cssi/SciSciGPT-SciSciNet huggingface dataset:
Extracellular signal–regulated kinase 5 promotes acute cellular and systemic inflammation

Inflammatory critical illness is a syndrome that is characterized by acute inflammation and organ injury, and it is triggered by infections and noninfectious tissue injury, both of which activate innate immune receptors and pathways. Although reports suggest an anti-inflammatory role for the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5), we previously found that ERK5 mediates proinflammatory responses in primary human cells in response to stimulation of Toll-like receptor 2 (TLR2). We inhibited the kinase activities and reduced the abundances of ERK5 and MEK5, a MAPK kinase directly upstream of ERK5, in primary human vascular endothelial cells and monocytes, and found that ERK5 promoted inflammation induced by a broad range of microbial TLR agonists and by the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Furthermore, we found that inhibitors of MEK5 or ERK5 reduced the plasma concentrations of proinflammatory cytokines in mice challenged with TLR ligands or heat-killed Staphylococcus aureus, as well as in mice that underwent sterile lung ischemia-reperfusion injury. Finally, we found that inhibition of ERK5 protected endotoxemic mice from death. Together, our studies support a proinflammatory role for ERK5 in primary human endothelial cells and monocytes, and suggest that ERK5 is a potential therapeutic target in diverse disorders that cause inflammatory critical illness.
Design of an All-Magnetic Computing System: Part II-Logical Design

A logical design technique is developed for use with the particular module developed for this system. The detailed properties of this module, as well as the philosophy that led to its particular form, were covered in Part I of the paper. Briefly, the module forms the (inclusive) OR function of two input variables. This function can subsequently be transmitted to three receivers, each transfer being independently logically positive or negative. The read-outs are nondestructive and the transmitter module must be explicitly cleared before read-in is again possible. In view of the relatively small fan-in and fan-out for this module, and since only the OR function can be directly formed during any single transfer, complex logic functions must be formed slowly, a step at a time. This step-by-step generation of functions results in the need for more modules than might otherwise be required, but aside from that, the synthesis techniques are not particularly different from those of customary logical design. In particular, the design of an arithmetic unit designed for decimal addition, subtraction and multiplication is outlined. Some comparisons are noted between this particular all-magnetic logic scheme and conventional core-diode schemes. Comparisons are also made between magnetic logic schemes in general and some other realization schemes, such as ac-operated parametrons and conventional transistor systems.
Types and Effects of Tsunamis

A teletsunami (TEL-leh-soo-NAH-mee) is a tsunami generated more than 1000 kilometers from the affected area, traveling over long distances to opposite shores, sometimes crossing entire oceans. Teletsunamis are usually associated with subduction zones. In a subduction zone, continental crustal plates, colliding with the heavier oceanic plates, force the underthrusting of the heavier plate under the continental plate creating ocean trenches and building great stress in the contact zone between the plates. The resulting earthquakes (stress releases) can cause tsunamis to propagate great distances. Teletsunamis are the principal type of tsunamis affecting Hawai’i and the U.S. West Coast. Most teletsunamis occur in the Pacific Ocean. Only two reports of teletsunamis affecting the Caribbean, in 1755 and 1761, are contained in the known history.
A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size

Leucine carboxyl methyltransferase-1 (LCMT1) and protein phosphatase methylesterase-1 (PME-1) are essential enzymes that regulate the methylation of the protein phosphatase 2A catalytic subunit (PP2AC). LCMT1 and PME-1 have been linked to the regulation of cell growth and proliferation, but the underlying mechanisms have remained elusive. We show here an important role for an LCMT1-PME-1 methylation equilibrium in controlling mitotic spindle size. Depletion of LCMT1 or overexpression of PME-1 led to long spindles. In contrast, depletion of PME-1, pharmacological inhibition of PME-1 or overexpression of LCMT1 led to short spindles. Furthermore, perturbation of the LCMT1-PME-1 methylation equilibrium led to mitotic arrest, spindle assembly checkpoint activation, defective cell divisions, induction of apoptosis and reduced cell viability. Thus, we propose that the LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division.
Abstract T P155: The Vascular Distribution of Stroke Among Patients with Hypercoagulable State

Background: Hypercoagulable state (HCS) may increase the risk for acute ischemic stroke (AIS). The relationship between HCS and the location of the stroke has never been described. Objective: To determine if HCS is associated with an increased the frequency of strokes in specific vascular distributions. Methods: Patients who consecutively presented to our center with AIS between 06/2008-09/2013 were selected from our prospective stroke registry. Patients who did not receive HCS blood tests were excluded from the analysis. Diffusion weighted MRI sequences were used to identify the vascular distribution of each stroke. Results: Among the 1,466 AIS cases presented during the study period, 395 AIS patients met our inclusion criteria; 187 patients had an HCS (77.4% Black, 51.4% Female, 55 years median age); 208 patients did not have an HCS (60.4% Black, 42.3% Female, 56 years median age). There was no significant difference in the frequency of anterior circulation strokes (p=0.130) or posterior circulation strokes (p=0.060) between the groups. Patient with HCS were more likely to have a stroke in the posterior inferior cerebellar artery (PICA) territory (9.1% vs. 2.1%, p=0.001). After adjusting to the stroke subtype, patients with HCS were at nearly 5 times higher odds of having a PICA stroke (OR=4.47, 95%CI 1.42-14.1, p=0.010). The two groups did not differ in the frequency of anterior, middle or posterior cerebral artery strokes. We did not detect a significant difference in the vertebral artery, basilar artery or anterior inferior cerebellar artery strokes. Conclusion: In our sample, hypercoagulable state was associated with significantly higher frequency of PICA territory strokes. Patients with PICA distribution stroke and no cardiac or large vessel etiology identified might benefit from expanding the work-up to include hypercoagulation studies.
Regulation of Glucokinase by Intracellular Calcium Levels in Pancreatic β Cells

Glucokinase (GCK) controls the rate of glucose metabolism in pancreatic β cells, and its activity is rate-limiting for insulin secretion. Posttranslational GCK activation can be stimulated through either G protein-coupled receptors or receptor tyrosine kinase signaling pathways, suggesting a common mechanism. Here we show that inhibiting Ca(2+) release from the endoplasmic reticulum (ER) decouples GCK activation from receptor stimulation. Furthermore, pharmacological release of ER Ca(2+) stimulates activation of a GCK optical biosensor and potentiates glucose metabolism, implicating rises in cytoplasmic Ca(2+) as a critical regulatory mechanism. To explore the potential for glucose-stimulated GCK activation, the GCK biosensor was optimized using circularly permuted mCerulean3 proteins. This new sensor sensitively reports activation in response to insulin, glucagon-like peptide 1, and agents that raise cAMP levels. Transient, glucose-stimulated GCK activation was observed in βTC3 and MIN6 cells. An ER-localized channelrhodopsin was used to manipulate the cytoplasmic Ca(2+) concentration in cells expressing the optimized FRET-GCK sensor. This permitted quantification of the relationship between cytoplasmic Ca(2+) concentrations and GCK activation. Half-maximal activation of the FRET-GCK sensor was estimated to occur at ∼400 nm Ca(2+). When expressed in islets, fluctuations in GCK activation were observed in response to glucose, and we estimated that posttranslational activation of GCK enhances glucose metabolism by ∼35%. These results suggest a mechanism for integrative control over GCK activation and, therefore, glucose metabolism and insulin secretion through regulation of cytoplasmic Ca(2+) levels.
The Use of Affinity Tags to Overcome Obstacles in Recombinant Protein Expression and Purification

Research and industrial demands for recombinant proteins continue to increase over time for their broad applications in structural and functional studies and as therapeutic agents. These applications often require large quantities of recombinant protein at desirable purity, which highlights the importance of developing and improving production approaches that provide high level expression and readily achievable purity of recombinant protein. E. coli is the most widely used host for the expression of a diverse range of proteins at low cost. However, there are common pitfalls that can severely limit the expression of exogenous proteins, such as stability, low solubility and toxicity to the host cell. To overcome these obstacles, one strategy that has found to be promising is the use of affinity tags or carrier peptide to aid in the folding of the target protein, increase solubility, lower toxicity and increase the level of expression. In the meantime, the tags and fusion proteins can be designed to facilitate affinity purification. Since the fusion protein may not exhibit the native conformation of the target protein, various strategies have been developed to remove the tag during or after purification to avoid potential complications in structural and functional studies and to obtain native biological activities. Despite extensive research and rapid development along these lines, there are unsolved problems and imperfect applications. This focused review compares and contrasts various strategies that employ affinity tags to improve bacterial expression and to facilitate purification of recombinant proteins. The pros and cons of the approaches are discussed for more effective applications and new directions of future improvement.
Network Planning and Economic Analysis of an Innovative New Optical Transport Architecture: The Digital Optical Network

This paper describes the attributes and network implications of a new network architecture, termed the Digital Optical Network, based on the use of recently developed large-scale photonic integrated circuits to implement frequent, affordable OEO conversion within an optical transport network. This architecture shows promise for providing the service flexibility, rapid reconfigurability, manageability and robustness of digital SONET/SDH networks, with the capacity scalability and cost-effectiveness of WDM networks. The viability of this architecture is modeled on a typical North American nation-wide network, and results demonstrate the potential cost- effectiveness of this architecture for use in a wide range of metro, regional and long-haul network applications.
On Being in Solidarity with Others While Divided Against Oneself: Hegel and DuBois on Identity, Institutions, and the Global Economy

How, if at all, should "individuals" think and feel about distant others who are unjustly disadvantaged by the design of international political and economic institutions? My paper begins to answer this question using the resources made available by the unlikely pair of W.E.B. DuBois and G.W.F. Hegel. As Shamoon Zamir has shown, DuBois's thought - and "The Souls of Black Folk" particularly - owes a significant debt to Hegel. While Zamir focuses on the relationship between DuBois's concept of double-consciousness and Hegel's "Phenomenology of Spirit", I read this concept against the background of Hegel's "Philosophy of Right" and its account of how political institutions shape the subjectivity of individual citizens. Where Hegel considers this influence for just and rational states, in which the smooth functioning of political institutions effortlessly produces a patriotic disposition, DuBois's double-consciousness enables us to consider our non-ideal world and to ask the question: if just institutions significantly cause individuals to develop the dispositions and habits appropriate to an ethical society, what dispositions ought an individual cultivate in an unjust world, where institutions have both just and unjust effects on our subjectivity? To answer this question, I explore the concept of solidarity, both domestically and internationally, and argue for its utility for responding to injustices that create unjust privilege for one party out of the oppression of the other.
Effects of Viscous Sublayer on Dispersion

The dimensionless dispersion coefficient for a pollutant ejected into a uniform turbulent flow is shown to depend on the characteristics of the viscous sublayers; calculations are carried out to demonstrate this dependence. The results have shown that the dimensionless dispersion coefficient increases quite substantially for turbulent pipe flow at low Reynolds number and high Schmidt number. The increased dispersion coefficient is due to the fact that extremely small diffusivity occurs in the viscous sublayer.
Cavity Formation in Simox Structures

We have investigated the effect of different implantation parameters on cavity formation in the top Si layer in SIMOX structures. Cavities were found to occur in the temperature range between 600 and 675°C. The nucleation and growth kinetics of cavities could be reasonably explained using classical theory, and showed a behavior similar to that of irradiation-induced voids in metals. A similar dependence on instantaneous current and beam scanning frequency was also observed. Post implantation annealing at a temperature of 1150°C for 80 min showed cavities starting to facet, and a threading dislocation density of < 105 cm2. SIMOX structures formed in (111) silicon are also presented.
Quality of Life and Psychosocial Issues in Narcolepsy: Implications for Management

Quality of life (QOL) in health care is traditionally measured by assessing the functional status of individuals. The meaning of QOL is personal and complex and varies according to individuals’ perceptions of what is salient in their lives, type of impairment, and other sociocultural variables. The construct of QOL is different from the concept of health status; however, health status is often used as an indicator of QOL. A review of the literature on QOL in narcolepsy shows extensive negative effects on the physical and mental health, work, and social health of patients. Moreover, treatment of narcolepsy is not optimal; even after successful treatment of the symptoms, patients may have adjustment problems. Social support enhances individuals’ capacity to cope with their disabilities and improve the quality of their lives. Various modes of providing social support are presented. Implications for developing comprehensive management strategies as well as further research on QOL indicators, the dynamics underlying the recovery process in narcolepsy, and the importance of longitudinal studies in group processes are discussed.
The utilization of surgical physician assistants: Policy implications for the future

It is anticipated that there will be a major growth in the role of surgical physician assistants in the immediate future. The authors believe that this trend will improve the quality of surgical care in the United States, reduce the number of surgeons being trained, and enable practicing surgeons to be more productive and hence more proficient.
Robust hardware true random number generators using DRAM remanence effects

A True Random Number Generator (TRNG) is an important security primitive used in a variety of applications including cryptographic algorithms, communication systems, simulations, etc. It is critical to be able to produce outputs consisting of fully unpredictable and unbiased bits in a cost-effective manner. In this paper, we present a robust hardware TRNG based on the Dynamic RAM (DRAM) remanence effect, which is a condition whereby information remains in a DRAM even after powering it down. The advantage of our hardware TRNG is that it forms from existing components with no extra circuitry. We assessed and tested the randomness of our proposed hardware TRNG by applying the NIST Statistical Test which indicates the unpredictability and nonrepeatability of our data. Given its strong NIST results, we believe that there is a potential for immediate cryptographic applications.
Structure of the Dimerization Interface in the Mature HIV-1 Capsid Protein Lattice from Solid State NMR of Tubular Assemblies.

The HIV-1 capsid protein (CA) forms the capsid shell that encloses RNA within a mature HIV-1 virion. Previous studies by electron microscopy have shown that the capsid shell is primarily a triangular lattice of CA hexamers, with variable curvature that destroys the ideal symmetry of a planar lattice. The mature CA lattice depends on CA dimerization, which occurs through interactions between helix 9 segments of the C-terminal domain (CTD) of CA. Several high-resolution structures of the CTD-CTD dimerization interface have been reported, based on X-ray crystallography and multidimensional solution nuclear magnetic resonance (NMR), with significant differences in amino acid side chain conformations and helix 9-helix 9 orientations. In a structural model for tubular CA assemblies based on cryogenic electron microscopy (cryoEM) [Zhao et al. Nature, 2013, 497, 643–646], the dimerization interface is substantially disordered. The dimerization interface structure in noncrystalline CA assemblies and the extent to ...
Conversations on restorative justice: a talk with Kay Pranis

Kay Pranis is a restorative justice advocate specialising in peacemaking circles. She began her work in criminal justice as the director of research services at the Citizen’s Council on Crime and J...
When Relatedness is Damaged or Undeveloped: A New Consideration of the Link between Relational Psychoanalysis and Object Relations Theory

The author discusses Lisa Director’s concept of being a catalyst, an enlivening presence, and Robert Grossmark’s concept of companioning, in their work with patients whom I think of as being in the autistic contiguous position. Director and Grossmark each provide a moving example of a long-term, successful treatment with patients who are often seen as unanalyzable and dismissed. These patients are very challenging, having great difficulty entering relationships; either floating through space in a dull, disconnected manner or violently crashing into others in order to make contact and maintain a minimal sense of cohesiveness and connection. I discuss these two exceptional clinical papers using object relations theory, which can provide a more generalizable approach to the treatment of such difficult patients.
Markers of Iron Overload Are Poor Prognostic Factors in Stem Cell Transplantation.

Transfusional iron overload is common in survivors of acute leukemia and hematopoietic stem cell transplantation and might cause long-term liver dysfunction. Routine evaluation for iron overload in such patients is recommended because excess iron can be readily removed from the body via phlebotomy or chelation. Iron overload might be associated with worse survival after stem cell transplantation in these diseases. We were interested in determining whether levels of the iron binding protein ferritin or the serum transferrin receptor (TfR) were predictive for survival. In a prospective study, we examined the correlation between iron parameters at the time of transplantation and overall survival. Serum ferritin, transferrin saturation, and TfR were measured before preparative regimen on patients who underwent hematopoietic stem cell transplantation between 1999 and 2004 for the diagnosis of aplastic anemia, MDS or acute leukemia (n=79). We used the number of transfusions before transplantation as a measure of iron load. Among these iron markers, serum ferritin correlated the most with the number of transfusions, regardless of remission status. High ferritin (>1,500 ng/ml), low TfR (≤4 μg/ml) and low TfR/log ferritin ratio (≤2) were associated with shorter survival (p=0.005, 0.04, and 0.001 respectively)(Figure 1). Among acute leukemia patients in remission, there was no difference in overall survival between patients with high or low iron markers. Markers of iron excess (serum ferritin >1,500 ng/ml, TfR/log ferritin ratio ≤2) at the time of stem cell transplantation is associated with shorter survival in MDS, aplastic anemia and acute leukemia with active disease. These results demonstrate that knowledge of patient ferritin and TfR levels can aid in risk stratification. The results also suggest that patients with high levels of ferritin may benefit from iron chelation before treatment.
Mother and Child Ratings of Child Anxiety: Associations With Behavioral Avoidance and the Role of Family Accommodation

SYNOPSISObjective. This study compared mother and child ratings of child anxiety to each other and to an objective measure of the child’s avoidant behavior, using a novel motion-tracking paradigm. The study also examined the moderating role of family accommodation for the link between mother ratings of child anxiety and child behavioral avoidance. Design. Participants were 98 children (7- to 14-years-old) and their mothers. Children met criteria for a primary anxiety disorder. Measures included parent and child versions of the Multi-Dimensional Anxiety Scale for Children and the Screen for Child Anxiety Related Emotional Disorders. Children also completed the Spider Phobia Questionnaire for children and the Family Accommodation Scale for Anxiety—Child Report. The Yale Interactive Kinect Environment Software platform was used to measure children’s behavioral avoidance of spider images. Results. Mother and child ratings of child anxiety were moderately correlated. Only child ratings of child anxiety were as...
Disinfection susceptibility of waterborne pseudomonads and legionellae under simulated space vehicle conditions

The sensitivity of waterborne bacteria from iodinated systems to iodine is examined with particular attention to the recovery of the organisms. The use of iodine as a disinfectant for space-vehicle water is described, and references are made to studies of iodine sensitivity and the relationship between growth rate and iodine sensitivity. Growth following iodination is discussed, and bacterial responses to nutrient restriction are examined for both P aeruginosa and Legionella pneumophila. The low level of organic nutrients in spacecraft water allows the selection for bacteria that are less sensitive to halogens. The formation of biofilms within the water-treatment system enhances bacterial resistance to iodine, and in the case of high-quality water it is shown that sublethal doses of iodine can stimulate bacterial growth. Water treatment should therefore be based on antecedent growth conditions, nutrient limitation, biofilm formation, and ambient selective pressures.
Combining ability, heterosis, and genetic distance among nine elite American Pima cotton genotypes ( Gossypium barbadense )

American Pima cotton (Gossypium barbadense L.) is grown in the southwest United States, and no Pima cotton hybrid is commercially grown. In this study, six commercial Pima cultivars (Pima S-7, Pima S-6, Phy 76, BR 007, DP 340, and DP 744) and three elite germplasm lines (SI 1331, 93252, and 8810) were crossed in a diallel mating scheme without reciprocals, and their 36 F2 and F3 progeny were planted in replicated tests at two locations (L) in 2004–2005. Yield and fiber traits were analyzed using Griffing’s Model 1, Method 2 diallel analysis. Genetic distance (GD) of parent lines was determined using 661 AFLP molecular markers. Across locations, significant genotype (G) and general combining ability (GCA) effects were detected for yield, boll size, lint percent, micronaire, 2.5% fiber length, fiber strength, and elongation. Significant specific combining ability (SCA) effects were detected for yield, micronaire, and strength. Lint yield and the yield components- boll size and lint percent exhibited significant G × L interactions. Significant GCA × L interactions occurred for yield and lint percent. Yield, boll size, and micronaire also had significant SCA × L interactions. No significant GCA or SCA by L interactions were detected for fiber length, strength, and elongation. The mean mid-parent heterosis (MPH) of the 36 hybrids in lint yield was low in F2, but non-existent in F3. Among the nine parents, Pima S-7 and DP 340 had the highest and significant positive GCA effects for lint yield, lint percent, and boll weight across tests. Only several F2 hybrids with Pima S-7 and DP 340 as one parent displayed some levels of useful heterosis in lint yield in the two locations, as compared to Pima S-7 as the check. MPH for other agronomic and fiber quality traits was low to non-existent in both generations. The average GD of the parents were not significantly correlated with their GCA effects, and GD between parents was also not correlated with SCA and MPH of their hybrids, with the exception of lint yield at the Las Cruces location where a significant negative correlation was obtained. However, GD of the parents was correlated with the performance of hybrids in lint yield, fiber length, fiber strength and elongation in one or two tests. This study represented one of the first studies to estimate heterosis, combining ability, and their relationship with genetic distance of parents in a representative subset of Pima cotton genotypes.
Structural basis for the alternating access mechanism of the cation diffusion facilitator YiiP

YiiP is a dimeric antiporter from the cation diffusion facilitator family that uses the proton motive force to transport Zn2+ across bacterial membranes. Previous work defined the atomic structure of an outward-facing conformation, the location of several Zn2+ binding sites, and hydrophobic residues that appear to control access to the transport sites from the cytoplasm. A low-resolution cryo-EM structure revealed changes within the membrane domain that were associated with the alternating access mechanism for transport. In the current work, the resolution of this cryo-EM structure has been extended to 4.1 A. Comparison with the X-ray structure defines the differences between inward-facing and outward-facing conformations at an atomic level. These differences include rocking and twisting of a four-helix bundle that harbors the Zn2+ transport site and controls its accessibility within each monomer. As previously noted, membrane domains are closely associated in the dimeric structure from cryo-EM but dramatically splayed apart in the X-ray structure. Cysteine crosslinking was used to constrain these membrane domains and to show that this large-scale splaying was not necessary for transport activity. Furthermore, dimer stability was not compromised by mutagenesis of elements in the cytoplasmic domain, suggesting that the extensive interface between membrane domains is a strong determinant of dimerization. As with other secondary transporters, this interface could provide a stable scaffold for movements of the four-helix bundle that confers alternating access of these ions to opposite sides of the membrane.
Regional Anesthesia for the Acute Trauma Patient

This chapter reviews recent literature to describe the utility of regional analgesic techniques in the pre-hospital, emergency department, and perioperative management of acute pain in trauma. Peripheral nerve block (PNB) techniques were once rarely taught outside the discipline of anesthesiology. Some European health systems are beginning to offer pre-hospital PNB for selected trauma patients, particularly those with femur fractures. Although the safety profile of ultrasound versus landmark-guided techniques remains uncertain, broader ultrasound availability enables more rapid learning of PNB techniques and contributes to expansion beyond perioperative care. The acute emergency setting is an attractive time to offer PNB, providing early analgesia to avoid side effects of systemic sedatives and opioids, facilitating painful procedures, and potentially shortening time to discharge/transfer. Although acute pain after trauma is highly prevalent, studies to define outcome benefits of specific analgesic techniques are an area of ongoing inquiry. Numerous special considerations are necessary when selecting and performing PNB in trauma patients to optimize patient safety and clinical outcome.
Mathematics and Its History. By John Stillwell

(1991). Mathematics and Its History. By John Stillwell. The American Mathematical Monthly: Vol. 98, No. 6, pp. 569-574.
Thalamic Cortical Error–Related Responses in Adult Social Drinkers: Sex Differences and Problem Alcohol Use

Abstract Background Error-related brain activities are altered in individuals with substance use disorders. Here we examined error-related activities in relation to problem drinking in nondependent alcohol drinkers. In particular, we investigated sex differences and whether altered error responses are related to post-error behavioral control. Methods A sample of 145 nondependent drinkers (77 women) performed the stop-signal task during functional magnetic resonance imaging. Imaging data were processed and modeled using statistical parametric mapping. Independent sample t test and linear regression were employed to examine sex differences in error response and relationship between error response and problem drinking. Results Compared with men, women showed greater error-related (stop error > go success) activations in the bilateral thalamus, right middle/superior temporal cortex, and bilateral dorsal anterior cingulate cortex. In whole-brain linear regression of error responses against the Alcohol Use Disorders Identification Test score, a wide swath of cortical and subcortical regions, including the thalamus, showed decreased activation in association with problem drinking in women but not in men. However, men and women were not different in the extent of post-error slowing and decreased thalamic error response in association with problem drinking was not related to the extent of post-error slowing in women. Conclusions The results suggest sex differences in error-related activations with heavier drinking associated with reduced error activations in women but not in men. These differences in cerebral activations may reflect higher physiological arousal in response to errors and greater vulnerability of saliency-related arousal response to problem drinking in female as compared with male social drinkers.
Mass imprisonment and the extended family

This study employs microsimulation techniques to provide an accounting of exposure to imprisoned or formerly imprisoned kin. We characterize the risk and prevalence of imprisonment within full kinship networks and find that the life course trajectories of familial imprisonment experienced by black and white Americans take on qualitatively distinct forms: the average black American born at the height of the prison boom experienced the imprisonment of a relative for the first time at age 7 and by age 65 belongs to a family in which more than 1 in 7 working-age relatives have ever been imprisoned. By contrast, the average white American who experiences the imprisonment of a relative does not do so until age 39 and by age 65 belongs to a family in which 1 in 20 working-age relatives have ever been imprisoned. Future reductions in imprisonment rates have the potential to meaningfully reduce these racial disparities in family imprisonment burden.
Temporal evolution of biomedical research grant collaborations across multiple scales--a CTSA baseline study

The evolution of biomedical research grant collaborations (BRGC) across time (2006, 2009) and hierarchically related scales (Staff, Department) at the University of Arkansas for Medical Sciences (UAMS) is investigated using network abstractions. This baseline study is a part of the Clinical Translational Science Award (CTSA) efforts in promoting team science and exploring network science approaches for CTSA evaluation. The BRGC data were retrieved from the internally developed grants management system (Automated Research Information Administrator, ARIA). Our analysis revealed the BRGC networks to be disconnected with mutually exclusive research clusters. However, a dominant weakly-connected cluster with positively skewed degree centrality and betweenness distribution was observed across scales and time. Variation in the centrality measures, clustering coefficient, and the impact of perturbing the most-influential nodes as a function of time and scale is investigated. The results presented provide novel insights into the complex nature of BRGC networks that may persist across similar settings.
Geospatial Technologies and Homeland Security: Challenges and Opportunities

The acronym GIS can be decoded in three distinct ways: GISystems, GIScience, and GIStudies. This framework is used to provide an overarching synthesis, and to ask whether the chapters of the book provide a complete picture of geospatial issues and applications to homeland security. Three characteristics distinguish homeland security applications from other domains: the need for speed; the difficult environments in which technology must operate; and the impossibility of anticipating many relevant kinds of events in either space or time. One of the strongest factors impeding the effective use of geospatial technologies is lack of collaboration between institutions and the cultures of emergency response and GIS. The final section identifies four themes that are largely missing from this book, but nevertheless represent opportunities and challenges for the future.
Perspectives and experiences of adults who use AAC on making and keeping friends

Research on friendship consistently finds that individuals with disabilities, including those who use augmentative and alternative communication (AAC), have fewer friendships than individuals without disabilities, and that those friendships lack depth. Although the literature relating to the friendship experiences of individuals who use AAC is limited, some first-hand accounts written by individuals who use AAC describe positive interactions with friends and robust social networks. The purpose of this qualitative study was to explore the concept of friendship for individuals who use AAC from their own perspective. For the study, eight adults who used AAC participated in online interviews and focus groups to answer questions about friendship experiences. The research team identified patterns in the data and analyzed information according to the following themes: Definitions of Friendship, Factors Related to Self, Factors Related to Peers/Friends, Factors Related to the Environment, and Factors Related to Time. While many of the definitions and factors discussed could apply to any friendship, some factors specific to AAC and individuals who use AAC were identified. Implications for stakeholders relevant to the identified facilitating factors are discussed.
Abstract 3747: Translating the functional interactions of checkpoint kinase 2 and the androgen receptor into more effective therapies for the treatment of prostate cancer

Prostate cancer remains the most diagnosed cancer among men in the United States behind skin cancer, and advanced prostate cancer is the third leading cause of cancer-related deaths, with a 5-year survival rate of 26%. Radiation is the standard of care for the treatment of prostate cancer at the early and late stages. Checkpoint kinase 2 (CHK2) is a serine/threonine protein kinase whose main function is regulating the DNA damage response (DDR) induced by ionizing radiation. The androgen receptor (AR) is a major driver of prostate cancer, even at the castration-resistant stage of the disease. The development of the second-generation anti-androgen enzalutamide, which is a selective AR antagonist, highlights the enduring importance of the AR. We have previously demonstrated that CHK2 is a critical negative regulator of prostate cancer cell growth, androgen sensitivity, and AR transcriptional activity. We have now uncovered novel molecular interactions between CHK2 and AR that provide mechanistic insight into our observation that CHK2 regulates prostate cancer growth. The AR directly interacts with CHK2, and that interaction increases with radiation. We found that the interaction of CHK2 and AR occurs at sites of DNA damage. The binding of CHK2 with AR can be disrupted with CHK2 kinase inhibitors suggesting that the kinase activity of CHK2 is required. This was verified using kinase-impaired CHK2 variants, including the K373E variant associated with 4.2% of prostate cancer. Furthermore, the radiation-induced increase in CHK2-AR interactions requires AR phosphorylation on both serine 81 and serine 308. Interestingly, CHK2-depletion in LNCaP cells increases ionizing radiation induced AR expression and DNA damage. Together, these data provide the rationale for targeting the CHK2-AR signaling axis to improve the effectiveness of prostate cancer therapies. The combination of CHK2 or CDK1 inhibitors with androgen deprivation therapy (ADT) and radiation shows an additive effect on the repression of tumor cell growth. Nearly every patient with disseminated prostate cancer will relapse following ADT and develop incurable castration-resistant prostate cancer. We have uncovered the molecular details of a signaling axis involving CHK2 and AR that, when perturbed in combination with ADT and/or ionizing radiation, effectively inhibits prostate cancer cell growth. This may enable resensitization of castration-resistant prostate cancer to the currently approved treatment options. Citation Format: Huy Q. Ta, Natalia Dworak, Rosalie Sleppy, Jeffery A. Allende, Daniel Gioeli. Translating the functional interactions of checkpoint kinase 2 and the androgen receptor into more effective therapies for the treatment of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3747.
Enhancing simulation education using expired materials

Simulation centres are now a mainstream teaching venue in academic medical centres, and medical simulation training is now required in several residency programmes.1–3 Simulation centres have varying operating budgets from the startup ‘one room school house’ lab to the multimillion-dollar brick and mortar centre responsible for training thousands of students annually. Many centres around the world struggle to keep up with the needs of learners, especially as it relates to disposable materials utilised during simulation training. These materials can be very expensive and as many centres face increasing budgetary demands and cutbacks, the failure to acquire such materials limits the ability of faculty to offer the highest level of instruction. The USA produces between 2 and 4 million tons of medical waste annually, and a large portion of this is expired materials or single-use devices.4 5 The reutilisation of some of these medical supplies can help save on purchases for a simulation centre, while also helping to reduce the healthcare cost associated with incineration and landfill fees.4 Expired materials play a role in care delivery in low-resource settings. This has resulted in the WHO creating four guiding principles for use of old or unwanted supplies for donation in an effort to reduce the burden of inappropriate supplies on the receiving organisation.6 It is estimated that around 70% of equipment donated to low-income and middle-income countries is not suitable for the needs of the population.7 Simulation centre leadership must ensure that their centre’s vision, goals and objectives can be met within its current operating budget. Creative and strategic opportunities to acquire and utilise equipment must be identified by simulation leaders to meet the growing demands of students.8 Several strategies exist to keep budgets balanced, find additional materials and equipment, as well as leverage community resources not …
Preparation of Lipid Nanodiscs with Lipid Mixtures

Lipid nanodiscs provide a native-like lipid environment for membrane proteins, and they have become a valuable platform for the study of membrane biophysics. A range of biophysical and biochemical analyses are enabled when membrane proteins are captured in lipid nanodiscs. Two parameters that can be controlled when capturing membrane proteins in lipid nanodiscs are the radius, and hence the surface area of the lipid surface, and the composition of the lipid bilayer. Despite their emergence as a versatile tool, most studies with lipid nanodiscs in the literature have focused on nanodiscs of a single radius with a single lipid. In light of the complexity of biological membranes, it is likely that nanodiscs with multiple membrane components would be more sophisticated models for membrane research. It is possible to prepare nanodiscs with more complex lipid mixtures to probe the effects of lipid composition on several aspects of membrane biochemistry. Detailed protocols are described here for the preparation of nanodiscs with mixtures of phospholipids, incorporation of cholesterol, and incorporation of a spectroscopic lipid probe. These protocols provide starting points for the construction of nanodiscs with more physiological membrane compositions or with useful biophysical probes. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Assembly of mixed lipid nanodiscs Basic Protocol 2: Assembly of nanodiscs with cholesterol Basic Protocol 3: Incorporation of laurdan into nanodiscs for membrane fluidity measurements.
Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology

Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between ALDH2*2 mutation and Alzheimer’s Disease (AD). Other studies have linked chronic alcohol consumption as a risk factor for AD. In the present study, we show that fibroblasts of an AD patient that also has an ALDH2*2 mutation or overexpression of ALDH2*2 in fibroblasts derived from AD patients harboring ApoE e4 allele exhibited increased aldehydic load, oxidative stress, and increased mitochondrial dysfunction relative to healthy subjects and exposure to ethanol exacerbated these dysfunctions. In an in vivo model, daily exposure of WT mice to ethanol for 11 weeks resulted in mitochondrial dysfunction, oxidative stress and increased aldehyde levels in their brains and these pathologies were greater in ALDH2*2/*2 (homozygous) mice. Following chronic ethanol exposure, the levels of the AD-associated protein, amyloid-β, and neuroinflammation were higher in the brains of the ALDH2*2/*2 mice relative to WT. Cultured primary cortical neurons of ALDH2*2/*2 mice showed increased sensitivity to ethanol and there was a greater activation of their primary astrocytes relative to the responses of neurons or astrocytes from the WT mice. Importantly, an activator of ALDH2 and ALDH2*2, Alda-1, blunted the ethanol-induced increases in Aβ, and the neuroinflammation in vitro and in vivo. These data indicate that impairment in the metabolism of aldehydes, and specifically ethanol-derived acetaldehyde, is a contributor to AD associated pathology and highlights the likely risk of alcohol consumption in the general population and especially in East Asians that carry ALDH2*2 mutation.
Effect of modified atmosphere packaging (MAP) and NatureSeal® treatment on the physico-chemical, microbiological, and sensory quality of fresh-cut d’Anjou pears

Abstract Modified atmosphere packaging (MAP) is used to preserve the quality and shelf life of fruits and vegetables. The present study was undertaken with the objective of applying MAP in combination with 2 % NatureSeal and evaluating the following quality attributes during 21-d storage at 4 °C: headspace CO2 and O2, color, total soluble solids (TSS), pH, titratable acidity (TA), bacteria and yeast plus mold loads. Sensory quality was assessed after 10 days. The headspace CO2 level in MAP samples increased significantly, reaching 35.3 % at the end of storage; while O2 decreased significantly. Color values were affected by MAP, with no changes in Hunter L and a values, which decreased and increased, respectively, only in the control. Whereas, a values increased for both the control and MAP, but the increases were significantly higher in the control from day 7 to 21. MAP also preserved the sensory quality of fresh-cut pears evaluated on day-10.
PRE-HOSPITAL USE OF CPR-ASSIST DEVICES AND RETURN OF SPONTANEOUS CIRCULATION: NATIONWIDE EXPERIENCE FROM THE NEMSIS DATABASE

There are approximately 320,000 annual Out-of-Hospital Cardiac Arrests (OHCA) in the US with a 3-22% survival to discharge. Emergency Medical Services (EMS) are often the first line response to an OHCA and use a variety of CPR assist devices based on resources, availability, and local training
Leveling of a model paint film with a yield stress

The coating dynamics of a drying paint film with a yield stress is studied. The liquid is modeled as a binary mixture with one volatile component, solvent, and one nonvolatile component, resin. When the solvent has a different surface tension than the resin, solvent evaporation can lead to the creation of surface tension gradients which can potentially overcome the yield stress and dramatically affect the flow history. Using the lubrication approximations to derive the flux of the liquid film parallel to the substrate, we find that the presence of the yield stress causes several distinct flow regimes. The total flux of each of these regimes is summed, and using the continuity equation we derive an evolution equation giving the height of the free surface as a function of the distance along the substrate and time. The resulting equations are discretized and solved numerically using finite differences. High order derivative is treated implicitly, allowing for large time steps and reducing the computational requirements. We find that the presence of a yield stress greatly affects the leveling behavior of the coating. Critical yield stresses exist that can cause maximal leveling of the coating film.
Using Performances in a Flipped Classroom Setting.

The purpose of this study is to explain how performances are used within a flipped classroom environment in a university educational psychology class. This instructional approach also incorporates the concept of “integrated assessment” where assessment and instruction are intimately connected. Examples of student-led instruction using performances are provided. Results of a teacher-developed assessment administered during the past several years to elicit student evaluations of these instructional practices have provided evidence that using this instructional approach is effective for most but not all students.