cssi/SciSciGPT-SciSciNet huggingface dataset:
Virtual CGH: Prediction of Novel Regions of Chromosomal Alterations in Tumor from Gene Expression Profiling

The identification of genetic alterations using array comparative genomic hybridization (CGH) would provide important insights into the mechanisms of tumorogenesis. High resolution array CGH are very expensive and the experiment require a separate sample, therefore, we developed a computational method for predicting gains and losses of genomic DNA segments based on mRNA expression profiles of tumor cell lines, and called this method a virtual CGH (vCGH) predictor. VCGH is performed through a novel algorithm in which each chromosomal segment is evaluated by the gene transcriptional profiles. The calculation yields a log of odds (LOD) score for each chromosomal segment and this likelihood-based score is used to predict the correlation between mRNA expression patterns and DNA copy number alterations. By aligning all regions of gains and losses from multiple cell lines we can identify minimal common regions of gains and losses which may contain potential oncogenes or tumor suppressors. This method can be used to screen transcriptional profiles of other malignancies for the identification of DNA segmental loss or gain
Diffractive Raman scattering in focused geometry

The coupled pump and Stokes differential equations are solved by using a rotationally symmetric Gauss–Laguerre decomposition. Three examples of the Stokes and pump intensity are presented.
Closing Schools in Response to the 2009 Pandemic Influenza A H1N1 Virus in New York City: Economic Impact on Households

Understanding the effectiveness of a school closure in limiting social interaction and the economic impact of school closure on households is critical when developing guidelines to prevent spread of pandemic influenza. A New York City survey conducted in June 2009 in 554 households affected by the 2009 pandemic influenza H1N1-related school closures showed that, during closure, 30% of students visited at least 1 locale outside their homes. If all the adults in the home were employed, an ill child was less likely to leave home. In 17% of the households, at least 1 adult missed some work because of the closure. If all adults in the home were employed, someone was more likely to take time off work. If other children were in the household, it was less likely that an adult took time off work. The findings of our study will be important when developing future pandemic school-closure guidance.
Community, integration, and stability in multinational Yugoslavia

In 1981 a higher proportion of the multinational population of Yugoslavia chose to declare “Yugoslav” in place of an ethnic identity in response to the census question on nationality than ever before. We present arguments to support the interpretation of Yugoslav identity as evidence of shared political identity, and carry out an analysis of aggregate data on the level of social and material development, political socialization, and interethnic contact in the country's nearly five hundred counties to discover the sources of that identity. We find that with certain important regional variations, Yugoslav identity seems to be the product of interethnic contact and higher education rather than the level of material well-being. These findings support an interpretation of Yugoslav identity as evidence of diffuse support for the existence of a shared political community and suggest both the sources and vulnerabilities of Yugoslav stability.
An intelligent assistant for software information checking using a non-monotonic reasoning system

The knowledge representation of software component relations using nonmonotonic logic to assist the validity and integrity checking of software information is presented. Software components and their interconnection information are represented by axioms that exhibit the structure and behavior of the software system. Another set of axioms represents the basic truisms about a software system in general. These axioms can easily be extended to cover a wide variety of software systems architectures. In the software development and maintenance phases, information about the software system can be derived from these axioms using an automated reasoning system, and the software system itself can easily be checked against a specification of the system and compared for validity. This knowledge-based system will provide programmers with useful software information and assist the software development and maintenance process. >
An Integrated Pest Management Adoption Survey of Sweet Corn Growers in the Great Lakes Region

Sweet corn is one of the most common fresh market vegetable crops grown throughout the north central and north east regions of the United States. In 2008, the Great Lakes Vegetable Working Group measured integrated pest management (IPM) practice adoption by growers of this crop using online and hardcopy surveys over a 10-mo period. The survey asked growers from nine states and Ontario, Canada, which pest management practices they used on their farm operation in the following sections: education, preplant, at-plant, in-season, postharvest, scouting, and demographics. Each individual survey question was ranked by a panel of university specialists and designated as a low, moderate, or high IPM valued activity, with points assigned accordingly. On survey completion, the total points accumulated by the grower would place them into one of three categories; low, moderate, or high IPM adopter. Of the 407 respondents, 130 were placed in the low IPM adoption category, 251 were deemed moderate IPM adopters, and 26 were placed in the high IPM category. Some key general attributes of a high IPM adopter include someone who has grown vegetables for at least 10 yr and has a farm >51 acres (67%) and raises between 21-50 acres of sweet corn (44%). Some key general attributes of a low IPM adopter include less experience on smaller acreage, with 56% having grown vegetables for fewer than 10 yr with 57% on farms smaller than five acres.
System overview and applications of a panoramic imaging perimeter sensor

This paper presents an overview of the design and potential applications of a 360-degree scanning, multi-spectral intrusion detection sensor. This moderate-resolution, true panoramic imaging sensor is intended for exterior use at ranges from 50 to 1500 meters. This Advanced Exterior Sensor (AES) simultaneously uses three sensing technologies (infrared, visible, and radar) along with advanced data processing methods to provide low false-alarm intrusion detection, tracking, and immediate visual assessment. The images from the infrared and visible detector sets and the radar range data are updated as the sensors rotate once per second. The radar provides range data with one-meter resolution. This sensor has been designed for easy use and rapid deployment to cover wide areas beyond or in place of typical perimeters, and tactical applications around fixed or temporary high-value assets. AES prototypes are in development. Applications discussed in this paper include replacements, augmentations, or new installations at fixed sites where topological features, atmospheric conditions, environmental restrictions, ecological regulations, and archaeological features limit the use of conventional security components and systems.
Antarctic ice-rafted detritus (IRD) in the South Atlantic: Indicators of iceshelf dynamics or ocean surface conditions?

Ocean sediment core TN057-13PC4/ODP1094, from the Atlantic sector of the Southern Ocean, contains elevated lithogenic material in sections representing the last glacial period compared to the Holocene. This ice-rafted detritus is mainly comprised of volcanic glass and ash, but has a significant input of what was previously interpreted as quartz during peak intervals (Kanfoush et al., 2000, 2002). Our analysis of these clear mineral grains indicates that most are plagioclase, and that South Sandwich Islands is the predominant source, similar to that inferred for the volcanic glass (Nielsen et al., in review). In addition, quartz and feldspar with possible Antarctic origin occur in conjunction with postulated episodes of Antarctic deglaciation. We conclude that while sea ice was the dominant ice rafting agent in the Polar Frontal Zone of the South Atlantic during the last glacial period, the Holocene IRD variability may reflect Antarctic ice sheet dynamics.
Understanding Science Through the Computational Lens

This article explores the changing nature of the interaction between computer science and the natural and social sciences. After briefly tracing the history of scientific computation, the article presents the concept of computational lens, a metaphor for a new relationship that is emerging between the world of computation and the world of the sciences. Our main thesis is that, in many scientific fields, the processes being studied can be viewed as computational in nature, in the sense that the processes perform dynamic transformations on information represented as digital data. Viewing natural or engineered systems through the lens of their computational requirements or capabilities provides new insights and ways of thinking. A number of examples are discussed in support of this thesis. The examples are from various fields, including quantum computing, statistical physics, the World Wide Web and the Internet, mathematics, and computational molecular biology.
Effect of Proton Pump Inhibitor Pantoprazole on Growth and Morphology of Oral Lactobacillus Strains

Objectives: Proton pump inhibitors (PPI) used to suppress acid secretion in the stomach are among the most widely prescribed medications. There is emerging evidence of proton secretion elsewhere in the aerodigestive tract, and acidic microenvironments are integral to oral flora such as Lactobacillus. The hypothesis of this study is that the growth rate and morphology of oral Lactobacillus strains are effected by PPIs. Methods: Nineteen different strains of Lactobacilli were inoculated in microtiter plates at pH of 4.5 to 6.5 and exposed to twofold dilutions of pantoprazole at a range of 2.5 mg/mL to 2.5 μg/mL. Bacterial growth was monitored, and the minimum inhibitory concentration (MIC) of the drug was determined for the strains most sensitive to pantoprazole. Results: In the unexposed (control) group, nine Lactobacilli strains were affected by pH changes from 6.5 to 4.5. In the group exposed to pantoprazole, 9 of the 19 Lactobacilli strains were found to have an MIC below 625 μg/mL, with L. plantarum 14917 being the most sensitive (MIC = 20 μg/mL). In some strains, such as L. s. salivarius 11741, Gram-staining revealed conformational changes in the bacteria when grown in the presence of pantoprazole. Conclusion: Growth rates and morphology of oral Lactobacillus are affected by the pH of the environment. Pantoprazole at supraphysiologic doses further affects growth rates and conformation in some strains. Significance: The balance of oral flora and upper digestive tract homeostasis may be affected by unexpected targets of PPI pharmacotherapy, with possible unanticipated consequences.
Clinical experiences with systemically administered siRNA-based therapeutics in cancer

Small interfering RNA (siRNA)-based therapies are emerging as a promising new anticancer approach, and a small number of Phase I clinical trials involving patients with solid tumours have now been completed. Encouraging results from these pioneering clinical studies show that these new therapeutics can successfully and safely inhibit targeted gene products in patients with cancer, and have taught us important lessons regarding appropriate dosages and schedules. In this Review, we critically assess these Phase I studies and discuss their implications for future clinical trial design. Key challenges and future directions in the development of siRNA-containing anticancer therapeutics are also considered.
Propidium: Induction of petites and recovery from ethidium mutagenesis in Saccharomycescerevisiae

Abstract It was shown that petite induction in growing cells of Saccharomyces cerevisiae by ethidium was strongly stimulated by the presence of propidium, a phenanthridinium dye of similar structure to ethidium. Propidium itself also induced petites in growing but not in resting cells. Furthermore, propidium could prevent petite induction in resting cells and caused recovery from ethidium induction with prolonged incubation. A possible mode of action of propidium in the ethidium-induced petite mutagenesis is discussed.
A serologic follow-up of the 1942 epidemic of post-vaccination hepatitis in the United States Army.

An epidemic of icteric hepatitis in 1942 affected approximately 50,000 U.S. Army personnel. This outbreak was linked to specific lots of yellow-fever vaccine stabilized with human serum. To identify the responsible virus and the consequences of the epidemic, during 1985 we interviewed and serologically screened 597 veterans who had been in the army in 1942. These subjects were selected from three groups. Group I consisted of patients who had received the implicated vaccine and had jaundice; Group II had received the implicated vaccine but remained well; Group III had received a new, serum-free vaccine, with no subsequent jaundice. Ninety-seven percent of Group I, 76 percent of Group II, and 13 percent of Group III were positive for antibodies to hepatitis B virus. Only one subject had hepatitis B surface antigen, for a carrier rate of 0.26 percent among recipients of the implicated vaccine. The prevalence of hepatitis A antibody was similar in all three groups, and no subject had antibody to hepatitis delta virus. We conclude that hepatitis B caused the outbreak, that about 330,000 persons may have been infected, that the hepatitis B virus carrier state was a rare consequence, and that the outbreak induced hepatitis B antibodies that appear to persist for life.
The Formation of Molecular Composites by a Modified Solgel Process

Standard sol-gel procedures have been modified to permit sol-gel synthesis to be performed at varying hydrogen ion concentrations and in a variety of organic solvents. These modifications greatly expand the variety of guest molecules that can be incorporated into nondense glassy environments. Processing conditions can be controlled such that the guest compounds generally retain their solution properties thereby allowing new molecular composites to be formed. Reported herein is the incorporation of both porphyrins and metalloporphyrins into silica matrices. Electronic absorption, vibrational, and excited state luminescence properties of the resulting composites clearly demonstrate that the molecular and electronic structure of the porphyrins and metalloporphyrins are preserved during sol-gel processing and in the ceramic matrices. This retention of properties has been shown for guest molecules doped into monoliths as well as films.
Effects of Massive Doses of P32 and Ca45 on Laying Hens

Abstract THE current use and potential presence of radioactive isotopes creates a need for information concerning the tolerance of various animal species to their radiations. Dixon (1948) gave lethal and sublethal doses of P32 to 17 day old chicks and observed the red blood cells and various leucocytes until death, or at time of sacrifice 17 days later. Dixon observed less hemorrhage in chicks than that described for other species exposed to equivalent amount s of radiation. Warren and Whipple (1923) found birds more resistant to x-ray than mammals. The present study was made to determine the tolerance of laying hens to P32 and Ca45. Red and white blood cell counts as well as differential white cell counts were made, and in the tissues of the hens that succumbed to the P32, the intensity of radiation was determined in term s of Roentgens equivalent physical. Also the excretion of the isotopes …
Confinement-induced resonances in a cross-dimensional configuration

A lattice-induced opacity is identified in the scattering process of a normally incident matter wave colliding with a two dimensional lattice of atoms. This system can be treated as an analog of a confinement-induced resonance. Specifically, by modifying the $s$-wave scattering length between atoms in the incident matter wave and the lattice-confined atoms, the transmission of the matter wave can be tuned controllably throughout the range from zero to one. The theoretical treatment shows how the mathematical description of confinement-induced resonances can be viewed as an extension of Bragg scattering theory, with alternate opportunities for transmission control.
The “Need for Success” Untying International Peace Interventions in Mostar

This article critically engages with the need for success, a deep structure influencing, as we will argue, not only the outcome of international peace interventions today, but the very ways we think, understand, and evaluate interventions. We engage with this deep structure through a deconstructive double reading of the representations it creates and the influence of those representations on the everyday life of those exposed to it in the city of Mostar, in Bosnia and Herzegovina.
Developing a Registry for Thyroid Incidentalomas: Lessons Learned and the Path Forward

Background: Incidentalomas are findings on an imaging test done for other reasons, for which there are no matching symptoms in the patient. They are common in the adrenal gland, pancreas, liver, and thyroid, among other sites. Incidentalomas are a problem because we have a limited understanding of their natural history: it is difficult to know how much of a threat they pose to individual patients. An observational registry that would allow a systematic study of thyroid incidentalomas could reveal their natural history and the effect of detection on patients' lives, as well as document the cost to the healthcare system. A registry would help to determine which incidentalomas could be monitored and which require action. Study design: A cohort study was conducted, with case identification via radiology imaging reports with follow-up through a minimum of one year post-identification. Results: In one year, >109,000 imaging studies were performed that might reveal an incidental thyroid finding (computed tomogra...
The Preparation of Ni Nanoarray in Alumina Template

AAO template synthesis technology is one of the most important methods for the preparation of nanostructure and it is hot spot in nanomaterial research.AAO template synthesis technology has many advantages over other preparation methods.Lots of metal nanoarrays have been made in AAO template.Ni nanoarray has a lot of advantages and the widespread application value and prospect.In this paper porous alumina membrane is used as template to synthesize Ni nanoarray and electrical deposition is applied.AAO template and Ni nanoarray are characterized by XRD、TEM and SEM.
Analysis of Microbiological Test of 215 Samples of Cooked Products in Cooked meat shops

[Objective]To learn the microbial contamination status of the cooked products in Zhongyuan District of Zhengzhou city,and provide scientific evidence for the managements of sanitation to strengthen the surveillance,prevention and control of the occurrence of food-borne disease. [Methods]According to the principle of random,cooked meat shops in the street markets of Zhongyuan district were conducted health quality inspection and product sampling for the analysis. [Results]Of 215 samples,85 (39.53%)were qualified; 126 (58.60%) were qualified in colony count. 91(42.33%) were qualified in coliform group. The differences of the qualified rates of cooked products between different operation places including street market and fair trade market was significant (χ2=8.91,P0.01).[Conclusion]The over scope of business such as selling the cold and dressed vegetable with sauce exists commonly in cooked meat shops. And the selling foods have terrible issues of microbial contamination,especially in the market. The health-related supervision department should attach great importance to the existed hidden dangers in cooked food.
Operationstrauma und extracelluläre Flüssigkeit

Bei acht Patienten wurden Blutvolumen und extracellulare Flussigkeit mit51Cr und35S vor und nach allgemeinchirurgischen Eingriffen gemessen. Nach den Operationen war das Erythrocytenvolumen um durchschmittlich 3,4% und das Plasmavolumen um 15,9% vermindert. Die interstitielle Flussigkeit war um 22,8% und die extracellulare Flussigkeit um 15,5% vermehrt. Die Zunahme der extracellularen Flussigkeit war bedingt durch massive Flussigkeitsinfusionen wahrend der Operation und in der fruhen postoperativen Phase.
Basic primary rhinoplasty.

This article presents the guest editor’s views on basic primary rhinoplasty at this time, and explains changes in techniques during the past 30 years of his practice.
Math Circles: A Tool for Promoting Engagement among Middle School Minority Males.

Background:This article presents results of a case study of a math circle designed for low income, minority students from an inner city middle school. The students were 6th, 7th and 8th grade African American and Hispanic males enrolled in a science, technology, engineering and mathematics focused charter school. The study focused on the impact of participation in the math circle on students and the design features of the experience that were most effective at promoting engagement and positive reactions from students.Materials and methods:The math circle leaders were participant observers and used interviews, observations and surveys to study the inner workings of the math circle.Results:Participating students reported increases in their interests in mathematics, their confidence in their ability to tackle mathematics problems, and in their enjoyment of mathematics. Competitions and affirmation by a mathematician were key motivating factors for students.Conclusions:Implications for the design of math circles that promote positive mathematical identifies among marginalized populations of students are discussed.
Identification of BECN1 and ATG14 Coiled-Coil Interface Residues That Are Important for Starvation-Induced Autophagy

Autophagy, an essential eukaryotic homeostasis pathway, allows the sequestration of unwanted, damaged, or harmful cytoplasmic components in vesicles called autophagosomes, permitting subsequent lysosomal degradation and nutrient recycling. Autophagosome nucleation is mediated by class III phosphatidylinositol-3-kinase complexes that include two key autophagy proteins, BECN1/Beclin 1 and ATG14/BARKOR, which form parallel heterodimers via their coiled-coil domains (CCDs). Here we present the 1.46 A X-ray crystal structure of the antiparallel, human BECN1 CCD homodimer, which represents BECN1 oligomerization outside the autophagosome nucleation complex. We use circular dichroism and small-angle X-ray scattering (SAXS) to show that the ATG14 CCD is significantly disordered but becomes more helical in the BECN1:ATG14 heterodimer, although it is less well-folded than the BECN1 CCD homodimer. SAXS also indicates that the BECN1:ATG14 heterodimer is more curved than other BECN1-containing CCD dimers, which has important implications for the structure of the autophagosome nucleation complex. A model of the BECN1:ATG14 CCD heterodimer that agrees well with the SAXS data shows that BECN1 residues at the homodimer interface are also responsible for heterodimerization, allowing us to identify ATG14 interface residues. Finally, we verify the role of BECN1 and ATG14 interface residues in binding by assessing the impact of point mutations of these residues on co-immunoprecipitation of the partner and demonstrate that these mutations abrogate starvation-induced upregulation of autophagy but do not impact basal autophagy. Thus, this research provides insights into structures of the BECN1 CCD homodimer and the BECN1:ATG14 CCD heterodimer and identifies interface residues that are important for BECN1:ATG14 heterodimerization and for autophagy.
Quality and Ergonomics

Numerous assertions have been made that ergonomics leads to improved quality. Indeed, this notion was embodied in Deming's system of profound knowledge (Deming 1990), which emphasized the importance of "people systems" and of "maximizing..
Ring and Module

A list of topics in this chapter includes ring, module, endomorphism ring, biendomorphism ring (= bicentralizer) of a module, left ideals, nilpotency, simplicity in categories (e.g. simple groups, simple modules, simple rings), representations of simple rings in complete rings of linear transformations (the prelude to the Chevalley-Jacobson density theorem proved in Chapter 19), matrix rings, dual modules, dual basis lemma for projective modules, the “dual” theorem for generators of the category mod-R of all right R-modules, the trace of a module, additive categories and functors, exact sequences, left (right, half) exact functors, the left exactitude of the morphism (horn) functors h A : mod-R ➦ mod-ℤ and h A : mod-R ➦ mod-ℤ, for any object A of mod-R, Baer’s criterion for injectivity, enough injectives, and the existence of injective cogenerators of mod-R, fully faithful functors, idealizers, orthogonal idempotents and direct decompositions of modules, and fully invariant submodules of a module, including the radical and the socle.
Developmental Changes in Hepatic Organic Cation Transporter OCT1 Protein Expression from Neonates to Children.

Organic cation transporter 1 (OCT1) plays an important role in the disposition of clinically important drugs, and the capacity of OCT1 activity is presumed to be proportional to the protein expression level in organ tissues. Knowledge of OCT1 protein expression in children, especially neonates and small infants, is currently very limited. Here, we report on the characterization of OCT1 protein expression in neonatal, infant, and pediatric liver samples performed using immunoblot analysis. OCT1 protein expression was detected in liver samples from neonates as early as postnatal days 1 and 2. This youngest group showed significantly lower OCT1 expression normalized by glyceraldehyde-6-phosphate dehydrogenase (values given as means ± S.D. in arbitrary units; 0.03 ± 0.02, n = 7) compared with samples from patients aged 3 to 4 weeks (0.08 ± 0.03, n = 5, P
The transmembrane domain of diphtheria toxin improves molecular conjugate gene transfer

Vectors based on the formation of a soluble DNA-polycation complex are being developed for the treatment of human diseases. These complexes are rapidly taken up by receptor-mediated endocytosis, but are inefficiently delivered to the nucleus owing to entrapment in membrane-bound vesicles. In this study we introduced the transmembrane domain of diphtheria toxin into a DNA-polycation conjugate complex in an effort to increase gene transfer by membrane perturbation. The transmembrane domain of diphtheria toxin was expressed in Escherichia coli as a maltose-binding protein fusion and chemically coupled to high-molecular-mass poly-L-lysine. Incorporation of this conjugate into a traditional complex formed with a luciferase-containing plasmid with an asialo-orosomucoid-polycation conjugate significantly increased transfection efficiency in vitro in a manner proportional to the amount of diphtheria toxin incorporated. The delivery of luciferase RNA transcript was similarly increased when complexed with similar polycation conjugates. This study uses the structural biology of a bacterial protein to improve polycation-based gene delivery.
Molecular Mechanisms of Amyotrophic Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder whose pathological hallmark is the loss of motor neurons of the corticospinal pathway. While ALS is a heterogeneous disorder, numerous mechanistic themes, including impaired RNA processing, protein aggregation, intracellular stress, and gliosis, are common to many forms of ALS. In this review we discuss how these mechanisms contribute to selective motor neuron vulnerability and degeneration. In doing so, we synthesize knowledge gained from genetic, molecular, and biochemical studies of human ALS patients and ALS model systems. We conclude with a systematic discussion of the interplay of disease mechanisms and opportunities these mechanisms afford for therapeutic intervention.
Next Generation Evolutionary Sampling and Energy Function Guided ab initio Protein Structure Prediction

The conformation of a protein is vital to understand its function. Homology and ab initio modeling are the two major strategies to solve the protein structure prediction from sequence. The homology methods are not applicable in the absence of homologous sequences. This makes the ab initio modeling unavoidable. The development of ab initio method hinges on the effective conformational space sampling and the accurate energy function to guide the search process. In addition, recent studies demonstrates that it is possible to sample and predict good quality protein structure without using native fragments from known protein structures. Towards this goal, we developed an ab initio method that applies a memory assisted Evolutionary Algorithm (EA) to sample the energy hyper-surface of the protein folding process, looking for the global minimum or the native fold of the protein. Sampling of the energy hyper-surface of the protein is achieved by novel mutation and crossover operations based on angular rotation and translation capabilities. Furthermore, the crossover operations in current generation are enhanced by the use of the best parent selected from previous generation. In addition, we developed and employed a knowledge-based novel energy function, called 3DIGARS, which can differentiate the native structure that corresponds to the most thermodynamically stable state, compared to the possible decoy structures most effectively. The 3DIGARS energy function is an optimized combination of crucial properties such as hydrophobic versus hydrophilic properties, sequence-specific predicted accessibility and ubiquitous phi-psi angular characterization. The samples obtained from the sampling of the energy hyper-surface are scored using 3DIGARS and passed through the EA operators for natural selection and processing. The merits of the proposed approach has been rigorously examined and found to be effective.
Analytic saddlepoint approximation for ionization energy loss distributions

Abstract We present a saddlepoint approximation for ionization energy loss distributions, valid for arbitrary relativistic velocities of the incident particle 0 v / c 1 , provided that ionizing collisions are still the dominant energy loss mechanism. We derive a closed form solution closely related to Moyal’s distribution. This distribution is intended for use in simulations with relatively low computational overhead. The approximation generally reproduces the Vavilov most probable energy loss and full width at half maximum to better than 1% and 10%, respectively, with significantly better agreement as Vavilov’s κ approaches 1.
Inflammatory Markers and Frailty

As the aging population increases rapidly worldwide, caring for frail older adults has become the mandate of modern medicine. As such, frailty has been increasingly recognized as an important geriatric syndrome. This is further supported by the recent development of an operational definition, validation of a set of criteria, and evidence for its syndromic nature. Frailty is characterized by decreased functional and physiologic reserve, increased vulnerability to stressors, as well as high risk for serious adverse health outcomes including disability, dependency, and mortality. Although the pathogenesis of this syndrome is far from being elucidated, frail older adults demonstrate dysregulations in multiple physiologic systems. As discussed elsewhere in this handbook, low grade, chronic systemic inflammation manifested in older adults, so-called “inflamm-aging,” is an important feature of immunosenescence. Activation of the inflammation system marked by elevated levels of inflammatory markers, above and beyond age-related increases, is considered the most prominent pathophysiological feature of frailty. This chapter provides an overview of the syndrome of frailty and its relationship with several molecular and cellular inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), and white blood cell (WBC) and its specific subpopulations. It also discusses the potential role of chronic systemic inflammation, directly and/or through other intermediary systems, in the pathogenesis of frailty.
Probabilistic Invasion Underlies Natural Gut Microbiome Stability

Species compositions of gut microbiomes impact host health [1-3], but the processes determining these compositions are largely unknown. An unexplained observation is that gut species composition varies widely between individuals but is largely stable over time within individuals [4, 5]. Stochastic factors during establishment may drive these alternative stable states (colonized versus non-colonized) [6, 7], which can influence susceptibility to pathogens, such as Clostridium difficile. Here we sought to quantify and model the dose response, dynamics, and stability of bacterial colonization in the fruit fly (Drosophila melanogaster) gut. Our precise, high-throughput technique revealed stable between-host variation in colonization when individual germ-free flies were fed their own natural commensals (including the probiotic Lactobacillus plantarum). Some flies were colonized while others remained germ-free even at extremely high bacterial doses. Thus, alternative stable states of colonization exist even in this low-complexity model of host-microbe interactions. These alternative states are driven by a fundamental asymmetry between the inoculum population and the stably colonized population that is mediated by spatial localization and a population bottleneck, which makes stochastic effects important by lowering the effective population size. Prior colonization with other bacteria reduced the chances of subsequent colonization, thus increasing the stability of higher-diversity guts. Therefore, stable gut diversity may be driven by inherently stochastic processes, which has important implications for combatting infectious diseases and for stably establishing probiotics in the gut.
A phase I study of carboplatin and talazoparib in patients with and without DNA repair mutations.

2527Background: Talazoparib is a novel PARP inhibitor (PARPi) in clinical development. Synergistic anti-tumor effects of PARPi and chemotherapy have been observed in preclinical models. Overlapping toxicity may limit tolerability in patients with germline DNA repair defects. Methods: In a dose escalation Phase 1 trial, we tested the safety, tolerability, pharmacokinetics (PK), and efficacy of talazoparib and carboplatin in patients with and without germ line mutations. Results: 24 patients with solid tumors were enrolled in 4 cohorts evaluating talazoparib 0.75 or 1 mg daily and carboplatin AUC 1 or 1.5 mg/mL/min 2 or 3 weeks of a 3-week cycle. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia. Other grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). Post cycle 2 hematologic toxicities required dose delays/reductions in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. O...
Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect

Traumatic brain injury produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of traumatic brain injury using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223, and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization. Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out mice expression of type I interferons IFNα and IFNβ, as well as interferon regulatory factor 1 and interferon-induced chemokine CXCL10 was decreased after TBI relative to WT mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluorojade C staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI.
Resolving distinct molecular origins for copper effects on PAI-1

Components of the fibrinolytic system are subjected to stringent control to maintain proper hemostasis. Central to this regulation is the serpin plasminogen activator inhibitor-1 (PAI-1), which is responsible for specific and rapid inhibition of fibrinolytic proteases. Active PAI-1 is inherently unstable and readily converts to a latent, inactive form. The binding of vitronectin and other ligands influences stability of active PAI-1. Our laboratory recently observed reciprocal effects on the stability of active PAI-1 in the presence of transition metals, such as copper, depending on the whether vitronectin was also present (Thompson et al. Protein Sci 20:353–365, 2011). To better understand the molecular basis for these copper effects on PAI-1, we have developed a gel-based copper sensitivity assay that can be used to assess the copper concentrations that accelerate the conversion of active PAI-1 to a latent form. The copper sensitivity of wild-type PAI-1 was compared with variants lacking N-terminal histidine residues hypothesized to be involved in copper binding. In these PAI-1 variants, we observed significant differences in copper sensitivity, and these data were corroborated by latency conversion kinetics and thermodynamics of copper binding by isothermal titration calorimetry. These studies identified a copper-binding site involving histidines at positions 2 and 3 that confers a remarkable stabilization of PAI-1 beyond what is observed with vitronectin alone. A second site, independent from the two histidines, binds metal and increases the rate of the latency conversion.
AB0338 Heads-up! sarcoidosis and rheumatoid arthritis co-exist

Background Sarcoidosis and rheumatoid arthritis (RA) uncommonly co-occur. How dual diagnosis affects these patients9 clinical phenotype is unknown. Objectives To characterize the clinical and laboratory phenotype and to increase awareness of the coexistence of sarcoidosis and RA. Methods We searched PubMed from 1980–2016 for relevant articles using key words “sarcoidosis” and “rheumatoid arthritis,” excluding cases with tumor necrosis factor inhibitors. We found 12 cases, omitted 5 lacking clinical detail, and added 2 from our experience at the Cleveland Clinic. Clinical features, laboratory and imaging findings were reviewed and summarized. Results Females comprised 7/9 cases (77%). Our cases are the first to describe men with dual diagnosis. Of the 8 cases reporting ethnicity, 4 (50%) were white. The mean age at time of diagnosis was 35.3 years for RA and 51.0 years for sarcoidosis. In 5/9 cases (55%), RA preceded sarcoidosis. RA affected the hands in 8/9 patients (88.9%). Of the 8 cases reporting symptoms of sarcoidosis, 5 (62.5%) had dyspnea. All cases (100%) had elevated rheumatoid factor (RF) and, when checked, anti-citrullinated peptide (anti-CCP) antibodies. Angiotensin converting enzyme (ACE) was elevated in 6/9 patients (66.6%). Of the 5 patients with joint imaging, 4 (80%) had inflammatory changes. All sarcoidosis (100%) was biopsy-proven. One case (11.1%) demonstrated concomitant pulmonary RA and sarcoidosis. Conclusions Sarcoidosis and RA coexist in seropositive patients, most commonly in women in their fourth through sixth decades of life. RA preceded sarcoidosis about half the time. Hand arthritis and dyspnea were the most common symptoms for RA and sarcoidosis, respectively. Awareness of this dual diagnosis may help identify RA and sarcoidosis earlier and prevent treatment delay. References Enzenauer RJ and West SG. Sarcoidosis in autoimmune disease. Arth & Rheum, 1992; 22(1):1–17. Menard O, et al. Association of histologically proven rheumatoid arthritis with pulmonary sarcoidosis. Eur Respir J, 1995; 8;472–3. Kobak S, et al. Co-occurrence of rheumatoid arthritis and sarcoidosis. BMJ Case Rep, 2015;1–3. Kucera, MRF. A possible association of rheumatoid arthritis and sarcoidosis. Chest, 1989; 95:604–06. Leo G, et al. Simultaneous pulmonary involvement, histologically proven, of sarcoidosis and rheumatoid arthritis. Clin Exp Rheumatol, 2009;27(1):164. Takashita M, et al. Mutilating rheumatoid arthritis associated with sarcoidosis: A case report. Clin rheum, 1995;14(5):576–9. Disclosure of Interest None declared
Prevalence of Coronary Artery Lesion(S) in Pati ents Aged 40-50 Years Undergoing Rheumatic Valvular Surgery

Objective: To determine the prevalence of coronary artery disease in patients undergoing valve surgery for rheumatic heart disease between age 40-50 years, usefulness, and indication of pre-operative coronary angiography. Methods: This is an observational prospective study that took place in 2 hospitals (National Heart Institute and Nasser Institute) within the period starting from January 2013 to January 2015. We included 454 rheumatic patients that were admitted for elective primary mitral, aortic or double valve surgery, and that had a coronary angiogram in their regular preoperative workup. All coronary angiographies were performed by injecting right and left coronaries by using 80-100 ml of iodinated contrast to obtain the standard views of both right and left coronaries using Philips or Siemens machines in both hospitals. Coronary artery disease (CAD) of 50% is considered to be a positive finding. Results: There was no correlation between rheumatic heart disease in this age group and CAD as only 1.76% had the significant stenosis. Male gender, family history of CAD, age above 45yrs, hypertension, and smoking showed significant correlation with the CAD in this study. Conclusion: Our results suggest that the overall prevalence of coronary artery disease in patients undergoing rheumatic valve surgery in our population is not comparable with the prevalence reported in international data. So, multicenter studies are needed in developing countries to set their own guidelines. Therefore, our study can be the nucleus for these guidelines in our country.
Effect of field-effect transistor geometry on charge ordering of transition-metal oxides

We examine the effect of field-effect transistor (FET) geometry on the charge ordering phase diagram of transition-metal oxides using numerical simulations of a semiclassical model including long-range Coulomb fields, resulting in nanoscale pattern formation. We find that the phase diagram is unchanged for insulating layers thicker than approximately twice the magnetic correlation length. For very thin insulating layers, the onset of a charge ``clump'' phase is shifted to lower values of the strength of the magnetic dipolar interaction, and intermediate diagonal stripe and geometric phases can be suppressed. Our results suggest that, for sufficiently thick insulating layers, charge injection in FET geometry can be used to experimentally probe the intrinsic charge ordering phases in these materials.
Depressive Symptoms, Antidepressant Use, and Hypertension in Young Adulthood.

Background Among adults, depressive symptoms are associated with higher rates of cardiovascular disease; however, the evidence is mixed regarding the association between depressive symptoms and hypertension, especially among young adults. The deleterious effects of some antidepressant medications on blood pressure may contribute to mixed findings. Methods Adolescents enrolled in Add Health (N = 11,183) (1994-2008) completed an abbreviated Center for Epidemiologic Studies Depression Scale at three waves (mean ages, 16, 22, and 29). Antidepressant use was measured at age 22 and at age 29. Hypertension at age 29 was defined as measured systolic blood pressure of 140 mm Hg or greater, diastolic blood pressure of 90 mm Hg or greater, or staff-inventoried anti-hypertensive medication use. Results The prevalence of hypertension at age 29 was 20%. High depressive symptoms in adolescence or young adulthood were not associated with hypertension in young adulthood. Antidepressant use at age 29 was associated with increased prevalence of hypertension (prevalence ratio [PR], 1.4; 95% CI, 1.2, 1.7) and an interaction with sex was observed (PRMen, 1.6; 95% CI, 1.2, 2.0; PRWomen, 1.2; 95% CI, 0.89, 1.6; pinteraction = 0.0227). Selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor antidepressant use were associated with hypertension (PRSSRI, 1.3; 95% CI, 1.0, 1.6; PRnon-SSRI, 1.6; 95% CI, 1.2, 2.1). Conclusions In this sample, antidepressant use, but not depressive symptoms, was associated with hypertension in young adulthood. Further research is recommended to examine joint and independent relationships between depression and antidepressant use and hypertension among young adults. See video abstract at, http://links.lww.com/EDE/B355.
Activation of catecholamine neurons in the ventral medulla reduces CCK-induced hypophagia and c-Fos activation in dorsal medullary catecholamine neurons.

Catecholamine (CA) neurons within the A1 and C1 cell groups in the ventrolateral medulla (VLM) potently increase food intake when activated by glucose deficit. In contrast, CA neurons in the A2 cel...
The role of tetramethylene diradicals in photo-induced “charge-transfer” cycloadditions and copolymerization

A mechanism for the photo-induced copolymerization of donor monomers with acceptor monomers is proposed based on a combination of the results from organic chemistry and the results from thermal polymerizations and photopolymerizations. Under certain conditions, tetramethylene diradicals, the proposed key intermediates, are formed from the exciplex between the monomer pairs and undergo cyclization and initiate copolymerization.
Supracondylar Humerus Fractures

Supracondylar humerus fractures are the most common pediatric elbow fracture and the second most common pediatric fracture overall. According to Cheng and colleagues (1999), supracondylar humerus fractures constitute approximately 18% of all fractures in children. They are second only to distal radius fractures, which represent approximately 20% of pediatric fractures. When stratified by age, supracondylar humerus fractures represent the most common fracture among both infant to 3-year-olds and 4–7-year-olds. In these age groups, supracondylar humerus fractures comprise approximately 27 and 32% of fractures, respectively. Supracondylar humerus fractures occur most frequently in children ages 5–7 years. There is no clear difference in incidence between genders.
The Nature of the Catalytic Sites in HZSM-5- Activity Enhancement

The catalytic activity of HZSM-5, when carefully prepared in the absence of water vapor, is strictly proportional to its tetrahedral Al content. All sites have equal activity, which includes sites having zero (single) and one (paired) next nearest neighbor Al atoms. While severe steaming reduces the catalytic activity, mild steaming produces catalysts of higher activity. New catalytic sites are generated with a specific activity 45-75 times greater than that of the normal sites. The resulting zeolite has a combination of enhanced activity sites and normal activity sites. Paired Al framework atoms appear to be required for the formation of enhanced acidic centers. A kinetic model encompassing rates of enhanced site generation, their decomposition and dealumination has been developed.