cssi/SciSciGPT-SciSciNet huggingface dataset:
Mutations in Pneumococcal cpsE Generated via In Vitro Serial Passaging Reveal a Potential Mechanism of Reduced Encapsulation Utilized by a Conjunctival Isolate

ABSTRACT The polysaccharide capsule of Streptococcus pneumoniae is required for nasopharyngeal colonization and for invasive disease in the lungs, blood, and meninges. In contrast, the vast majority of conjunctival isolates are acapsular. The first serotype-specific gene in the capsule operon, cpsE , encodes the initiating glycosyltransferase and is one of the few serotype-specific genes that can tolerate null mutations. This report characterizes a spontaneously arising TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication in cpsE which results in duplication of Ala and Ile at positions 45 and 46. This strain (AI45dup) possessed more exposed phosphorylcholine and was hypersusceptible to C3 complement deposition compared to the wild type. Accordingly, the mutant was significantly better at forming abiotic biofilms and binding epithelial cells in vitro but was avirulent in a sepsis model. In vitro serial passaging of the wild-type strain failed to reproduce the AI45dup mutation but instead led to a variety of mutants with reduced capsule harboring single nucleotide polymorphisms (SNPs) in cpsE . A single passage in the sepsis model after high-dose inoculation readily yielded revertants of AI45dup with restored wild-type capsule level, but the majority of SNP alleles of cpsE could not revert, suppress, or bypass. Analysis of cpsE in conjunctival isolates revealed a strain with a single missense mutation at amino acid position 377, which was responsible for reduced encapsulation. This study supports the hypothesis that spontaneous, nonreverting mutations in cpsE serve as a form of adaptive mutation by providing a selective advantage to S. pneumoniae in niches where expression of capsule is detrimental. IMPORTANCE While the capsule of Streptococcus pneumoniae is required for colonization and invasive disease, most conjunctival isolates are acapsular by virtue of deletion of the entire capsular operon. We show that spontaneous acapsular mutants isolated in vitro harbor mostly nonrevertible single nucleotide polymorphism (SNP) null mutations in cpsE , encoding the initiating glycosyltransferase. From a small collection of acapsular conjunctival isolates, we identified one strain with a complete capsular operon but containing a SNP in cpsE that we show is responsible for the acapsular phenotype. We propose that acapsular conjunctival isolates may arise initially from such nonreverting SNP null mutations in cpsE , which can be followed later by deletion of portions or all of the cps operon.
The Element of Choice in Criteria of Death

Death is easier to undergo than to understand. It comes unbidden or we can attain it with minimal effort. Yet the willfulness of human nature makes it difficult for us to settle for the easy; it is understanding of it we want, not the experience.
Intracellular Compartmentalization of Leukotriene Biosynthesis

Leukotrienes (LTs) are potent bioactive lipids derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid (AA) metabolism. Although they have been conventionally viewed as paracrine mediators of inflammatory disease processes such as asthma (1), more recent information suggests that they are also important participants in disease processes characterized by cellular proliferation and fibrogenesis (2-4), and that they subserve a homeostatic role in antimicrobial host defense (5). In view of the actions and importance of LTs, substantial effort has been directed at increasing our understanding of the regulation of their synthesis. An extensive body of research, reviewed elsewhere in this symposium, has identified three key factors that regulate LT synthesis: (1) the steady state levels of key proteins necessary for AA release and 5-LO metabolism; (2) posttranslational modifications (such as phosphorylation) that alter the catalytic activities of these proteins; and (3) the concentrations of small molecules (e.g., Ca 2+ , ATP, and glutathione) that serve as cofactors for certain of these proteins. One additional determinant of LT biosynthesis that has been recognized is the intracellular compartmentalization of these LT-forming proteins. This topic has become a focus of investigation in our own and other laboratories, and this article reviews the current state of knowledge in this area. Indeed, a number of unexpected findings that have emerged from these studies underscore the appropriateness of a perspective on LT biology that transcends conventional notions.
XML schema refinement through redundancy detection and normalization

As XML becomes increasingly popular, XML schema design has become an increasingly important issue. One of the central objectives of good schema design is to avoid data redundancies: redundantly stored information can lead not just only to a higher data storage cost but also to increased costs for data transfer and data manipulation. Furthermore, such data redundancies can lead to potential update anomalies, rendering the database inconsistent. One strategy to avoid data redundancies is to design redundancy-free schema from the start on the basis of known functional dependencies. We observe that XML databases are often "casually designed" and XML FDs may not be determined in advance. Under such circumstances, discovering XML data redundancies from the data itself becomes necessary and is an integral part of the schema refinement (or re-design) process. We present the design and implementation of the first system, DiscoverXFD, for efficient discovery of XML data redundancies. It employs a novel XML data structure and introduces a new class of partition-based algorithms. The XML data redundancies are defined on the basis of a new notion of XML functional dependency (XML FD) that (1) extends previous notions by incorporating set elements into the XML FD specification, and (2) maintains tuple-based semantics through the novel concept of Generalized Tree Tuple (GTT). Using this comprehensive XML FD notion, we introduce a new normal form (GTT-XNF) for XML documents, and provide comprehensive comparisons with previous studies. Given the set of data redundancies (in the form of redundancy-indicating XML FDs) discovered by DiscoverXFD, we describe a normalization algorithm for converting any original XML schema into one in GTT-XNF.
Partisan Heterogeneity and International Cooperation The Case of the European Development Fund

This article analyzes the relationship between partisan heterogeneity and cooperation in international organizations. We argue that partisan heterogeneity increases distributional conflict among states during intergovernmental negotiations, thereby increasing the costs of cooperation. This decreases governments’ willingness to contribute to cooperative efforts. We test the theory against data on governments’ financial contributions to the European Development Fund. The empirical analyses robustly demonstrate that partisan heterogeneity reduces governments’ incentives to contribute to European cooperation on international development. On a more general level, we offer new perspective on the role of domestic politics in international cooperation.
Statistical Postprocessing of High-Resolution Regional Climate Model Output

AbstractStatistical postprocessing techniques have become essential tools for downscaling large-scale information to the point scale, and also for providing a better probabilistic characterization of hydrometeorological variables in simulation and forecasting applications at both short and long time scales. In this paper, the authors assess the utility of statistical postprocessing methods for generating probabilistic estimates of daily precipitation totals, using deterministic high-resolution outputs obtained with the Weather Research and Forecasting (WRF) Model. After a preliminary assessment of WRF simulations over a historical period, the performance of three postprocessing techniques is compared: multinomial logistic regression (MnLR), quantile regression (QR), and Bayesian model averaging (BMA)—all of which use WRF outputs as potential predictors. Results demonstrate that the WRF Model has skill in reproducing observed precipitation events, especially during fall/winter. Furthermore, it is shown tha...
Lynx Habitat Suitability In and Near Voyageurs National Park

ABSTRACT: Voyageurs National Park (VNP) is within the historical distribution of Canada lynx (Lynx canadensis), a federally threatened species. Sightings of lynx in and near VNP have existed since the 1970s, and three recent sightings have been confirmed with DNA analysis. However, population status and habitat suitability for lynx in VNP are unknown. We used remote cameras and snow-tracking to search for lynx in and near VNP in 2007 and 2008 and did not document lynx presence. We estimated the density of the lynx's primary prey, snowshoe hare (Lepus americanus), with hare pellet counts, extrapolated hare density to the landscape level, and compared habitat in VNP to habitat in lynx home ranges in northeastern Minnesota. Hare pellet densities in VNP were about half of hare pellet densities in lynx home ranges in northeastern Minnesota. Even though patches of high-density hare habitat exist in the VNP area, the low density of snowshoe hares at the landscape level would not support resident lynx, and most o...
Inhibition of Nitrate Reduction by Chromium(VI) in Anaerobic Soil Microcosms

Chromium is often found as a cocontaminant at sites polluted with organic compounds. For nitrate-respiring microbes, Cr(VI) may be not only directly toxic but may also specifically interfere with N reduction. In soil microcosms amended with organic electron donors, Cr(VI), and nitrate, bacteria oxidized added carbon, but relatively low doses of Cr(VI) caused a lag and then lower rates of CO2 accumulation. Cr(VI) strongly inhibited nitrate reduction; it occurred only after soluble Cr(VI) could not be detected. However, Cr(VI) additions did not eliminate Cr-sensitive populations; after a second dose of Cr(VI), bacterial activity was strongly inhibited. Differences in microbial community composition (assayed by PCR-denaturing gradient gel electrophoresis) driven by different organic substrates (glucose and protein) were smaller than when other electron acceptors had been used. However, the selection of bacterial phylotypes was modified by Cr(VI). Nine isolated clades of facultatively anaerobic Cr(VI)-resistant bacteria were closely related to cultivated members of the phylum Actinobacteria or Firmicutes. In Bacillus cereus GNCR-4, the nature of the electron donor (fermentable or nonfermentable) affected Cr(VI) resistance level and anaerobic nitrate metabolism. Our results indicate that carbon utilization and nitrate reduction in these soils were contingent upon the reduction of added Cr(VI). The amount of Cr(VI) required to inhibit nitrate reduction was 10-fold less than for aerobic catabolism of the same organic substrate. We speculate that the resistance level of a microbial process is directly related to the diversity of microbes capable of conducting it.
A Model for Analyzing Instructional Components To Facilitate Generalization for Severely Handicapped Students

A model is presented for analyzing the components of instructional programs that are likely to affect generalization with severely handicapped students. The literature is summarized in terms of such issues as natural vs. artificial environments, materials, cues, and contingencies. The authors also review empirical evidence about the relative efficacy of serial vs. concurrent presentation, prompts vs. corrections, and various instructional arrangements. Suggestions are offered for implementation, and research needs are described for several components. Future research on the interactive effects of the components with each other and with the learners' characteristics are discussed.
Attachment dimensions and the big five personality traits: Associations and comparative ability to predict relationship quality

Abstract Several studies have explored associations between measures of adult attachment style and the Big Five personality traits or factors, but the studies have not included current dimensional measures of attachment style ( Brennan, Clark, & Shaver, 1998 ) or the most complete (NEO-PI-R; Costa & McCrae, 1992 ) and frequently used (BFI; John, Donahue, & Kentle, 1991 ) measures of the Big Five. Moreover, most studies after Shaver and Brennan’s (1992) have not compared attachment style and Big Five measures as predictors of relationship quality. Here, we summarize past research and report two studies comparing Brennan et al.’s two-dimensional measure of attachment style with the BFI and NEO-PI-R measures of the Big Five. There are consistent and theoretically meaningful associations between the attachment-style and personality trait measures, but attachment-style dimensions still predict relationship quality better than measures of the Big Five. Implications are discussed.
Parochial Altruists or Ideologues? An Agent Based Model of Commitment to Self Sacrifice

What motivates suicide attackers remains an open question. From an evolutionary perspective, commitment to suicide missions is puzzling since such behavior is fitness reducing. We model suicide terrorism by drawing on two fundamental human motivations: altruism and selfishness. Martyrdom can be viewed as altruistic- benefiting group members at a cost to oneself, as well as selfish- ideological belief in a profitable afterlife. Our simulations identify that some degree of both behaviors are essential in order to facilitate a commitment to sacrifice. Thus, manipulations of ideology and altruism can tip the threshold and set the agents on the path of martyrdom.
Case studies and pervasive instruction: Using journalism education techniques in the information literacy classroom

Purpose – The purpose of this paper is to explore whether journalism education techniques can be adapted for use in the information literacy classroom as a means of teaching the ethical use of information. Design – The author uses personal experience as a journalist and graduate of journalism education programs to examine the similarities between journalism pedagogy and information literacy and whether any aspect of journalism pedagogy is transferrable to the information literacy classroom. Findings – Journalism educators deliver a potent anti-plagiarism message using case studies and “war stories” from the newsroom delivered through the pervasive instruction method or stand-alone ethics class. Using case studies from a variety of different disciplines in information literacy classes could help students make a stronger connection between honest writing in all subjects. However, until information literacy is taught more widely in libraries as semester-long classes, it would be difficult to use journalism’s...
A different function for a critical tryptophan in c-Raf and Hck

The similarity of the catalytic domains of Raf and Src family members suggests that functions of homologous residues may be similar in both kinase families. A tryptophan residue, W260, in the WEI region of the Src family kinase Hck has an important role in regulating ATP binding. We tested the hypothesis that the tryptophan, W342, in the WEI region of c-Raf may have a similar role to the W260 of Hck. Mutation of W260 to A in Hck activates kinase activity, but we found that mutation of W342 to A in c-Raf inactivates the kinase activity. Mutating W342 to aspartate (D), lysine (K) or histidine (H) also inactivated c-Raf whether assayed as a purified immunoprecipitate or when recruited to the plasma membrane. A constitutively active c-Raf can be generated by mutating two regulatory tyrosines to aspartate. When placed into this active c-Raf mutant, mutation of W342 to D, K or H enabled phosphorylation and activation of the c-Raf substrate MEK at the plasma membrane but not in an immunoprecipitation assay. We conclude that (1) Tryptophan has a different role in the WEI regions of c-Raf and Hck, (2) W342 is not directly involved in MEK binding as both positive and negative residues at 342 are permissive for MEK activation at the membrane in a constitutively active c-Raf mutant, (3) Factors at the membrane are capable of potentiating activation of c-Raf containing mutated W342 in a hyperactivated c-Raf, but not in a wild type c-Raf and (4) There is a stringent structural requirement for W at residue 342 in c-Raf.
Experiments on the Antidermatitis Component of the Filtrate Factor in Rats

SummaryA purified but still crude zinc salt of pantothenic acid proved to be active in the cure of specific skin lesions and in promotion of growth in rats fed a diet devoid of the filtrate fraction. Autoclaving at pH 10 destroyed the activity of the preparation.‡
Intrachannel Conflict and Use of Power: A Reply:

Etgar, in his interesting comment, "Intrachannel Conflict and Use of Power" [4], states that my original article [5], "Sources of Power: Their Impact on Intrachannel Conflict," (1) fails to acknowledge the "dynamic" nature of conflict [4, p. 2731, (2) lacks "clarity as to the direction of the relationship between the use of power sources and channel conflict" [4, p. 273], and (3) "assumes that the use of power is a cause of intrachannel conflict" [4, p. 273]. I shall show that (1) a careful reading of my article will reveal all three of the preceding statements to be false, (2) the authorities cited by Etgar actually disagree with him, and (3) the preponderance of evidence in the literature does not suggest that the use of power is the end result rather than a cause of conflict. First, Etgar states that I fail to recognize the dynamic nature of conflict and cites Pondy [6] and Rosenberg and Stern [8] as support for the notion that conflict is a dynamic process. However, in my article I also cite [5, p. 383] Pondy [6] and Rosenberg and Stern [8] as support for the notion that conflict is a process. I am in agreement with the theoretical frameworks of Pondy and Rosenberg and Stern on this point. Second, Etgar suggests that my research lacks "clarity as to the direction of the relationship between the use of power sources and channel conflict" [4, p. 273]. A careful examination of my article will reveal that I clearly state the direction of the relationship between the use of power sources and conflict. More specifically, I state that ". . . threats of coercion as a response to conflict tend to intensify and increase the frequency of conflict" [5, p. 383]. Importantly, in this statement I recognize that threats of coercion come after conflict (i.e., a response), but also tend to heighten the level of conflict. Finally, Etgar believes I assume that the use of
STUDIES ON THE TOTAL BILE : VI. THE INFLUENCE OF DIET UPON THE OUTPUT OF CHOLESTEROL IN THE BILE

The development of a method for the collection of total bile from dogs in a sterile state and uninfluenced by the gall bladder, day after day for weeks, has rendered possible an accurate study of the influence of diet upon the cholesterol output of the secretion. When a diet rich in cholesterol is given the amount of the substance in the bile greatly increases. Not only this but the concentration per cc. is, in almost every instance, greater. An increase in the total food intake, by the addition to the ordinary ration of a bone mash diet containing only a slight additional amount of cholesterol (200 mg.) produces a similar, though lesser, increase. In the fasting dog, the cholesterol yield is greatly cut down. The increase in the cholesterol after food rich in the substance does not depend on the cholagogue action of this latter, though it is true that the concentration of cholesterol in the bile usually increases with the bile volume. Though fasting cuts down the cholesterol of bile, the concentration of the substance per cc. is greatly increased. On an ordinary diet the yield of it fluctuates abruptly and considerably from day to day. In general the rule holds that an animal eating largely puts out not only much more bile but much more cholesterol. The relation between bile quantity and cholesterol yield is anything but a fixed one, however. The cholesterol yield of the bile does not parallel that of bilirubin. The pigment output from day to day remains relatively constant as compared with that of cholesterol.
Influence of Touchable Nodes Deviation on Grounding Grids Corrosion Diagnosis and Its Correction

To evaluate the influence of the touchable nodes deviation due to the normalization of down lead line positions to the nearby nodes on grounding grids corrosion diagnosis,a Monte-Carlo based approach is put forward. The branch resistance vectors are set randomly,based on which,the accuracy and the testability of the results of grounding grids corrosion diagnosis are analyzed. A Tabu search based correction approach is suggested. The diagnosis results in case of deviation are used as the initial solution. The index is to minimize the summation of the squared differences between the observed voltages and the voltages after correction. The results of correction are accessed in quantity. An experimental grounding grid with sixty branches is used as an example,the results of which show that the proposed approach is feasible and that even if there is somewhat uneven corrosion,the correction still works well.y
Nuclear size measurement for distinguishing urothelial carcinomas from reactive urothelium on tissue sections.

Background Pathological diagnosis of urothelial carcinoma (UC) is primarily based on cytological atypia. It has previously been shown that high-grade (HG) UC, particularly UC in situ cells (CIS), can be over five times the size of a lymphocyte. However, this has not been demonstrated in comparison to reactive urothelium. The objective of this study was to empirically compare the difference in nuclear size of UC cells with reactive urothelial cells.
Institutional Variation in Productivist Welfare Capitalism

Challenging those who view welfare states in the developing world as either mostly identical or tremendously heterogeneous, some political economy scholars have recently discussed the possibility of systematic variation in welfare capitalism in less developed countries. Rudra (2007), for example, argues that the developing world has systematically evolved into two ideal types: the protective welfare state that emphasizes the government’s role in the “decommodification” of social welfare, and the productive welfare state that aims to integrate labor productivity into social policy. Interestingly, the result of the analysis identifies all of the observed East Asian countries as productive welfare states. Indeed, East Asian countries share some intriguing characteristics distinctive from most Western European and North American states, where the provision of social welfare has long been assumed as being one of the most important policy tasks. The newly industrialized economies (NIEs) in East Asia have invested heavily in human capital formation such as education and job training, with a focus on the “productive” function of social policy, while being less committed to the provision of “protective” programs such as pensions, health care, and income supports (Haggard and Kaufman 2008). More interestingly, East Asian NIEs have achieved impressive policy outcomes in many important areas, including infant mortality, life expectancy, and literacy rates, even without substantial increases in taxation and spending on welfare.
Types of kinematic connections of two–simple planetary three–gear trains

This paper presents general consideration of types of kinematic connections of two–simple planetary three–gear trains. For these types of kinematic connections of two–simple planetary three–gear trains the basic equations of train values have been developed by using the general equation of motion for planetary and standard gear trains (Krstich, 1985a, and 1985b). It is pointed out that there are five different ways of kinematic connections of two–simple spur or bevel planetary three–gear trains and at the same time there are five basic equations of train values as well. These types of kinematic connections of two–simple planetary three–gear trains and their basic equations of train values will aid designers and analysts in determining correct train values of these types of planetary gear train configurations.
A honeybee hive monitoring system: From surveillance cameras to Raspberry Pis

In recent years, there has been a significant loss in the number of honeybee hives due to several natural phenomena that are referred to as the Colony Collapse Disorder (CCD). Several research programs have been established to monitor honeybee hives and to understand the behavior of the bees. A reliable monitoring system is important as it provides the beekeepers an opportunity to remotely observe the progress of their hives without the need to actually open them. This paper will present the results of several years of study and investigation for creating a reliable and inexpensive hive monitoring system. Our goal has been to create an inexpensive and modular system which sends sensor data acquired from beehives to a server for further analysis. Our initial efforts utilized video surveillance system but evolved to a more reliable system that utilizes Raspberry Pis and ATmega328Ps as its framework. This paper will provide details on the initial system and how it evolved to a new system that we are calling Beemon with its data acquisition capabilities. The early video and audio recordings obtained by the system are used in some image and signal processing analysis which are not presented on this paper.
Economic Costs of Bias-Based Bullying

Because many school districts receive funding based on student attendance, absenteeism results in a high cost for the public education system. This study shows the direct links between bias-based bullying, school absenteeism because of feeling unsafe at school, and loss of funds for school districts in California. Data from the 2011-2013 California Healthy Kids Survey and the California Department of Education were utilized. Results indicate that annually, California school districts lose an estimated $276 million of unallocated funds because of student absences resulting from feeling unsafe at school. Experiences of bias-based bullying were significantly associated with student absenteeism, and the combination of these experiences resulted in a loss of funds to school districts. For example, the absence of students who experienced bullying based on their race or ethnicity resulted in a projected loss of $78 million in unallocated funds. These data indicate that in addition to fostering student safety and well-being, schools have the societal obligation and economic responsibility to prevent bias-based bullying and related absenteeism. (PsycINFO Database Record
Risk factors for subtherapeutic levels of posaconazole tablet

Background Posaconazole is the prophylactic antifungal of choice for patients with haematological malignancies at high risk of invasive fungal infections (IFIs). Studies have demonstrated that subtherapeutic concentrations of posaconazole are associated with breakthrough fungal infections and specific risk factors for subtherapeutic troughs associated with the suspension formulation have been identified. However, these risk factors have not been evaluated in a large patient population with the recently approved tablet formulation. Objectives To determine the risk factors for subtherapeutic posaconazole troughs associated with the tablet formulation in patients receiving posaconazole as IFI prophylaxis. Patients and methods From 1 February 2013 to 31 March 2015 all posaconazole serum trough concentrations were evaluated. A total of 157 patients receiving posaconazole tablet for prophylaxis during induction therapy for haematological malignancies and allogeneic stem cell transplant recipients with graft-versus-host disease were included for analysis. Results Overall, 28 patients (18%) had subtherapeutic troughs ( 90 kg (n = 14; 48%) (P = 0.047). Conclusions While the posaconazole tablet has provided more consistent therapeutic concentrations when compared with the suspension there may still be a role for therapeutic drug monitoring (TDM). These results may guide us to a specific population in which TDM is necessary to identify subtherapeutic troughs.
An overview of molecular layer deposition for organic and organic–inorganic hybrid materials: mechanisms, growth characteristics, and promising applications

It has been a strong desire for researchers to control material growth at the molecular and atomic levels. Molecular and atomic layer deposition (MLD and ALD) are two such techniques. In comparison to a huge amount of studies invested on ALD, the research on MLD is still relatively limited due to the difficulty in finding suitable coupling precursors, but the recently successful applications of MLD are very encouraging in many areas such as surface engineering, new energies, and catalysis. In order to further stimulate more research enthusiasm and educate beginners, we contribute this thorough survey on the progress of MLD. This review is a comprehensive account of MLD processes for organic and organic–inorganic materials, covering precursors, surface chemistry, growth characteristics, film properties, and promising applications. The work provides a complete summary of over 80 MLD processes for growing over 20 types of pure polymeric and metal-based hybrid polymeric materials. Given their similarities in mechanisms, we made a comparative description between ALD and MLD, and discussed the uncountable possibilities to combine both ALD and MLD for advanced materials with desirable properties. To feature and highlight the significance of MLD, this review specially gives some detailed discussions on MLD's applications in several important areas, including novel nanostructured materials, surface engineering, new energies (i.e., batteries, supercapacitors, solar cells, and water splitting), catalysis, and rewritable data storage. With this work, we expect to boost research interest and attempts at advanced materials using MLD as well as ALD.
Canonical Notch Signaling Directs the Fate of Differentiating Neurocompetent Progenitors in the Mammalian Olfactory Epithelium

The adult olfactory epithelium (OE) has the remarkable capacity to regenerate fully both neurosensory and non-neuronal cell types after severe epithelial injury. Lifelong persistence of two stem cell populations supports OE regeneration when damaged: the horizontal basal cells (HBCs), dormant and held in reserve; and globose basal cells, a heterogeneous population most of which are actively dividing. Both populations regenerate all cell types of the OE after injury, but the mechanisms underlying neuronal versus non-neuronal lineage commitment after recruitment of the stem cell pools remains unknown. We used both retroviral transduction and mouse lines that permit conditional cell-specific genetic manipulation as well as the tracing of progeny to study the role of canonical Notch signaling in the determination of neuronal versus non-neuronal lineages in the regenerating adult OE. Excision of either Notch1 or Notch2 genes alone in HBCs did not alter progenitor fate during recovery from epithelial injury, whereas conditional knock-out of both Notch1 and Notch2 together, retroviral transduction of progenitors with a dominant-negative form of MAML (mastermind-like), or excision of the downstream cofactor RBPJ caused progeny to adopt a neuronal fate exclusively. Conversely, we show that overexpressing the Notch1-intracellular domain (N1ICD) either genetically or by transduction blocks neuronal differentiation completely. However, N1ICD overexpression requires both alleles of the canonical cofactor RBPJ to specify downstream lineage. Together, our results suggest that canonical RBPJ-dependent Notch signaling through redundant Notch1 and Notch2 receptors is both necessary and sufficient for determining neuronal versus non-neuronal differentiation in the regenerating adult OE.SIGNIFICANCE STATEMENT Despite the substantial reconstitution of the olfactory epithelium and its population of sensory neurons after injury, disruption and exhaustion of neurogenesis is a consequence of aging and a cause of olfactory dysfunction. Understanding the mechanisms underlying the generation of replacement neurons and non-neuronal cells is critical to any therapeutic strategy aimed at rebuilding a functional neuroepithelium. The results shown here demonstrate that canonical Notch signaling determines the balance between neurons and non-neuronal cells during restoration of the epithelium after injury. Moreover, the complexities of the multiple Notch pathways impinging on that decision are dissected in detail. Finally, RBPJ, the canonical Notch transcriptional cofactor, exhibits a heretofore unreported haploinsufficiency in setting the balance among the regenerating populations.
A Unique All-Payer Rate-Setting System Controls the Cost but Not the Racial Disparity in Lower Extremity Revascularization Procedures

Background Patients with peripheral arterial disease often have high comorbidity burden that may complicate post-interventional course and drive increased health-care expenditures. Racial disparity had been observed in lower extremity revascularization (LER) patterns and outcomes. In 2014, Maryland adopted an all-payer rate-setting system to limit the rising hospitalization costs. This resulted in an aggregate payment system in which hospital compensation takes place as an overall per capita expenditure for hospital services. We sought to examine racial differences and other patient-level factors that might lead to discrepancies in LER hospital costs in the State of Maryland. Methods We used International Classification of Diseases, Ninth Revision codes to identify patients who underwent infrainguinal open bypass (open) and endovascular repair (endo) in the Maryland Health Services Cost Review Commission database (2009–2015). Multivariable generalized linear model regression analysis was conducted to report cost differences adjusting for patient-specific demographics, comorbidities, and insurance status. Logistic regression analysis was used to assess quality metrics: intensive care unit (ICU) admission, 30-day readmission, protracted length of stay (pLOS) (endo: pLOS >9, open: pLOS > 10 days) and in-hospital mortality. Results Among patients undergoing open, costs were higher for nonwhite patients (African-American [AA]: $6,092 [4,682–7,501], other: $3,324 [437–6,212]; both P ≤ 0.024), diabetics ($2,058 [837–3,279]; P Conclusions This study showed that the all-payer rate-setting system has curbed the LER rising costs, but these costs remained disproportionally higher for disadvantaged populations such as AA and Medicaid communities. This underpins the existing racial disparity in LER. AA patients had higher LER costs, most likely driven by extended hospitalization and ICU admission. Efforts could be directed to evaluate the contributing socioeconomic factors, invest in primary prevention of comorbid conditions that had shown to be associated with prohibitive costs, and identify mechanisms to overcome the existing racial disparity in LER within the promising cost-saving payment system at the State of Maryland.
Beech Bark Disease Complex

This is a story of ecological succession—of interrelationships between a fungus and an insect, and the secondary roles played by other fungi and other insects. The disease, or more properly the disease complex, occurs on the American beech in the Northeastern United States and the Maritime provinces of Canada. The beech scale, Cryptococcus fagi, feeds on the bark (Fig. 31-1B) and the fungus, Nectria coccinea var.
ACETALDEHYDE OXIDATION BY ISOLATED HEPATIC ALDEHYDE DEHYDROGENASE, MITOCHONDRIA AND PARENCHYMAL CELLS, AND BY PERFUSED INTACT LIVER OF THE RAT

Semi-purified low-Km aldehyde dehydrogenase (1-AldDH), mitochondria (Mt) and parenchymal cells (LC) isolated from normal rat liver, and intact perfused liver have been used to study in vivo liver acetaldehyde oxidation. 1-AldDH activity was maximum at 5 μM acetaldehyde (AA), decreasing above 25 μM acetaldehyde. In intact Mt the state 2 respiration was maximally shifted to the state 3 at 5 μM AA and gradually inhibited above 40 μM. At approximately 310 μM AA, however, reactivation of O2 consumption occurred. The rotenone-treated Mt showed activated O2 consumption at 70 μM AA in the presence of supplemental cytochrome c and NAD+. On the other hand, in intact Mt, 100 μM AA caused an inhibition of state 3 respiration using B-hydroxybutyrate but no inhibition of succinate respiration. In the isolated LC, AA induced a transient reduction of NAD+, flavoprotein, and cytochrome c. Treating LC with both propyl pyrazole and a low concentration of NaN3 increased the response to AA of NAD+, flavoprotein, and cytochrome c, so it was possible to detect the redox change of these three components in response to AA at concentrations as low as 2 μM. A fast and subsequently slow pronounced biphasic response was produced by AA of more than 20 μM. The v-log(S) plot of the fast phase in the NAD+ reduction revealed the presence of at least two components of NAD+-linked Aldehyde Dehydrogenase in the liver cells. A steady state titration in the perfused liver supports the existence of biphasic in vivo acetaldehyde oxidation. These results suggest the following: at AA at less than 50 μM, AA seems to be oxidized both on the inside and outside of Mt. At greater AA concentrations, 1-AldDH is partially substrate-inhibited and other enzymes contributed to the AA oxidation. Submillimolar levels of AA effect inhibition at the mitochondrial energy coupling site 1.
A phase I pharmacokinetic and pharmacodynamic study of GTI-2040 in combination with gemcitabine in patients with solid tumors

GTI-2040 is a novel antisense oligonucleotide inhibitor of the R2 subunit of ribonucleotide reductase. This phase I study assessed safety and maximum tolerated dose (MTD) of GTI-2040 in combination with weekly gemcitabine in patients with advanced solid tumors. GTI-2040 was given as a 14-day continuous intravenous infusion, while gemcitabine was administered on days 1, 8, and 15. This combination was repeated every 4 weeks and study followed a modified 3 + 3 Fibonacci schema. Incidence, severity of adverse events, pharmacokinetics (PK), and pharmacodynamics (PD) was assessed. Responses were assessed using RECIST criteria version 1.0 with CT scans performed after every other cycle. A total of 16 patients received at least one dose of GTI-2040/gemcitabine and were included in the safety analysis. The MTD of this regimen is 100 mg/m2/day of GTI-2040 over 14 days combined with 400 mg/m2/day of gemcitabine administered weekly on days 1, 8, and 15. The dose-limiting toxicities (DLTs) included grade 3 fatigue and thrombocytopenia with hematemesis (both at 100/600 mg/m2/day). The most common adverse events were grade 1/2 fatigue, nausea, vomiting, diarrhea, and anorexia. There was no evidence of alteration in gemcitabine PKs. PD modulation of R2mRNA expression in peripheral blood mononuclear cells was observed. No objective tumor response was observed although stable disease was seen in 25% patients. The combination of GTI-2040 and gemcitabine has an acceptable safety profile in a heavily pre-treated patient population with advanced solid tumors. No clear signal of anti-tumor activity was observed; however, several patients had prolonged stable disease.
The Relationship Between 2011 METAR and TAF Data at Chicago-Midway and Seattle-Tacoma Airports

This study examined the relationship between expected meteorological conditions as specified by TAF reports and actual ground conditions as specified by hourly METAR reports for Chicago-Midway (MDW) and Seattle-Tacoma (SEA) airports for the period September–December 2011. MDW and SEA were targeted because they had the highest and lowest percentage of delays, respectively, for 2011. The rationale was to determine if one of the contributing factors for the difference in percentage delays was because of the relationship between TAF and METAR reports. The primary hypothesis was that the relationship between the forecasts and actual ground conditions at MDW would be weaker than the corresponding relationship at SEA. TAF and METAR data were acquired from the respective TAF and METAR products pages at “Aviation Weather Charts Archive” (2012). Descriptive statistics revealed that MDW had less total departures than SEA (86,834 vs. 100,133) for all of 2011, but it also had nearly five times as many weather-related departure delays than SEA. Chi square analyses indicated that although the relationship between TAF and METAR at each airport was statistically significant, the corresponding Kappa agreement coefficients showed that this relationship was nearly twice as strong at MDW (.60) than at SEA (.35). Plausible explanations include that 70% of the weather conditions at MDW were VFR as opposed to only 56% at SEA, MDW had one-third the number of special METARS than SEA (374 vs. 917), and MDW had approximately one-fifth the number of LIFR conditions than SEA (70 vs. 337). The analysis also revealed that SEA had difficulty correctly forecasting IFR and LIFR conditions, especially under rapidly changing conditions. Based on the study’s findings, it appears that the relationship between TAF and METAR was not a contributing factor to departure delays at both MDW and SEA during the September– December 2011 period.
RFI Cancellation for an Array Radio Astronomy System With Receiver Nonlinearity

Radio frequency interference (RFI) is an important problem for a radio astronomy system (RAS) due to the very weak radio astronomical signals. Rapid expansions of active wireless systems (AWSs), as well as more demands for spectrum access by both AWS and RAS will result in scenarios with strong RFI. This will cause RAS's low-noise amplifier (LNA) to operate in a nonlinear region and impose a more challenging nonlinear RFI issue. We address this issue for RAS with the antenna array. We develop a new signal model at the output of RAS array processing when the LNA at each RAS receiver behaves nonlinearly. We show that the two existing methods to address RFI in RAS array systems fail to deal with the nonlinear RFI. Next, we propose two modified methods to address the nonlinear RFI. Analysis of the squared error of the RAS signal correlation estimate is also presented. The numerical results show the severe effects of nonlinear RFI and the capability of the proposed methods to keep the squared error almost as low as that of a linear system.
Food security and food self-sufficiency around the world: A typology of countries.

The particularities of agriculture, as a sector which ensures food supply, result from many factors, including the multilateral interaction between the environment and human activity. The extent of human intervention in the food production process is usually measured with the amount of capital expenditure. Therefore, the food production potential and the resulting food security depend on both natural and economic factors. This paper identifies the current status of food security in different countries around the world, considering both aspects (physical and economic availability) combined together. The variables published by FAO were used together with a variable estimated based on the author’s own methodology to identify 8 groups of countries characterized by economic development level, net trade in agricultural products, and selected variables related to agriculture and food situation. As shown by this study, the degree to which food security is ensured with domestic supply varies strongly across the globe. Domestic production provides a foundation for food security in wealthy countries, usually located in areas with favorable conditions for agriculture (including North America, Australia, New Zealand, Kazakhstan) and in countries which, though characterized by a relatively small area of arable land per capita, demonstrate high production intensity (mainly European countries). International trade largely contributes to food security in Middle East and North African countries as well as in selected South American countries which are net importers of food products. The most problematic food situation continues to affect Sub-Saharan Africa and Central Asia.
Treatment in autism spectrum disorder: Areas of unmet need in the United States

Abstract Studies on outcomes for persons with autism spectrum disorder can be conceptualized using broad long-term and short-term constructs, short-term targeted constructs, and most recently, critical elements. This chapter reviews the literature from a top-down perspective and synthesizes outcomes in relation to evidenced-based interventions and available services. In the United States, community treatment has shown significant results treating some of the characteristic features of the disorder such as language and behavior. Social domains and comorbid symptoms show a great deal of promise while adaptive skills have not been well served. Developmental deficits identified during the preschool period tended to remain significant at follow-up, and services were lacking. The research is discussed with a focus on these areas of need that are currently not well served by existing treatment options in the United States.
Large Animal Models of Inherited Retinal Degenerations: A Review

Studies utilizing large animal models of inherited retinal degeneration (IRD) have proven important in not only the development of translational therapeutic approaches, but also in improving our understanding of disease mechanisms. The dog is the predominant species utilized because spontaneous IRD is common in the canine pet population. Cats are also a source of spontaneous IRDs. Other large animal models with spontaneous IRDs include sheep, horses and non-human primates (NHP). The pig has also proven valuable due to the ease in which transgenic animals can be generated and work is ongoing to produce engineered models of other large animal species including NHP. These large animal models offer important advantages over the widely used laboratory rodent models. The globe size and dimensions more closely parallel those of humans and, most importantly, they have a retinal region of high cone density and denser photoreceptor packing for high acuity vision. Laboratory rodents lack such a retinal region and, as macular disease is a critical cause for vision loss in humans, having a comparable retinal region in model species is particularly important. This review will discuss several large animal models which have been used to study disease mechanisms relevant for the equivalent human IRD.
Endovascular Aneurysm Repair in a Patient with Severe Aortic Neck Angulation Using Aorfix™ Device

A 91-year-old male underwent endovascular aneurysm repair (EVAR) for a 7.5 cm (transverse diameter) abdominal aortic aneurysm (AAA) with a severely angulated aortic neck using Aorfix™ device. Patient had a significant shrinkage of the aneurysm sac and did well for subsequent 5 years till his death unrelated to AAA.