cssi/SciSciGPT-SciSciNet huggingface dataset:
Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites

Laser microirradiation is a powerful tool for real-time single-cell analysis of the DNA damage response (DDR). It is often found, however, that factor recruitment or modification profiles vary depending on the laser system employed. This is likely due to an incomplete understanding of how laser conditions/dosages affect the amounts and types of damage and the DDR. We compared different irradiation conditions using a femtosecond near-infrared laser and found distinct damage site recruitment thresholds for 53BP1 and TRF2 correlating with the dose-dependent increase of strand breaks and damage complexity. Low input-power microirradiation that induces relatively simple strand breaks led to robust recruitment of 53BP1 but not TRF2. In contrast, increased strand breaks with complex damage including crosslinking and base damage generated by high input-power microirradiation resulted in TRF2 recruitment to damage sites with no 53BP1 clustering. We found that poly(ADP-ribose) polymerase (PARP) activation distinguishes between the two damage states and that PARP activation is essential for rapid TRF2 recruitment while suppressing 53BP1 accumulation at damage sites. Thus, our results reveal that careful titration of laser irradiation conditions allows induction of varying amounts and complexities of DNA damage that are gauged by differential PARP activation regulating protein assembly at the damage site.
Hyperthermia and radiation-induced dominant lethals and chromosome loss in female Drosophila melanogaster

The hyperthermia treatment, 38 degrees C for 1 hour significantly increased the dominant lethals induced by 1000R of X-rays in immature oocytes. The viability and chromosome loss in mature eggs were affected by either heat treatment or radiation. Hyperthermia treatment given before radiation exposure also significantly increased radiation-induced loss of the X chromosome in immature oocytes. Heat treatment did not increase radiation-induced nondisjunction of the chromosomes.
Structure and Functional Studies of an Oxygen-evolving Photosystem II Preparation

Photosystem II(PSII) provides the electrons for plastoquinone reduction and the positive charges for water oxidation. The secondary electron transfer events associated with PSII, such as plastoquinone reduction and water oxidation, remain to be elucidated. In the present work, we have examined the composition and functional properties of a resolved PSII preparation capable of oxygen evolution and plastoquinone photoreduction. Because this preparation is devoid of PSI and deficient in the cytochrome b/f complex, it is ideal for detailed structural analysis.
Anisotropic Elastic Moduli of the Mancos B Shale- An Experimental Study

With the increasing interest in oil shale and shale gas reserves understanding elastic properties of shales have gained prominence. A lot of researchers have investigated into the elastic properties of various kinds of shales and their anisotropy, however not much research has been focused in understanding the frequency dependence. Kaarsberg et al. (1959) performed experimental studies on elastic properties of shales. P-wave velocities were measured in both artificial and natural shale samples in three mutually perpendicular directions as a function of drying time under atmospheric conditions. The samples were tested to be transversely isotropic. Later on studies by Jones and Wang (1981), Lo et al. (1986), Johnston and Christensen (1995) all indicate that shales are transversely isotropic in nature. They related the velocity anisotropy in shales to either the preferred orientation of clay minerals or to cracks aligned parallel to bedding at elevated pressures. A very detailed study performed by Vernik et al. (1996, 1997) have related velocity anisotropy in shales to thermal maturity and kerogen content. Hornby et al. (1996) performed measurements of P-wave and S-wave velocities on two fluid saturated shale samples under drained conditions. Measurements were made on samples cut at 0, 90 and at 45 to the bedding. Anisotropy values were estimated to be up to 26% and 4% for P-wave and S-wave velocities respectively; and were found to decrease with increasing pressure. Few comprehensive studies have been conducted and published discussing anisotropy in shales. Wang (2002a, 2002b) published data from 16 shale samples, which showed a strong correlation between Pwave and S-wave anisotropy. He showed that anisotropy decreases with increased pressure and decreased porosity. A comparison of data from experimental study of Wang (2001), with field studies by Sarkar & Tsvankin (2004) showed that anisotropic parameters exhibit frequency dependence. They attributed the variations to the measurement scales. Very few studies have been done comparing the elastic properties of shales over a large range of frequencies. White et al. (1983) observed that Pwave velocity from Sonic logs in the Pierre Shale were 6% higher than velocities derived from VSP. Hornby et al. (1995) showed that P-wave velocities were much higher from ultrasonic measurements compared to sonic log measurements. Duranti et al (2005) performed experiments on shale samples within a wide frequency band (from seismic to ultrasonic band). They observed substantial dispersion effect for some of the elastic properties while some components of the stiffness showed no dispersion at all. They concluded that increasing frequency resulted in increasing stiffness and that more measurements are required to verify the results.
HEDGING ONE'S BETS: UNCERTAINTY ABOUT CONTINUED SUCCESS REDUCES THE DESIRE FOR PROCEDURAL FAIRNESS.

The authors argue that the mere anticipation of possibly receiving unfavorable outcomes may be threatening to the self-esteem, leading to a reduced preference for high procedural fairness. The self...
Investigation on an outbreak of measles caused by new virus (d11 genotype) imported from Myanmar

Objective To study the relevant factors on an measles outbreak caused by imported new virus (d11 genotype)from Myanmar and to develop effective strategies and measures.Methods On-site investigation on the outbreak was carried out. Results There were four townships (66%) in Menglian county reported 15 cases of measles, with 7 cases aged 6 months to 5 years old, 2 cases with the history of measles vaccination (MV). Another 8 cases were 21 to 49 year-olds but their histories on immunization were unclear. 14 of the measles cases with Myanmar citizenship came to China for treatment. They were aged 10 months to 13 years old, with only one case had ever received MV vaccination. For all the 29 cases, except for one case who did not adopt the sample case of Myanmar, the remaining 28 patients were positive for measles IgM antibodies. 6 cases of measles virus RNA were detected in the amplified sequence which showed genotype d11, and was considered Myanmar imported wild virus. 184 people received the MV inoculation, with a rate of 61.96% and the serum samples showed a measles IgG antibody positive rate of 87.50%. Manner MV emergency vaccination was carried out timely in that county so the measles outbreak was effectively controlled.Conclusion Imported measles cases from foreign countries might lead to epidemic, indicating the difficulty and challenge in the elimination of measles in our province. Emergent vaccination of MV could interrupt the transmission of the disease. Our experience showed that MV was effective in the prevention of d11 genotypes measles infection in the area. Key words: Measles virus; Outbreak; Myanmar input
Use of chemical modification and mass spectrometry to identify substrate-contacting sites in proteinaceous RNase P, a tRNA processing enzyme

Among all enzymes in nature, RNase P is unique in that it can use either an RNA- or a protein-based active site for its function: catalyzing cleavage of the 5'-leader from precursor tRNAs (pre-tRNAs). The well-studied catalytic RNase P RNA uses a specificity module to recognize the pre-tRNA and a catalytic module to perform cleavage. Similarly, the recently discovered proteinaceous RNase P (PRORP) possesses two domains - pentatricopeptide repeat (PPR) and metallonuclease (NYN) - that are present in some other RNA processing factors. Here, we combined chemical modification of lysines and multiple-reaction monitoring mass spectrometry to identify putative substrate-contacting residues in Arabidopsis thaliana PRORP1 (AtPRORP1), and subsequently validated these candidate sites by site-directed mutagenesis. Using biochemical studies to characterize the wild-type (WT) and mutant derivatives, we found that AtPRORP1 exploits specific lysines strategically positioned at the tips of it's V-shaped arms, in the first PPR motif and in the NYN domain proximal to the catalytic center, to bind and cleave pre-tRNA. Our results confirm that the protein- and RNA-based forms of RNase P have distinct modules for substrate recognition and cleavage, an unanticipated parallel in their mode of action.
Antibiotic And Steroid Therapy of Massive Systemic Bacillus Calmette-Guerin Toxicity

Intravesical bacillus Calmette-Guerin (BCG) is the most effective treatment of carcinoma in situ available today and is superior to chemotherapy in the prevention of bladder tumor recurrence. While therapy is generally well tolerated, serious and even life threatening toxicity can occur. Treatment options for serious infection include isoniazid, rifampin, ethambutol, and cycloserine, but shock may also be secondary to hypersensitivity and require the addition of corticosteroids. The morbidity and mortality of systemically BCG-infected mice treated with single and combined antimicrobial and/or corticosteroid therapies was evaluated. BCG immunized mice were unable to survive doses of BCG which were uniformly tolerated in naive mice. The addition of cycloserine increased survival in mice treated with isoniazid and rifampin, but optimal survival was achieved with isoniazid, rifampin, and prednisolone. These experimental results support the previously reported clinical success of isoniazid, rifampin and prednisolone in patients with septic BCG reactions.
A behavioral View of Investor Protection

When, in the early 1980s, I first began to think and write about legal issues, I did so as an assistant professor of economics. I had had firstrate training in that field and felt that I was on my way to fully understanding the discipline of microeconomics. The core tool in my explanatory toolkit was rational choice theory, the theory that human beings, at least in making economic decisions (such as what to buy and how much to pay for it, how much to work and how much to play, what to save from one’s income and what to consume, and so on), know their own tastes and preferences, inform themselves about matters relevant to their preference-satisfaction (up to the point at which the cost of a little more information is just equal to the expected benefit of that information), and plan and act so as to maximize their well-being, subject to income, time, and other constraints that they face. It is a powerful theory, and its application to economic analysis has yielded important results. The application of rational choice theory to legal analysis was, in the early 1980s, revolutionizing that discipline. Someone who had command of rational choice theory could throw new light on old issues in the law, such as the real differences between the negligence and strict liability standards in tort, or provide economic efficiency justifications for seemingly mysterious legal doctrines, such as the attorney-client privilege. There was, however, a nagging small voice that kept asking how appropriate it was to use rational choice theory to examine
A Well-Defined Isocyano Analogue of HCo(CO)4. 2: Relative Brønsted Acidity as a Function of Isocyanide Ligation

The m-terphenyl isocyanide complex, HCo(CNArMes2)4 (ArMes2 = 2,6-(2,4,6-Me3C6H2)2C6H3), serves as a unique example of a well-defined isocyano analogue to HCo(CO)4. Given the well documented Bronsted acidity of HCo(CO)4 in both protic and nonprotic media, the Bronsted acidity of HCo(CNArMes2)4 was assessed for a quantitative comparison. Acid bracketing experiments in THF solution revealed that HCo(CNArMes2)4 has a Morris relative pKαTHF value of 38.5–40.7, which is considerably higher than that of HCo(CO)4 (pKαTHF(calc) = 11.4) and thereby indicates insignificant Bronsted acidity. Furthermore, the relative acidity of HCo(CNArMes2)4 rivals that of tetra-phosphine cobalt hydrides (i.e., HCo(PR3)4; pKαTHF(calc) ≥ 48), despite the good π-acidity properties of the isocyano unit. To systematically determine the effect of substituting an isocyanide for a CO ligand on the acidity of the Co–H unit in HCoL4 complexes, the full series of HCo(CO)n(CNArMes2)4–n monohydrides and [Co(CO)n(CNArMes2)4–n]− (n = 1–4) metalat...
Bayesian Belief models for integrating match scores with liveness and quality measures in a fingerprint verification system

Recent research has sought to improve the resilience of fingerprint verification systems to spoof attacks by combining match scores with both liveness measures and image quality in a learning-based fusion framework. Designing such a fusion framework is challenging because quality and liveness measures can impact the match scores and, therefore, the influence of these variables on the match score has to be modelled. Further, these measures themselves are influenced by many latent factors, such as the fabrication material used to generate fake fingerprints. We advance the state-of-the-art by proposing two Bayesian Belief Network (BBN) models that can utilize these measures effectively, by appropriately modelling the relationship between quality, liveness measure and match scores with the consideration of latent variables. We demonstrate the efficacy of the proposed models on the LivDet 2011 fingerprint spoof dataset.
Hedgehog and Tyrosine Kinase inhibitors for treating breast cancer

M of breast cancer patients relapse and progress to metastatic disease despite initial response to chemotherapy. The reasons for chemoresistance include presence of cancer stem cell (CSC) sub-populations possessing tumorigenic potential and upregulated oncogenic pathways. Therefore, the objective of this study was to investigate the anti-proliferative effects of two tyrosine kinase inhibitors (afatinib and gefitinib) and two hedgehog inhibitors (vismodegib and cyclopamine) to identify potential synergistic combinations for treating breast cancer. The effect of afatinib, gefitinib, cyclopamine and vismodegib on the growth of breast cancer cells in vitro was first examined. Using a combination of MTT assay, isobologram analysis and response surface modeling, combination of afatinib or gefitinib with vismodegib or cyclopamine was observed to be synergistic in their ability to inhibit breast cancer cell growth. This effect was found to be dose, time, cell line and schedule dependent. Also, since the anticancer agents studied are extremely hydrophobic, polymeric micelles were fabricated using lactic acid and carbonate based copolymers to improve drug solubility. Polymeric micelle formulations were found to increase the aqueous solubility of these compounds several fold.
Emergency Medicine Resident Orientation: How Training Programs Get their Residents Started

ABSTRACT Introduction. The first formal orientation program for incoming emergency medicine (EM) residents was started in 1976. The last attempt to describe the nature of orientation programs was by Brillman in 1995. Now almost all residencies offer orientation to incoming residents, but little is known about the curricular content or structure of these programs. The purpose of this project was to describe the current composition and purpose of EM resident orientation programs in the United States (U.S.). Methods. In autumn of 2014, we surveyed all U.S. emergency medicine residency program directors (n=167). We adapted our survey instrument from one used by Brillman (1995). The survey was designed to assess the orientation program’s purpose, structure, content, and teaching methods. Results. The survey return rate was 63% (105 of 167). Most respondents (77%) directed 3-year residencies, and all but one program offered intern orientation. Orientations lasted an average of nine clinical (Std. Dev.=7.3) and 13 non-clinical days (Std. Dev. =9.3). The prototypical breakdown of program activities was 27% lectures, 23% clinical work, 16% skills training, 10% administrative activities, 9% socialization and 15% other activities. Most orientations included activities to promote socialization among interns (98%) and with other members of the department (91%). Many programs (87%) included special certification courses (ACLS, ATLS, PALS, NRP). Course content included: use of electronic medical records (90%), physician wellness (75%), and chief complaint-based lectures (72%). Procedural skill sessions covered: ultrasound (94%), airway management (91%), vascular access (90%), wound management (77%), splinting (67%), and trauma skills (62%). Conclusion. Compared to Brillman (1995), we found that more programs (99%) are offering formal orientation and allocating more time to them. Lectures remain the most educational common activity. We found increases in the use of skills labs and specialty certifications. We also observed increases in time dedicated to clinical work during orientation. Only a few programs reported engaging in baseline or milestone assessments, an activity that could offer significant benefits to the residency program.
A Probabilistic Model-Based Prognostics Using Meshfree Modeling: A Case Study on Fatigue Life of a Cantilever Beam

Accurate prediction of remaining useful life (RUL) will improve reliability and reduce maintenance cost. Therefore, prognostics is essential to predict the RUL of systems and components. However, a big issue of uncertainty prevails in prognostics due to the fact that prognostics pertains to prediction of future state, which is affected by uncertainty. While various researches have been done in areas of prognostics and health management, they lack to perform RUL predictions efficiently. There is a need for an efficient comprehensive framework for quantifying uncertainty in prognostics. The research question to this study is: can meshfree modeling be used in probabilistic prognostics to efficiently predict RUL? The specific aims developed to answer the research question are (1) develop a computational framework for probabilistic prognostics of a fatigue life of a component using meshfree modeling, and (2) perform case study analyses on fatigue life of a cantilever beam. A probabilistic framework was developed that efficiently predicts the RUL of a component using a combination of the meshfree method known as local radial point interpolation method and a fatigue degradation model. Loading uncertainty is quantified and employed in the framework. The computational framework is easily customizable and computationally efficient and, hence, aids in decision making and fault mitigation. As a case study, the RUL of a cantilever beam under plane stress subjected to fatigue loadings was analyzed. Uncertainties in the RUL were quantified in terms of probability density functions, cumulative distribution functions, and 98% bounds of confidence interval. Sensitivity analysis was studied and computational efficiency of the framework was also investigated using first order reliability method and Monte Carlo method. When compared to the Monte Carlo method, first order reliability method provides reasonably good results and is found to be computationally more efficient.Copyright © 2016 by ASME
Opportunities for network coding: To wait or not to wait

It has been well established that reverse-carpooling based network coding can significantly improve the efficiency of multi-hop wireless networks. However, in a stochastic environment when there are no opportunities to code because of packets without coding pairs, should these packets wait for a future opportunity or should they be transmitted without coding? To help answer that question we formulate a stochastic dynamic program with the objective of minimizing the long-run average cost per unit time incurred due to transmissions and delays. In particular, we develop optimal control actions that would balance between costs of transmission against those of delays. In that process we seek to address a crucial question: what should be observed as the state of the system? We analytically show that just the queue lengths is enough if it can be modeled as a Markov process. Subsequently we show that a stationary policy based on queue lengths is optimal and describe a procedure to find such a policy. We further substantiate our results with simulation experiments for more generalized settings.
Best of Milan 2017-repair of the emphysematous lung: mesenchymal stromal cell and matrix.

The European Respiratory Society (ERS) Annual Meeting is hosting sessions focused on lung regeneration and repair more and more frequently in the past few years. During the 2017 ERS conference in Milan, a symposium on mechanisms involved in repair of the emphysematous lung focused on the cutting-edge findings on mesenchymal stromal cells and matrix and their contribution to repair of the emphysematous lung.
Impact of Volatile Anesthetic Agents on Early Clinical Outcomes in Liver Transplantation.

Abstract Background Few studies have assessed the ability of inhaled anesthetic agents to ameliorate ischemia-reperfusion injury (IRI) in liver transplantation (LT). This study compares inhaled anesthetics in early liver allograft IRI. LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. Methods LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. The choice of primary anesthetic agent was at the discretion of the anesthesiologist. Serum alanine aminotransferase (ALT) and total bilirubin (TB) levels were measured daily in the post-transplant period as measures of early graft injury and function. Survival and clinical outcomes are reported. Results There were 1291 primary LTs included in the analysis, with 3 primary inhaled agents: isoflurane (62%), desflurane (8%), and sevoflurane (30%). In the first 7 days post-transplant, the peak ALT level was lowest for desflurane (352), followed by sevoflurane (411) and isoflurane (481) (P = .09). All groups had similar ALT and TB by 7 days post-transplant. Graft survival for all 3 groups was statistically similar at 1, 7, and 30 days, with equivalent patient and graft survival at 1 year. Conclusions All 3 agents had similar rates of early allograft dysfunction and renal dysfunction. Subgroup analysis of high-risk donor grafts showed no statistical difference. In conclusion, administration of desflurane or sevoflurane may provide some early hepatoprotection against IRI, but longer-term outcomes were equivalent for all agents.
A - α Zero Sets: New Methods and Techniques

We give a detailed presentation of the theory of A -α zero sequences and of the underlying density concepts, based on new methods and techniques.
Biomedical informatics meets data science: current state and future directions for interaction

There are an ever-increasing number of reports and commentaries that describe the challenges and opportunities associated with the use of big data and data science (DS) in the context of biomedical education, research, and practice. These publications argue that there are substantial benefits resulting from the use of data-centric approaches to solve complex biomedical problems, including an acceleration in the rate of scientific discovery, improved clinical decision making, and the ability to promote healthy behaviors at a population level. In addition, there is an aligned and emerging body of literature that describes the ethical, legal, and social issues that must be addressed to responsibly use big data in such contexts. At the same time, there has been growing recognition that the challenges and opportunities being attributed to the expansion in DS often parallel those experienced by the biomedical informatics community. Indeed, many informaticians would consider some of these issues relevant to the core theories and methods incumbent to the field of biomedical informatics science and practice. In response to this topic area, during the 2016 American College of Medical Informatics Winter Symposium, a series of presentations and focus group discussions intended to define the current state and identify future directions for interaction and collaboration between people who identify themselves as working on big data, DS, and biomedical informatics were conducted. We provide a perspective concerning these discussions and the outcomes of that meeting, and also present a set of recommendations that we have generated in response to a thematic analysis of those same outcomes. Ultimately, this report is intended to: (1) summarize the key issues currently being discussed by the biomedical informatics community as it seeks to better understand how to constructively interact with the emerging biomedical big data and DS fields; and (2) propose a framework and agenda that can serve to advance this type of constructive interaction, with mutual benefit accruing to both fields.
“Well Built, But Poorly Roofed”: Notes on The Remains of Architectural History

This article proposes a new perspective on the contemporary standing of architectural history by examining the transition from architectural histories grounded in and upon textuality to an architec...
Gender differences in subjective stress and neuroendocrine response to a stress task among individuals with opioid dependence: A pilot study.

Abstract Background Opioid dependence is a significant public health problem in the United States and the number of opioid overdose deaths among women has increased dramatically in comparison to men in the last few years. In this context, understanding the biological mechanisms underlying gender differences in vulnerability to opioid dependence is essential. Methods The current pilot study examined gender differences in subjective stress, heart rate (HR), and cortisol/dephydroepiandrosterone (DHEA) response to a laboratory stressor (Trier Social Stress Test; TSST) or a no-stress condition, and drug cue paradigm among men (n = 21) and women (n = 18) with opioid dependence. Results Significant group (TSST vs. no stress) differences emerged in self-reported stress [F(1,35) = 23.8, p Conclusions Although women with opioid dependence reported greater subjective stress when exposed to a laboratory stress paradigm as compared to men, the neuroendocrine response was more robust in men. This pattern was similar to gender findings in men and women with cocaine and tobacco use disorders. The blunted cortisol combined with an increased subjective response among women may be a sign of HPA axis dysregulation which could increase vulnerability to relapse in women.
6.11 – Neurotransmitter Receptors☆

Neurotransmitter receptors play a vital role in the normal functioning of the nervous system. Controlled modulation of neurotransmitter receptors is critical for proper signaling between nerve cells and effector organs. Factors that disrupt normal neurotransmitter signaling can alter the homeostasis of the cells or tissues, leading to adverse effects. The release of neurotransmitters at the presynaptic neuron and the subsequent activation of postsynaptic receptors lead to stimulation or inhibition of neuronal transmission. The excitatory neurotransmission involves depolarization of the postsynaptic neuron or cell due to a decrease in the polarity of the cells by the influx of cations such as sodium ions. The excitatory neurotransmission is mainly carried out by glutamate receptors in the mammalian nervous system. The inhibitory neurotransmission is due to hyperpolarization of the cells by either influx of anions such as chloride ions or efflux of cations such as potassium ions. The GABA and glycine receptors serve as major inhibitory neurotransmitter receptors. Toxins and toxicants can interfere with neuronal transmission by directly binding receptors and modulating their function or by altering transmitter synthesis, release, and reuptake mechanisms. Therefore, neurotoxins can impair neuronal transmission at the synapse by either presynaptic modulation or postsynaptic modifications. Due to the intricate network of the nervous system, impairment of the receptor functions in the synapse can lead to regional network dysfunction, eventually resulting in adverse cellular effects and behavioral deficits. Therefore, a thorough knowledge of neurotransmitter receptor modulation by toxins and toxicants is essential for future development of therapies against adverse effects of these neurotoxic substances.
Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.

Abstract Seizures and brain injury lead to water and Cl− accumulation in neurons. The increase in intraneuronal Cl− concentration ([Cl−]i) depolarizes the GABAA reversal potential (EGABA) and worsens seizure activity. Neocortical neuronal membranes have a low water permeability due to the lack of aquaporins necessary to move free water. Instead, neurons use cotransport of ions including Cl− to move water. Thus, increasing the extracellular osmolarity during seizures should result in an outward movement of water and salt, reducing [Cl−]i and improving GABAA receptor-mediated inhibition. We tested the effects of hyperosmotic therapy with a clinically relevant dose of mannitol (20 mM) on epileptiform activity, spontaneous multiunit activity, spontaneous inhibitory post-synaptic currents (sIPSCs), [Cl−]i, and neuronal volume in layer IV/V of the developing neocortex of C57BL/6 and Clomeleon mice. Using electrophysiological techniques and multiphoton imaging in acute brain slices (post-natal day 7–12) and organotypic neocortical slice cultures (post-natal day 14), we observed that mannitol: 1) decreased epileptiform activity, 2) decreased neuronal volume and [Cl−]i through CCCs, 3) decreased spontaneous multi-unit activity frequency but not amplitude, and 4) restored the anticonvulsant efficacy of the GABAA receptor modulator diazepam. Increasing extracellular osmolarity by 20 mOsm with hypertonic saline did not decrease epileptiform activity. We conclude that an increase in extracellular osmolarity by mannitol mediates the efflux of [Cl−]i and water through CCCs, which results in a decrease in epileptiform activity and enhances benzodiazepine actions in the developing neocortex in vitro. Novel treatments aimed to decrease neuronal volume may concomitantly decrease [Cl−]i and improve seizure control.
Variation in Life History May Allow Colonization of Diverse Habitats in an Invasive Fish Species

Successful colonization by an invasive species is often associated with flexibility in life-history traits. The number and timing of reproductive events are among the most important of those life-history traits and are often strongly influenced by habitat stability. An invasive fish, Brook Stickleback (Culaea inconstans), was first detected in eastern Washington in 1999. They have subsequently expanded their range into water bodies of variable habitat stability, i.e., permanent, semi-permanent, and ephemeral water bodies. We hypothesized that Brook Stickleback living in unstable and unpredictable habitats would exhibit “fast” life-history traits relative to Brook Stickleback living in more stable habitats. Brook Stickleback were collected from 18 water bodies and standard length was measured. Otoliths were then extracted to determine age. Average age of Brook Stickleback in permanent wetlands was significantly greater than that of fish in semi-permanent and ephemeral wetlands, but there was no significant difference in age structure between semi-permanent and ephemeral wetlands (permanent x = 1.24, semi-permanent x = 0.73, ephemeral x = 0.76, P < 0.001). Average length at age class 0+ was significantly less than age classes I, II, and III; however, there was no significant difference between age classes I, II, and III (0+: x= 39.73; I: x = 46.42; II: x= 45.14; III: x= 49.10; P < 0.001). The results suggest that Brook Stickleback exhibit different life-history characteristics depending upon the habitats in which they are found. Brook Stickleback in unstable habitats may be functionally semelparous; however, it is possible that some individuals may produce multiple clutches within a single spawning season. Finally, we found that the only accurate way to measure Brook Stickleback age is through otolith analysis, drawing into question the conclusions of previous work in which length was used as a surrogate for age.
E to Z Photoisomerization of Phytochrome Cph1Δ Exceeds the Born-Oppenheimer Adiabatic Limit.

The Born–Oppenheimer adiabatic limit applies broadly in chemistry because most reactions occur on the ground electronic state. Photochemical reactions involve two or more electronic states and need not be subject to this adiabatic limit. The spectroscopic signatures of nonadiabatic processes are subtle, and therefore, experimental investigations have been limited to the few systems dominated by single photochemical outcomes. Systems with branched excited-state pathways have been neglected, despite their potential to reveal insights into photochemical reactivity. Here we present experimental evidence from coherent three-dimensional electronic spectroscopy that the E to Z photoisomerization of phytochrome Cph1 is strongly nonadiabatic, and the simulations reproduce the measured features only when the photoisomerization proceeds nonadiabatically near, but not through, a conical intersection. The results broaden the general understanding of photoisomerization mechanisms and motivate future studies of nonadiab...
Serum Cotinine and Silent Myocardial Infarction in Individuals Free from Cardiovascular Disease.

Serum cotinine is a sensitive and specific marker of tobacco exposure, including second-hand smoke exposure. We sought to explore the association of tobacco exposure determined by serum cotinine with electrocardiographic silent myocardial infarction (SMI). A total of 7,006 participants (59.0 ± 13.3 years; 52.6% women, 49.7% non-Hispanic whites) without cardiovascular disease from the Third National Health and Nutrition Examination Survey (NHANES III) were included in this analysis. SMI was defined as electrocardiographic evidence of MI in the absence of a history of MI. Multivariable logistic regression analysis was used to examine the association between SMI and serum cotinine tertiles. SMI was detected in 114 (1.63%) of the participants. The prevalence of SMI was higher among those with higher levels of serum cotinine (SMI prevalence was 1.25%, 1.49%, and 2.14% across serum cotinine lower [0.03 to 0.12 ng/ml], middle [0.12 to 1.39 ng/ml], and higher [1.40 to 1890 ng/ml] tertiles, respectively). In a model adjusted for potential confounders, participants within the highest serum cotinine tertile had significantly greater odds of SMI (odds ratio [95% confidence interval]: 2.51 [1.55 to 4.08]) compared with those with serum cotinine levels in the first tertile. Each 10 ng/ml increase in serum cotinine levels was associated with a 2% (p
Possible solution to the cosmological-constant problem.

Classically, the unimodular theory of gravity with a constrained determinant ${\mathit{g}}_{\mathrm{\ensuremath{\mu}}\ensuremath{\nu}}$ is equivalent to general relativity augmented by an arbitrary cosmological constant \ensuremath{\Lambda}, which arises as an integration constant. At the quantum level we argue that an integration over \ensuremath{\Lambda} should be included in the Euclidean path integral for the vacuum functional. The fully renormalized \ensuremath{\Lambda}=0 overwhelmingly dominates all other contributions yielding a zero observed cosmological constant. While the technical part of our argument is similar to that of the ``wormhole'' argument, the two approaches are logically different.
A Conversation with Robert Fulton.

Robert Fulton was Professor of Sociology (Emeritus) at the University of Minnesota. In 1969, he founded and directed the Center for Death Education and Research at the University of Minnesota. Upon...
We are Just People: Transgender Individuals’ Experiences of a Local Equal Rights Debate

AbstractThis phenomenological inquiry investigated the experiences of 13 transgender individuals living in Houston, Texas, when an ordinance providing protections for transgender persons was passed...
Hybrid System Model of Microextrusion-Based Direct-Write Additive Manufacturing

Flowrate control in Direct-Write (DW) Additive Manufacturing (AM) continues to be a challenge due to a capacitative energy storage in the system and the absence of suitable flowrate sensors at the micro-scale. Lack of precise control leads to an excess or a lack of ink while printing, resulting in manufacturing defects. The incorporation of a pressure sensor and a feedback controller is a potential approach for precisely controlling the flowrate. However, in the case where the ink loses contact with the pressure sensor, there will be an abrupt loss in feedback signal, which could potentially result in instability in the closed loop. In this paper, we present a hybrid model that represents the continuous dynamics of microextrusion with discrete switching between three different modes that captures the presence or loss of a sensed pressure. The simulation results demonstrate that the model captures the continuous dynamics of microextrusion while switching between three discrete modes: normal printing mode, retracted ink leading edge mode, and loss of pressure signal mode. The hybrid model presented here paves the way for switched controller synthesis to create stable feedback controllers.
An ionophore-based persistent luminescent ‘Glow Sensor’ for sodium detection

Optical sensors have numerous positive attributes such as low invasiveness, miniaturizability, biocompatibility, and ease of signal transduction. Recently, there has been a strong research focus on using phosphorescent readout mechanisms, specifically from long-lifetime phosphorescent or ‘persistent luminescence’ particles, for in vitro and in vivo sensors. Persistent luminescence readouts can avoid cellular autofluorescence during biological monitoring, leading to an improved signal-to-noise ratio over a more traditional fluorescence readout. In this study, we show for the first time an ionophore-based optical bulk optode sensor that utilizes persistent luminescence microparticles for ion detection. To achieve this, we combined long-lifetime strontium aluminate-based ‘glow-in-the-dark’ microparticles with a non-fluorescent pH-responsive dye in a hydrophobic plasticized polymer membrane along with traditional ionophore-based optical sensor components to create a phosphorescent ‘Glow Sensor’. The non-fluorescent pH indicator dye gates the strontium aluminate luminescence signal so that it decreases in magnitude with increasing sodium concentration. We characterized the Glow Sensor in terms of emission lifetime, dynamic range, response time, reversibility, selectivity, and stability.
Transnational Educational Research in Four Countries: Promoting Critical Border Praxis

This research took place in the following four countries: Malaysia, Mexico, Canada, and the United States (US). Educators in each country reported on how they addressed US international policies in their respective curricula. Critical border praxis emerged as a theoretical construct as a result of these transnational studies. Critical border praxis provides a contemplation of the intersection of place-based and border pedagogies, as well as how pedagogies are central to understanding one’s own situatedness. The findings of this study include recommendations for additional in-depth discussions of international policies in the US social studies curriculum. Implications for educators elsewhere are also articulated.
Applying Mixed Methods Research to Healthcare Simulation

Mixed methods has the potential to add values to simulation research by informing healthcare simulations, developing assessments and measures, and evaluating the effectiveness of simulations. However, it seems under-utilized relative to other single methodology designs. This chapter provides an introduction to mixed methods in simulation research and evaluation. We introduce mixed methods and cover major designs. Each form of research brings unique strengths. We highlight the integration of qualitative and quantitative research as a central feature of mixed methods and discuss integration strategies. To illustrate the application of mixed methods to simulation, we discuss studies that have used mixed methods to: (1) evaluate simulations by integrating qualitative and quantitative data, (2) use qualitative methods to develop simulations and its features, and (3) to develop assessments and surveys for use in simulation research, such as developing models of learner experiences. Finally, we provide recommended criteria that apply to writing and reviewing for publication or funding proposals.
ISG15 pathway knockdown reverses pancreatic cancer cell transformation and decreases murine pancreatic tumor growth via downregulation of PDL-1 expression.

Interferon-stimulated gene 15 (ISG15) is a 15 kDa protein induced by type I interferons (IFN-α and IFN-β) and is a member of the ubiquitin-like superfamily of proteins. The ISG15 pathway is highly expressed in various malignancies, including pancreatic ductal adenocarcinoma (PDAC), suggesting a potential role of the ISG15 pathway (free ISG15 and ISG15 conjugates) in pancreatic carcinogenesis. However, very little is known about how the ISG15 pathway may contribute to pancreatic tumorigenesis. In the current study, we demonstrate that ISG15 pathway knockdown reverses the KRAS-associated phenotypes of PDAC cells such as increased proliferation and colony formation. Furthermore, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated ISG15 knockdown decreased tumor programmed death ligand-1 (PDL-1) expression leading to increased number of CD8+ tumor-infiltrating lymphocytes and decreased pancreatic tumor growth. In addition, the syngeneic subcutaneous mouse model revealed that knocking down the ISG15 pathway significantly decreased the rate of tumor incidence and increased the survival rate. Interestingly, the ISG15 knockdown-mediated PDL-1 downregulation in pancreatic tumors increased the efficacy of anti-programmed cell death protein-1 (PD-1) treatment. ISG15 knockdown in combination with anti-PD-1 treatment synergistically increased the number of CD8+ tumor-infiltrating lymphocytes. Additionally, ISG15 knockdown alone significantly decreased the number of tumor-infiltrating regulatory T cells (Tregs) compared to wild type tumors treated with anti-PD-1 antibody. Overall, these findings suggest that strategies to target the ISG15 pathway by itself or in combination with immunotherapy may lead to improved survival for patients diagnosed with PDAC.
Structures of the AMPA receptor in complex with its auxiliary subunit cornichon

In the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes are critical for synaptic plasticity, learning, and memory. The two major categories of AMPAR auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs); these subunits share little homology and play distinct roles in controlling ion channel gating and trafficking of AMPAR. Here, I report high-resolution cryo-electron microscopy structures of AMPAR in complex with CNIH3. Contrary to its predicted membrane topology, CNIH3 lacks an extracellular domain and instead contains four membrane-spanning helices. The protein-protein interaction interface that dictates channel modulation and the lipids surrounding the complex are revealed. These structures provide insights into the molecular mechanism for ion channel modulation and assembly of AMPAR/CNIH3 complexes.
Coevolution of song and egg coloration: multimodal mating signals?

Abstract The divergence of reproductive traits frequently underpins the evolution of reproductive isolation. One of the most enduring puzzles on this subject concerns the variability in egg coloration among species of tinamou (Tinamidae) —a group of birds endemic to neotropics (Cabot 1992). Specifically, some tinamous lay glossy and colorful eggs while others lay less colorful eggs. Here I tested the hypothesis that tinamou egg coloration is a mating signal and its diversification was driven by reinforcement. For most tinamou species, the male guard the nest that is sequentially visited and laid eggs in by multiple females. The colorations of the existing eggs in the nest could signal mate quality and species identities to the upcoming females to the nest, preventing costly hybridization, thus were selected to diverge among species. If so, egg colors should coevolve with the known mating signals as the tinamou lineages diverged. The tinamou songs are important mating signals and are highly divergent among species. I found that the egg luminance was significantly associated with the first principle component of the song variables among 31 tinamou species (after correcting for phylogenetic signal). Egg color and songs could be multimodal mating signals that are divergently selected as different tinamou species diverged. Mating signal evolution could be opportunistic and even exploit post-mating trait as premating signals.
Some Applications and Some Limitations

Historians of ideas often argue about how early the romantic movement began. The dispute will turn, ultimately, on whether a particular poet (or painter, or novelist) was or was not a “romantic.” If this term remains undefined, or if it is defined in terms of private, subjective indices,1 they cannot tell (nor can we) whether, when they call a given poem “romantic” they are in real agreement, nor whether, when they differ, they are in more than verbal disagreement. It is not surprising, under these circumstances, that there is as yet no consensus about the dates of the romantic period, or even about whether there was a romantic period at all.
You might die tomorrow: by K. Manser, Highline House Publishing, 2020, $14.99 (Paperback), $24.99 (Hardcover)

Kate Manser, author of You Might Die Tomorrow, addresses the nature of our death-phobic society by focusing on subjective, transcendental experiences that opened her eyes to what “living” really me...
Neuroendocrine Tumors of the Pancreas

Neuroendocrine tumors of the pancreas are the second most common malignant neoplasm of the pancreas. While they are less aggressive than ductal adenocarcinoma, they are often discovered at advanced clinical stage, and overall survival is only 45% at 10 years. This tumor has recently received increased attention as public figures such as Steve Jobs, cofounder of Apple Computer Corporation have succumbed to the disease. This article focuses on the clinical and pathologic features of pancreatic neuroendocrine tumors, including diagnosis, classification, and treatment. In addition, genetic syndromes defined by or associated with the development of pancreatic neuroendocrine tumors are discussed. Finally, our current understanding of the molecular mechanisms underlying pancreatic neuroendocrine tumorigenesis is explored, and areas for future research are highlighted.