cssi/SciSciGPT-SciSciNet huggingface dataset:
Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions.

Abstract Late in the terminal differentiation of epidermis and cultured epidermal cells, a protein envelope located beneath the plasma membrane becomes cross-linked by cellular transglutaminase. The process of cross-linking can be initiated in cultured epidermal cells by agents affecting cell membrane permeability—nonionic detergents, high salt concentrations and ionophores. These agents initiate the cross-linking process by making calcium ions available to the transglutaminase. A soluble precursor of the cross-linked envelope has been identified in crude extracts of cultured epidermal cells by its ability to incorporate labeled amines through the action of transglutaminase. The protein has been purified to homogeneity by gel filtration and chromatography on columns of DEAE-cellulose and hydroxyapatite. Comprising an estimated 5–10% of the soluble cell protein, it has a molecular weight of about 92,000, is isoelectric at pH 4.5±0.3 and has an unusual amino acid composition (46% Glx residues). It is chemically and immunochemically unrelated to keratins. The following evidence confirms that the protein becomes incorporated into cross-linked envelopes: first, washed cross-linked envelopes bind antibody to the purified protein, as shown by indirect immunofluorescence; second, absorption of the antiserum with washed envelopes removes all detectable antibodies to the purified protein; and third, the protein cannot be extracted from keratinocytes after their envelopes have become cross-linked. Examination of sections of epidermis by immunofluorescence, using antiserum to the purified protein, reveals that in addition to the stratum corneum, the living cells of the outer half of the spinous layer react strongly. The envelope precursor is present in the cytoplasm, but becomes concentrated at the cell periphery, where it will be cross-linked later, when the cells have passed through the granular layer. The protein is also concentrated in a peripheral location in cultured epidermal cells.
Pseudomonas aeruginosa AlgG is a polymer level alginate C5-mannuronan epimerase.

Alginate is a viscous extracellular polymer produced by mucoid strains of Pseudomonas aeruginosa that cause chronic pulmonary infections in patients with cystic fibrosis. Alginate is polymerized from GDP-mannuronate to a linear polymer of beta-1-4-linked residues of D-mannuronate and its C5-epimer, L-guluronate. We previously identified a gene called algG in the alginate biosynthetic operon that is required for incorporation of L-guluronate residues into alginate. In this study, we tested the hypothesis that the product of algG is a C5-epimerase that directly converts D-mannuronate to L-guluronate. The DNA sequence of algG was determined, and an open reading frame encoding a protein (AlgG) of approximately 60 kDa was identified. The inferred amino terminus of AlgG protein contained a putative signal sequence of 35 amino acids. Expression of algG in Escherichia coli demonstrated both 60-kDa pre-AlgG and 55-kDa mature AlgG proteins, the latter of which was localized to the periplasm. An N-terminal analysis of AlgG showed that the signal sequence was removed in the mature form. Pulse-chase experiments in both E. coli and P. aeruginosa provided evidence for conversion of the 60- to the 55-kDa size in vivo. Expression of algG from a plasmid inan algG (i.e., polymannuronate-producing) mutant of P. aeruginosa restored production of an alginate containing L-guluronate residues. The observation that AlgG is apparently processed and exported from the cytoplasm suggested that it may act as a polymer-level mannuronan C5-epimerase. An in vitro assay for mannuronan C5 epimerization was developed wherein extracts of E. coli expressing high levels of AlgG were incubated with polymannuronate. Epimerization of D-mannuronate to L-guluronate residues in the polymer was detected enzymatically, using a L-guluronate-specific alginate lyase of Klebsiella aerogenes. Epimerization was also detected in the in vitro reaction between recombinant AlgG and poly-D-mannuronate, using high-performance anion-exchange chromatography. The epimerization reaction was detected only when acetyl groups were removed from the poly-D-mannuronate substrate, suggesting that AlgG epimerization activity in vivo may be sensitive to acetylation of the D-mannuronan residues. These results demonstrate that AlgG has polymer-level mannuronan C5-epimerase activity.
Adoption and perceived effectiveness of financial improvement strategies in critical access hospitals.

Purpose: To ascertain the use and perceived success of strategies to improve the financial performance of Critical Access Hospitals (CAHs). Methods: Information about the use and perceived effectiveness of 44 specific strategies to improve financial performance was collected from an online survey of 291 CAH Chief Executive Officers and Chief Financial Officers. Responses were merged with financial and operational characteristics of the respondents’ hospitals obtained from Medicare cost reports. Use rates and perceived success and failure were calculated for each strategy. A cluster analysis was applied to classify strategies based on their use and success. Finally, CAH characteristics were examined to predict the use of individual strategies. Findings: Financial improvement strategies are pervasive among CAHs. The administrators who responded to the survey in this study reported using an average of 17.0 of the maximum 44 strategies listed in the survey questionnaire. Revenue/cost, human resource, and capital strategies were more frequently used than service expansion and reduction strategies. Overall, CAH characteristics did not explain the use or perceived success of specific strategies, but they did partially predict the number of strategies attempted. Conclusions: CAH administrators have used multiple strategies to improve financial performance with a wide variety of reported success. More research into the effectiveness of specific interventions is needed to help administrators select evidence-based strategies.
Survivability of MEMS Accelerometer Under Sequential Thermal and High-G Mechanical Shock Environments

Reliability data on MEMS accelerometers operating in harsh environments is scarce. Micro-electro-mechanical systems (MEMS) are used in a variety of military and automotive applications for sensing acceleration, translation, rotation, pressure and sound. This research work focuses on dual axis MEMS accelerometer reliability in harsh environments. Structurally an accelerometer behaves like a damped mass on a spring. Commercially there are three types of accelerometers namely piezoelectric, piezoresistive and capacitive depending on the components that go into the fabrication of the MEMS device. Previously, majority of concentration was focused on an effective internal design, performance enhancement of CMOS-MEMS accelerometers and packaging techniques Cheng [2002], Qiao [2009], Lou [2005], and Weigold [2001]. Studies have also been conducted to obtain an enhanced inertial mass SOI MEMS process using a high sensitivity accelerometer Jianbing [2013], Chen [2005]. There have been prior test(s) conducted on MEMS accelerometers, Jiang [2004], Cao [2011], Chun-Sun [2009], Lou [2009], Tanner [2000] and Yang [2010] but the availability of data on reliability degradation of such devices in harsh environments Brown [2003] is almost little to none which thereby generates the importance of this work and also makes way for a whole new path involving the reliability assessment techniques for MEMS devices. Concentration of our work is primarily on the reliability of this accelerometer upon sequential exposure to harsh environment(s) and drop-shock. Reliability of accelerometers in high G environments is unknown. The effects of these pre-conditions along with the drop test condition has been studied and analyzed. In this piece of research work, a test vehicle with a MEMS accelerometer, ADXL278 dual axis capacitive accelerometer, has been tested under high/low temperature exposure followed by subjection to high-g and low-g shock loading environments. The test boards have been subjected to mechanical shocks using the method 2002.5, condition G, under the standard MIL-STD-883H test. The stress environment and the test condition used for this paper are 1500g and 70g respectively where 70g is the full scale range output of ADXL278 in the drop direction with pulse duration set to 0.5millisecond. The deterioration of the accelerometer output has been characterized using the techniques of Mahalanobis distance and Confidence intervals. Scanning Electron Microscopy (SEM) has been used to study the different failure modes inside of the accelerometer, which were potted and polished and later de-capped. Furthermore, the non-destructive evaluations of the MEMS accelerometer have been demonstrated through X-rays and micro-CT scans.Copyright © 2015 by ASME
Hydrometeorological Characteristics of Rain‐on‐Snow Events Associated with Atmospheric Rivers

Atmospheric rivers (ARs) are narrow, elongated, synoptic corridors of enhanced water vapor transport that play an important role in regional weather/hydrology. Rain-on-snow (ROS) events during ARs present enhanced flood risks due to the combined effects of rainfall and snowmelt. Focusing on California's Sierra Nevada, the study identifies ROS occurrences and their connection with ARs during the 1998–2014 winters. AR conditions, which occur during 17% of all precipitation events, are associated with 50% of ROS events (25 of 50). Composite analysis shows that compared to ARs without ROS, ARs with ROS are on average warmer by ~2 K, with snow water equivalent loss of ~0.7 cm/d (providing 20% of the combined water available for runoff) and ~50% larger streamflow/precipitation ratios. Atmospheric Infrared Sounder retrievals reveal distinct offshore characteristics of the two types of ARs. The results highlight the potential value of observing these events for snow, rain, and flood prediction.
The end of Russian philosophy: tradition and transition at the turn of the 21st century

History has a way of mocking any millenarian pronouncement that declares the end of anything. Just when Francis Fukuyama announced the end of history (divining it in the collapse of the Soviet Expe...
Asymptotic Construction of a Generalized Reissner-Mindlin Model for Multilayer Piezoelectric Plates

The variational asymptotic method is used to construct a generalized Reissner-Mindlin model for multilayer piezoelectric plates with faces surfaces or other surfaces parallel to the reference surface coated with electrodes. Without invoking a priori kinematic assumptions, we asymptotically split the original three-dimensional electromechanical problem into a one-dimensional through-the-thickness analysis and a two-dimensional plate analysis. The through-the-thickness analysis is implemented using the finite element method into the computer program VAPAS (Variational Asymptotic Plate and Shell Analysis). The resulting model is as simple as an equivalent single-layer, first-order shear deformation theory with accuracy comparable to higher-order layerwise theories. Numerical results of cylindrical bending problems for piezoelectric plates have been compared with 3D exact solutions to validate the present model.Copyright © 2007 by ASME
Tracing Formative Influences on Event Recall: A Test of Mannheim's Sensitivity Hypothesis

Evidence is presented in support of Karl Mannheim's theory that people are more sensitive to events that occur during their formative years than to those that occur later in the life course. Accordingly, a cohort anlaysis is performed on recall data from a questionnaire survey of Wilson scholars. Methodological problems in the analysis of cohort tables are considered, inspiring discussions of data transformations, stagewise regression, nonlinear regression techniques, and goodness-of-fit tests. The recent controversy over the proper procedure to use in the separation of age, period, and cohort effects has led to an unfortunate distraction from the social theories these techniques were developed to test. Routinely, researchers have emphasized identifying birth cohorts with distinctive attitudinal profiles or have stressed determining whether such profiles are the natural product of aging or historical processes. In so doing, theoretical explanations about how generational processes occur have generally been ignored. Although in 1928 Karl Mannheim (1952) offered a still plausible explanation for the development of generations, his writings are only occasionally cited in quantitative studies of generational processes (e.g., Wuthnow 1976). Here one specific aspect of Mannheim's theory of generations is tested, namely his contention that people are more sensitive to social phenomena that occur during their formative years. Since this test raises problems of identification analogous to those in the analysis of cohort tables, a methodological detour is taken in order to discuss this and other statistical issues. First, however, we begin with a brief review of Mannheim's theory.
The effect of a coding cue on verbal discrimination learning

This study investigated the effect of the oral presentation of an English word as a coding cue for the correct CVC in a verbal discrimination task. The Ss were 22 undergraduates, 11 to a group. It was found that the group given the English words similar to the corresponding nonsense syllables made significantly fewer errors on the test trial.
Action of l-Ascorbic Acid upon the Isolated Frog Heart.

It was recently reported that hydrogen peroxide is the cause of the positive inotropic and of the irreversible systolic effect upon the frog heart of ascorbic acid solutions.1 The evidence available in the literature indicates that the hydrogen peroxide formation in ascorbic acid solutions is related to the dehydrogenation of the molecule, and, more specifically, to the catalytic action of copper in this process.2 It is known that the catalytic action of copper can be prevented by the formation of complexes between the metal and suitable substances like protein3 or diethyl-dithiocarbamate.4 Serum globulin and sodium diethyldithiocarbamate were therefore used to determine whether copper inhibitors were able to diminish or prevent the action of l-ascorbic acid solutions upon the frog heart.Method. 50 to 100 mg of l-ascorbic acid were dissolved in one cc of distilled water; and this solution, after neutralization with sodium bicarbonate, was diluted to an initial concentration of approximately 1:10,000 with ...
2016: A ‘Mitochondria’ Odyssey

The integration of the many roles of mitochondria in cellular function and the contribution of mitochondrial dysfunction to disease are major areas of research. Within this realm, the roles of mitochondria in immune defense, epigenetics, and stem cell (SC) development have recently come into the spotlight. With new understanding, mitochondria may bring together these seemingly unrelated fields, a crucial process in treatment and prevention for various diseases. In this review we describe novel findings in these three arenas, discussing the significance of the interplay between mitochondria and the cell nucleus in response to environmental cues. While we optimistically anticipate that further research in these areas can have a profound impact on disease management, we also bring forth some of the key questions and challenges that remain.
A cohort study on the relationship between different hip circumference levels and the events of cerebrovascular diseases and deaths in Mongolian peasants and herdsmen

Objective To learn the relationship between different hip circumference levels and the events of cerebrovascular diseases and deaths in Mongolians. Methods Prospective cohort study was used. A total of 2 586 peasants and herdsmen was followed in Tongliao,Inner Mongolia,who had the age over 20. Follow-up outcome events were cardiovascular and cerebrovascular disease( including stroke and coronary heart disease) and death in 2008,2009,2010. We calculated cumulative incidence and incidence density to describe the occurrence of cardiovascular diseases and death in outcome events,to analyze the baseline of outcome occurred. Multivariate Cox proportional hazards model was used,multioutcome events( cardiovascular and cerebrovascular diseases and deaths) were defined as stroke,coronary heart disease and death,HR value and its 95% CI of hip circumference levels and other risk factors were calculated. Results During the follow-up period,stroke and coronary heart disease cumulative incidence was 5. 64%,the incidence density was 787. 4/100 thousands per year,and the cumulative mortality was 4. 44%,the death density was 620. 2 /100 thousands per year. Multivariate multiple Cox proportional hazards model showed that,after adjusted the three traditional risk factors of age, gender and family history of hypertension,different hip circumference levels were related with the outcome events,compared to the first level,the second,third and fourth levels related with the ending events( cardio-cerebrovascular disease and death events),HR( 95% CI) value was 0. 64( 0. 45-0. 91),0. 75( 0. 53-1. 04),0. 65( 0. 46-0. 92),respectively( all P 0. 05). Conclusions Hip circumference levels negatively related with cardiovascular disease and death,and may have independent predictor for cardiovascular and cerebrovascular diseases and death.
New Approaches for Virus Detection through Multidisciplinary Partnerships.

A critical requirement for controlling outbreaks of viral infection is sensitive and accurate diagnostics, which can be expensive and are frequently located in resource-intensive clinical laboratories. Outbreaks of many viral infections occur in countries where healthcare resources are limited and clinical laboratories scarce. This creates a fulfillment gap, one that could be filled through the development of inexpensive, sensitive, easy to use, and portable diagnostics. Here we describe our efforts to develop a diagnostic technology that detects viruses without needing to label the particle directly. Our approach has the advantage of speed and assay simplicity while maintaining high sensitivity. Essential in this approach has been the assembly of an integrated, diverse, and interdisciplinary team that worked together to evaluate technologies, spin-out a company, and produce a product for infectious disease diagnostics. The synergy of different individuals with complementary skills has been critical for t...
The Research and Assessment of Topographic Registration and Correction of Chang'E-1 IIM Data Based on LRO LOLA DEM Data

The characteristics of the visible and near-infrared reflectance from lunar surface are key information for the inversion and mapping of chemical elements in lunar exploration. Due to the dimply topography, hyperspectral dataobtained from IIM should be introduced with topographic correction before the application of practical inversion to get the actual reflectivity information. There ported longitudes and latitudes of the IIM data generally did not match with the conventional data from the LOLA DEM. Consequently, the accuracy of the topographic correction might be affected and decreased. In this paper, a case study was done related to the lunar crater. More specifically, a certain number of ground control points in a crater with same characteristic were selected for both images to match the IIM data and LOLA DEM data. The results from polynomial correction method were different from the correction results calculated directly from lunar longitude and latitude. There was approximately 3.5 pixels' offset in the direction of longitude and about 1.95 pixels' offset in the direction of latitude between IIM data and LOLA DEM data. The conventional topographical correction used on earth(i.e. C correction method) was introduced for a possible topographical correction on the moon, where there is almost no atmosphere scattering. The results showed that the performance of the matched topographical correction data was much better than those from unmatched data. After the application of registration and C correction, the slope of the linear correlation equation between the incident angle cosine value and the reflectance was reduced by 89.4percent, the terrain effects of the shadow area and the highlight area on the lunar surface was eliminated. We concluded that the actual reflectivity information from lunar surface could be closely assessed after applying registration and topographic correction to IIM data, which could provide a sound basis for the inversion of chemical elements and minerals based on IIM data.
Pedestrian Verification for Multi-Camera Detection

In this paper, we introduce an approach to multi-camera, multi-object detection that builds on low-level object localization with the targeted use of high-level pedestrian detectors. Low-level detectors often identify a small number of candidate locations, but suffer from false positives. We introduce a method of pedestrian verification, which takes advantage of geometric and scene information to (1) drastically reduce the search space in both the spatial and scale domains, and (2) select the camera(s) with the highest likelihood of providing accurate high-level detection. The proposed framework is modular and can incorporate a variety of existing detection methods. Compared to recent methods on a benchmark dataset, our method improves detection performance by 2.4 %, while processing more than twice as fast.
A dataflow graph transformation language and query rewriting system for RDF ontologies

Users interested in biological and biomedical information sets on the semantic web are frequently not computer scientists. These researchers often find it difficult to use declarative query and view definition languages to manipulate these RDF data sets. We define a language IML consisting of a small number of graph transformations that can be composed in a dataflow style to transform RDF ontologies. The language's operations closely map to the high-level manipulations users undertake when transforming ontologies using a visual editor. To reduce the potentially high cost of evaluating queries over these transformations on demand, we describe a query rewriting engine for evaluating queries on IML views. The rewriter leverages IML's dataflow style and optimizations to eliminate unnecessary transformations in answering a query over an IML view. We evaluate our rewriter's performance on queries over use case view definitions on one or more biomedical ontologies.
A seventh-order member of KdV6 hierarchy and its (2+1)-dimensional extensions

In this work, we investigate a completely integrable seventh-order member of the KdV6 hierarchy. We develop two extensions of (2+1) dimensions for this equation. We show that the dispersion relations are distinct that will reflect on the structures of the obtained solutions. We use the simplified Hirota’s method to determine multiple soliton solutions for these three equations. The integrability of the extended equations is tested by using the Painleve analysis.
SUSY Breaking and Moduli Stabilization

In string models all couplings, i.e. both gauge and Yukawa couplings, depend on the values of moduli. In addition, the size of the extra 6 dimensions also depend on the size of moduli. Finally, the value of the GUT symmetry breaking scale and proton decay rates depend on the size of the extra dimensions. In addition, in order to stabilize all the moduli one must necessarily spontaneously break supersymmetry.
Personality and Marital Relationships: Developing a Satisfactory Relationship with an Imperfect Partner

Two partners tying a marital knot cannot possibly fathom the complexity of the relationship that lies ahead. Once married, the success or failure of marriage is determined by a myriad of factors. Each partner is a unique agglomeration of stable personal dispositions that influence marital relationships. During courtship, partners typically idealize their relationship and maintain a positive illusion about their significant other, and behaviors and traits that may later threaten the developing relationship are mostly ignored. In the early marriage years, however, the process of marital disillusionment begins and the personal dispositions that were dismissed earlier become increasingly conspicuous and hard to ignore. Eventually, partners come to grips with reality and experience a decline in love. Acknowledging that personal dispositions are ingrained in the genetics and are reinforced by the early experiences and attachment bonds, this paper reviews the role of personal dispositions on marital outcomes and examines how negative outcomes can be curbed by therapeutic interventions. In this context, the acceptance and commitment therapy (ACT; an experiential acceptance-based behavior therapy) that targets experiential avoidance and increases psychological flexibility is discussed.
Cytochrome P-450

Cytochrome P-450 is a group of nonspecific hydroxylating systems that hydroxylate substrates of widely varying structure (Ullrich, 1979). Cytochrome P-450 is important in the degradative hydroxylation of drugs in the body (Gillette et al., 1972). The enzyme can hydroxylate steroids and hydrocarbons. For example,Corynebacterium utilizes P-450 to oxidize n-octane to 1-octanol (Cardini and Justishuk, 1970), and fatty acids are hydroxylated at the ω and (ω-1) positions (Bjorkhem and Danielson, 1970; Ellinet al., 1972; Ichihara et al., 1979). Either cytochrome P-450 or similar iron-containing monooxygenases cleave inositol to n-glucuronic acid (Charalampous, 1959, 1960).
Ventral hernia repair with poly-4-hydroxybutyrate mesh

Biomaterial research has made available a biologically derived fully resorbable poly-4-hydroxybutyrate (P4HB) mesh for use in ventral and incisional hernia repair (VIHR). This study evaluates outcomes of patients undergoing VIHR with P4HB mesh. An IRB-approved prospective pilot study was conducted to assess clinical and quality of life (QOL) outcomes for patients undergoing VIHR with P4HB mesh. Perioperative characteristics were defined. Clinical outcomes, employment status, QOL using 12-item short form survey (SF-12), and pain assessments were followed for 24 months postoperatively. 31 patients underwent VIHR with bioresorbable mesh via a Rives–Stoppa approach with retrorectus mesh placement. The median patient age was 52 years, median body mass index was 33 kg/m2, and just over half of the patients were female. Surgical site occurrences occurred in 19% of patients, most of which were seroma. Hernia recurrence rate was 0% (median follow-up = 414 days). Patients had significantly improved QOL at 24 months compared to baseline for SF-12 physical component summary and role emotional (p < 0.05). Ventral hernia repair with P4HB bioresorbable mesh results in favorable outcomes. Early hernia recurrence was not identified among the patient cohort. Quality of life improvements were noted at 24 months versus baseline for this cohort of patients with bioresorbable mesh. Use of P4HB mesh for ventral hernia repair was found to be feasible in this patient population. (ClinicalTrials.gov Identifier: NCT01863030).
Alcohol Use, Age, and Self-Rated Mental and Physical Health in a Community Sample of Lesbian and Bisexual Women

Abstract Purpose: Given that self-perceptions of mental and physical health are important predictors of health outcomes and well-being, particularly among older adults, this study focuses on associations among age, alcohol consumption, and indicators of both self-rated mental health and self-rated physical health in a sample of sexual minority women (SMW). Methods: This study uses a community sample of SMW to examine the associations among age, drinking, and self-rated mental and physical health. Results: Heavy drinking among older adult SMW (55+) was less prevalent than among young SMW, ages 18–25 and ages 26–39, but similar to rates reported among SMW ages 40–54. In addition, older SMW reported significantly higher levels of self-rated mental health, compared with SMW in the other age groups, but we found no significant associations between age and self-rated physical health. Across all age groups, moderate drinkers reported better self-rated physical health than alcohol abstainers. Conclusions: Overall...
Periodic Solutions of Two-Dimensional Forced Systems: The Massera Theorem and Its Extension

We assume that all solutions of a two-dimensional, periodically forced differential system (of period T) can be continued for all future time. If there exists one solution that is future bounded, then there exists a solution of period T (Theorem 3.4). This is the Massera theorem. To extend the Massera theorem, we assume that there exists a future bounded solution that is also bounded away from a known T-periodic solution ζ. We prove that either there is another periodic solution of period qT for some integer q ≥ 1 or all compact motions that remain a finite distance from ζ have a well-defined irrational rotation number about ζ (Theorem 4.3).
Formation and Removal of Methylated Nucleosides in Nucleic Acids of Mammalian Cells

This chapter compares the formation, turnover, and possible functions of methylated nucleosides present in nucleic acids under normal conditions and after exposure to alkylating agents. No attempt is made to provide a totally comprehensive review of the occurrence and biochemistry of such products. Many recent reviews have covered portions of this field, and to summarize such a broad area is probably impossible and unlikely to be useful. More relevantly, it is also outside the limited capabilities of the author. Attention, therefore, is concentrated on the methylation of DNA by certain carcinogens which may have environmental importance and on selected references to certain areas of the immense biochemical literature relating to normal cellular methylations.
Potential Therapeutic Uses of Thyroid Hormone

At the outset, I must admit my bias and conflict of interest on this topic as I have US Patent Number 5,951,989 for the use of topical thyroid hormone in treating xerosis. Regardless of that fact, it is clear that the therapeutic use of thyroid hormone has been considered a neglected stepchild compared to hormones of the same nuclear receptor subfamily: corticosteroids, retinoids, and vitamin D. Indeed, a PubMed search performed on Independence Day (July 4th) 2007 revealed 10,081 references for topical corticosteroids and only 69 for topical thyroid hormone. As explained in this chapter, thyroid hormone has profound effects on the skin and its appendages and has the potential to treat myriad conditions, including disorders of keratinization, alopecia, wound healing, xerosis, and chronic idi-opathic urticaria. This subject was chosen for the concluding chapter of this text because I hope the reader will have already come to the realization that not only are thyroid–cutaneous interactions important in health and disease but also that further research in this discipline may foster novel concepts and therapies utilizing thyroid hormone to alleviate human suffering.
Towards the Next Millennium: Challenges and Prospects with Plant Associated Bacteria

The 20th century accelerated discovery of bacterial plant pathogens and some of their properties. It is humbling, however, to consider that a major management tool for fireblight, incited by the first scientifically described bacterial plant pathogen, Erwinia amylovora, is still at its more primitive stage, namely cutting off parts of trees or destroying them. A similar situation exists for citrus canker in the U.S., namely destruction of trees in efforts to eradicate Xanthomonas campestris pv. citri.
Eicosanoids in insect immune signal transduction.

Eicosanoid is a collective term for all biologically active, oxygenated metabolites of arachidonic acid and two other C20 polyunsaturated fatty acids. There are three major groups of eicosanoids. The prostaglandins (PGs), so named because they were first discovered in seminal fluids originating in the prostate gland, are products of the cyclooxygenase pathways. The cytochrome P450 “epoxygenase pathways” yield the epoxyeicosatrienoic acids. Various lipoxygenase pathways are responsible for biosynthesizing a wide range of compounds, including leukotrienes and hydroxyeicosatetraenoic acids. The biosynthesis and structures of representatives of the major groups of eicosanoids are outlined in Figure 1, and described in detail elsewhere (Stanley, 1999). One or more members of the major eicosanoid groups have been detected in virtually all mammalian tissues and body fluids, where they serve as lipid mediators of cellular events. Among their important actions, eicosanoids modulate ion transport physiology, mediate contraction or relaxation of smooth muscles and exert tremendous influence in host defense mechanisms. It would be difficult to exaggerate the importance of eicosanoids in the vertebrate immune system. Sir John Vane shared in the 1982 Nobel Prize in Medicine or Physiology, which recognized his discovery that the analgesic effects of aspirin are due to inhibition of prostaglandin biosynthesis. This discovery launched a very large pharmaceutical research enterprise aimed at discovery of new non-steriodal anti-inflammatory drugs, all of which act through their inhibitory influence on prostaglandin biosynthesis.
Pathophysiology of Menopausal Hot Flushes

In women, the most common and characteristic symptom of the climacteric is an episodic disturbance consisting of sudden flushing and perspiration, referred to as a “hot flush or flash.” It has been observed in 65–76% of women who go through the physiological menopause or have a bilateral ovariectomy (Hannan, 1927; Neugarten and Kraines, 1965; Jaszmann et al., 1969; Thompson et al.,1973; McKinlay and Jeffreys, 1974). Of those having flushes, 82% will experience the disturbance for more than 1 year (Jaszmann et al.,1969) and 25–50% will complain of the symptom for more than 5 years (Neugarten and Kraines, 1965; Thompson et al., 1973). Although hot flushes occur in millions of women, there have been few attempts to understand the pathophysiology of this symptom until recently.
INVESTIGATION OF COOLING FOR A HOT HUMID CLIMATE: DESICCANT DEHUMIDIFICATION COUPLED WITH EVAPORATIVE COOLING FOR A RESIDENCE IN KARACHI, PAKISTAN

ABSTRACT Out of a concern for an increasing demand for energy to provide comfort in buildings in Pakistan, this research examines the impact of employing passive methods to promote comfort to a proposed residence in Karachi where the climate in summer is hot and humid. As an alternative to employing high energy consumptive compression refrigeration for cooling that is becoming widespread in use in Karachi, this paper examines the possibilities of producing cooling by coupling the processes of desiccant dehumidification and evaporative cooling when passive methods alone cannot provide comfort conditions. Building energy simulation programs are used to predict inside temperatures and building loads, and to determine the Comfort Index when the process of dehumidification together with evaporative cooling is employed. By using solar energy and/or auxiliary heat to reactivate the absorbent and evaporatively cool dehumidified air, it can be observed through computer simulations that a Comfort Index of nearly 100% can be achieved throughout the summer months.
Nail Surgery Overview and Approach

Nail surgery represents a fundamental subset of dermatologic surgery. Nearly every cutaneous condition and tumor may develop on the nail unit – frequently the practitioner will find the need to perform a surgical procedure on or around the nail, for either diagnosis or as a part of therapy. Successful surgery requires an understanding of the unique nail anatomy, appropriate surgical consent, complete anesthesia, and often manipulation of the plate and/or nail folds to achieve adequate surgical exposure. When armed with tools that address these issues, nail surgery becomes as straightforward as that on the skin.
Relative efficacy of systemic treatments for atopic dermatitis

Background Systemic medications are often required for severe atopic dermatitis (AD) refractory to topical therapies. Biologic medications are a recent advancement in the field and a comparison with standard systemic approaches would be beneficial. Objective To compare efficacies of systemic therapies for the treatment of AD. Methods A systematic literature review was performed using Medline, Ovid, and Embase. Randomized controlled trials looking at the efficacy of systemic treatments for AD in adults and children were included. Results A total of 41 studies met criteria and were included in our final analysis. Consistent improvements in Eczema Area and Severity Index and Scoring Atopic Dermatitis were reported with dupilumab and cyclosporine. Phase 2 clinical trials for lebrikizumab and tralokinumab were effective and would benefit from phase 3 trials. No study reported efficacy of biologic medications in pediatric patients; however, cyclosporine improved clinical severity by the greatest amount in this group. Limitations A lack of well controlled comparison studies make direct comparisons between the treatments difficult. Conclusion For treatment of severe AD, the strongest evidence currently exists for dupilumab and cyclosporine at improving clinical disease severity. Further research is required to determine long-term safety and efficacy of biologic medications.
Transforming Redox Properties of Clusters Using PhosphineLigands

Organic ligands that protect the surfaces of clusters and nanoparticles against reactions and control the rate of growth are generally considered to be inert passive coatings. Here, we demonstrate ...
Do countries learn from experience in infrastructure public–private partnerships? Public–private partnerships practice and contract cancellation

Learning from experience to improve future infrastructure public-private partnerships is a focal issue for policy makers, financiers, implementers, and private sector stakeholders. An extensive body of case studies and “lessons learned” aims to improve the likelihood of success and attempts to avoid future contract failures across sectors and geographies. This paper examines whether countries do, indeed, learn from experience to improve the probability of success of public-private partnerships at the national level. The purview of the paper is not to diagnose learning across all aspects of public-private partnerships globally, but rather to focus on whether experience has an effect on the most extreme cases of public-private partnership contract failure, premature contract cancellation. The analysis utilizes mixed-effects probit regression combined with spline models to test empirically whether general public-private partnership experience has an impact on reducing the chances of contract cancellation for future projects. The results confirm what the market intuitively knows, that is, that public-private partnership experience reduces the likelihood of contract cancellation. But the results also provide a perhaps less intuitive finding: the benefits of learning are typically concentrated in the first few public-private partnership deals. Moreover, the results show that the probability of cancellation varies across sectors and suggests the relative complexity of water public-private partnerships compared with energy and transport projects. An estimated $1.5 billion per year could have been saved with interventions and support to reduce cancellations in less experienced countries (those with fewer than 23 prior public-private partnerships).
Learning-based automatic segmentation of arteriovenous malformations on contrast CT images in brain stereotactic radiosurgery.

Purpose Stereotactic radiosurgery (SRS) is widely used to obliterate arteriovenous malformations (AVMs). Its performance relies on the accuracy of delineating the target AVM. Manual segmentation during a framed SRS procedure is time consuming and subject to inter- and intraobserver variation. To address these drawbacks, we proposed a deep learning-based method to automatically segment AVMs on CT simulation image sets. Methods We developed a deep learning-based method using a deeply supervised three-dimensional (3D) V-Net with a compound loss function. A 3D supervision mechanism was integrated into a residual network, V-Net, to deal with the optimization difficulties when training deep networks with limited training data. The proposed compound loss function including logistic and Dice losses encouraged similarity and penalized discrepancy simultaneously between prediction and training dataset; this was utilized to supervise the 3D V-Net at different stages. To evaluate the accuracy of segmentation, we retrospectively investigated 80 AVM patients who had CT simulation and digital subtraction angiography (DSA) acquired prior to treatment. The AVM target volume was segmented by our proposed method. They were compared with clinical contours approved by physicians with regard to Dice overlapping, difference in volume and centroid, and dose coverage changes on original plan. Results Contours created by the proposed method demonstrated very good visual agreement to the ground truth contours. The mean Dice similarity coefficient (DSC), sensitivity and specificity of the contours delineated by our method were >0.85 among all patients. The mean centroid distance between our results and ground truth was 0.675 ± 0.401 mm, and was not significantly different in any of the three orthogonal directions. The correlation coefficient between ground truth and AVM volume resulting from the proposed method was 0.992 with statistical significance. The mean volume difference among all patients was 0.076 ± 0.728 cc; there was no statistically significant difference. The average differences in dose metrics were all less than 0.2 Gy, with standard deviation less than 1 Gy. No statistically significant differences were observed in any of the dose metrics. Conclusion We developed a novel, deeply supervised, deep learning-based approach to automatically segment the AVM volume on CT images. We demonstrated its clinical feasibility by validating the shape and positional accuracy, and dose coverage of the automatic volume. These results demonstrate the potential of a learning-based segmentation method for delineating AVMs in the clinical setting.
A tumor-localized approach to bypass anti-4-1BB immuno-toxicity

4-1BB (CD137) is an important costimulatory molecule upregulated on antigen-experienced T cells, however, clinical development of 4-1BB agonists has stalled because of significant liver immuno-toxicity. Using rational protein engineering, a next-generation anticalin-antibody-based therapy achieved localized 4-1BB activation triggered by tumor-expressed antigen, helping to revitalize this pathway in immuno-oncology.See related article by Hinner et al., p. 5878.
First-Principles-Based Multiphysics Modeling and Simulation of On-Chip Cu-Graphene Hybrid Nanointerconnects in Comparison With Simplified Model-Based Analysis

Cu-Graphene (Cu-G) hybrid nanointerconnects, as well as many graphene-based devices, have a potential to significantly advance the technology of on-chip integrated circuits (IC). However, their modeling and simulation for a long time has relied on simplified steady-state models of graphene. To examine the validity and accuracy of existing simplified models in high-frequency and subnanometer applications, in this article, we theoretically analyze the assumptions made in existing simplified models. Meanwhile, we develop a first-principles-based multiphysics modeling and simulation algorithm to numerically assess the accuracy of the simplified model-based analysis of Cu-G interconnects. In this algorithm, the Maxwell's equations, the equation characterizing graphene, and the Boltzmann equation are cosimulated in time domain. A significant difference is observed between the first-principles-based analysis and the simplified model-based one when the frequency is high or/and the dimension of the Cu-G structure is small, which necessitates the first-principles-based multiphysics modeling and simulation for the design of advanced Cu-G interconnects.
Black Box Attack on Machine Learning Assisted Wide Area Monitoring and Protection Systems

The applications for wide area monitoring, protection, and control systems (WAMPC) at the control center, help with providing resilient, efficient, and secure operation of the transmission system of the smart grid. The increased proliferation of phasor measurement units (PMUs) in this space has inspired many prudent applications to assist in the process of decision making in the control centers. Machine learning (ML) based decision support systems have become viable with the availability of abundant high-resolution wide area operational PMU data. We propose a deep neural network (DNN) based supervisory protection and event diagnosis system and demonstrate that it works with very high degree of confidence. The system introduces a supervisory layer that processes the data streams collected from PMUs and detects disturbances in the power systems that may have gone unnoticed by the local monitoring and protection system. Then, we investigate compromise of the insights of this ML based supervisory control by crafting adversaries that corrupt the PMU data via minimal coordinated manipulation and identification of the spatio-temporal regions in the multidimensional PMU data in a way that the DNN classifier makes wrong event predictions.
The impact of rapid diagnostic testing, surveillance software, and clinical pharmacist staffing at a large community hospital in the management of Gram-negative bloodstream infections.

Abstract Rapid diagnostic testing (RDT) combined with an antimicrobial stewardship program (ASP) has shown improved outcomes in bloodstream infections (BSIs). We assessed the impact of RDT, surveillance software, and ASP pharmacist staffing on time to optimal therapy (TOT) in Gram-negative BSIs. Adults with Gram-negative BSIs were included in this retrospective evaluation across 2 study periods. The preimplementation group (n = 121) had longer TOT than the postimplementation group (n = 120) (59.6 ± 36.2 h versus 29.0 ± 24.2 h, P P P P
Impact of Surgical Experience on Operative Mortality After Reoperative Cardiac Surgery

Background Learning curves and skill attrition with aging have been reported to impair outcomes in select surgical subspecialties, but their role in complex cardiac surgery remains unknown. Methods From 1986 to 2019, 2314 patients underwent reoperative cardiac surgery: coronary artery bypass grafting (n = 543), valve (n = 1527), or combined coronary artery bypass grafting and valve (n = 244). Thirty-four different surgeons in practice between 1 and 39 years were included. Standardized mortality ratio (observed-to-expected) was determined for all surgeons in each post-training year of experience. Results Risk-adjusted cumulative sum change-point analysis was used to define five distinct career phases: 0 to 4 years, 5 to 8 years, 9 to 17 years, 18 to 28 years, and 29 to 39 years. With 5 to 8 years and 18 to 28 years of experience, standardized mortality ratio was near unity (0.95 and 1.05, respectively) and lowest with 9 to 17 years of experience (0.78, P = .03). In the youngest experience group (0 to 4 years), observed and expected mortality were both highest, and standardized mortality ratio was elevated at 1.29, which approached statistical significance (P = .059). In the oldest experience group (29 to 39 years), expected mortality was low compared with most other groups but observed mortality increased, yielding a significantly elevated standardized mortality ratio at 1.53 (P = .032). Conclusions Standardized mortality ratios with reoperative cardiac surgery were highest early and late in a surgeon’s career and lowest in mid career. As surgeons gain experience, outcomes improve through the first two career decades, then stabilize in the third decade before declining in the fourth decade.
Virtual Reality Job Interview Training in Transition Services: Results of a Single-Arm, Noncontrolled Effectiveness-Implementation Hybrid Trial.

This study reports the results of a single-arm, noncontrolled, Type 3 hybrid effectiveness-implementation trial evaluating virtual reality job interview training (VR-JIT) delivered in five preemplo...