cssi/SciSciGPT-SciSciNet huggingface dataset:
Cadherin-11 Overexpression Induces Extracellular Matrix Remodeling and Calcification in Mature Aortic Valves.

Objective— Calcific aortic valve (AoV) disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. Enhanced cell–cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. Cadherin-11 (Cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. This study aims to elucidate the specific functions of Cad-11 and its downstream targets, RhoA and Sox9, in extracellular matrix remodeling and AoV calcification. Approach and Results— We conditionally overexpressed Cad-11 in murine heart valves using a novel double-transgenic Nfatc1 Cre ;R26-Cad11 TglTg mouse model. These mice developed hemodynamically significant aortic stenosis with prominent calcific lesions in the AoV leaflets. Cad-11 overexpression upregulated downstream targets, RhoA and Sox9, in the valve interstitial cells, causing calcification and extensive pathogenic extracellular matrix remodeling. AoV interstitial cells overexpressing Cad-11 in an osteogenic environment in vitro rapidly form calcific nodules analogous to in vivo lesions. Molecular analyses revealed upregulation of osteoblastic and myofibroblastic markers. Treatment with a Rho-associated protein kinase inhibitor attenuated nodule formation, further supporting that Cad-11–driven calcification acts through the small GTPase RhoA/Rho-associated protein kinase signaling pathway. Conclusions— This study identifies one of the underlying molecular mechanisms of heart valve calcification and demonstrates that overexpression of Cad-11 upregulates RhoA and Sox9 to induce calcification and extracellular matrix remodeling in adult AoV pathogenesis. The findings provide a potential molecular target for clinical treatment.
Screening Empire from Itself: Imperial Preference, Represented Communities, and the Decent Burial of the Indian Cinematograph Committee Report (1927–28)

On 7 July 1896, within weeks of the first moving picture being screened by the Lumiere brothers in Paris, the same film was shown in Bombay at Watson’s Hotel by their cameraman, Maurice Sestier.1 Two years later, films were being shown in tents set up on the city’s new Oval Maidan, as well as in Madras and Calcutta, where daily screenings were advertised in local papers. By the end of the century, H.S. Bhatavdekar had filmed a wrestling match, several photography journals had begun to cover moving pictures, and cinema societies had sprouted in the major port cities of India. Bhatavdekar moved from wrestling matches to historical events of somewhat greater national significance, producing and screening short films on subjects like the Delhi Durbar of 1903, which marked the enthronement of Edward VII as emperor of India. In 1912, Coronation Cinematograph released Pundalik, about a Hindu saint, shown in a double feature with a foreign film entitled, A Dead Man’s Child, and the next year, D.G. Phalke released Raja Harishchandra, the first self-consciously ‘swadeshi,’ India-made film. In the decade following, more than a dozen studios and film companies were formed in India. These firms produced about 1300 films in the silent era, exceeding British production and, indeed, all other empire production combined.
Revised Phase System for the Globe-Miami and Tonto Basin Areas, Central Arizona

ABSTRACTA proposed realignment of State Route 88 near Miami, Arizona, necessitated the excavation of eight small prehistoric sites. Material culture representative of Hohokam, Salado, and Apache occupations was recovered. This recent work has contributed to the refinement of the poorly known chronology for the Globe-Miami and Tonto Basin areas. A new phase, the Miami phase, is introduced for the Globe-Miami area, spanning the time period of around A.D. 1150 to 1200.
Combating the Decline in Information Systems Majors: The Role of Instrumental Assistance

The sharp decline in the number of students pursuing information systems (IS) degrees is a source of great concern not only for academic institutions offering IS degrees, but also for companies in need of hiring qualified professionals. In response, university educators are searching for mechanisms to generate larger pools of IS graduates. This study focuses on one such mechanism, instrumental assistance, to promote student choice of IS as a primary field of study. Using Social Cognitive Career Theory as a guiding framework, instrumental assistance is found to boost student confidence (i.e., self-efficacy) and expectations of valued rewards (i.e., outcome expectations). In turn, self-efficacy and outcome expectations elevate student interest, which ultimately influences students' aspirations to choose IS as a major. The study provides important insights into how a particular intervention strategy can be implemented to attract more students to the IS field.
Signaling revisited: The use of signals in the market for IPOS

Research summary: Scholars have actively researched the initial public offering ( IPO) underpricing phenomenon as it relates to the issuing firm's resource acquisition and entrepreneur's wealth retention. In this study, we attempt to replicate three studies that examine how top management and board-level characteristics impact IPO underpricing using signaling theory. Focusing on a different time period and using a new sample of 234 U.S. IPO firms, we do not find evidence for the signaling effects of top management, governance structure, and social ties on resource acquisition and wealth retention during the IPO process. We propose possible theoretical and empirical reasons for our results and discuss two major external changes that researchers should account in future research. Managerial summary: Past studies on initial public offering ( IPO) underpricing have systematically documented the effectiveness of signals (i.e., having seasoned CEO and top management team, director independence, and director network) that influence the amount of money entrepreneurs 'leave on the table' during the IPO process. Since these studies were conducted before the ongoing information revolution, we re-examined the effectiveness of these signals in the current IPO market. Despite using similar methodological approaches that past studies used, we do not find evidence supporting the prior findings. To explain our findings, we discuss two notable recent changes-unprecedented access to information and a regulatory change-that future researchers should examine in the context of IPO underpricing research. Copyright © 2016 John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]
Magnetic vortex racetrack memory

Abstract We report a new type of racetrack memory based on current-controlled movement of magnetic vortices in magnetic nanowires with rectangular cross-section and weak perpendicular anisotropy. Data are stored through the core polarity of vortices and each vortex carries a data bit. Besides high density, non-volatility, fast data access, and low power as offered by domain wall racetrack memory, magnetic vortex racetrack memory has additional advantages of no need for constrictions to define data bits, changeable information density, adjustable current magnitude for data propagation, and versatile means of ultrafast vortex core switching. By using micromagnetic simulations, current-controlled motion of magnetic vortices in cobalt nanowire is demonstrated for racetrack memory applications.
Noise characterization in double-heralded generation of two-photon-states by spontaneous four-wave-mixing

In quantum optics experiments, heralding, a form of conditional state preparation, is a useful tool for creating photon-number states from nonlinear optical sources for quantum-information science experiments. Heralding occurs when one photon from a correlated pair is detected to herald the presence of the other photon, labeled the signal photon. However, as heralding is extended to two or more photon pairs, the presence of noise photons in the herald channel quickly degrades the photon statistics of the signal photons. We create two-photon number states from a non-degenerate, third-order nonlinear optical fiber source with double heralding and present a method for verifying these photon-number states. The consequences of noisy heralding on the statistics of states created via third-order nonlinear processes are analyzed. We present a method for estimating the effects of noise photons on the signal photon statistics. Additionally, we prove the equivalence between noise in the herald channel and a loss in the signal channel. We utilize this equivalence to infer the photon statistics of the photon-number states in the signal channel that would be present in the absence of noise in the herald channel. By measuring the statistics of the signal channels with noise in the herald channel and comparing to the inferred, noise-free distribution, we can estimate the potential benefits of additional noise-reducing procedures on the experiment.
IV to oral conversion programs for anti-infectives in the United States: Prevalence and characteristics

Purpose: Despite the documented success of IV to oral anti-infective conversion programs, it is still unclear what the current standard of practice is in the US. A survey was conducted to evaluate the prevalence and characteristics of conversion programs throughout the nation. Methods: A questionnaire was mailed to 890 randomly chosen hospital pharmacy directors. A preset cutoff date of 4 weeks from the initial mailing was set for responses; a second mailing was sent to those directors that did not respond initially. Results: A total of 237 (27%) institutions responded. Of these, 74% had instituted conversion programs. More programs required prior physician notification compared with allowing pharmacists to proactively transition candidates (70% vs 30%, P < 0.001). The most common anti-infectives converted were the fluoroquinolones and fluconazole. Common conversion criteria included adequate oral intake and fever reduction. Characteristics associated with an increased likelihood of a conversion program were pharmacy residency programs (RR 1.3; 95% CI 1.132 to 1.477), clinical pharmacists (RR 1.6; 95% CI 1.262 to 2.123), ID specialty pharmacists (RR 1.3; 95% CI 1.153 to 1.499), ID physician consult service (RR 1.2; 95% CI 1.028 to 1.459), and teaching hospitals (RR 1.2; 95% CI 1.038 to 1.386). Hospitals with conversion programs employed a greater number of clinical pharmacists (P = 0.02). Multivariate analysis revealed that the presence of a clinical pharmacist was the most significant variable predicting implementation (P < 0.001). Conclusion: The majority of hospitals responding to this survey had an intravenous to oral conversion program. While most programs still required prior physician notification, the presence of clinical pharmacists significantly influenced the prevalence of implementation and proactive transition.
Long-Term Outcomes of a Multidisciplinary Weight Management Intervention for Youth with Disabilities.

Abstract Background: Youth with disabilities are at increased risk for obesity compared with their typically developing peers and face unique barriers to healthy lifestyles. A limited number of wei...
Is Psychology Headed in the Right Direction

Is psychology headed in the right direction? In this essay, I share my views on the answer to this question. I begin by describing how recent advances in technology, heightened levels of interdisciplinary collaboration, a renewed emphasis on considering the broader implications of basic psychological research, and field-wide efforts to encourage optimal research practices have combined to tilt psychology's trajectory upward. I then offer three suggestions for how to maintain the field's upward slanting course: (a) collaborate more to build cumulative knowledge, (b) improve the way we communicate contextual factors in psychological research, and (c) examine the psychological effects of technology. I conclude by offering a single piece of advice for new researchers and a few closing comments.
Restructuring Rural Health Care: Expanding the PACE for Rural Elders

The Balanced Budget Act (BBA) of 1997 created an opportunity for improving long-term care for the rural frail elderly by granting permanent provider status to the Program of All-Inclusive Care for Elders (PACE) under Medicare. PACE is a unique managed care model that provides comprehensive, integrated acute and long-term services for frail elders and program providers assume full financial risk. However, all existing PACE sites are currently located in urban settings. This article reviews the PACE provisions in the BBA legislation and describes the current PACE model. Two possible adaptations of the model are discussed for expanding PACE into rural areas. Keywords: Balanced Budget Act of 1997, long-term care, rural, frail elders, family caregivers, Program of All-Inclusive Care (PACE), Medicare restructuring http://dx.doi.org/10.14574/ojrnhc.v2i1.476
A Novel Ultrasound Imaging Method for 2D Temperature Monitoring of Thermal Ablation

Accurate temperature monitoring is a crucial task that directly affects the safety and effectiveness of thermal ablation procedures.
Age, Sex, and Dose Effects of Nonbenzodiazepine Hypnotics on Hip Fracture in Nursing Home Residents.

Abstract Objective The Food and Drug Administration recommends a reduced dose of nonbenzodiazepine hypnotics in women, yet little is known about the age-, sex-, and dose-specific effects of these drugs on risk of hip fracture, especially among nursing home (NH) residents. We estimated the age-, sex-, and dose-specific effects of nonbenzodiazepine hypnotics on the rate of hip fracture among NH residents. Design and Setting Case-crossover study in US NHs. Participants A total of 691 women and 179 men with hip fracture sampled from all US long-stay NH residents. Measurements Measures of patient characteristics were obtained from linked Medicare and the Minimum Data Set (2007–2008). The outcome was hospitalization for hip fracture with surgical repair. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) from conditional logistic regression models for nonbenzodiazepine hypnotics (vs nonuse) comparing 0 to 29 days before hip fracture (hazard period) with 60 to 89 and 120 to 149 days before hip fracture (control periods). We stratified analyses by age, sex, and dose. Results The average RR of hip fracture was 1.7 (95% CI 1.5–1.9) for any use. The RR of hip fracture was higher for residents aged ≥90 years vs Conclusions The rate of hip fracture in NH residents due to use of nonbenzodiazepine hypnotics was greater among older patients than among younger patients and, possibly, with higher doses than with lower doses. When clinicians are prescribing a nonbenzodiazepine hypnotic to any NH resident, doses of these drugs should be kept as low as possible, especially among those with advanced age.
Design of an assistant system for industrial maintenance tasks and implementation of a prototype using augmented reality

As the complexity of work tasks rises for maintenance workers in modern production facilities, new technologies will be required to support and integrate the service worker of tomorrow. This paper gives an insight into an ongoing research project examining the potential of smart glasses used as a component of assistant systems for workers performing maintenance tasks in an industry 4.0 context. A human centered design process is used to identify the needs of workers and to specify requirements for the assistant system being developed. Thereby, the maintenance of a CNC lathe is used as an example and assistant functions were developed for one specific maintenance task. The architecture of the assistant system proposed in this paper is based on an analysis of the work system including the tasks of the maintenance worker. Finally, the implementation of a first prototype, using state-of-the-art augmented reality smart glasses, is described.
Advantages of Adobe Photoshop Elements 2.0* over the full version of Photoshop*

The high cost of Photoshop and its increasing complexity with each new version can leave the user longing for a version that is a fraction of the price, but still contains the basic features. That longing may be met with Adobe's Photoshop Elements. Certainly its price is attractive at $99.00, making the purchase a 2-for-1. Elements is a pared down version of Photoshop, but it is still a viable solution for almost all image processing needs. Simply because it is pared down, it becomes very attractive for occasional users who do not desire to re-learn the full version of Photoshop, let alone yet another upgrade and yet more frustrating minutea to discover.
A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin

The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N-cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-A and 2.57-A resolution, respectively, revealed that N-cyclohexyltaurine binds to the heart of the conserved HA RBS. N-cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-π interactions with the HA. In H3/HK68, N-cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.
Meta-analysis of the incidence and patterns of second neoplasms after photon craniospinal irradiation in children with medulloblastoma.

Background Second neoplasms (SNs) are a well-established long-term adverse effect of radiation therapy (RT), but there are limited data regarding their incidence and location relative to the radiation field, specific to medulloblastoma (MB) survivors after craniospinal irradiation (CSI). Methods A systematic literature review, per Preferred Reporting Items for Systematic Reviews and Meta-Analyses, identified six studies reporting the incidence and locations of SNs for 1,114 patients with MB, after CSI, with a median follow-up of ∼9 years (7.6-15.4 years). The study-specific cumulative incidence (CI) of SNs, second benign neoplasms (SBNs), and second malignant neoplasms (SMNs) were standardized to a 10-year time frame. Meta-analysis was performed using random effects models, with pooled data from selected studies and an institutional cohort of 55 patients. Results The 10-year CI was 6.1% for all SNs (excluding skin cancer and leukemia), 3.1% for SBNs, and 3.7% for SMNs. Fifty-eight percent of SNs were malignant; high-grade glioma was the most common SMN (15/33; 45%) and meningioma, the most common SBN (16/24; 67%). Forty percent of SNs occurred outside the target central nervous system (CNS) field, with a majority in areas of exit RT dose. Seventy-four percent of extra-CNS tumors (17/23) were malignant, most commonly thyroid carcinoma (7/17; 41%) and bone and soft-tissue tumors (6/17, 35%). Conclusions Survivors of MB are at risk of SNs both within and outside the CNS. A significant proportion of SNs occur in areas of exit RT dose. Studies are needed to determine whether the use of proton therapy, which has no exit RT dose, is associated with a lower incidence of SNs.
Genome-wide scan reveals signatures of selection related to pollution adaptation in non-model estuarine Atlantic killifish (Fundulus heteroclitus).

Abstract In many human-altered ecosystems, organisms are increasingly faced with more diverse and complex environmental stressors and pollutant mixtures, to which the adaptations necessary to survive exposure are likely to be numerous and varied. Improving our understanding of the molecular mechanisms that underlie complex polygenic adaptations in natural settings requires significant toxicological, biochemical, physiological, and genomic data rarely available for non-model organisms. Here, we build upon two decades of study of adaptation to anthropogenic pollutants in a population of Atlantic killifish (Fundulus heteroclitus) that inhabits the creosote-contaminated Atlantic Wood Industries Superfund (AW) site on the Elizabeth River, Virginia in the United States. To better understand the genotypes that underlie previously characterized resistance to PCBs and PAHs, we performed Restriction site-Associated DNA sequencing (RADseq) on killifish from AW and two relatively clean reference sites (King’s Creek–KC, and Mains Creek–MC). Across the genome, we analyzed over 83,000 loci and 12,000 single nucleotide polymorphisms (SNPs). Shared across both comparisons of killifish from polluted (AW) and relatively unpolluted (KC and MC) sites, we found eight genomic regions with smoothed FST values significantly (p
Optical Properties of Tensilely Strained Ge Nanomembranes

Group-IV semiconductors, which provide the leading materials platform of micro- electronics, are generally unsuitable for light emitting device applications because of their indirect- bandgap nature. This property currently limits the large-scale integration of electronic and photonic functionalities on Si chips. The introduction of tensile strain in Ge, which has the effect of lowering the direct conduction-band minimum relative to the indirect valleys, is a promising approach to address this challenge. Here we review recent work focused on the basic science and technology of mechanically stressed Ge nanomembranes, i.e., single-crystal sheets with thicknesses of a few tens of nanometers, which can sustain particularly large strain levels before the onset of plastic deformation. These nanomaterials have been employed to demonstrate large strain-enhanced photoluminescence, population inversion under optical pumping, and the formation of direct-bandgap Ge. Furthermore, Si-based photonic-crystal cavities have been developed that can be combined with these Ge nanomembranes without limiting their mechanical flexibility. These results highlight the potential of strained Ge as a CMOS-compatible laser material, and more in general the promise of nanomembrane strain engineering for novel device technologies.
Soluble fiber and energy regulation. Current knowledge and future directions.

Americans are becoming fatter. Recent longitudinal data from the National Health and Nutrition Examination Survey1 shows that the median body mass index of adult men and women increased from 25.3 to 26.3 kg/m2 between the periods 1960–1962 and 1988–1991, corresponding to a body weight gain of 8 lb. While it is clear that the immediate underlying cause of this increase can be traced to an energy intake greater than energy expenditure, the underlying causes of the imbalance remain unclear. Has metabolizable energy intake increased, or has energy expenditure fallen, or has a combination of these two events occurred? If metabolizable energy intake has increased, why has this happened? In this brief review we focus on the potential role of soluble fiber in influencing energy intake and hence body weight regulation, and on some experimental considerations for future investigational studies in this area.
Geospatial Analysis of West Nile Virus (WNV) Incidences in a Heterogeneous Urban Environment: A Case Study in the Twin Cities Metropolitan Area of Minnesota

West Nile virus (WNV) infected dead bird sites and human cases are frequently located in the densely populated, urban areas primarily because they are reported by people. However, the spatial pattern (i.e. morphology) of the urban landscape features could also contribute to the location of WNV incidences. This study has two objectives: (1) analyzing the association of urban environmental features that facilitated the viral activities of WNV infection in the TCMA from 2002 to 2007 and (2) comparing the spatial association between WNV infected mosquito pools and human cases with heterogeneous urban characteristics. It also addresses the question of how urban morphology affects human health. Using a combination of factorial ecology, geospatial techniques, and hierarchical cluster analysis, urban landscape classes are derived from the environmental and built environment risk-factors hypothesized to be associated with WNV transmission. The infection rate among, birds, mosquitoes, and human cases are then compared to these urban classes. Results indicate that the WNV infection rate is considerably higher in the urban class located just outside the cities of Minneapolis and Saint Paul. The dominant features of this class are close proximity to bogs and swamps, parks, sewerage system, waste water discharge sites, trails, high density of catch basins, moderate density of single family houses, and medium vegetation cover with stagnant waters. In general, the rate of infection decreases with increasing distance from the urban core. This is critical, in terms of vector control policies, because two out of four WNV carrying vectors, Culex restuans and Culex pipiens are predominantly urban mosquitoes.
Ten Years of TeenHealthFX.com. A Case Study of an Adolescent Health Web Site.

The Internet, in contrast to in-person interactions with health providers, allows anonymous and nonpunitive ease of access. Adolescents have long sought honest, direct answers to important but embarrassing questions about health; emerging technologies provide a venue to obtain relevant information without geographic, time, financial, and personal barriers. This article is a case study of TeenHealthFX.com. Those interested in how youth access online health information can learn of the positive and negative aspects of delivering messages through the Internet. This article discusses the process involved in creating and maintaining TeenHealthFX and the challenges of providing online health information to adolescents via new technology.
Disparate Growth Strategies within Aetosauria: Novel Histologic Data from the Aetosaur Coahomasuchus chathamensis

Aetosaurs comprise a clade of quadrupedal, armored, omnivores to herbivores that lived across much of the supercontinent of Pangea during the Late Triassic. Their relative abundance in many units, and the rarity of other Triassic herbivores, points to them as key components of Late Triassic ecosystems. Debate persists about whether they were growing more or less slowly when compared to extant crocodylians, and bone histology is sparsely sampled within the group. We undertook a histological examination of Coahomasuchus chathamensis to address its ontogenetic trajectory and characterize its histology. We sampled a paramedian osteoderm from the holotype specimen, as well as five osteoderms (two paramedian, one lateral, and two of uncertain position) and two incomplete limb bones (radius and fibula), from referred specimens discovered at the type locality. Using these we estimated specimen ages with lines of arrested growth (LAGs) to determine that the study individuals reached from 2 to 7 years old. All of the sampled elements contained woven-fibered bone with extensive vasculature within the internal cortex. In some specimens, more poorly vascularized, parallel-fibered bone is evident externally. The holotype of C. chathamensis represents a juvenile individual, and raises the possibility that the holotype of C. kahleorum is a juvenile as well, complicating aetosaur systematics and diversity. When compared to aetosaurs of similar size, it is clear that C. chathamensis was growing comparatively rapidly, about 3 times the rate of similarly sized specimens of Aetosauroides scagliai from Argentina. This discovery reveals the presence of disparate growth strategies within Aetosauria. Anat Rec, 302:1504-1515, 2019. © 2018 American Association for Anatomy.
Increasing deictic gesture use to support the language development of toddlers from high poverty backgrounds

Abstract This study uses a single-case, multiple probe design to investigate the effects of a naturalistic intervention on deictic gesture use in toddlers who are from low-SES backgrounds. The month-long study included strategies drawn from the literature on early communication interventions to increase the rate of child gesture use in toddlers at-risk for later delays. These strategies include frequent modeling of deictic gestures (points, shows, reaches, and gives), creating opportunities for the child to gesture by using environmental arrangements, choices, and wait time, and by responding and expanding each gesture. All three child participants made gains in their rates of deictic gestures after the onset of intervention with no overlap between the intervention and baseline conditions. Children also made gains to gesture + vocalization combinations and gesture + word combinations in this short-term intervention. This study offers preliminary evidence that prelinguistic interventions for children at-risk can be used to increase rates of communication in toddlers in poverty.
Dysregulated transmethylation leading to hepatocellular carcinoma compromises redox homeostasis and glucose formation

Abstract Objective The loss of liver glycine N-methyltransferase (GNMT) promotes liver steatosis and the transition to hepatocellular carcinoma (HCC). Previous work showed endogenous glucose production is reduced in GNMT-null mice with gluconeogenic precursors being used in alternative biosynthetic pathways that utilize methyl donors and are linked to tumorigenesis. This metabolic programming occurs before the appearance of HCC in GNMT-null mice. The metabolic physiology that sustains liver tumor formation in GNMT-null mice is unknown. The studies presented here tested the hypothesis that nutrient flux pivots from glucose production to pathways that incorporate and metabolize methyl groups in GNMT-null mice with HCC. Methods 2H/13C metabolic flux analysis was performed in conscious, unrestrained mice lacking GNMT to quantify glucose formation and associated nutrient fluxes. Molecular analyses of livers from mice lacking GNMT including metabolomic, immunoblotting, and immunochemistry were completed to fully interpret the nutrient fluxes. Results GNMT knockout (KO) mice showed lower blood glucose that was accompanied by a reduction in liver glycogenolysis and gluconeogenesis. NAD+ was lower and the NAD(P)H-to-NAD(P)+ ratio was higher in livers of KO mice. Indices of NAD+ synthesis and catabolism, pentose phosphate pathway flux, and glutathione synthesis were dysregulated in KO mice. Conclusion Glucose precursor flux away from glucose formation towards pathways that regulate redox status increase in the liver. Moreover, synthesis and scavenging of NAD+ are both impaired resulting in reduced concentrations. This metabolic program blunts an increase in methyl donor availability, however, biosynthetic pathways underlying HCC are activated.
Genome-wide sequence-based genotyping supports a nonhybrid origin of Castanea alabamensis

Abstract The genus Castanea in North America contains multiple tree and shrub taxa of conservation concern. The two species within the group, American chestnut (Castanea dentata) and chinquapin (C. pumila sensu lato), display remarkable morphological diversity across their distributions in the eastern United States and southern Ontario. Previous investigators have hypothesized that hybridization between C. dentata and C. pumila has played an important role in generating morphological variation in wild populations. A putative hybrid taxon, Castanea alabamensis, was identified in northern Alabama in the early 20th century; however, the question of its hybridity has been unresolved. We tested the hypothesized hybrid origin of C. alabamensis using genome-wide sequence-based genotyping of C. alabamensis, all currently recognized North American Castanea taxa, and two Asian Castanea species at >100,000 single-nucleotide polymorphism (SNP) loci. With these data, we generated a high-resolution phylogeny, tested for admixture among taxa, and analyzed population genetic structure of the study taxa. Bayesian clustering and principal components analysis provided no evidence of admixture between C. dentata and C. pumila in C. alabamensis genomes. Phylogenetic analysis of genome-wide SNP data indicated that C. alabamensis forms a distinct group within C. pumila sensu lato. Our results are consistent with the model of a nonhybrid origin for C. alabamensis. Our finding of C. alabamensis as a genetically and morphologically distinct group within the North American chinquapin complex provides further impetus for the study and conservation of the North American Castanea species.
A Decomposition Method for Distributionally-Robust Two-stage Stochastic Mixed-integer Cone Programs

We develop a decomposition algorithm for distributionally-robust two-stage stochastic mixed-integer convex cone programs, and its important special case of distributionally-robust two-stage stochastic mixed-integer second order cone programs. This generalizes the algorithm proposed by Sen and Sherali~[Mathematical Programming 106(2): 203-223, 2006]. We show that the proposed algorithm is finitely convergent if the second-stage problems are solved to optimality at incumbent first stage solutions, and solution to an optimization problem to identify worst-case probability distribution is available. The second stage problems can be solved using a branch-and-cut algorithm. The decomposition algorithm is illustrated with an example. Computational results on a stochastic programming generalization of a facility location problem show significant solution time improvements from the proposed approach. Solutions for many models that are intractable for an extensive form formulation become possible. Computational results suggest that solution time requirement does not increase significantly when considering distributional robust counterparts to the stochastic programming models.
Transport mechanisms in iontophoresis. I. A theoretical model for the effect of electroosmotic flow on flux enhancement in transdermal iontophoresis.

Bulk fluid flow or volume flow in the direction of counterion flow is a probable mechanism for enhanced flux of uncharged species by iontophoresis. Both the electrical volume force effect, resulting from the interaction of the “ion atmosphere” and the electric field, and an induced osmotic pressure effect produce volume flow in the same direction as counterion flow through the membrane. Since each of these effects is proportional to the membrane charge and the imposed electric field, we classify both as electroosmotic flow. This research develops a detailed theoretical model which allows the effect of volume flow on flux enhancement to be evaluated. A detailed theoretical result for the electroosmotic flow coefficient also results from the analysis. The model assumes that transport occurs in three types of aqueous pores: positively charged, neutral, and negatively charged. For hairless mouse skin (HMS), pore size, charge, and number are evaluated from transference number, volume flow, and electrical resistance data. The flux enhancement ratio is J1/J1D= ΣAiαi/[l –exp( –αi)], where i = pore type, and the summation runs over the three pore types. Ai is the area fraction of pore type i effective for transport; J1 and J1D are flux of species 1 with and without the electric field, respectively; and αi is given by αi = F(–ΔΦ/RT)[ z1 + (−zmi)Bari2Cmi(Gi + F)]. Here F = Faraday's constant; −ΔΦ = voltage drop; R = gas constant; T = absolute temperature; zmi = charge of pore i; Cmi = charge concentration in membrane pore of radius, ri; B is a known collection of constants; a is the Stokes radius of the transported solute; Gi, is a function of membrane charge and pore radius coming from the electrical volume force effect; and F is a function of membrane charge and ion mobility arising from the induced osmotic pressure effect. For transdermal iontophoresis, F 0) or a neutral species (z1 = 0) in a negatively charged pore. The theoretical results are consistent with data in the literature.
Customer Resources and Economic Sustainability of Online Channels

In this chapter, I used the strategy dynamics methodology, which is a combination of the resource-based theory and system dynamics, to explain the sustained ability of two online channels to deliver economic value to its users. I posed that since spam and file-sharing applications are acutely dependent on customer resources they both can be understood in terms of the limits-to-growth generic feedback structure. That insight led to a conclusion that these digital channels were able to survive and thrive due to their underlying feedback structure. The computer experiments, however, made it clear that despite their apparent invulnerability commercial e-mail and file-sharing can succumb to strong external shocks.
Improved Glioma Grading Using Deep Convolutional Neural Networks.

BACKGROUND AND PURPOSE: Accurate determination of glioma grade leads to improved treatment planning. The criterion standard for glioma grading is invasive tissue sampling. Recently, radiomic features have shown excellent potential in glioma-grade prediction. These features may not fully exploit the underlying information in MR images. The objective of this study was to investigate the performance of features learned by a convolutional neural network compared with standard radiomic features for grade prediction. MATERIALS AND METHODS: A total of 237 patients with gliomas were included in this study. All images were resampled, registered, skull-stripped, and segmented to extract the tumors. The learned features from the trained convolutional neural network were used for grade prediction. The performance of the proposed method was compared with standard machine learning approaches, support vector machine, random forests, and gradient boosting trained with radiomic features. RESULTS: The experimental results demonstrate that using learned features extracted from the convolutional neural network achieves an average accuracy of 87%, outperforming the methods considering radiomic features alone. The top-performing machine learning model is gradient boosting with an average accuracy of 64%. Thus, there is a 23% improvement in accuracy, and it is an efficient technique for grade prediction. CONCLUSIONS: Convolutional neural networks are able to learn discriminating features automatically, and these features provide added value for grading gliomas. The proposed framework may provide substantial improvement in glioma-grade prediction; however, further validation is needed.
Co-administration of meloxicam and gabapentin does not compromise beef bull semen quality

Feet and leg soundness are of critical importance for breeding bulls, and lameness is a common problem affecting bulls. Lameness pain in the bovine typically has both inflammatory and neuropathic components, and often coincides with a decline in fertility. As neuropathic pain is refractory to non-steroidal anti-inflammatory drugs (NSAIDs), y-aminobutyric acid (GABA) analogues are commonly used in conjunction with NSAIDs to treat lameness in cattle. Meloxicam, an NSAID, and gabapentin, a GABA analogue, are frequently used extra-label under the supervision of a veterinarian to mitigate pain associated with lameness. Though neither of these compounds is currently labeled for use in bovines in the United States, previous research has indicated that the pharmokinetic profiles of these drugs support further evaluation for clinical use as analgesics in bovines. A decline in fertility is often observed in lame bulls; however, the pathogenesis of this transient subfertility is unknown. Currently, no controlled studies have been conducted to evaluate the effects of meloxicam and gabapentin analgesics on bull fertility. Thus, the objective of the present study was to evaluate the effects of meloxicam and gabapentin combination therapy on beef bull semen quality. It was hypothesized that treatment with meloxicam and gabapentin might have deleterious effects on semen quality.
Prudent Adventure: how does political status affect localgovernment innovations?

What are the concerns and motivations behind policy innovations? Theories claim that local policymakers carry out policy innovations mainly because of economic reasons or other internal concerns but seldomly notice the political structure they face. This study constructs a unique dataset of Chinese local government innovations during 2001-2016 and categorizes them with Natural Language Processing (NLP) techniques. We then examine how economic factors affect policy innovations and how political status brings better explanations. In a centralized authoritarian state like China, local politicians concern political resources and risks more than economic development. We argue that local officials can take the adventure to make institutional rearrangements when enabled but ultimately have to be prudent when closely bonded with the center.
The metabolism of T4 phage ghost-infected cells: I. Macromolecular synthesis and transport of nucleic acid and protein precursors

Abstract Whether the phage protein coat (ghost) plays an integral part in the shutoff of host macromolecular syntheses during T4 phage infection is being investigated. Ghosts have been purified by sucrose gradient centrifugation and some of their properties examined. It has been found that: (1) DNA, RNA, and protein synthesis are completely inhibited within 2 min of the addition of ghosts to a culture of host cells; (2) the dose-response curve for the above effects follows “one-hit” kinetics; (3) chloramphenicol does not protect the host cell from the effect of the ghost; (4) the transport of nucleosides and nucleotide bases is inhibited in ghost-infected cells, but is not affected in phage-infected cells, even in the presence of inhibitors of protein synthesis or in cells infected with mutants of phage which are unable to synthesize DNA; (5) after ghost infection the soluble pools of nucleotides are completely depleted, being lost to the surrounding medium, while phage-infected cells have the ability to maintain their soluble pools at their preinfection level. A model is presented to explain these events.
The Sample Complexity of Learning Fixed-Structure Bayesian Networks

We consider the problem of PAC learning probabilistic networks in the case where the structure of the net is specified beforehand. We allow the conditional probabilities to be represented in any manner (as tables or specialized functions) and obtain sample complexity bounds for learning nets with and without hidden nodes.
Wing upstroke and the evolution of flapping flight

Movements of the wing during upstroke in birds capable of powered flight are more complex than those of downstroke1,2,3. The m. supracoracoideus (SC) is a muscle with a highly derived morphology that is generally considered to be the primary elevator of the wing4,5,6. This muscle arises from the ventrally oriented sternum and its tendon of insertion passes craniodorsally through a special bony canal, around a bony process which deflects it laterally, to attach on the dorsal aspect of the humerus above the glenohumeral joint (Fig. 1). We studied the contractile properties of the SC in situ and related them to wing kinematics in the European starling (Sturnus vulgaris). Our findings indicate that the primary role of the SC is to impart a high-velocity rotation about the longitudinal axis of the humerus. This rapid ‘twisting’ of the humerus, coupled with limited humeral elevation, is responsible for positioning the forearm and hand so that their subsequent extension orients the outstretched wing appropriately for the following downstroke. This reinterpretation of the primary function of the SC provides insight into the selective advantage of its unique musculoskeletal organization in the evolution of powered flapping flight in birds.
Switched-compensation technique in switched-capacitor circuit for achieving fast settling performance

A switched-compensation technique (SCT) is proposed for switched-capacitor circuit applications to provide fast settling performance while reducing the quiescent power consumption. The SCT can be easily implemented into flip-around switched-capacitor amplifier in which the settling time requirement is a critical index of performance. Simulation results based on a 0.13µm CMOS process are presented. Compared with a conventional switched-capacitor amplifier, a SCT-based implementation reduces the quiescent power consumption by 75% and settling time within 1% error by half.
Movement-related inputs to intermediate cerebellum of the monkey

1. The primary goal of this study was to characterize the information about single-joint forelimb movements supplied to intermediate cerebellar cortex by mossy fibers. Discharge of mossy fibers and Golgi cells was studied while monkeys operated six devices that required movements about specific joints. Additional control experiments in anesthetized cats and monkeys established criteria for identification of mossy fibers and Golgi cells. 2. The control experiments demonstrate that mossy fibers can be distinguished from Purkinje and Golgi cells by the waveshapes of their action potentials. Asynaptic activation from the inferior cerebellar peduncle, in combination with histological localization of recording sites in granular layer or subcortical white matter, verified that mossy fibers produce a variety of waveshapes that are characterized by brief initial phases and relatively small amplitudes. The same waveshapes were observed for the mossy fiber recordings from awake monkeys, and many identified mossy fibers had sensory properties similar to those found in the awake animals. From these combined criteria, we conclude that the recordings in the awake animals were from mossy fibers. Golgi cells, recorded exclusively in the granular layer of cerebellar cortex, were characterized by action potentials of longer duration and larger amplitude as compared with mossy fibers, and none were asynaptically activated from the inferior cerebellar peduncle. 3. Units were isolated while the monkeys made free-form and tracking movements. We studied movement-related discharge of 80 mossy fibers and 12 Golgi cells. Mossy fibers showed high modulations during use of at least one of the six manipulanda and had clear preferences for movement about a specific joint, although they often showed consistent but weaker firing during movement about a neighboring joint. Separation of movements by more than one joint produced a large reduction in discharge: shoulder units never fired well to movements of the finger, and finger units never fired well to movement of the shoulder. 4. The tracking task required maintenance of fixed limb positions (a static phase) as well as movements between these positions (a dynamic phase). Of 80 mossy fibers, 18% had purely tonic discharge patterns, 63% were phasic-tonic, and 20% were purely phasic. Discharge patterns were reciprocal (45%), bidirectional (42%), or unidirectional (13%). 5. Eighty percent of the mossy fibers exhibited tonic discharge that was significantly (P < 0.01) correlated with joint angle (r = 0.65 +/- 0.19, mean +/- SD), and about one third had phasic components that were significantly correlated with movement velocity.(ABSTRACT TRUNCATED AT 400 WORDS)