cssi/SciSciGPT-SciSciNet huggingface dataset:
Successive pregnancies in multiple sclerosis.

In this issue of Neurology ®, Benoit et al.1 describe results of a multicenter collaborative study designed to identify the association between relapses in the periods before, during, and after 2 successive pregnancies in women with multiple sclerosis (MS). MS is the leading cause of chronic neurologic disability in young adults worldwide, and because it disproportionately affects women of childbearing age, issues associated with pregnancy are of great importance to patients and their health care providers. Pregnancy is accompanied by a reduction in annualized relapse rates (ARRs), followed by an increased risk for relapses in the postpartum period (reviewed in Vukusic and Marignier2). It is unlikely that MS hampers either fertility or pregnancy outcome3,4 and hence multiple pregnancies among patients with MS is a common and often-desired scenario. Naturally, the potential for relapse after delivery is of concern to patients who wish to plan additional pregnancies. To evaluate MS disease activity in multiple pregnancies, Benoit and collaborators analyzed relapse data in a cohort of patients (n = 93) who had at least 2 successive pregnancies during a 10-year period from 1993 to 2013. Demographic, disease, and pregnancy-specific data were available from 1 French and 4 Italian MS centers participating in the European Database for Multiple Sclerosis (EDMUS; France) and the iMed database (Merck Serono-Geneva; Italy). As a possible control for disease severity, 68 French patients who had only 1 pregnancy during the study period were also included.
Prevalence of Headache in School Children

The prevalence of migraine and other headaches in 7-year-old children, in 1974 and 1992, was determined by school physicians at the time of medical examinations, using the identical study design and a similar urban child population of the same age group, and the data analysed in the Department of Child Neurology, University of Turku, Finland.
Parametric Study of the Formation of Cone Cracks in Brittle Materials

Brittle materials such as ceramics and oxide glasses are widely employed because they possess a variety of useful properties including hardness, strength, wear resistance and/or transparency. Normal and oblique impacts of spherical projectiles on brittle materials are similar to the classical Hertzian sphere indentation problem, yet different in significant ways. In the case of oblique impacts, these differences can result in the formation of unique damage patterns, including cone cracks, which are not axisymmetric, and they are distinct from partial cone cracks formed by sliding indentation. Some selected results of oblique sphere impacts on brittle targets are shown and discussed, identifying unique features. A parametric study of the factors contributing to the differences between normal and oblique impacts is reported. The effects of normal and tangential velocity, friction, and softening are investigated as factors influencing the peak principal stresses produced by oblique impacts. Friction and projectile softening were found to have a significant impact on peak maximum principal stress values. An obliquely impacting projectile’s lateral motion and its interaction with the sides of the cone crack were also found to have a significant effect on the stress field and the shape of the resulting cone crack.
A Randomized, Double Blinded Study of Risedronate Versus Placebo for the Prevention of Bone Loss in Patients Receiving High Dose Corticosteroids for the Treatment of Acute Lymphocytic Leukemia and Lymphoblastic Lymphoma

Abstract 1486 Background: Corticosteroid therapy is a well-known cause of osteoporosis. Studies have shown that the use of bisphosphonates such as risedronate can prevent bone loss in patients receiving moderate to high doses of corticosteroids. Patients with acute lymphoblastic leukemia and lymphoblastic lymphoma (ALL/LL) are at high risk of bone loss due to both leukemia and high dose steroids used in chemotherapy regimens. Objectives: The primary objective was to determine whether the use of risedronate decreases the amount of bone loss in adult patients with ALL/LL receiving chemotherapy with high dose corticosteroids when compared to placebo. Methods: Adult patients with newly diagnosed ALL/LL receiving Hyper-CVAD or BFM were randomly assigned to receive either risedronate 35 mg weekly or placebo. Both patients and physicians were blinded to the treatment assignment. Patients in both arms were given vitamin D and calcium. Bone mineral density (BMD) using DEXA scan was measured at baseline and at 6 months. Patients who lost more than 10% BMD when compared to baseline measurements were taken off the study and unblinded. We excluded patients with osteoporosis. Results: 36 patients were randomized to each treatment arm. Median age was 29 years in the risedronate arm and 42 years in the placebo arm (p=0.06). 22 patients had an available 6 month DEXA scan in the risedronate arm and 29 in the placebo arm. Patients on the placebo arm had a greater decrease in BMD at the left hip (mean −0.12) and right hip (mean −0.11) when compared to baseline than patients in the risedronate arm (left hip mean −0.08; right hip mean −0.078) and this was statistically significant (p=0.03 and p=0.04, respectively). There were no significant differences observed in the lumbar spine between the two groups. 11/22 (50%) patients in the risedronate arm were taken off study for significant % decrease in BMD at any site, and 18/29 (62%) patients in the placebo arm (p=0.28). Two patients, 1 in each arm, experienced a vertebral fracture during the first 6 months of chemotherapy. Conclusions: Adult ALL/LL patients receiving high dose corticosteroids with HyperCVAD have profound bone loss and should be monitored for this while receiving chemotherapy. Risedronate significantly reduced bone loss at the hips, but did not have a significant effect at the lumbar spine. Despite treatment with risedronate, 50% of patients had profound bone loss during the first 6 months of chemotherapy, thus a more potent bisphosphonate may be necessary to preserve bone mass, particularly at the lumbar spine. Whether a potent bisphosphonate or an agent such as a monoclonal antibody to RANK ligand will reduce fractures and improve quality of life should be studied in future clinical trials. Disclosures: Hu: Amgen: Research Funding, Speakers Bureau. Cabanillas: Procter and Gamble: Research Funding.
In-silico prediction of concentration-dependent viscosity curves for monoclonal antibody solutions

Early stage developability assessments of monoclonal antibody (mAb) candidates can help reduce risks and costs associated with their product development. Forecasting viscosity of highly concentrated mAb solutions is an important aspect of such developability assessments. Reliable predictions of concentration-dependent viscosity behaviors for mAb solutions in platform formulations can help screen or optimize drug candidates for flexible manufacturing and drug delivery options. Here, we present a computational method to predict concentration-dependent viscosity curves for mAbs solely from their sequence-structural attributes. This method was developed using experimental data on 16 different mAbs whose concentration-dependent viscosity curves were experimentally obtained under standardized conditions. Each concentration-dependent viscosity curve was fitted with a straight line, via logarithmic manipulations, and the values for intercept and slope were obtained. Intercept, which relates to antibody diffusivity, was found to be nearly constant. In contrast, slope, the rate of increase in solution viscosity with solute concentration, varied significantly across different mAbs, demonstrating the importance of intermolecular interactions toward viscosity. Next, several molecular descriptors for electrostatic and hydrophobic properties of the 16 mAbs derived using their full-length homology models were examined for potential correlations with the slope. An equation consisting of hydrophobic surface area of full-length antibody and charges on VH, VL, and hinge regions was found to be capable of predicting the concentration-dependent viscosity curves of the antibody solutions. Availability of this computational tool may facilitate material-free high-throughput screening of antibody candidates during early stages of drug discovery and development.
Increasing Fairness by Delegating Decisions to Autonomous Agents

There has been growing interest in autonomous agents that act on our behalf, or represent us, across various domains such as negotiation, transportation, health, finance, and defense. As these agent representatives become immersed in society, it is critical we understand whether and, if so, how they disrupt the traditional patterns of interaction with others. In this paper, we study how programming agents to represent us, shapes our decisions in social settings. Here we show that, when acting through agent representatives, people are considerably less likely to accept unfair offers from others, when compared to direct interaction with others. This result, thus, demonstrates that agent representatives have the potential to promote fairer outcomes. Moreover, we show that this effect can also occur when people are asked to "program" human representatives, thus revealing that the act of programming itself can promote fairer behavior. We argue this happens because programming requires the programmer to deliberate on all possible situations that might arise and, thus, promote consideration of social norms -- such as fairness -- when making their decisions. These results have important theoretical, practical, and ethical implications for designing and the nature of people's decision making when they act through agents that act on our behalf.
Fault-Tolerance Support for Responsive Computer Systems

A number of projects related to supporting fault-tolerance in responsive systems are described. One area of work concerns the development of appropriate system abstractions. The focus here has been on designing and implementing Consul, a communication substrate for constructing fault-tolerant distributed programs. The other area concerns improving programming language support. The main projects in this area include a high-level distributed programming language called FT-SR, and a version of the Linda coordination language with fault-tolerance enhancements.
AMP-activated protein kinase/myocardin-related transcription factor-A signaling regulates fibroblast activation and renal fibrosis

Chronic kidney disease is a major cause of death, and renal fibrosis is a common pathway leading to the progression of this disease. Although activated fibroblasts are responsible for the production of the extracellular matrix and the development of renal fibrosis, the molecular mechanisms underlying fibroblast activation are not fully defined. Here we examined the functional role of AMP-activated protein kinase (AMPK) in the activation of fibroblasts and the development of renal fibrosis. AMPKα1 was induced in the kidney during the development of renal fibrosis. Mice with global or fibroblast-specific knockout of AMPKα1 exhibited fewer myofibroblasts, developed less fibrosis, and produced less extracellular matrix protein in the kidneys following unilateral ureteral obstruction or ischemia-reperfusion injury. Mechanistically, AMPKα1 directly phosphorylated cofilin leading to cytoskeleton remodeling and myocardin-related transcription factor-A nuclear translocation resulting in fibroblast activation and extracellular matrix protein production. Thus, AMPK may be a critical regulator of fibroblast activation through regulation of cytoskeleton dynamics and myocardin-related transcription factor-A nuclear translocation. Hence, AMPK signaling may represent a novel therapeutic target for fibrotic kidney disease.
A Voice That Could Stir an Army: Fannie Lou Hamer and the Rhetoric of the Black Freedom Movement

Fannie Lou Hamer’s affinity for the spoken word, her self-perception as a prophet, and the lasting impact her use of symbols had upon those who experienced her discourse suggest that a sustained rh...
The Politics of Policy: The Initial Mass Political Effects of Medicaid Expansion in the States

Whether public policy affects electoral politics is an enduring question with an elusive answer. We identify the impact of the highly contested Patient Protection and Affordable Care Act (ACA) of 2010 by exploiting cross-state variation created by the 2012 Supreme Court decision in National Federation of Independent Business v. Sebelius. We compare changes in registration and turnout following the expansion of Medicaid in January of 2014 to show that counties in expansion states experience higher political participation compared to similar counties in nonexpansion states. Importantly, the increases we identify are concentrated in counties with the largest percentage of eligible beneficiaries. The effect on voter registration persists through the 2016 election, but an impact on voter turnout is only evident in 2014. Despite the partisan politics surrounding the ACA–a political environment that differs markedly from social programs producing policy feedbacks in the past—our evidence is broadly consistent with claims that social policy programs can produce some political impacts, at least in the short-term.
Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System.

Extracellular vesicles (EVs), including exosomes, are nanoscale membrane particles shed from cells and contain cellular proteins whose makeup could inform cancer diagnosis and treatment. Most analyses have focused on surface proteins while analysis of intravesicular proteins has been more challenging. Herein, we report an EV screening assay for both intravesicular and transmembrane proteins using a nanoplasmonic sensor. Termed iNPS (intravesicular nanoplasmonic system), this platform used nanohole-based surface plasmon resonance (SPR) for molecular detection. Specifically, we (i) established a unified assay protocol to detect intravesicular as well as transmembrane proteins; and (ii) engineered plasmonic substrates to enhance detection sensitivity. The resulting iNPS enabled sensitive (0.5 μL sample per marker) and high-throughput (a 10 × 10 array) detection for EV proteins. When applied to monitor EVs from drug-treated cancer cells, the iNPS assay revealed drug-dependent unique EV protein signatures. We ...
Adrenal-dependent and -independent stress-induced Per1 mRNA in hypothalamic paraventricular nucleus and prefrontal cortex of male and female rats.

Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body’s master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extr...
Psychological Outcomes of Within-Group Sexual Violence: Evidence of Cultural Betrayal.

Cultural betrayal trauma theory is a new framework for understanding trauma-related mental health outcomes in immigrant and minority populations. The purpose of the current study is to empirically test cultural betrayal trauma theory. We hypothesized that the association between within-group sexual violence and mental health outcomes would be stronger for minorities. Participants (N = 368) were minority and majority college students, who completed online measures of sexual violence victimization and mental health outcomes. A MANOVA revealed that the link between within-group sexual violence and total trauma symptoms, depression, sexual abuse sequelae, sleep disturbance, and sexual problems was stronger for minorities. This study provides evidence for cultural betrayal trauma theory, as the findings suggest that outcomes from the same experience—within-group sexual violence—is affected by minority status. This work has implications for how mental health is understood, investigated, and treated in immigrant and minority populations.
RIPK1 and RIPK3 – emerging targets in cancer?

Abstract: RIPK1 and RIPK3 are homologous Ser/Thr kinases, which act in concert within the necrosome complexes to initiate a sub-type of regulated necrosis, termed necroptosis. Necroptosis has gradually emerged as a highly clinically relevant form of necrosis, which can be targeted therapeutically. Besides necroptosis, RIPK1 and RIPK3 have been implicated in other pathophysiologically-relevant responses, including regulation of apoptosis and inflammation. More recently, it became evident that RIPK1/RIPK3 pathways may be systematically altered in cancers. Status of these pathways may provide a prognostic value, and therapeutic modulation of RIPK1/RIPK3 signaling may represent a new strategy against various forms of human cancer.
Detecting Ultra-low Light Level Signals with Optical Fiber Probe for Intrinsic Neural Signals in vivo

A photodiode in photovoltaic mode was introduced for ultra-low-light-level detection to study brain activity in rats using a miniaturized probe. Studies conducted with simultaneous measurement of 3 wavelengths demonstrated clear optical responses to neuronal activity.
Multiple factors, including arena size, shape the functional responses of ladybird beetles

Functional response studies are often used to determine the suitability of predators as biocontrol agents. Ladybird beetles (Coleoptera: Coccinellidae) are often used for the control of crop pests such as aphids. However, most functional response studies on coccinellids compare a limited number of species at different life stages, temperatures or sexes. A large‐scale comparison of ladybird beetle functional responses is needed to evaluate the utility of these species as potential biocontrol predators and to understand the traits that influence the interaction strength between ladybird beetles and their prey. We compiled 158 ladybird beetle functional responses from 30 studies and tested for effects of taxa, traits, temperature and arena size on functional response parameters using linear mixed‐effects models. Our results show that functional response parameters (handling time and space clearance rate) are affected by predator stage, predator mass, prey type, temperature and arena size. Although complicated by interaction terms, space clearance rate generally increased with predator size, temperature and predator stage, while handling time decreased with predator size, temperature and predator stage. Coleopteran prey induced the highest handling times. Our results also show that experimental arena size has a large, consistent effect on space clearance rate. Arena size is more important in determining foraging rates at low prey densities than any other factor considered here, including predator mass and temperature. Efforts to use laboratory‐based functional response experiments to evaluate the efficacy of biocontrol predators are therefore confounded by the choice of arena size. Synthesis and applications. In addition to confirming known body mass and temperature effects, our study reveals previously unclear age‐related effects and the importance of prey types, which can be used to optimize biocontrol programmes. The arena size effect is unexpected and problematic because failure to account for arena size precludes accurate comparison of biocontrol predator effectiveness. We suggest managers and biocontrol practitioners re‐evaluate the efficacy of candidate biocontrol predators, perhaps by statistically controlling for arena size to minimize the influence of this widely unconsidered factor on functional response estimates.
Potential gene therapy for alcoholism

Genes that have an actual or a potential relationship to alcoholism may he useful targets for therapy. Candidate genes are considered in relationship to family studies, differences in alcohol preferences in various rodent strains, biochemical reactions, physiologic response mechanisms, and alterations in brain pharmacology. Suggestions are made concerning the identification of candidate genes, design of gene antisense constructs, and techniques for their organ-specific delivery. The complexities surrounding alcoholism in humans make it likely that several simultaneous approaches may be required for effective therapy for alcoholism.
Local Times, Occupation Times, and the Lebesgue Measure of the Range of a Levy Process

Let X = (X t:t ≥ 0) be a Levy process on the line for which singletons are non-polar. We assume that X does not have the form \({\tilde X_t} + bt\), where \(\tilde X\) is a compound Poisson process. Let N t(a) denote the occupation time, up to time t, of (0, a] if a > 0, and the negative of the occupation time, up to time t, of (a, 0] if a ≤ 0. Let R t(a) denote the Lebesgue measure of the partial range \(\left \{X_s:0\leq s\leq t \right \}\) intersected with (0,a] if a > 0 (and the negative of the measure of this range intersected with (a, 0] if a ≤ 0). Our purpose in this paper is to investigate the L 2-differentiability of a → Nt(a) and a → R t(a). As it turns out, the derivatives of N t(a) coincide with certain “local times,” even when singletons are semipolar for X. These local times also arise as limits of upcrossing and downcrossing processes. In the following discussion we consider the cases “0 regular for {0}” and “0 irregular for {0}” separately.
Phi-Features in Animal Cognition

This paper argues that the core phi-features behind grammatical person, number, and gender are widely used in animal cognition and are in no way limited to humans or to communication. Based on this, it is hypothesized (i) that the semantics behind phi-features were fixed long before primates evolved, (ii) that most go back as far as far as vertebrates, and (iii) that some are shared with insects and plants.
Holding Students to High expectations is Everybody's Business:

Our job is not to weed out students who don't belong, but to provide the means for all to achieve at high levels.
Far-Infrared Remote-Sensing Enabled by Room-Temperature Thermopile Imagers

This work presents a large-format thermopile focal plane module based on kilo-pixel arrays able to image from UV to far-infrared scenes. The spectral selectivity is achieved by means of butcher block filters integrated into sub-assembly modules as part of the optical telescope of the instrument.
Advances in City-State Research, with an Example from Mesoamerica

The last 20 years have seen advances in the understanding of city-states, especially in ancient Greece, where textual information fuels new theories about institutions and the ancient economy. Archaeological research makes significant contributions with data comparable across multiple city-states on settlement patterns, urban and rural development, political and ritual activities, and other materializations of institutionalized behavior. Using a new corpus of 74 city-states from Oaxaca, Mexico, I show that city-states differ from one another in patterned ways, and I argue that this variation depends on internal factors such as the social mode of production and external factors including place in regional and interregional exchange.
Initiation of evidence-based psychotherapies in Veterans with posttraumatic stress disorder

ABSTRACTThe Department of Veterans Affairs (VA) requires that all VA hospitals and clinics provide access to evidence-based psychotherapies (EBPs). Despite these widespread dissemination efforts, o...
Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity.

Summary Human pluripotent stem cells can be rapidly converted into functional neurons by ectopic expression of proneural transcription factors. Here we show that directly reprogrammed neurons, despite their rapid maturation kinetics, can model teratogenic mechanisms that specifically affect early neurodevelopment. We delineated distinct phases of in vitro maturation during reprogramming of human neurons and assessed the cellular phenotypes of valproic acid (VPA), a teratogenic drug. VPA exposure caused chronic impairment of dendritic morphology and functional properties of developing neurons, but not those of mature neurons. These pathogenic effects were associated with VPA-mediated inhibition of the histone deacetylase (HDAC) and glycogen synthase kinase-3 (GSK-3) pathways, which caused transcriptional downregulation of many genes, including MARCKSL1, an actin-stabilizing protein essential for dendritic morphogenesis and synapse maturation during early neurodevelopment. Our findings identify a developmentally restricted pathogenic mechanism of VPA and establish the use of reprogrammed neurons as an effective platform for modeling teratogenic pathways.
Recruitment and retention: A randomized controlled trial of video-enhanced versus standard consent processes within the E-OPTIMAL study.

Background/aims:In this study, we compared two research consent techniques: a standardized video plus usual consent and usual consent alone.Methods:Individuals who completed 24-month outcomes (comp...
Introduction to Bayesian Inference

This chapter describes the interpretation of the components of Bayes’ Theorem. The relevant parts of the theorem are described, and a simple example is demonstrated using both a discrete and continuous prior distribution.
“Todas las poems que están creative”: Language Ideologies, Writing and Bilingual Children

This research employs a language ideologies framework to examine the language practices and beliefs of bilingual first grade students in an ESL classroom, in which the teacher valued and encouraged...
Liberals Report Lower Levels of Attitudinal Ambivalence than Conservatives

Political conservatism has been shown to be positively correlated with intolerance of ambiguity, need for closure, and dogmatism and negatively correlated with openness to new experiences and uncer...
Navigating the Curricular Maze: Examining the Complexities of Articulated Pathways for Transfer Students in Engineering

States and institutions employ articulation agreements to streamline curricular pathways. We investigate the efficacy of that streamlining by considering how course sequences, enacted through pre- ...
Stroke-Induced Peripheral Immune Dysfunction in Vitamin D–Deficient Conditions: Modulation by Progesterone and Vitamin D

Vitamin D deficiency (Ddef) alters morphology and outcomes after a stroke. We investigated the interaction of Ddef following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. Ddef rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were measured along with immune cell populations from the spleen, thymus, and blood. Severely altered outcomes were observed in the Ddef group compared to the D-sufficient (Dsuf) group. Stroke caused peripheral immune dysfunction in the Dsuf group which was worse in the Ddef group. Systemic inflammation exacerbated injury outcomes in the Dsuf group and these were worse in the Ddef group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. Ddef as a comorbid condition with stroke worsens stroke outcomes and can delay functional recovery. Combination treatment with P and D might be promising for future stroke therapeutics in Ddef.
Social Work: Evaluation and Social Supports

Hematopoietic cell transplant (HCT) is a complex treatment that often results in high levels of psychological distress and social/financial strain for patients and their families. The procedure and the ensuing recovery can test even the most adaptive functional patient and support system. Indeed, the psychosocial issues can be the most challenging for transplant teams. In order to fully evaluate and support patients and their support systems coming to transplant, it is important to understand the psychosocial aspects and concerns that will need to be addressed in the process.
Electromechanical coupling mechanism for activation and inactivation of an HCN channel.

Pacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels exhibit a reversed voltage-dependent gating, activating by membrane hyperpolarization instead of depolarization. Sea urchin HCN (spHCN) channels also undergo inactivation with hyperpolarization which occurs only in the absence of cyclic nucleotide. Here we applied transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels. We found that removing cAMP produced a largely rigid-body rotation of the C-linker relative to the transmembrane domain, bringing the A’ helix of the C-linker in close proximity to the voltage-sensing S4 helix. In addition, rotation of the C-linker was elicited by hyperpolarization in the absence but not the presence of cAMP. These results suggest that — in contrast to electromechanical coupling for channel activation — the A’ helix serves to couple the S4-helix movement for channel inactivation, which is likely a conserved mechanism for CNBD-family channels. Sea urchin hyperpolarization-activated cyclic nucleotide-gated (spHCN) ion channels channels are activated by membrane hyperpolarization instead of depolarization and undergo inactivation with hyperpolarization. Here authors apply transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels.
Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages

Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus' host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum-two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.
Investigating the Use of a Serious Game to Improve Opioid Safety Awareness Among Adolescents: A Quantitative Study.

BACKGROUND The misuse of opioid medications among adolescents is a serious problem in the United States. Serious games (SGs) are a novel way to promote safe and responsible management of opioid medications among adolescents, thereby reducing the number of adolescent opioid misuse cases reported annually. OBJECTIVE This study aimed to examine the effect of the SG MedSMA℞T: Adventures in PharmaCity on adolescents' opioid safety knowledge, awareness, behavioral intent, and self-efficacy. METHODS A nationally representative sample of adolescents age 12 to 18 years old were recruited online through Qualtrics panels from October to November 2020. Data collection consisted of a pre-game survey, 30 minutes of gameplay, and a post-game survey. The pre- and post-game survey included 66 items examining participants' baseline opioid knowledge, safety, and use, and demographic information. The post-game survey had 25 additional questions regarding the MedSMA℞T game. Gameplay scenarios included five levels intended to mimic adolescents' daily life while educating players about appropriate opioid storage and disposable practices, negative consequences of sharing opioid medications, and use of Narcan®. Survey questions were divided into 10 categories to represent key concepts and summarized into concept scores. Differences in concept scores were described by overall mean (SD) when stratified by gender, race, school, grade, and age. Differences of change in concept score were analyzed using Kruskal-Wallis and correlation tests. RESULTS A total of 117 responses were analyzed. Results showed significant improvement on all concept scores except for Narcan® knowledge (mean change = -0.04, SD = 0.29, p = 0.600) and safe storage (mean change = 0.03, SD = 0.20, p = 0.088). Female participants had greater improvement than males for safe disposal (female mean (SD) = 0.12 (0.25), male = 0.04 (0.17), p = 0.050). Male participants had higher improvement than females for misuse behavior (female mean (SD) = 0.05 (0.28) male = 0.14 (0.27), p = 0.043). Perceived knowledge for participants who were non-white or Hispanic had higher improvement than non-Hispanic white participants (non-white mean (SD) = 1.10 (1.06), white = 0.75 (0.91), p = 0.026). Older grades were associated with greater improvement in opioid knowledge (correlation coefficient -0.23 (95% CI -0.40 to -0.05), p = 0.012). There were 28 (23.9%) participants who played all 5 levels of the game and had better improvement in opioid use self-efficacy. CONCLUSIONS Findings suggest MedSMA℞T: Adventures in PharmaCity can be used as an effective tool to educate adolescents on the safe and responsible use of prescribed opioid medications. Future testing of the effectiveness of this SG should involve a randomized control trial. Additionally, the feasibility of implementing and disseminating MedSMA℞T: Adventures in PharmaCity in schools and healthcare settings, such as adolescent health or primary care clinics, emergency departments, and pharmacies, should be investigated. CLINICALTRIAL
Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA.

Extrachromosomal circular DNA (eccDNA) originates from linear chromosomal DNA in various human tissues under physiological and disease conditions. The genomic origins of eccDNA have largely been investigated using in vitro-amplified DNA. However, in vitro amplification obscures quantitative information by skewing the total population stoichiometry. In addition, the analyses have focused on eccDNA stemming from single-copy genomic regions, leaving eccDNA from multicopy regions unexamined. To address these issues, we isolated eccDNA without in vitro amplification (naive small circular DNA, nscDNA) and assessed the populations quantitatively by integrated genomic, molecular, and cytogenetic approaches. nscDNA of up to tens of kilobases were successfully enriched by our approach and were predominantly derived from multicopy genomic regions including segmental duplications (SDs). SDs, which account for 5% of the human genome and are hotspots for copy number variations, were significantly overrepresented in sperm nscDNA, with three times more sequencing reads derived from SDs than from the entire single-copy regions. SDs were also overrepresented in mouse sperm nscDNA, which we estimated to comprise 0.2% of nuclear DNA. Considering that eccDNA can be integrated into chromosomes, germline-derived nscDNA may be a mediator of genome diversity.
Some Results and Conjectures in the Gradient Theory of Phase Transitions

In the van der Waals-Cahn-Hilliard theory of phase transitions the energy depends not only on the density, but also on the density gradient, a dependence introduced to account for the interface between phases. Within this theory the stable density-distributions u(x) for a fluid confined to a container Ω are characterized by the variational problem: (Ph) minimize $$ {{\text{E}}_{\text{h}}}{\text{(u) = }}\int_{\Omega } \{ {\text{W(u(x)) + }}{{\text{h}}^2}{\left| {{\text{gradu(x)}}} \right|^2}\} {\text{dx}} $$ subject to the constraint $$ \int_{\Omega } {\text{u}} {\text{(x)dx = m}} $$ Here W(u) is the coarse-grain energy, assumed nonconvex, h is a constant which characterizes capillary effects, and m is the total fluid mass.
Component based normalization for PET systems with depth of interaction measurement capability

The number of lines of response (LOR) in a system with small crystals and depth of interaction (DOI) measurement capability can require prohibitive amounts of memory and computational resources. The number of independent LORs in the small animal imaging system evaluated in this study is /spl sim/2 /spl times/ 10/sup 9/. We propose a method to adapt the component-based normalization model to include (1) DOI and (2) large field of view (FOV) to system inner bore volume percentage (near 100%) or percentage of view (POV) considerations without an order of magnitude increase in computational resources. This method can also compensate for bin location errors made during the LOR calculation. Included in the study were radial, axial and interference geometric efficiency and crystal absorption factors. We have observed a large effect on sensitivity from axial geometric factors, distance between positioned coincident photon interactions, and amount of crystal surrounding any particular crystal in our system. Assessing direct plane sinograms of direct normalization data (infinitely thin cylindrical annulus), we have observed that there are LORs that received zero counts due to inter-module gaps. Component based normalization pre-correction weights significantly improved the coefficient of variation for the reconstructed 1.5 mm and 1.75 mm spheres in the row nearest the center line in the axial image slices by 17%, 32%, and 51% in the z = 0 cm, z = 1.5 cm, and z = 3.0 cm axial planes, respectively.
Relativistic matter fields admitting Ricci collineations and elated conservation laws

This paper focuses attention on the important role of Ricci collineations admitted by certain relativistic matter fields and the related conservation laws that may be admitted in the corresponding Riemannian space-times. Accordingly, one of the main objects of the present investigation is to show that Ricci collineations provide an invariant classification scheme for certain types of matter fields. These results are elaborated in terms of a number of theorems connecting particular symmetry properties with special properties of the eigenvalues and eigenvectors of the matter tensor characterizing the given matter fields. Finally, consideration is given to conservation laws relating to particular properties of the timelike principal-curve congruence of the given matter field and to the fact that certain symmetries may be admitted. Some of the results obtained are applied to the Robertson-Walker cosmological metrics. It is shown that a special class of metrics, belonging to the cosmological model, admits a particular nondegenerate Ricci collineation and the corresponding conservation law relating to matter conservation. Moreover, brief consideration is given to the appropriate specialization of these results which could be of interest at the level of ordinary relativistic hydrodynamics and plasma physics in flat space-time.
Stencil Printing of Underfill for Flip Chips on Organic-Panel and Si-Wafer Substrates

A high-throughput method of postassembly underfill is presented in this paper. Emphasis is placed on the proposal of a specially designed stencil to print the underfill material for flip chips on large organic-panel and Si-wafer assemblies. After printing, the organic-panel or Si-wafer assemblies are placed on a hot plate for the underfill to totally fill the space between the chips, solder joints, and substrates by capillary action, and then cured. The cured assemblies are characterized by the C-mode scanning acoustic microscopy, X-ray, shear test, cross sectioning, and scanning electron microscopy. The effects of the viscosity, thermal enhancement, and multiple prints of underfills are examined. It is found that stencil printing of underfill for flip chips on organic-panel and Si-wafer substrates is a very high-throughput, simple, and low-cost process.
OpenHPI: an open source reference implementation of the SA forum hardware platform interface

OpenHPI is production ready reference implementation of the SA Forum HPI specification. It is designed to be easy to setup and use, as well as utilize and compliment existing hardware management standards. OpenHPI is available as open source so it can be easily productized by anyone requiring an HPI implementation for their hardware.
Psychotherapy for Individuals with Intellectual Disability

Dr. Robert Fletcher is the editor of an excellent overview of psychotherapy for individuals with co-occurring mental health issues and intellectual disability (ID). He has assembled a group of tale...
Cynthia Schoolar Williams, Hospitality and the Transatlantic Imagination, 1815-1835

Review by Evan Gottlieb (Oregon State University) of Cynthia Schoolar Williams, Hospitality and the Transatlantic Imagination, 1815-1835 . New York: Palgrave Macmillan, 2014. Pp. 235. $90. ISBN 9781137340047.
Directed Lithiation of Aromatic Compounds: (2‐Dimethylamino‐5‐Methylphenyl)Diphenylcarbinol

Directed lithiation of aromatic compounds: (2-dimethylamino-5-methylphenyl)diphenylcarbinol product: (2-dimethylamino-5-methylphenyl)diphenylcarbinol catalyst: 8.8 g. (0.076 mole of N,N,N′,N′-tetramethylethylenediamine Keywords: arylation; metalation reactions, lithium; assay methods, for butyllithium, with 2-butanol, menthol, 2-pentanol, or 2-propanol, 1,10-phenanthroline indicator; tetramethylethylenediamine
Piezoceramic material with anisotropic graded porosity

Porous PZT ceramics were produced at increasing porosity content to a maximum of 40 vol.%. Anisotropic porosity was obtained by adding lamellar graphite as pore forming agent. The elasto-piezo-dielectric properties of the samples with uniform porosity were correlated to the increasingly higher degree of anisotropy introduced as the total pore volume increases. Higher anisotropy enhances the decoupling of the longitudinal to transverse effect. A piezoelectric bending actuator with functionally graded microstructure (FGM) was produced by stacking layer by layer, in the green state, the PZT powder at increasing graphite content, followed by die pressing and co-firing. The final pore distribution measured across the section and the performance of the porosity graded material arise from the combination of the properties of the homogeneous layers. This makes it possible to precisely tailor the performance of the porosity graded material.
The Application of Scanning Acoustic Microscopy in a Bone Remodeling Study

Scanning acoustic microscopy (SAM) was used in the evaluation of bone remodeling around a cylindrical unicortical defect. SAM is a technique for the nondestructive evaluation of materials, and has only recently been employed as an orthopaedic research tool. The utility of SAM was demonstrated by using it to measure an elastic property known as acoustic impedance. Specifically, the acoustic impedance of bone formed by remodeling around a cylindrical defect was measured. The defects were filled with either a low modulus "void" or rigid inclusion to create various states of stress in the bone in the vicinity of the defect. After six months of implantation of the inclusions in the sheep metatarsal, new bone formation on periosteal and endosteal surfaces about the defect region was observed. These regions of new bone were less stiff and had 18.0 +/- 6.5% lower acoustic impedance than the pre-existing bone in the intracortical region of the metatarsal. There was no difference in the degree of new bone formation about void and rigid inclusions. Both underwent significant adaptational changes in response to the elevated stress about the defect. These changes affected the basic structure of the bone cross-section at the level of the defect and effectively reduced the stress levels about the defect. By using SAM to measure acoustic impedance, it was seen that little internal remodeling occurred in the intracortical region. Hence, the primary mechanism of strain-induced bone remodeling observed in this experimental model was surface remodeling.
Identification of corticotropin-releasing factor (CRF) target cells and effects of dexamethasone on binding in anterior pituitary using a fluorescent analog of CRF.

A fluorescein-conjugated bioactive analog of corticotropin-releasing factor (CRF) was synthesized and used to label cells that have high affinity CRF-binding sites. Of cultured bovine anterior pituitary cells, 6.1 ± 0.6% were visible by fluorescence microscopy after incubation with the analog. Fluorescence was eliminated by coincubation with a 200-fold excess of unlabeled CRF. Treatment with dexamethasone (10−9−10−7 m) decreased visible fluorescence in a dose-dependent manner. These results demonstrate the utility of a fluorescent CRF analog for identification of cells with specific CRF-binding sites and suggest that binding of CRF to anterior pituitary cells is altered by glucocorticoids. (Endocrinology 119: 2376-2382, 1986)
Economic ordering policy for jointly replenished items

Abstract In this paper a heuristic method is given for determining nearly optimal operating policy in joint replenishment inventory problems. The performance of the heuristic method is compared with some of the other known heuristic methods available for solving such problems.
Control of a Biped Robot Using the Robot Operating System

This paper presents the development of a simplified model of the lower limbs of a biped robot, composed, basically, of a waist, two femurs, two tibiae and two feet. This mechanical structure has six degrees of freedom and has the approximate dimensions of a human being. The control system was implemented on the Robot Operating System (ROS). Contrariwise to most ROS controllers, a multi-input, multi-output (MIMO) controller using the computed-torque technique is proposed. The Gazebo simulator is used to validate the model and the control system.
An Accessible Hydrophobic Surface Is a Key Element of the Molecular Chaperone Action of Atp11p

Atp11p is a soluble protein of mitochondria that binds unassembled β subunits of the F1-ATPase and prevents them from aggregating in the matrix. In this report, we show that Atp11p protects the insulin B chain from aggregating in vitro and therefore acts as a molecular chaperone. The chaperone action of Atp11p is mediated by hydrophobic interactions. An accessible hydrophobic surface in Atp11p was identified with the environment-sensitive fluorescent probe 1,1′-bis(4-anilino-5-napththalenesulfonic acid (bis-ANS). The spectral changes of bis-ANS in the presence of Atp11p indicate that the probe binds to a nonpolar region of the protein. Furthermore, the dye quenches the fluorescence of Atp11p tryptophan residues in a concentration-dependent manner. Although up to three molecules of bis-ANS can bind cooperatively to Atp11p, the binding of only one dye molecule is sufficient to virtually eliminate the chaperone activity of the protein.