cssi/SciSciGPT-SciSciNet huggingface dataset:
Prohormone processing in the trans-Golgi network: endoproteolytic cleavage of prosomatostatin and formation of nascent secretory vesicles in permeabilized cells

Many peptide hormones are synthesized as larger precursors which undergo endoproteolytic cleavage at paired basic residues to generate a bioactive molecule. Morphological evidence from several laboratories has implicated either the TGN or immature secretory granules as the site of prohormone cleavage. To identify the site where prohormone cleavage is initiated, we have used retrovirally infected rat anterior pituitary GH3 cells which express high levels of prosomatostatin (proSRIF) (Stoller, T. J., and D. Shields. J. Cell Biol. 1988. 107:2087-2095). By incubating these cells at 20 degrees C, a temperature that prevents exit from the Golgi apparatus, proSRIF accumulated quantitatively in the TGN and no proteolytic processing was evident; processing resumed upon shifting the cells back to 37 degrees C. After the 20 degrees C block, the cells were mechanically permeabilized and pro-SRIF processing determined. Cleavage of proSRIF to the mature hormone was approximately 35-50% efficient, required incubation at 37 degrees C and ATP hydrolysis, but was independent of GTP or cytosol. The in vitro ATP-dependent proSRIF processing was inhibited by inclusion of chloroquine, a weak base, CCCP, a protonophore, or by preincubating the permeabilized cells with low concentrations of N-ethylmaleimide, an inhibitor of vacuolar-type ATP-dependent proton pumps. These data suggest that: (a) proSRIF cleavage is initiated in the TGN, and (b) this reaction requires an acidic pH which is facilitated by a Golgi-associated vacuolar-type ATPase. A characteristic feature of polypeptide hormone-producing cells is their ability to store the mature hormone in dense core secretory granules. To investigate the mechanism of protein sorting to secretory granules, the budding of nascent secretory vesicles from the TGN was determined. No vesicle formation occurred at 20 degrees C; in contrast, at 37 degrees C, the budding of secretory vesicles was approximately 40% efficient and was dependent on ATP, GTP, and cytosolic factors. Vesicle formation was inhibited by GTP gamma S suggesting a role for GTP-binding proteins in this process. Vesicle budding was dependent on cytosolic factors that were tightly membrane associated and could be removed only by treating the permeabilized cells with high salt. After high salt treatment, vesicle formation was dependent on added cytosol or the dialyzed salt extract. The formation of nascent secretory vesicles contrasts with prosomatostatin processing which required only ATP for efficient cleavage. Our results demonstrate that prohormone cleavage which is initiated in the TGN, precedes vesicle formation and that processing can be uncoupled from the generation of nascent secretory vesicles.
Certainty, uncertainty, and climate change

Despite the continued efforts of skeptics motivated by a desire for attention or short-term economic interests (Oreskes and Conway 2010), we can be certain about a number of basic facts: human activities have resulted in dramatic increases in the atmospheric concentration of carbon dioxide and a number of other greenhouse gasses; those increased concentrations are changing the climate and will continue to do so; one of those changes will be average warming on a planetary scale. Another unambiguous consequence of rising atmospheric concentrations of carbon dioxide will be the continued acidification of the world’s oceans, which are already 30% more acidic today than they were in pre-industrial times. While we still do not understand all the details of the physics, we can also be certain that factors such as clouds and water vapor, aerosol loadings, the extent of ice cover, and the strength of ocean circulation all play a key role in shaping the climate of today and of the future. In its periodic reviews, the IPCC routinely discusses and provides consensus judgments about the nature and extent of scientific uncertainty about these and other factors. Thanks largely to the work of Moss and Schneider (2000) these discussions are no longer couched only in terms of general uncertainty words such as “likely” or “unlikely.” Indeed, the climate science community has made more progress in understanding the importance of linking such words to quantitative statements about probability ranges than has any other community I know that is engaged in performing scientific assessments. Climatic Change (2011) 108:707–721 DOI 10.1007/s10584-011-0184-8
Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats

1. The consequences of extended exposure to the human immunodeficiency viral protease inhibitor ritonavir (RIT) on the expression and function of CYP3A isoforms in the liver and in enteric mucosal cells, and on the expression of the efflux transport protein P-glycoprotein (P-gp) in enteric mucosa and in brain microvessel endothelial cells, were evaluated in rat. Dexamethasone (DEX), a known inducer of CYP3A and P-gp in rodents, served as a positive control. 2. Male CD-1 rats received RIT (20 mg kg(-1)), DEX (80 mg kg(-1)) or vehicle by oral/duodenal gavage once daily for 3 days. 3. Compared with vehicle control, CYP3A activity in liver microsomes (intrinsic clearance for triazolam hydroxylation in vitro) was increased by a factor of 2-4 by RIT, and by 10-14-fold by DEX. Similar increases were observed in expression of immunoactive CYP3A protein. Overall, maximum reaction velocity and immunoactive protein were highly intercorrelated (r2 = 0.89). Both RIT and DEX also increased function and expression of enteric CYP3A, although to a more modest extent (about 1.7-fold for RIT, about 3.3-fold for DEX). 4. Enteric P-gp expression was equally induced (by 2.8-fold) by both RIT and DEX. P-gp expressed in brain microvessel endothelial cells was increased by a factor of 1.3 by both compounds. 5. Thus, increased expression of CYP3A isoforms and of P-gp occurs with 3 days of exposure to RIT in rats. Qualitatively similar changes occur in human cell culture models and in clinical studies, and might contribute to drug interactions involving RIT (and other antiretroviral agents) in humans.
Genome Engineering at the Dawn of the Golden Age

Genome engineering—the ability to precisely alter the DNA information in living cells—is beginning to transform human genetics and genomics. Advances in tools and methods have enabled genetic modifications ranging from the “scarless” correction of a single base pair to the deletion of entire chromosomes. Targetable nucleases are leading the advances in this field, providing the tools to modify any gene in seemingly any organism with high efficiency. Targeted gene alterations have now been reported in more than 30 diverse species, ending the reign of mice as the exclusive model of mammalian genetics, and targetable nucleases have been used to modify more than 150 human genes and loci. A nuclease has also already entered clinical trials, signaling the beginning of genome engineering as therapy. The recent dramatic increase in the number of investigators using these techniques signifies a transition away from methods development toward a new age of exciting applications.
Emotional challenges of adult learners in higher education

Through acts of hope, adults face four challenges of emotion in their pursuits of collegiate learning.
The attitude control problem

A general framework for the analysis of the attitude tracking control problem for a rigid body is presented. A large family of globally stable control laws is obtained by using the globally nonsingular unit quaternion representation in a Lyapunov function candidate whose form is motivated by the consideration of the total energy of the rigid body. The controllers share the common structure of a proportional-derivative feedback plus some feedforward which can be zero (the model-independent case), the Coriolis torque compensation, or an adaptive compensation. These controller structures are compared in terms of the requirement on the a priori model information, guaranteed transient performance, and robustness. The global stability of the Luh-Walker-Paul robot end-effector controller is also analyzed in this framework. >
Activation of Mitogen-Activated Protein Kinases and AP-1 Transcription Factor in Ovotoxicity Induced by 4-Vinylcyclohexene Diepoxide in Rats

Abstract Previous studies have demonstrated that ovotoxicity induced in small preantral (primordial and primary) ovarian follicles by 4-vinylcyclohexene diepoxide (VCD) in rats is likely via acceleration of the normal process of atresia (apoptosis). This acceleration is associated with increased activities of caspase cascades, changes in subcellular distribution of Bcl-2 family members, and alteration of estrogen receptor-mediated signaling pathways. The present study was designed to investigate possible effects of VCD dosing on the mitogen-activated protein kinases (MAPK)/AP-1 signaling pathways in rat ovarian small follicles. Female F344 rats were given a single dose of VCD (80 mg/kg i.p., 1 day—a time when ovotoxicity has not been initiated) or dosed daily for 10 or 15 days (80 mg/kg i.p.; 10 days—a time when the earliest signs of impending follicular destruction is seen, 15 days—a time when significant ovotoxicity is underway). Four hours following the final dose, ovaries and livers were collected. Ov...
Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody

Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules.
Low and high melatonin excretors among healthy individuals

To meet the need of establishing firm normative data regarding the secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy volunteers was measured in samples collected monthly over a period of 1 year. Low melatonin excretors (N = 8) were distinguished from high melatonin excretors (N = 8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap in any of the monthly melatonin values between the two groups, while their annual rhythms of melatonin excretion were not different in shape. Since no obvious factors (age, sex, height, weight, etc.) were responsible for the observed differences, the distinction between low and high nocturnal excretion and by inference secretion of melatonin most likely reflects genetically determined variable levels of the noradrenergic secretory drive and/or variable N-acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the night.
Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity.

We investigated the biochemical profile of regenerated venom of the scorpion Parabuthus transvaalicus in relation to its metabolic cost and toxicity. Using a closed-system respirometer, we compared oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 192 h of subsequent venom synthesis. Milked scorpions had a substantially (21%) higher mean metabolic rate than unmilked scorpions, with the largest increases in oxygen consumption occurring at approximately 120 h, 162 h, and 186 h post-milking. Lethality tests in crickets indicated that toxicity of the regenerated venom returned to normal levels within 4 d after milking. However, the chemical profile of the regenerated venom, as evaluated by FPLC and MALDITOF mass spectrometry, suggested that regeneration of different venom components was asynchronous. Some peptides regenerated quickly, particularly those associated with the scorpion’s “prevenom,” whereas others required much or all of this time period for regeneration. This asynchrony could explain the different spikes detected in oxygen consumption of milked scorpions as various peptides and other venom components were resynthesized. These observations confirm the relatively high metabolic cost of venom regeneration and suggest that greater venom complexity can be associated with higher costs of venom production.
Mother or Wife? An African Dilemma Tale and the Psychological Dynamics of Sociocultural Change

Inspired by “Mother or Wife” African dilemma tales, the present research utilizes a cultural psychology perspective to explore the dynamic, mutual constitution of personal relationship tendencies and cultural-ecological affordances for neoliberal subjectivity and abstracted independence. We administered a resource allocation task in Ghana and the United States to assess the prioritization of conjugal/nuclear relationships over consanguine/kin relationships along three dimensions of sociocultural variation: nation (American and Ghanaian), residence (urban and rural), and church membership (Pentecostal Charismatic and Traditional Western Mission). Results show that tendencies to prioritize nuclear over kin relationships – especially spouses over parents – were greater among participants in the first compared to the second of each pair. Discussion considers issues for a cultural psychology of cultural dynamics.
ATP depletion stimulates calcium-dependent protein breakdown in chick skeletal muscle

The contribution of metabolic energy to the degradation of intracellular proteins in skeletal muscle was investigated. Isolated chick skeletal muscles deprived of oxygen and muscles incubated in bu...
Nucleoside diphosphokinase : a functional link between intermediary metabolism and nucleic acid synthesis

Publisher Summary This chapter discusses the functional link between intermediary metabolism and nucleic acid synthesis. Nucleoside diphosphokinase plays a pivotal role in metabolism, as it catalyzes the predominant reaction in synthesizing all but one of the eight common ribo- and deoxyribonucleoside triphosphates. The large DNA virus, on infection of E. coli , causes the rate of DNA synthesis to increase about 10-fold relative to the preinfection rate. This is necessary because of the large size of the genome and the rapid rate of reproduction of the virus. By use of affinity chromatography with an immobilized enzyme as the ligand, specific interactions between T4 dCMP hydroxymethylase and several replication proteins were demonstrated.
STUDIES ON INFLAMMATION : V. THE MECHANISM OF FIXATION BY THE INFLAMMATORY REACTION.

Microscopic studies show the presence of a network of fibrin within the tissues and numerous thrombosed lymphatics at the site of inflammation. Precipitated iron compounds, possibly coagulated horse serum, or particulate matter caught in this fibrinous reticulum will disseminate less readily than trypan blue from the site of inflammation. Trypan blue injected at the periphery of an inflamed area fails to enter the site of inflammation. This failure of penetration is caused by the occlusion of lymphatic vessels and by the presence of a fine network of fibrin in the tissue spaces of the inflamed area. Fixation of foreign substances by the inflammatory reaction is therefore primarily due to mechanical obstruction caused by a network of fibrin and by thrombosed lymphatics at the site of inflammation. There is another phase of the problem which still requires more accurate information. This concerns the relation between exudation from blood vessels and changes in flow of lymph from the inflamed area. Further experiments are being conducted to investigate this question. The reaction of fixation which occurs extremely early in the inflammatory process circumscribes the irritating substance and allows a definite period of time for the leucocytes to assemble for the purpose of phagocytosis. It is through a delicate regulating mechanism of this kind that, to use the expression of Opie (7), "the vital organs are protected at the expense of local injury."
The Fall: Aligning The Best Care With Standards Of Care At The End Of Life

When her mother is hurt, a health care executive finds that the standardized care she championed isn’t always appropriate.
Supervised Sentence Fusion with Single-Stage Inference

Sentence fusion—the merging of sentences containing similar information— has been shown to be useful in an abstractive summarization context. We present a new dataset of sentence fusion instances obtained from evaluation datasets in summarization shared tasks and use this dataset to explore supervised approaches to sentence fusion. Our proposed inference approach recovers the highest scoring output fusion under an n-gram factorization using a compact integer linear programming formulation that avoids cycles and disconnected structures. In addition, we introduce simple fusion-specific features and constraints that outperform a compression-inspired baseline as well as a variant that relies on human-identified concept spans for perfect content selection.
Principal theories of practice: Mapping the cognitive structure and effects of instructional leadership

PRINCIPAL THEORIES OF PRACTICE: MAPPING THE COGNITIVE STRUCTURE & EFFECTS OF INSTRUCTIONAL LEADERSHIP Gary W. Houchens May 12, 2008 This dissertation builds on the work of Argyris and Schon (1974), who explained patterns of organizational learning using a concept called theories of practice, cognitive formulas for professional problem solving. Theories of practice consist of deeply held assumptions that logically imply certain action strategies. Argyris and Schon hypothesized that by engaging in deep reflection on assumptions and action strategies, professionals could develop more effective theories of practice based on alternate assumptions and action strategies. This dissertation explores the instructional leadership theories of practice of four successful school principals using a naturalistic, qualitative, multi-case design. Data gathering methods included interviews, observations, and a written reflective exercise completed by principals. The researcher used constant comparative analysis to categorize data until the theories of practice for each principal emerged. Three research questions framed the study. The first question identified the principals’ instructional leadership theories of practice. Findings revealed that these principals used three to six theories of practice based on strong moral and utilitarian assumptions regarding the inherent dignity and worth of both teachers and students, and the positive academic effects of recognizing and affirming that worth. Action strategies included building positive relationships, inviting teacher input, fostering collaboration, unifying staff around a common mission, and encouraging continuous teacher professional growth. The second research question investigated the effect of principal theories of practice on teachers. Teachers from the case study schools reported that principal theories of practice affected them in a variety of positive ways, including higher levels of job satisfaction and motivation, strong affiliation with the school, and a sense of personal responsibility for student outcomes. The third research question explored the extent to which principals engaged reflection on their practice. Findings were limited to only two examples: (a) principals engaged in double-loop learning by developing “special case” theories of practice for correcting underperforming teachers who failed to respond to the principals’ preferred methods of leadership, and (b) by learning from feedback to place more emphasis on inviting teacher input. The final chapter discusses the study’s implications for principal preparation programs, school districts, policy makers, and principal professional development.
Response of the magnocellular system in rats to hypovolemia and cholecystokinin during pregnancy and lactation

To define changes in the magnocellular neuroendocrine system during lactation and pregnancy, we compared plasma levels of oxytocin (OT) and vasopressin (VP) after polyethylene glycol (PEG)-induced hypovolemia and cholecystokinin (CCK) stimulation. Conscious virgin, pregnant (day 20), and lactating (day 6) Sprague-Dawley rats were injected with either PEG (70-600 mg/ml; 35 or 70 ml/kg sc), CCK (100 micrograms/ml; 4 ml/kg ip), or vehicle and decapitated 4 h (PEG) or 5 min (CCK) later. Changes in thresholds for release of hormone and the responsiveness (slopes relating [hormone] to blood volume depletion or to plasma osmolality) of the OT and VP systems were determined using an iterative nonlinear threshold regression model. After PEG, plasma osmolality increased coincident with a decrease in blood volume, with both stimuli contributing to the rise in plasma VP and OT. Compared with virgin rats, neither the threshold nor the responsiveness of the VP system was altered by the combined stimulus, whereas the oxytocinergic system of pregnant rats was more responsive to osmotic component. Lactating rats, however, had a higher threshold for VP release and an apparent elevation of the OT threshold beyond 25% volume depletion. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT. Intraperitoneal CCK elevated plasma [OT] in each reproductive state, although the response in lactating animals was attenuated. In virgin and lactating rats, plasma levels of VP also increased slightly but significantly in response to CCK. During gestation when cardiovascular volume is expanded, both the VP and OT neuroendocrine systems were reset, enabling secretion of both hormones in response to hypovolemia with hypertonicity. During lactation, both neuroendocrine systems are reset such that greater changes in fluid balance are needed to stimulate hormone release. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT, indicative of preferential release of VP with less than a 5% (virgin, pregnant) or a 20% (lactating) loss in blood volume.
Bahinabai and the Devoted Wife: To Affirm is to Question

ABSTRACTThe Indian saint Bahinabai (c. 1628–1700) became known to an Anglophone audience largely through A.K. Ramanujan's well-known essay, ‘On Women Saints’. As Ramanujan notes, Bahinabai's life diverges from the standard trajectory of Hindu women saints insofar as she did not reject her husband and family. However, her external conformity to the rules for women contrasts with her literary subversion of normative gender roles. I examine Bahinabai's autobiographical narrative, the Atmacharitra, to demonstrate that she claims spiritual rights for women by undermining the Brahmanical ideal of the devoted wife or pativrata. A rare example of pre-modern women's writing from South Asia, the Atmacharitra illustrates some of the diverse strategies Indian women have employed to circumvent the strictures against feminine self-expression.
How Affordable Is HUD Affordable Housing

AbstractThis article assesses the affordability of U.S. Department of Housing and Urban Development (HUD) rental assistance properties from the perspective of transportation costs. HUD housing is, by definition, affordable from the standpoint of housing costs due to limits on the amounts renters are required to pay. However, there are no such limitations on transportation costs, and common sense suggests that renters in remote locations may be forced to pay more than 15% of income, a nominal affordability standard, for transportation costs. Using household travel models estimated with data from 15 diverse regions around the United States, we estimated and summed automobile capital costs, automobile operating costs, and transit fare costs for households at 8,857 HUD rental assistance properties. The mean percentage of income expended on transportation is 15% for households at the high end of the eligible income scale. However, in highly sprawling metropolitan areas, and in suburban areas of more compact me...
5′ CAP methylation of homologous poly A(+) RNA by a RNA (guanine-7) methyltransferase from Neurosporacrassa

Abstract RNA (guanine-7) methyltransferase, partially purified from N. crassa mycelia, catalyzed the transfer of the methyl group from S-adenosylmethionine to the 5′ terminus of both N. crassa poly A(+) RNA and reovirus unmethylated mRNA. RNase T2 digestion of the in vitro methylated poly A(+) RNA from N. crassa yielded the “cap” structures m 7G(5′)pppAp and m 7G(5′)pppGp in a ratio of 2:1 respectively. RNase T2 digestion of the in vitro methylated reovirus mRNA yielded m 7G(5′)pppGp exclusively. The absence of mRNA 2′-0-methyltransferase activity in the enzyme preparation is consistent with the absence of 2′-0-methylation in N. crassa mRNA [Seidel, B. L. and Somberg, E. W. (1978) Arch. Biochem. Biophys. 187 , 108–112]. This is the first isolation of an eucaryotic, cellular RNA (guanine-7) methyltransferase that has been shown to methylate homologous substrate.
A Survey on the Isolation Status of Hand- Foot- Mouth Disease and Influenza in Children

Objective To investigate the isolation status of hand- foot- mouth disease and influenza in children,and try to understand its related factors. Methods Children cases of hand- foot- mouth disease( HFMD) and influenza which were reported in China Information System for Disease Control and Prevention between August and October of 2012 in Zhejiang province were randomly selected,questions on isolation,health habits,family and community health environment,and disease burden were asked through telephone survey. Risk factors between isolated group and non- isolated group were analyzed. Results A total number of 541 questionnaires were collected,with the response rate of 91. 23%. The proportion of being- required isolation was higher in isolated group than that in non-isolated group for both HFMD and influenza( all P 0. 01). For HFMD,compared to the non- isolated group,the isolated group had more children in kindergarten and primary schools,and bore greater burdens of treatment costs and parents work take- off. For influenza,the isolated group had greater economic losses because of parents work take- off with 7days comparing the non- isolated group( 1day).Conclusion The isolation rate for hand- foot- mouth disease and children influenza were low,the cost of isolation was relative higher,and whether the case was requested isolation by doctors was the main risk factor.
Spatial differences in trace element bioaccumulation in turtles exposed to a partially remediated coal fly ash spill

Large-scale releases of environmental contaminants from industrial facilities can cause considerable damage to surrounding ecosystems and require remediation. The expense and/or undesirable environmental side effects of physical removal may constrain remediation efforts. In 2008, approximately 4.1 million m3 of fly ash were released into the Emory River at a coal-burning power plant in Kingston, Tennessee, USA. Approximately 390 000 m3 of fly ash were not removed (hereafter “residual ash”), to avoid disturbing underlying legacy contamination from unrelated historical industrial activity. In 2011 and 2012, the authors measured trace element concentrations in an assemblage of freshwater turtles in 2 rivers impacted by the spill and in a third river that was unaffected. Concentrations of arsenic, copper, iron, mercury, manganese, selenium, and zinc were higher in turtles from rivers affected by the spill but low relative to concentrations known to be toxic to other vertebrates. Concentrations of some trace elements decreased with distance from the original spill site but were not strongly affected by nearby volumes of residual ash. Among-species differences in trace element bioaccumulation and/or the relatively low spatial resolution of available data on residual ash volumes may have obscured this effect. The results suggest that the spill influenced turtle bioaccumulation of trace elements but that distance from the spill site may be a more important factor than residual ash in influencing postremediation bioaccumulation. Environ Toxicol Chem 2017;36:201–211. © 2016 SETAC
Between the Sheets: Inter-Subunit Backbone Interactions at AChR Neurotransmitter Binding Sites

The two neuromuscular AChR agonist-binding pockets are sandwiched between β-structures of α and e/δ/γ subunits. Within the global, channel-opening gating isomerization, a low-to-high affinity change for the agonist at each site serves to increase PO. There are two conserved, vicinal prolines at the end strand β5’ in each non-α subunit. We used single-channel electrophysiology to estimate energy changes caused by mutations here (γP120 and γP121), with regard to unliganded gating and the affinity change. For both prolines, all mutations had little or no effect on constitutive activity in all subunits. AFLR mutations of the first proline had no effect on the affinity change for ACh in e and δ subunits, but a modest effect in γ. At γP121, R and L substitutions had a large effect on the affinity change (>+3kcal/mol) but AGY were off less consequence (for all mutations the effect was smaller for choline than for ACh). Mutant cycle analyses were used to measure free energy coupling regarding the affinity change for ACh between γP121 and other residues near the binding pocket. γP121A interacts strongly with αG147A (strand β7) and αY198A (strand β10), modestly with αW149A (loop B) and αY190A (loop C) and not at all with αY93A (loop A) and αG153A (loop B). There was no coupling between γP121A and its neighbor γW55A (strand β1). The results suggest that strand β5’ in the γ subunit interacts with strands β7 and β10 in the α subunit, but less-so with residues in flexible loops that nonetheless influence affinity. Our working hypothesis is that β strands of the α and non-α subunits exchange energy during the affinity change for the agonist.
Focus on Middle School: Using Inquiry-Based Learning to Keep Students Engaged and Learning in All Content Areas

According to the National Assessment of Educational Progress (NAEP, 2009, 2013), the majority of students in 8th grade are identified as less than proficient. These students tend to have a negative...
Lifelong quercetin enrichment and cardioprotection in Mdx/Utrn+/− mice

The current investigation provides first time evidence that quercetin provides physiological cardioprotection against dystrophic pathology and is associated with improved spontaneous physical activ...
A Review of Settler Identity and Colonialism in 21st Century Canada , by Emma Battell Lowman and Adam J. Barker

A Review of Battell Lowman, E., & Barker, A. J. (2015). Settler identity and colonialism in 21st century Canada. Halifax, NS: Fernwood Publishing.
Is prostate cancer stage migration continuing for black men in the PSA era

In the United States, disease-specific mortality from prostate cancer (PC) is highest among black men. While the introduction of widespread PSA testing has been associated with a downward stage migration, whether this trend continues in the late PSA era and for black men is unknown. The objective of our study was to evaluate current PC stage migration patterns in the United States by race. The Surveillance, Epidemiology and End Results (SEER) registry was queried to obtain all cases of PC reported between 2000 and 2013. Year of diagnosis was categorized into 2000–2003, 2004–2007, 2008–2010 and 2011–2013. Predictors of distant stage PC at diagnosis were determined using logistic regression adjusted for year of diagnosis, age at diagnosis, SEER region and race. A total of 791 184 PC cases were identified. The cohort comprised 78.9% (n=594 920) white and 14.1% (n=106 133) black men. The stage at diagnosis was 83.3% localized, 12.0% regional and 4.7% distant. Age-adjusted incidence demonstrated a steady decline for black men in all time groups while white men had a stable incidence of distant disease between 2000 and 2013. In univariate analysis, black men in the 2004–2007 (OR 0.86 (0.81–0.93)) and 2008–2010 cohorts (OR 0.85 (0.79–0.91)) were less likely to be diagnosed with metastatic PC as compared with the 2000–2003 baseline cohort. In multivariate analysis, the 2004–2007 black cohort was less likely to be diagnosed with distant PC (OR 0.90 (0.84–0.97)). This trend was not observed in white men who in multivariate analysis had an increased risk of distant PC in the 2004–2007 (OR 1.08 (1.04–1.11)), 2008–2010 (OR 1.22 (1.18–1.27)) and 2011–2013 (OR 1.65 (1.59–1.71)) groups. PC downward stage migration continues in black men but not in white men. Discontinuation of PSA-based screening for PC could disproportionately affect black men.
Thermal-Mechanical Model of Depression Formation in Steel Continuous Casting

Many serious defects in the continuous casting of steel, including surface cracks and depressions, are related to thermal-mechanical behavior during solidification in the mold. A finite-element model has been developed to simulate the temperature, stress, and shape of the steel shell near the strand surface, as it moves down the mold at the casting speed in a state of generalized plane strain. The thermal model simulates transient heat transfer in the solidifying steel and between the shell and the mold wall. It is coupled with a stress model that features temperature-, composition-, and phase-dependent thermal-elastic-visco-plastic constitutive behavior of the steel. Depressions are predicted to form when the shell is subjected to either excessive compression or tension, but the shapes differ. Predicted depression shapes are compared with previous plant observations. The model reveals new insights into the mechanisms of surface depressions and longitudinal cracks in this process.
Patterns and Interpretation

Franco Moretti, Danily C. and Laura Louise Bell Professor in the Humanities, Stanford University. Video recording of lecture presented on January 24, 2017, at Presidents Hall, Franklin Hall, Indiana University Bloomington.
Comprehensive epigenetic analysis of Notch pathway in high-grade serous ovarian cancer

Objectives Gene methylation and other epigenetic modifications of gene regulation have been implicated in the growth of ovarian cancer, but the clinical significance of such modifications in the Notch pathway in high-grade serous ovarian cancer (HGS-OvCa) is not well understood. We used The Cancer Genome Atlas (TCGA) data to study the clinical relevance of epigenetic modifications of Notch pathway genes.
Measuring the Digital and Media Literacy Competencies of Children and Teens

Because media literacy has been described as a “constellation of competencies,” diverse approaches have been used to measure it. Media literacy education includes the paradigms of empowerment and protection, which are used to conceptualize the potential benefits and risks of growing up in a media-saturated society. Performance- or competency-based measures examine the ability to critically analyze and/or create media, whereby learners engage in the practice of evaluating the message content, format, and techniques used to attract and hold attention. For example, in self-report measures, learners rate or agree with various statements that reflect attitudes, knowledge, or behaviors. Each approach to measuring media literacy competencies embodies core values in relation to a particular set of goals, contexts, and situations. Research is emerging that examines the intersection of cognitive and affective domains and the role of teacher motivations in shaping the learning outcomes and opening new opportunities to advance the field.
Chiari 1000 Registry Project: assessment of surgical outcome on self-focused attention, pain, and delayed recall.

Background Prior research has typically found a negative relationship between chronic pain and memory, and we examined whether cognitive control processes (e.g. reflection and rumination) moderated this relationship in individuals with Chiari malformation Type I (CM). CM is a neurological condition in which the cerebellar tonsils descend into the medullary and upper cervical spine regions potentially resulting in severe headaches and neck pain. Methods CM patients who had (n = 341) and had not (n = 297) undergone decompression surgery completed the McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ). Immediate recall scores were compared to those of 102 healthy controls, and delayed recall performance was compared across other variables within the CM group. Results CM patients performed more poorly on immediate recall than did controls. Within CM patients, we observed main effects for reflection and age, and a pain x reflection x surgical status (surgery v. no surgery) interaction in which non-decompressed individuals with low levels of pain and high levels of reflection showed superior delayed recall relative to non-decompressed individuals with higher pain and all decompressed individuals. Conclusions CM patients show an immediate recall deficit relative to controls, regardless of surgical status. High levels of reflection were associated with better delayed recall performance in non-decompressed CM patients with lower pain levels. High levels of chronic pain may overwhelm increased focused attention abilities, but higher levels of reflection partially overcome the distracting effects of pain and this may represent a type of resilience.
Patterns of Adolescent Aggression and Victimization: Sex Differences and Correlates

ABSTRACTThis study identified heterogeneous patterns of peer and dating aggression and victimization among boys and girls and examined their relation to risk and protective correlates. Girls (n = 1...
Bring the Real-World Digital Marketing Experience to Classroom: Google Online Marketing Challenge

Experiential learning is a process of learning through experience and reflection. It is different from the traditional didactic learning, in which students read or are told about others' experiences of the subject. In many university classrooms, faculty members have incorporated hands-on projects to stimulate learning experience. However, experience doesn't always lead to experiential learning. A well-designed experiential learning can produce benefits such as 1) enhancing deep learning, 2) ensuring engagement, and 3) developing employable skills. The students who enrolled in an advanced e-Commerce course participated in the Google Online Marketing Challenge (GOMC), in which each team used $250 provided from Google on helping small business clients to promote their businesses. Incorporating the GOMC project in class produced the aforementioned benefits of experiential learning. The experiential learning activity seems to be a promising pedagogy to engage students and prepare them to be the future workforce of fashion marketing and branding in this Internet era.
The design, performance, and analysis of slug tests

Introduction The Slug Test-What Is It? Why Is It So Prevalent? But Skepticism Abounds... Purpose of this Book Outline A Short Word on Terminology The Design of Slug Tests Chapter Overview Well Construction Well Development Verification of Conventional Theory Design Guidelines The Performance of Slug Tests Chapter Overview Slug-Test Equipment Test Initiation Degree of Head Recovery Performance Guidelines Pre-analysis Processing Chapter Overview Pre-analysis Data Processing Pre-analysis Processing Guidelines The Analysis of Slug Tests-Confined Formations Chapter Overview Theoretical Models for the Analysis of Response Data Slug Tests in Confined Formations The Analysis of Slug Tests-Unconfined Formations Chapter Overview Slug Tests in Unconfined Formations The Analysis of Slug Tests-Low-Conductivity Formations Chapter Overview Slug Tests in Log-Conductivity Formations The Analysis of Slug Tests-High-Conductivity Formulations Chapter Overview Slug Tests in High-Conductivity Formations The Analysis of Slug Tests-Well Skins Chapter Overview Slug Tests in the Presence of Well Skins The Analysis of Slug Tests-Multiwell Tests Chapter Overview Multiwell Slug Tests The Analysis of Slug Tests-Additional Issues Chapter Overview Slug Tests in Fractured Formations Slug Tests in Naturally Heterogeneous Formations Assessment of Prospective Observation Wells The Analysis of Slug Tests-Guidelines Chapter Overview Analysis Guidelines Final Comments Appendix A: A Brief Discussion of Analysis Software Appendix B: List of Notations References NTI/Sales copy (Already routed/approved)
Residual strain and texture in strontium-doped lanthanum manganite thin films

Thin films of La0.67Sr0.33MnO3 (LSMO) have been deposited using liquid-delivery metal-organic chemical vapor deposition (MOCVD). X-ray diffraction (XRD) 2θ/θ scans showed that all the films has a cubic structure. Studies of the in-plane crystallographic orientations (pole figure) revealed an (0 0 1) preferred growth structure on LAO, a weak (1 1 0) texture on Y-ZrO2 (YSZ), a random texture on sapphire (SAP) and silicon (Si). Our attention is focused on residual strain and its deviations from linearity for ɛϕψ vs. sin2ϕ plots. The strain evolution from 0<sin2ϕ<0.8 showed a curvature and a “snake-like” pattern. These anomalies are attributed to texture and strain gradients. In-plane strain decreased as the lattice mismatch increased and varied from 0.05 to 3.03% depending on the substrate. An attempt is made to establish a relationship between lattice mismatch, growth process, and residual strain.
Desorption of moisture from stainless steel tubes and alumina filters in high purity gas distribution systems

The mechanism of moisture desorption from both stainless steel and 80% alumina surfaces is studied. A difficulty associated with moisture is its strong adsorption on various gas distribution surfaces and its slow desorption due to a very high activation energy. A unique experimental setup to determine desorption under gas flow conditions by monitoring the moisture concentration at the system outlet is described. A simple analytical technique is presented to analyze the desorption data so acquired, in an effort to normalize the results and thus making them system independent. Desorption rate constants for stainless steel and ceramic (80% alumina) surfaces are calculated using this model at a constant temperature. >
Pipelines, Protest, and Property

This invited essay analyzes the recent Keystone XL and Dakota Access Pipeline protest movements through a property law lens, emphasizing for an interdisciplinary audience the complex social relationships implicated in most private property dynamics. It includes an overview of the Keystone XL and Dakota Access conflicts through the summer of 2017, but it does not attempt to resolve any of the lingering legal controversies. Instead, building on the progressive property literature, this essay uses these pipeline protests as an illustration of the inherent tensions in the private and public dimensions of property. Themes explored more specifically include (1) the prevalence of non-economic values imbedded in private resource claims, (2) the importance of accounting for private property’s impacts on both owners and non-owners (a point that is particularly salient when considering, as the essay does, the specific history of indigenous land claims in this context and the constructed nature of ownership itself), and (3) the relative dynamism of property over time (with examples from property-related reconciliations and reforms occurring inside and outside the legal system along the Nebraska pipeline route). Ultimately, this essay explores how these protests may leave lasting impacts on our collective understanding about the relative interconnectedness of private land uses in the Great Plains.
Sherlock Holmes: Expert Witness

This paper explains the treatment of expert witnesses in late-Victorian English courtrooms, using a scenario drawn from a Sherlock Holmes story -- “The Adventure of the Dancing Men” -- and a prosecution for murder.
Countering the Modern Metabolic Disease Rampage With Ancestral Endocannabinoid System Alignment

When primitive vertebrates evolved from ancestral members of the animal kingdom and acquired complex locomotive and neurological toolsets, a constant supply of energy became necessary for their continued survival. To help fulfill this need, the endocannabinoid (eCB) system transformed drastically with the addition of the cannabinoid-1 receptor (CB1R) to its gene repertoire. This established an eCB/CB1R signaling mechanism responsible for governing the whole organism's energy balance, with its activation triggering a shift toward energy intake and storage in the brain and the peripheral organs (i.e., liver and adipose). Although this function was of primal importance for humans during their pre-historic existence as hunter-gatherers, it became expendable following the successive lifestyle shifts of the Agricultural and Industrial Revolutions. Modernization of the world has further increased food availability and decreased energy expenditure, thus shifting the eCB/CB1R system into a state of hyperactive deregulated signaling that contributes to the 21st century metabolic disease pandemic. Studies from the literature supporting this perspective come from a variety of disciplines, including biochemistry, human medicine, evolutionary/comparative biology, anthropology, and developmental biology. Consideration of both biological and cultural evolution justifies the design of improved pharmacological treatments for obesity and Type 2 diabetes (T2D) that focus on peripheral CB1R antagonism. Blockade of peripheral CB1Rs, which universally promote energy conservation across the vertebrate lineage, represents an evolutionary medicine strategy for clinical management of present-day metabolic disorders.
Adriatic Circulation Experiment- Mesoscale Dynamics and Response to Strong Atmospheric Forcing

Abstract : We seek to understand the role played by three primary driving forces: (1) wintertime Bora winds, (2) weaker, along-basin Sirocco winds and (3) seasonal buoyancy input from the Po River and other sources, in governing the evolution of coastal filaments, eddies and fronts in the northern Adriatic. Additional efforts will focus on the dynamics of watermass formation and subduction in a shallow sea regime.
Operating characteristics of a subset selection procedure applied to a randomized response model for continuous data

The operating characteristics (OCs) of a subset ranking and selection procedure are derived for a randomized response model for continuous data. In this article the operating characteristics for th...