensity are consistent with the optimal tunes for minimum reflected power. Low limits of the H2 flow rate not causing plasma outages were explored within the range of the map. A tune region that allows lower H2 flow rate has been identified, which differs from the optimal tune f...
Paradigm Shift: Applying the Incident to Arrest Exception to Digital Devices

The Fourth Amendment guarantees the right to be secure in our persons and possessions by protecting citizens from unreasonable searches and seizures. As even a casual moviegoer knows, when you are arrested you have certain rights. However, these constitutional rights must now be balanced against legitimate law enforcement interests of protecting officers and seizing destructible evidence.Steve Jobs predicted that cell phones, and specifically the iPhone would change everything. Right now, courts are struggling to apply old search and seizure rules to these new devices resulting in a deep division of authority. The U.S. Supreme Court has accepted certiorari on two cases where they will take up this question. Paradigm shifting technology requires new legal rules. We have seen this before in the incident to arrest context with the automobile and we'll likely see it again within our lifetimes. I suggest that the way we can stay true to the timeless principles of the Fourth Amendment is by looking at all digital devices, not as a means of containing data, but a means of accessing it.
21. Prolonged QT Intervals in Patients with Out-of-Hospital Ventricular Tachycardia Cardiac Arrest

Objective : To determine the prevalence and outcome of out-of-hospital ventricular tachycardia (VT) cardiac arrest with a prolonged QT interval and to identify the subset with torsades de pointes (TdP). Methods : Design: Retrospective review. Setting: Fire department-based paramedic system. Participants: Non-traumatic VT cardiac arrest (1/91-12/94) with a supraventricular perfusing rhythm (SVPR) and a measurable QT interval. Interventions : QT interval was measured from a SVPR and corrected QT interval (QTc) was calculated (prolonged if ≥0.45 sec). VT was classified as polymorphic or monomorphic. Results : 190 patients met inclusion criteria. 51% of patients had a prolonged QTc (PQTc). The overall hospital discharge rate was 28.4%. No difference with respect to paramedic-witnessed arrests in each QTc group was found (25.8% normal QTc [NQTc] vs. 27.8% PQTc; p = 0.752). Patients with PQTc were less likely to be discharged from the hospital (19.6% vs. 37.6%; p = 0.01). Patients with PQTc were not more likely to have PVT (37% vs. 40%; p = 0.705). 16 (8.4%) patients had TdP. 27.8% of TdP and 26.8% of non-TdP patients were discharged ( p = 0.912).
Rapid detection of DEHP in packed red blood cells stored under European and US standard conditions.

Transfusion of packed red blood cells (RBC) is a lifesaving intervention for millions of people worldwide. Thorough statistical review of 31 randomised clinical trials concluded that, while “restrictive transfusion strategies are safe in most clinical settings, liberal transfusion strategies have not been shown to confer any benefit to patients but have the potential for harm”1. Though randomised clinical trials performed so far have not highlighted a major association between storage duration and mortality, the studies may have been underpowered to appreciate minor (<5%), but still significant effects (in terms of numbers of patients) on morbidity1. Despite the lack of definitive clinical evidence, recent laboratory studies have shown that biochemical alterations to packed RBC progressively accumulate during routine storage in the blood bank2. While the clinical relevance of such alterations is uncertain, the lesions to RBC during routine storage in the blood bank might be potentially harmful to massively or chronically transfused recipients, as might be exposure to plasticisers3. Phthalate esters are a group of plasticisers produced commercially to impart flexibility to an otherwise rigid polyvinylchloride (PVC) storage bag3. Bis(2-ethylhexyl) phthalate (DEHP) is the most common plasticiser and accounts for over 20% of the total phthalates produced annually3. During storage, DEHP leaches from PVC bags and intercalates into RBC membranes, reducing morphological lesions, vesiculation and haemolysis by 70% and 50%, respectively4. These beneficial effects on RBC structural stabilisation come with a potential risk though, as phthalate esters might promote release of pro-inflammatory cytokines5. Extensive laboratory studies have shown that long-term exposure to monoethlyhexyl phathalate (MEHP) (a metabolite of DEHP) has carcinogenic potential by activating two nuclear transcription factors, PPARα and PPARγ to induce cell differentiation6. Additionally, DEHP is suspected to disrupt or modulate endocrine signalling in development and reproduction7. The field is aware of these risks and new formulations are currently being tested8. Meanwhile, high performance liquid-chromatography (HPLC) or LC-mass spectrometry (MS) based methods have been proposed to detect phthalate esters and, in particular, DEHP in RBC stored in SAGM and AS-15,9,10 or in urine for autologous blood doping detection11,12. Here we propose an evolution of those methods using ultra-HPLC (UHPLC) and high resolution MS for the ultra-rapid detection (4 min vs 20 min and 10 min with the state-of-the-art methods5,13) to quantify DEHP in RBC stored in SAGM and AS-3. We also explore the potential of this method to detect additional compounds of interest, such as MEHP and phthalate catabolites.
Role of C/EBP homologous protein in retinal ganglion cell death after ischemia/reperfusion injury.

PURPOSE To investigate the role of C/EBP homologous protein (CHOP), a proapoptotic protein, and the unfolded protein response (UPR) marker that is involved in endoplasmic reticulum (ER) stress-mediated apoptosis in mouse retinal ganglion cell (RGC) death following ischemia/reperfusion (I/R) injury. METHODS Retinal I/R injury was induced in adult C57BL/6J wild-type (WT) and CHOP knockout (Chop(-/-)) mice by raising IOP to 120 mm Hg for 60 minutes. Expression of CHOP and other UPR markers was studied by Western blot and immunohistochemistry. Retinal ganglion cell counts were performed in retinal flat mounts stained with an RGC marker. Retinal ganglion cell function was evaluated by scotopic threshold response (STR) electroretinography. RESULTS In WT mice, retinal CHOP was upregulated by 30% in I/R-injured eyes compared to uninjured eyes 3 days after injury (P < 0.05). Immunohistochemistry confirmed CHOP upregulation specifically in RGCs. CHOP knockout did not affect baseline RGC density or STR amplitude. Ischemia/reperfusion injury decreased RGC densities and STR amplitudes in both WT and Chop(-/-) mice. However, survival of RGCs in I/R-injured Chop(-/-) mouse was 48% higher (P < 0.05) than that in I/R-injured WT mouse 3 days after I/R injury. Similarly, RGC density was significantly higher in Chop(-/-) eyes at 7, 14, and 28 days after I/R injury. Scotopic threshold response amplitudes of Chop(-/-) mice were significantly higher at 3 and 7 days after I/R than those of WT mice. CONCLUSIONS Absence of CHOP partially protects against RGC loss and reduction in retinal function after I/R injury, indicating that CHOP and, thus, ER stress play an important role in RGC apoptosis in retinal I/R injury.
Antagonistic Action of Dinitrothymol and Dinitrocresol on Cellular Respiration

In an extensive study of the biological effects of nitro and dinitrophenols1 it was found that extremely small concentrations of 2,4-dinitrothymol (1-hydroxy, 3-methyl, 6-isopropyl, 2,4-dinitro-benzene) blocked the cell division of fertilized sea urchin (Arbacia punctulata) eggs without, in any concentration, giving more than a slight stimulation of oxygen consumption. This behavior was in marked contrast to that of certain other nitro compounds, including 4,6-dinitrocarvacrol, the isomer of 2,4-dinitrothymol, which displayed a stimulating action on respiration, increasing to an optimum and then progressively disappearing as the concentration of reagent was made larger. These nitro compounds which stimulated respiration also reversibly blocked the cell division of fertilized sea urchin eggs, the initial concentration for division block being just equal to or slightly larger than that producing the optimum respiratory rise.The results with dinitrothymol suggest that the above outlined effects of 4,6-dinitr...
The Plot Thickens: Diet Microbe Interactions May Modulate Thrombosis Risk.

Thrombosis plays an important role in cardiovascular disease (CVD). Platelet activation is an essential step in the genesis and propagation of atherothrombotic complications. In a recent publication, Zhu and colleagues report that gut microbe-derived TMAO enhances platelet responsiveness and thrombosis, providing a novel mechanistic connection between microbes and CVD (Zhu et al., 2016).
American Learners' Comprehension of Russian Textual Humor.

Over the past decade, second language (L2) humor has attracted scholarly attention as both a means and a goal of L2 development. Much of this research, however, has focused on oral communication, whereas virtually no studies address humor as an aspect of reading comprehension. This exploratory study combines these two areas of inquiry, examining how L2 learners of Russian negotiate textual humor. In particular, the study addresses the role of textual properties (genre and humorousness), and the effects of proficiency on learners' ability to apprehend and appreciate textual humor. The findings suggest that learner comprehension is dynamic and often partial (cf. Bell, ), depending on familiarity with genre conventions and linguistic devices signaling humorous intent. The study also found that different stages of humor comprehension required discrete sets of knowledge: Detection, for example, relies on L2 linguistic knowledge, whereas understanding hinges largely on native cultural beliefs. Comparison of both groups suggested that the differences between learners and native speakers were both quantitative and qualitative. The role of proficiency was more complex than expected and primarily evidenced in the accuracy (rather than frequency) of humor recognition independent of text properties. The article concludes with pedagogical suggestions and outlines future research areas. [ABSTRACT FROM AUTHOR]
A Probe into the Principle of Nonstopped Execution of Lawsuit

Nonstopped executeion of lawsuit is not only an important principle in China's Procedural Law but also an important legal system.But with the development of administerative accusation practice and the jurisprudence research,the inharmony between this principle and the legislation and practice of administerative organizations' law enforcement is becoming more and more obvious.In face,whether accusation will lead to the stopped executeion of administrative actions depends on judges' balancing the related parties' interests and public interests.Based on the foreign experience and China's concrete situateions,China had better adopt the principle of nonstoped executeion of lawsuit.
Experimental study on effect of coenzyme Q_(10) on the ability of anti-fatigue and anoxia endurance in mice

Objective:To study the effect of Coenzyme Q10 on the ability of anoxia endurance and anti-fatigue in mice.Methods: Coenzyme Q10 was consecutively orally given to mice with the doses of 133.3,66.7 and 33.3 mg/kgBW for 35 days.Test of burdened swimming,lactic acid,hepatic glycogen and urea determination were used to assess the function of anti-fatigue.Tests of anoxia endurance under normal pressure,sodium nitrite posioning and acute cerebral ischemia(cutting head) were used to assess the function of anoxia endurance.Results: On the test condition,Coenzyme Q10 can prolong the time of burdened swimming,increase the hepatic glycogen store in liver,decrease the lactic acid and urea content in blood of mice after swimming.It can prolong the survival time under anoxia condition and the breathing time after head being cut.The survival time after poisoned by sodium nitrite was not significantly influenced.Conclusion: Coenzyme Q10 can enhance the function of anti-fatigue and anoxia endurance in mice.
Preparing for the twenty-first century: Report of the TOX-90's Commission

Abstract A clear consensus developed that toxicology will be driven by advances in related fields. New technology and knowledge developed by all relevant disciplines, therefore, must be integrated into toxicology; progress in toxicology demands that the discipline must increasingly address good science and the scientific method. Issues of critical importance to the field, such as risk estimation of the health effects of chemical and physical agents and the education of toxicologists, can only be addressed by meeting these objectives.
Proteomic Analysis of the Notch Interactome

Recent large-scale studies have provided a global description of the interactome-the whole network of protein interactions in a cell or an organism-for several model organisms. Defining protein interactions on a proteome-wide scale has led to a better understanding of the cellular functions of many proteins, especially those that have not been studied by classical molecular genetic approaches. Here we describe the resources, methods, and techniques necessary for generation of such a proteome-scale interactome in a high throughput manner. These procedures will also be applicable to low or medium throughput focused studies aimed at understanding interactions between members of specific pathways such as Notch signaling.
Developmental Outcomes of Prematurity: Autism Spectrum Disorder

Autism spectrum disorder (ASD) has been increasing in prevalence, and now is estimated to occur in 1 in 68 children. Children with prematurity, low birthweight, and neonatal medical complexity are at increased risk of having ASD. Neonatologists, particularly those involved in neonatal follow-up, must be aware of the vulnerability of NICU graduates to ASD, be able to identify early signs/symptoms, and be prepared to recommend the next steps for diagnosis and treatment.
Socialism in the North

In 1954, the government of the Democratic Republic of Vietnam needed the support of the poor peasant majority in the countryside in order to carry out its programmes. Although many of the richest landlords had been removed in the process of the previous struggle, the village oligarchies were either still intact or they could reconstitute themselves. Social change in the countryside depended on support of the government by the poor peasants. This was a lesson which had been learned from the Rent Reduction Campaign and its positive impact on soldiers at Dien Bien Phu.
Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis

Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria to the extracellular space. Here, we find that viable bacteria instead remain trapped within the cellular debris of pyroptotic macrophages. This trapping appears to be an inevitable consequence of how osmotic lysis ruptures the plasma membrane, and may also apply to necroptosis and some forms of nonprogrammed necrosis. Although membrane tears release soluble cytosolic contents, they are small enough to retain organelles and bacteria. We call this structure the pore-induced intracellular trap (PIT), which is conceptually parallel to the neutrophil extracellular trap (NET). The PIT coordinates innate immune responses via complement and scavenger receptors to drive recruitment of and efferocytosis by neutrophils. Ultimately, this secondary phagocyte kills the bacteria. Hence, caspase-1-driven pore-induced cell death triggers a multifaceted defense against intracellular bacteria facilitated by trapping the pathogen within the cellular debris. Bona fide intracellular bacterial pathogens, such as Salmonella, must prevent or delay pyroptosis to avoid being trapped in the PIT and subsequently killed by neutrophils.
Personalizing Therapy for Locally Advanced Rectal Cancer

Locally advanced rectal cancer is usually treated with chemotherapy, radiation therapy, and total mesorectal excision. Although effective, this trimodality therapy is arduous and associated with treatment-related toxicity. It has become clear that some patients may not need to undergo all three modalities of treatment and can thus avoid some of the treatment-associated morbidity. Two such approaches include selective use of preoperative radiation and nonoperative management. Limiting radiation can reduce treatment related toxicity and eliminate radiation-induced toxicity, fibrosis, and bowel and urogenital dysfunction. As an alternative to radical surgery, nonoperative management offers the considerable advantage of organ preservation. Efforts are under way to identify genetic markers that could be used to predict treatment response and better individualize treatment.
METHODS FOR REARING LARGE GERMFREE MAMMALS

This chapter describes the methods for rearing large germfree mammals. Germfree dogs, cats, and monkeys have been raised in flexible film isolators that are similar to those used for germfree rodents. The isolators are 6 feet long to provide space for a cage and for storage of the large amounts of food and water required. The cage is introduced through a hole in the chamber that is closed by a stainless steel end panel. Two pairs of gloves are desirables for delivery of the newborn animals and for restraint of the animals during subsequent experiments. To obtain germfree dogs, cats, and monkeys found hysterectomy is preferable to hysterotomy because there is less chance of accidental contamination and because the necessity for separate delivery and rearing isolators can be avoided. On the other hand, hysterectomy precludes the obtainment of subsequent litters from a valuable breeding female. To obtain germfree pigs, lambs, calves, and burros, hysterotomy is performed because of the large size of the gravid uterus.
Management of Immunosuppression in Liver Transplantation

Liver transplantation outcomes have significantly improved over the past few decades owing largely to the introduction of effective immunosuppression medications. Further comprehension of the unique immune microenvironment of the liver has led to the development of newer molecular targeted therapeutics. Understanding the mechanism of action and adverse effect profiles of these medications is crucial for appropriate management of posttransplant patients. In this review, the author describes the immunologic response elicited by liver transplantation, chronicles the various immunosuppressant drug classes, discusses the evidence behind their use, and evaluates the management of special subpopulations of posttransplantation patients.
The Princeton Web Transparency and Accountability Project

When you browse the web, hidden “third parties” collect a large amount of data about your behavior. This data feeds algorithms to target ads to you, tailor your news recommendations, and sometimes vary prices of online products. The network of trackers comprises hundreds of entities, but consumers have little awareness of its pervasiveness and sophistication. This chapter discusses the findings and experiences of the Princeton Web Transparency Project (https://webtap.princeton.edu/), which continually monitors the web to uncover what user data companies collect, how they collect it, and what they do with it. We do this via a largely automated monthly “census” of the top 1 million websites, in effect “tracking the trackers”. Our tools and findings have proven useful to regulators and investigatory journalists, and have led to greater public awareness, the cessation of some privacy-infringing practices, and the creation of new consumer privacy tools. But the work raises many new questions. For example, should we hold websites accountable for the privacy breaches caused by third parties? The chapter concludes with a discussion of such tricky issues and makes recommendations for public policy and regulation of privacy.
Structural basis for ligand binding to the guanidine-II riboswitch.

The guanidine-II riboswitch, also known as mini-ykkC, is a conserved mRNA element with more than 800 examples in bacteria. It consists of two stem-loops capped by identical, conserved tetraloops that are separated by a linker region of variable length and sequence. Like the guanidine-I riboswitch, it controls the expression of guanidine carboxylases and SugE-like genes. The guanidine-II riboswitch specifically binds free guanidinium cations and functions as a translationally controlled on-switch. Here we report the structure of a P2 stem-loop from the Pseudomonas aeruginosa guanidine-II riboswitch aptamer bound to guanidine at 1.57 A resolution. The hairpins dimerize via the conserved tetraloop, which also contains the binding pocket. Two guanidinium molecules bind near the dimerization interface, one in each tetraloop. The guanidinium cation is engaged in extensive hydrogen bonding to the RNA. Contacts include the Hoogsteen face of a guanine base and three nonbridging phosphate oxygens. Cation-π interactions and ionic interactions also stabilize ligand binding. The guanidine-II riboswitch utilizes the same recognition strategies as the guanidine-I riboswitch while adopting an entirely different and much smaller RNA fold.
Global proliferation of small hydropower plants – science and policy

Large‐scale electricity policies that embrace renewable resources have led to continued investments in hydropower. Despite evolving viewpoints regarding the sustainability of large hydropower installations, there has been a major increase in support for the widespread development of small hydropower plants (SHPs). A global synthesis reveals that 82,891 SHPs are operating or are under construction (11 SHPs for every one large hydropower plant) and that this number is estimated to triple if all potential generation capacity were to be developed. Fueled by considerable political and economic incentives in recent decades, the growth of SHPs has greatly outpaced available ecological science. We provide evidence for not only the lack of scientifically informed oversight of SHP development but also the limitations of the capacity‐based regulations currently in use. The potential indiscriminate expansion of SHPs under the pretense of promoting sustainable energy is concerning, and we identify several important steps to help ensure new scientific advances, effective management, and policy reform in the future.
Bottom boundary layer forced by finite amplitude long and short surface waves motions

Abstract A multiple-scale perturbation approach is implemented to solve the Navier–Stokes equations while including bottom boundary layer effects under a single wave and under two interacting waves. In this approach, fluid velocities and the pressure field are decomposed into two components: a potential component and a rotational component. In this study, the two components are exist throughout the entire water column and each is scaled with appropriate length and time scales. A one-way coupling between the two components is implemented. The potential component is assumed to be known analytically or numerically a prior, and the rotational component is forced by the potential component. Through order of magnitude analysis, it is found that the leading-order coupling between the two components occurs through the vertical convective acceleration. It is shown that this coupling plays an important role in the bottom boundary layer behavior. Its effect on the results is discussed for different wave-forcing conditions: purely harmonic forcing and impurely harmonic forcing. The approach is then applied to derive the governing equations for the bottom boundary layer developed under two interacting wave motions. Both motions—the shorter and the longer wave—are decomposed into two components, potential and rotational, as it is done in the single wave. Test cases are presented wherein two different wave forcings are simulated: (1) two periodic oscillatory motions and (2) short waves interacting with a solitary wave. The analysis of the two periodic motions indicates that nonlinear effects in the rotational solution may be significant even though nonlinear effects are negligible in the potential forcing. The local differences in the rotational velocity due to the nonlinear vertical convection coupling term are found to be on the order of 30% of the maximum boundary layer velocity for the cases simulated in this paper. This difference is expected to increase with the increase in wave nonlinearity.
Case Report: An incidental finding of an metastases noted in a "cancer to cancer adrenal tumor " from a large malignant nerve sheath tumor of the thigh.

Current guidelines are vague for the management of soft tissue sarcomas, specifically malignant peripheral nerve sheath tumors (MPNST), regarding staging the disease with the use of routine abdominal imaging. The most recent guidelines from the National Comprehensive Cancer Network (NCCN) recommends to “consider” abdominal/pelvic CT imaging for certain sub groups of sarcomas (e.g., myxoid/round cell liposarcoma, epithelial sarcoma, angiosarcoma, leiomyosarcoma), but provide no guidance on other sarcoma subtypes regardless of tumor size. We report a case of a very large large MPNST in a 40 year-old-female with neurofibromatosis type 1 who was incidentally found to have adrenal metastasis.
The Configurational Approach to Organization Design: Four Recommended Initiatives

The overall objective of this chapter is to reinvigorate interest in the configurational approach to organization design. Configurational analysis developed in promising ways in the 1970s and 1980s and then stalled. We believe, however, that the configurational approach can be improved such that it will serve the interests of scholars, managers, and organizational designers alike. We discuss four research initiatives that can be combined to produce a theoretically and practically useful approach: (1) adding the configurational elements of organizational capabilities and management philosophy; (2) incorporating into theory development a mechanism for anticipating future organizational forms and helping managers to consider those forms; (3) developing valid quantitative measures of capabilities and other intangible assets; and (4) improving the model of change that underlies the redesign process.
Keeping Junk Science Out of the Asbestos Litigation

There are two primary contexts in which junk science arises in the asbestos litigation. The first is misdiagnosis of unimpaired patients as having an asbestos-related lung or chest abnormality. This occurs when an expert claims to find a lung or chest abnormality and states that this abnormality is a manifestation of asbestosis, and the expert is wrong on one or both counts. The need for care in diagnosing asbestosis-related abnormalities is evident. Incipient or marginal asbestosis as picked up on an X-ray bears at least a superficial resemblance to more than 130 other lung inflammations. Many of the experts who diagnose asbestos-related disease are partisan hired guns. Courts should instead insist that neutral experts, retained by the court itself, be used to determine whether plaintiffs in class action cases show signs of asbestos-related disease. Moreover, any physician who testifies regarding a diagnosis of asbestos-related disease should be properly qualified. The appropriate test is the reasonable patient test: would a reasonable person who thought he had the asbestos-related abnormality that he is claiming in litigation go to the testifying physician for a diagnosis? The second important context in which junk science arises in the asbestos litigation is when an impaired plaintiff claims an injury that might be, but is not necessarily, related to asbestos exposure. Asbestos exposure can clearly cause lung cancer, and some scientists believe that other cancers, such as colon cancer, can also be caused by asbestos exposure. However, most instances of lung cancer have nothing to do with asbestos exposure, and even taking a generous view of the evidence, the vast majority of colon cancers and other cancers purported to be linked to asbestos have nothing to do with asbestos exposure. The most pressing causation issue in the asbestos litigation is whether fleeting exposure to minute amounts of asbestos causes disease. Until recently, courts were much too liberal about allowing doctors, especially treating physicians, to testify with respect to causation evidence. Fortunately, beginning in the early 1990s as part of a general trend toward stricter scrutiny of expert evidence, the federal courts have started to crack down on the use of unqualified physicians who seek to testify about causation. State courts should follow their lead. Even if experts testifying regarding causation are qualified, the testimony must, of course, meet the particular jurisdiction's reliability standards. In federal court, this means amended Rule 702, which incorporates the Daubert trilogy. State courts have a hodgepodge of standards. Some states have adopted various versions of the Daubert test, others apply various versions of the Frye general acceptance rule, and still others have idiosyncratic tests. Whatever test is used, courts should serve as gatekeepers that exclude unreliable evidence. If state courts are unwilling to do so, the legislature should step in where appropriate and adopt a state version of federal rule 702.
In-hospital cardiac arrest among patients with malignancy.

e21583Background: Malignancy is generally considered a poor prognosticator for in-hospital cardiopulmonary arrest. Recent studies have shown that overall survival in those with localized disease an...
What Should Be the Future of the Low-Income Housing Tax Credit Program?

This research examines the Low-Income Housing Tax Credit (LIHTC) developments in metropolitan areas nationwide. The results indicate that the LIHTC program contributes to the spatial concentration ...
Going Beyond a Single Story: Experiences and Education of Refugee Children at Home, in School, and in the Community

One of us (Wang) recently attended a talk by Viet Thanh Nguyen, the Vietnamese American author of The Refugees and The Sympathizer and a Pulitzer winner and 2017 MacArthur Foundation Fellow. He sha...
Application of Instructional Alignment to Promote Moderate-to-Vigorous Physical Activity during Physical Education

An important role of physical education (PE) is to provide students with opportunities to be physically active. Toward this end, instructional alignment is introduced in this article as a means of ...