cssi/SciSciGPT-SciSciNet huggingface dataset:
Human Endogenous Retrovirus K and Pulmonary Arterial Hypertension: A New Take on a Retro Idea

Article, see p 1920 Pulmonary arterial hypertension (PAH) is a deleterious disease of the lung vasculature characterized by endothelial dysfunction, medial hypertrophy and proliferation, and eventual occlusion of the pulmonary arterioles. Although a number of genetic and environmental triggers have been described as causative, the specific molecular origins of this vascular disease are still unknown. Multiple lines of evidence now converge to connect immune dysregulation to PAH in humans and animal models. Previous reports suggest that altered inflammatory dynamics, such as hematopoietic and myeloid expansion, B- and T-cell dysfunction, increased cytokine production, circulating autoantibodies, and tertiary lymphoid tissue neogenesis, may initiate or drive PAH.1 Clinically, a well-established causative link exists between autoimmune connective tissue disorders and PAH. Furthermore, infectious agents, such as Schistosoma mansoni and human immunodeficiency virus (HIV), are known to alter the immune cell repertoire and predispose to the development of PAH. However, a mechanistic understanding of the exogenous or endogenous factors that drive immune dysfunction remains largely undefined. Prior studies have aimed to characterize the role of exogenous viruses in PAH. For example, HIV-associated PAH has been attributed to decreased CD4+ T-cell function, indicating a role for T-cell–mediated immune dysregulation.2 Separately, HIV-encoded proteins such …
A Talented Duo: IFIT1 and IFIT3 Patrol Viral RNA Caps.

Hosts respond to viral infection by expressing interferon-stimulated genes, of which IFITs are potent inhibitors of viral RNA translation. Johnson et al. (2018) solved the structure of the IFIT1-IFIT3 complex bound cap 0 RNA and explored their concerted antiviral activity.
Chemical Probe to Identify the Cellular Targets of the Reactive Lipid Metabolite 2-trans-Hexadecenal

Lipid-derived electrophiles (LDEs) are reactive metabolites, which can covalently modify proteins and DNA and regulate diverse cellular processes. 2-trans-Hexadecenal (2-HD) is a byproduct of sphingolipid metabolism, involved in cytoskeletal reorganization, DNA damage, and apoptosis. In addition, the loss of ALDH3A2, an enzyme removing 2-HD in cells, is responsible for Sjorgen-Larsson Syndrome (SJS), suggesting that accumulation of 2-HD could lead to pathogenesis. However, the targets and the precise mechanisms of 2-HD are not well characterized. Herein, we report an alkyne-2-HD derivative as a bioorthogonal probe to explore the functions of 2-HD. We identified more than 500 potential cellular targets. Among them, the pro-apoptotic protein Bax can be covalently modified by 2-HD directly at the conserved Cys62 residue. Our work provided new chemical tools to explore the cellular functions of LDEs and revealed new mechanistic insights of the deregulation of lipid metabolism in diseases.
A Feature Selection Algorithm Capable of Handling Extremely Large Data Dimensionality.

With the advent of high throughput technologies, feature selection has become increasingly important in a wide range of scientific disciplines. We propose a new feature selection algorithm that performs extremely well in the presence of a huge number of irrelevant features. The key idea is to decompose an arbitrarily complex nonlinear models into a set of locally linear ones through local learning, and then estimate feature relevance globally within a large margin framework. The algorithm is capable of processing many thousands of features within a few minutes on a personal computer, yet maintains a close-to-optimum accuracy that is nearly insensitive to a growing number of irrelevant features. Experiments on eight synthetic and real-world datasets are presented that demonstrate the effectiveness of the algorithm.
Opportunities for Spiritual Awakening and Growth in Mothering

My experiences as a mother have been enhanced by spirituality and my spirituality has been transformed through the practice of mothering. I will argue that part of the transformation available in mothering is that one can go from thinking of oneself as an individual with free will, self autonomy, and independence to believing maybe we are all more connected and dependent upon each other than we thought. I intend to explore my personal spiritual journey from an academic perspective in order to gain and share knowledge. Intense emotional experiences such as childbirth, learning how to take care of a person who can not clearly communicate her or his desires, and learning to put the needs of someone else before your own, have the potential for both extreme pain and joy and the mother is forced to decide how to move forward. If mothers start to feel connected to their children, it can become easier to feel connected to other mothers, children, and humanity in general. This change which can occur within a mother can be a part of the spiritual awakening. American society, in general, would benefit from the recognition of the spiritual side of mothering and the awareness of the potential for a transformation in consciousness. My thesis topic is the spirituality of motherhood. More specifically, I explore how the practice of caring for children can transform the caregiver’s sense of spirituality iii which is the relationship between your self and the world. This thesis is based on a feminist literary review of texts about spirituality and motherhood and also uses my personal experiences as a mother to illustrate how mothering can be a spiritual awakening and opportunity for spiritual growth. It is feminist in nature because I am attempting to illuminate and privilege the knowledges and experiences of mothers. I want to celebrate female parenting and also recognize the difficulties imposed by our sexist society. Motherhood does not always have to be exploitive or repressive and spirituality is one way to transcend these challenges.
Preparation of Highly-Dispersed Ruthenium on Magnesium Oxide Supports: Comments on the Advantages of Non-Aqueous Catalyst Preparations

The difficulty of preparing highly-dispersed ruthenium catalysts on basic oxide supports is related to hydrolysis of the support by the aqueous phase. Use of anhydrous, aprotic solutions prevents the hydrolysis reactions with the hydroxyl groups of the support, allowing selective adsorption of ruthenium chloride onto the support. An adsorption preparation is not possible from aqueous solution due to the high pH values of the solutions. The preparation of well-dispersed ruthenium on MgO-washcoated monoliths was accomplished by a non-aqueous adsorption preparation. Aqueous solution preparations in contrast lead to ruthenium maldistribution with the metal poorly dispersed on this type of monolith support. Determination of the metal dispersion for supported ruthenium catalysts is complicated by a number of factors. One of the most important of these factors is multiple adsorption of CO on Ru catalysts. Ruthenium on alumina metal dispersions measured with H2. chemisorption do not agree with those measured with CO. We have, however, found for many ruthenium catalysts on MgO and on MgO/MgAl2O4, monoliths that there is good agreement between the metal dispersions obtained by H2 and CO. We propose that the CO/H2 ratio is a probe of the metal-support interaction of Ru with MgO.
A Game-Theoretic Approach to Modeling Cross-Cultural Negotiation

Faithful models of negotiation should capture aspects such as subjective incentives, imperfect information, and sequential interaction, while providing explanation for behaviors such as bluffing, trust building, and information revelation. All of these objectives are elegantly addressed by theory of sequential games, and some of these phenomena have no convincing explanation without game theory’s key assumption, namely, that of the rationality (or approximate rationality) of the negotiators. In this paper we discuss a game-theoretic approach to modeling negotiation. In addition to accounting for a range of behavior and reasoning styles we also address several aspects specific to cross-cultural negotiation. We argue that the existence of culture-specific beliefs and strategies can be explained by the existence of multiple game-theoretic equilibria. Within a culture, repeated interaction and learning lead to an equilibrium. On the other hand, across cultures, infrequent interaction leads with high probability to disparate (and often incompatible) equilibria. We hypothesize that inefficiency in cross-cultural negotiation can be attributed to this incompatibility. We discuss recently-developed algorithms that can be used to fit models of culture-specific behavior from data while incorporating rationality constraints. We anticipate that the additional structure imposed by rationality constraints will yield both statistical advantages and game theoretic insights.
Use of Air Quality Modeling Results in Health Effects Research

The most recent Global Burden of Disease study (Lim SS et al, Lancet 380(9859):2224–2260, 2012), for example, finds that combined exposure to ambient and indoor air pollution is one of the top five risks worldwide. Of particular concern is particulate matter (PM). Health researchers are now trying to assess how this mixture of air pollutants links to various health outcomes and how to tie the mixture components and health outcomes back to sources. This process involves the use of air quality models. As part of an EPA Clean Air Research Center, the Southeastern Center for Air Pollution and Epidemiology (SCAPE), a variety of air quality models are being developed and applied to provide enhanced temporal and spatial resolution of pollutant concentrations for use in epidemiologic analysis. Air quality models that are being further developed and used as part of the center include Bayesian-based ensemble methods and hybrid chemical transport-chemical mass balance modeling. The hybrid method uses knowledge of the emissions, modeling and measurement uncertainties, and can provide spatially and temporally complete pollutant fields.
Bearingless Motor Technology for Industrial and Transportation Applications

This paper reviews bearingless motor technology for use in large transportation and industrial applications. Historically, bearingless motors have resided in research settings and certain niche commercial applications. Significant literature has been dedicated to developing designs that feature highly-specific geometry, restricted by applications with a unique set of needs, oftentimes with low power requirements. The first part of this paper reviews existing and potentially new use-cases of magnetic levitation in transportation and industrial applications. The second part of the paper presents design sizing equations of promising bearingless motor topologies for these applications and highlights efforts to generalize and increase the power rating of bearingless motor technology.
Free space is valuable space: lessons from Chocolate Cities

In our reading of Chocolate Cities: The Black Map of American Life as a work of liberation sociology, we discuss contributions to Black critical thought and praxis this book uniquely makes. Hunter ...
Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L

Summary Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is conserved from yeast to humans. We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that makes it possible for histone-modifying enzymes to access residues within the nucleosome core.
p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise.

In the neurogenic niches – the dentate gyrus of the hippocampus and the subventricular zone (SVZ) adjacent to lateral ventricles – stem cells continue to divide during adulthood, generating progenitor cells and new neurons, and to self-renew, thus maintaining the stem cell pool. During aging the numbers of stem/progenitor cells in the neurogenic niches are reduced. The preservation of the neurogenic pool is committed to a number of antiproliferative genes, with the role of maintaining the quiescence of neural cells. The cyclin-dependent kinase inhibitor p16Ink4a, whose expression increases with age, controls the expansion of SVZ aging stem cells, since in mice its deficiency prevents the decline of neurogenesis in SVZ. No change of neurogenesis is however observed in the p16Ink4a-null dentate gyrus. Here we hypothesized that p16Ink4a plays a role as a regulator of the self-renewal of the stem cell pool also in the dentate gyrus, and to test this possibility we stimulated the dentate gyrus neural cells of p16Ink4a-null aging mice with physical exercise, a powerful neurogenic activator. We observed that running highly induced the generation of new stem cells in the p16Ink4a-null dentate gyrus, forcing them to exit from quiescence. Stem cells, notably, are not induced to proliferate by running in wild-type mice. Moreover, p16Ink4a-null progenitor cells were increased by running significantly above the number observed in wild-type mice. The new stem and progenitor cells generated new neurons, and continued to actively proliferate in p16Ink4a-null mice longer than in the wild-type after cessation of exercise. Thus, p16Ink4a prevents aging dentate gyrus stem cells from being activated by exercise. Therefore, p16Ink4a may play a role in the maintenance of dentate gyrus stem cells after stimulus, by keeping a reserve of their self-renewal capacity during aging.
The Mathematical Performance of At-Risk First Graders as a Function of Limited English Proficiency Status.

The purpose of this study was to explore interactions between limited English proficiency (LEP) status, as a function of risk status (low math performance at the start of the school year), on compu...
MECHANISM OF CYTOTOXICITY OF 2-CHLORO AND 2-BROMO DEOXYADENOSINE FOR A HUMAN LYMPHOBLASTIC CELL LINE, CCRF-CEM: 15

Cytotoxicity as measured by inhibition of growth and DNA synthesis (IC50) and by decrease in clonogenicity (EC50) has been compared with that of dAdo. IC50 for growth and for DNA synthesis is similar in all 3 cases. IC50 for 2-CldAdo (0.045 μM) is lower than for 2-BrdAdo (0.068 μM) and dAdo (0.9 μM). For 2-CldAdo and 2-BrdAdo, EC50 is somewhat higher than IC50 and much greater in the case of dAdo. About 20% of cells are resistant to concentrations of 2-BrdAdo >>EC50 but viability is decreased to approximately 2% by 18 hr exposure to 2-CldAdo at 20 × EC50 or to dAdo at 3 × EC50. Treatment with 2-CldAdo or dAdo sufficient to cause large losses in viability result in accumulation of cells at the G1/S border. The nucleosides are converted over 24 hr to increasing levels of the triphosphates. The latter inhibit reduction of CDP and of ADP by L1210 ribonucleotide reductase with IC50 in the order: 2-BrdATP < 2-CldATP < dATP << ara-ATP. In intact CCRF-CEM cells dAdo specifically decreases dGTP with other dNTPs increasing, whereas 2-CldAdo and 2-BrdAdo decrease dCTP and dATP with a transitory decrease in dGTP but dGTP and dTTP are elevated above controls by 24 hr. Data indicate that inhibition of ribonucleotide reductase possibly contributes to inhibition of DNA synthesis but is probably not the lesion critical for cell death. Supported by American Lebanese Syrian Associated Charities.
Using quantitative polymerase chain reaction (qPCR) and occupancy models to estimate atypical Aeromonas hydrophila (aAh) prevalence in catfish

Abstract A strain of atypical Aeromonas hydrophila (aAh) has caused issues within the channel catfish Ictalurus punctatus industry of the southeastern United States since 2009. These atypical pathotypes cause acute mortality events resulting in catastrophic losses, as opposed to more chronic mortality and lesions seen in typical infections of motile aeromonas septicemia (MAS). This study provides a basic framework for rapid field sampling negating the need for re-isolation or enrichment culture, thereby reducing the time between sampling and detection. Rapid and accurate quantitative PCR based methods for detection of aAh have been described and are important confirmative tools in research and diagnostic settings. These methods also have application in epidemiological surveys investigating the spread of disease and elucidating pathogen dynamics that may lead to outbreaks. To date, no field-based sampling technique for rapid aAh detection in resident pond populations has been explored. In this study, culture swabs taken from the gills and lower intestine of pond-raised catfish were assessed for their suitability as rapid field-based collection methods for downstream applications. Results showed the state of the pond has a significant effect on which swab location yields the highest proportion of PCR positive results. During an active outbreak, gill swabs identified more fish as aAh-positive; however, in apparently healthy populations, swabs taken from the lower intestine identified significantly more aAh-positive fish than gill swabs, despite no statistical difference in the concentration of aAh cell equivalents between swab sites. Naive prevalence estimates from the two swab types were compared to estimates provided by a hierarchical occupancy model. Prevalence estimates from gill swabs was 0.95% while vent swabs showed a prevalence of 2.2%; however, estimates based on the occupancy model were 6.6% and 9.8%, respectively. This multi-fold increase in prevalence estimates highlights the importance of accounting for imperfect detection in epidemiological studies and in assessing potential outbreak risk. Furthermore, occupancy models based on these data indicate resident fish can be aAh-positive carriers with no gross signs of infection, providing evidence aAh can reside in catfish ponds in the absence of disease. The presence of a carrier state indicates the pathogen may pose minimal risk to the host is compromised or a mechanical portal of entry into the blood stream is available. This provides an important direction for future research in understanding the mechanisms of aAh outbreaks in catfish aquaculture ponds.
Histone Deacetylases Regulation by δ-Opioids in Human Optic Nerve Head Astrocytes.

Purpose We determined whether δ-opioid receptor agonist (SNC-121) regulates acetylation homeostasis via controlling histone deacetylases (HDACs) activity and expression in optic nerve head (ONH) astrocytes. Methods ONH astrocytes were treated with SNC-121 (1 µM) for 24 hours. The HDAC activity was measured using HDAC-specific fluorophore-conjugated synthetic substrates, Boc-Lys(Ac)-AMC and (Boc-Lys(Tfa)-AMC). Protein and mRNA expression of each HDAC was determined by Western blotting and quantitative real-time PCR. IOP in rats was elevated by injecting 2.0 M hypertonic saline into the limbal veins. Results Delta opioid receptor agonist, SNC-121 (1 µM), treatment increased acetylation of histone H3, H2B, and H4 by 128 ± 3%, 45 ± 1%, and 68 ± 2%, respectively. The addition of Garcinol, a histone-acetyltransferase inhibitor, fully blocked SNC-121-induced histone H3 acetylation. SNC-121 reduced the activities of class I and IIb HDACs activities significantly (17 ± 3%) and this decrease in HDACs activities was fully blocked by a selective δ-opioid receptors antagonist, naltrindole. SNC-121 also decrease the mRNA expression of HDAC-3 and HDAC-6 by 19% and 18%, respectively. Furthermore, protein expression of HDAC 1, 2, 3, and 6 was significantly (P < 0.05) decreased by SNC-121 treatment. SNC-121 treatment also reduced lipopolysaccharide-induced TNF-α production from ONH astrocytes and glial fibrillary acidic protein immunostaining in the optic nerve of ocular hypertensive animals. Conclusions We provided evidence that δ-opioid receptor agonist activation increased histone acetylation, decrease HDACs class I and class IIb activities, mRNA, and protein expression, lipopolysaccharide-induced TNF-α production in ONH astrocytes. Our data also demonstrate that SNC-121 treatment decrease glial fibrillary acidic protein immunostaining in the optic nerves of animals with ocular hypertension.
A changing landscape? An intersectional analysis of race and gender disparity in access to social capital

We apply intersectional frameworks and use a nationally representative dataset to investigate patterns of differential access to social capital among six racial and gender groups. We define social ...
Nudge, Nudge or Shove, Shove — The Right Way for Nudges to Increase the Supply of Donated Cadaver Organs

Richard Thaler and Cass Sunstein (2008) contend that mandated choice is the most practical nudge for increasing organ donation. We argue that they are wrong, and their mistake results from failing to appreciate how perceptions of meaning can influence people’s responses to nudges. We favor a policy of default to donation that is subject to immediate family veto power, includes options for people to opt out (and be educated on how to do so), and emphasizes the role of organ procurement organizations and in-house transplant donation coordinators creating better environments for increasing the supply of organs and tissues obtained from cadavers. This policy will provide better opportunities for offering nudges in contexts where in-house coordinators work with families. We conclude by arguing that nudges can be introduced ethically and effectively into these contexts only if nudge designers collaborate with in-house coordinators and stakeholders.
Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney Failure

Background and objectives Patients with sickle cell disease-associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure. Design, setting, participants, & measurements Using a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998-2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk. Results Compared with their matched waitlisted candidates, 189 transplant recipients with sickle cell disease and 220,251 control recipients showed significantly lower mortality. The absolute risk difference at 10 years post-transplant was 20.3 (98.75% confidence interval, 0.9 to 39.8) and 19.8 (98.75% confidence interval, 19.2 to 20.4) percentage points in the sickle cell and control groups, respectively. The hazard ratio was also similar in the sickle cell (0.57; 95% confidence interval, 0.36 to 0.91) and control (0.54; 95% confidence interval, 0.53 to 0.55) groups (interaction P=0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72). Conclusions Patients with sickle cell disease-associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.
Bomb 137Cs in modern honey reveals a regional soil control on pollutant cycling by plants.

137Cs is a long-lived (30-year radioactive half-life) fission product dispersed globally by mid-20th century atmospheric nuclear weapons testing. Here we show that vegetation thousands of kilometers from testing sites continues to cycle 137Cs because it mimics potassium, and consequently, bees magnify this radionuclide in honey. There were no atmospheric weapons tests in the eastern United States, but most honey here has detectable 137Cs at >0.03 Bq kg−1, and in the southeastern U.S., activities can be >500 times higher. By measuring honey, we show regional patterns in the biogeochemical cycling of 137Cs and conclude that plants and animals receive disproportionally high exposure to ionizing radiation from 137Cs in low potassium soils. In several cases, the presence of 137Cs more than doubled the ionizing radiation from gamma and x-rays in the honey, indicating that despite its radioactive half-life, the environmental legacy of regional 137Cs pollution can persist for more than six decades. Radioactive 137Cs is a fission product remaining in the environment from mid-20th century nuclear testing. Here the authors show that vegetation thousands of kilometers from testing sites continues to cycle 137Cs, and consequently, bees magnify this contaminant in honey in regions with low soil potassium.
Community Inclusion and Social Determinants: From Opportunity to Health.

It is well documented that individuals with serious mental illnesses are disadvantaged in their employment, educational attainment, social relationships, family relationships, and other areas, whic...
A simple fault-tolerant adaptive and minimal routing approach in 3-D meshes

In this paper we propose a sufficient condition for minimal routing in 3-dimensional (3-D) meshes with faulty nodes. It is based on an early work of the author on minimal routing in 2-dimensional (2-D) meshes. Unlike many traditional models that assume all the nodes know global fault distribution or just adjacent fault information, our approach is based on the concept of limited global fault information. First, we propose a fault model called faulty cube in which all faulty nodes in the system are contained in a set of faulty cubes. Fault information is then distributed to limited number of nodes while it is still sufficient to support minimal routing. The limited fault information collected at each node is represented by a vector called extended safety level. The extended safety level associated with a node can be used to determine the existence of a minimal path from this node to a given destination. Specifically, we study the existence of minimal paths at a given source node, limited distribution of fault information, minimal routing, and deadlock-free and livelock-free routing. Our results show that any minimal routing that is partially adaptive can be applied in our model as long as the destination node meets a certain condition. We also propose a dynamic planar-adaptive routing scheme that offers better fault tolerance and adaptivity than the planar-adaptive routing scheme in 3-D meshes. Our approach is the first attempt to address adaptive and minimal routing in 3-D meshes with faulty nodes using limited fault information.
Preoperative Thrombelastography Predicts Transfusion Requirements During Liver Transplantation

Background: Thrombelastography (TEG) has become increasingly utilized in liver transplantation (LT). The implications of TEG at various stages of LT, however, remain poorly understood. Our goal was to examine TEG-based coagulopathy profiles in LT and determine whether preoperative TEG is predictive of transfusion requirements perioperatively. Methods: A retrospective review of 364 LTs from January 2013 to May 2017 at a single institution was performed. Patients were categorized as hypocoagulable or nonhypocoagulablebased on their preoperative TEG profile. The primary outcome was intraoperative transfusion requirements. Results: Of patients undergoing LT, 47% (n=170) were hypocoagulable and 53% (n=194) were non-hypocoagulable preoperatively. Hypocoagulable patients had higher transfusionrequirements compared to non-hypocoagulable patients, requiring more units of pRBC (7 vs.4, p 0.05). Conclusions: Coagulation abnormalities are common among LT patients and can be identified using TEG. Identification of a patient’s coagulation state preoperatively using TEG may predict transfusion requirements during LT. Preoperative TEG should be used when available to identify patients who may be higher risk for intraoperative coagulopathy and require increased perioperative resource utilization.
Peptide Mimicry of the Polysaccharide Capsule of Cryptococcus neoformans

Organisms that possess a polysaccharide capsule, such as Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, and Cryptococcus neoformans, are extremely important clinically because they are responsible for a majority of serious infections and for most deaths from meningitis. The reasons for searching for a peptide mimic of a carbohydrate structure are many-fold. In comparison to peptide chemistry, which is well-defined and relatively easy to manipulate, carbohydrate chemistry is more complex. C. neoformans is an environmentally ubiquitous encapsulated yeast that causes a life-threatening meningoencephalitis in 8% of AIDS patients in the United States and as many as 30% of HIV-infected people in Africa; it is the most common cause of central nervous system infections in New York City. Peptide binding monoclonal antibodies (MAbs) were obtained from mice immunized with P601E with the hope that their molecular structure would provide an explanation as to why they did not bind to glucuronoxylomannan (GXM). The antibody binding site of MAb 2H1 is a hydrophobic pocket delimited by CDR2 and CDR3 of the heavy chain and CDR1 and CDR3 of the light chain. The crystal structure of one of the peptides bound to MAb 2H1, combined with the molecular structure of the antipeptide MAbs elicited by another one of the peptides, provided a clue as to why our peptides were not good mimotopes. The 2H1 antibody does not change its conformation when it interacts with the peptide mimic, making it unlikely that changes in the site occur when it interacts with GXM.
Evaluating proxies for estimating subaerial beach volume change across increasing time scales and various morphologies

Proxies, such as changes in beach profiles and shoreline positions, are commonly used in management and research for estimating changes in subaerial beach volume; however, the accuracy of these proxies across increasing time scales and complex morphologies is unclear. Volume changes associated with along-beach morphologic variability may not be captured well by changes in profiles, while volume changes associated with across-beach morphologic variability may not be captured well by measuring shoreline change. This study assesses the impacts of morphologic variations, associated with beach cusps and nourishment material, on volume change estimates from profiles and shoreline change at 0.5 to 3.5 year time periods. Results indicate that profiles spaced ≥ 150 m apart and the shoreline-change proxy will likely estimate volume change inaccurately over periods ≤ 1 year at beaches that are consistently eroding or accreting and contain cusps. However, over longer time periods (1–3.5 years), estimates of volume change from both proxies improved at those types of beaches. Volume changes at the edges of nourishment areas are not captured well by profiles. When the nourishment material is graded to a ramped morphology, which minimizes across-beach morphologic variability, the shoreline-change proxy does accurately estimate volume changes. Both proxies estimate volume changes inaccurately at beaches where volume changes oscillate between erosion and accretion on both short and long time scales because the magnitude of small-scale changes in volume from the formation and erosion of morphologic features, such as cusps and berms, will always be similar to the longer-term net volume change. This study suggests that decadal records of shoreline change, which are commonly developed using aerial photography, can be used to help identify the best proxy for estimating volume change; however, recent anthropogenic modifications that impact patterns of beach sedimentation, including nourishment, terminal groins, and inlet-channel dredging, makes decadal records less useful. Copyright © 2013 John Wiley & Sons, Ltd.
Molecular Composition of Plant Vacuoles: Important but Less Understood Regulations and Roles of Tonoplast Lipids

The vacuole is an essential organelle for plant growth and development. It is the location for the storage of nutrients; such as sugars and proteins; and other metabolic products. Understanding the mechanisms of vacuolar trafficking and molecule transport across the vacuolar membrane is of great importance in understanding basic plant development and cell biology and for crop quality improvement. Proteins play important roles in vacuolar trafficking; such proteins include Rab GTPase signaling proteins; cargo recognition receptors; and SNAREs (Soluble NSF Attachment Protein Receptors) that are involved in membrane fusion. Some vacuole membrane proteins also serve as the transporters or channels for transport across the tonoplast. Less understood but critical are the roles of lipids in vacuolar trafficking. In this review, we will first summarize molecular composition of plant vacuoles and we will then discuss our latest understanding on the role of lipids in plant vacuolar trafficking and a surprising connection to ribosome function through the study of ribosomal mutants.
Association tests using unaffected-sibling versus pseudo-sibling controls.

We used family-matched case-control data to screen the genome for markers associated with disease in the simulated data set. Two different types of controls were considered: (1) unaffected siblings and (2) 'pseudo siblings,' a comparison sample created using the parental alleles. The scans were conducted on the first replicate of each study population. Overall, the two methods identified 14 marker loci associated with disease at the 0.001 significance level. Marker D1G24 (locus D) was the only true disease locus found by both approaches. No associations were found at any of the markers flanking the unobserved disease susceptibility loci (A, B, or C). We subsequently pooled the 25 replicates from a single population. This large sample still did not yield any associations at the flanking markers. We tested for association at locus D using a pseudo-sib approach restricted to alleles shared identical by descent between affected sib pairs. The power was 44% (11/25 replicates) at a significance level o 0.001f . ® 1999 Wiley-Liss, Inc. Key words: conditional likelihood, generalized transmission/disequilibrium test, genome screen, linkage disequilibrium
Learning interpretable classification rules using sequential rowsampling

In our previous work we have presented an approach to learn interpretable classification rules using a Boolean compressed sensing formulation. Our approach uses a linear programming (LP) relaxation and allows us to find interpretable (sparse) classification rules that achieve good generalization accuracy. However, the resulting LP representation for problems with either a large number of samples or large number of continuous features tends to become challenging for off-the-shelf LP solvers. We have explored a screening approach which allows us to dramatically reduce the number of active features without sacrificing optimality. In this work we explore reducing the number of samples in a sequential setting where we can certify reaching a near-optimal solution while only solving the LP on a small fraction of the available data points. In a batch setting this approach can dramatically reduce the computational complexity of the rule-learning LP formulation. In an online setting we derive stochastic upper and lower bounds on the the LP objective for unseen samples. This allows early stopping when we detect that the classifier will not change significantly with additional samples. The upper bounds are related to the learning curve literature in machine learning, and our lower bounds appear not to have been explored. Finally, we discuss a quick approach to compute the complete regularization path balancing rule interpretability versus accuracy.
Computer system performance problem detection using time series models

Computer systems require monitoring to detect performance anomalies such as runaway processes, but problem detection and diagnosis is a complex task requiring skilled attention. Although human attention was never ideal for this task, as networks of computers grow larger and their interactions more complex, it falls far short. Existing computer-aided management systems require the administrator manually to specify fixed "trouble" thresholds. In this paper we report on an expert system that automatically sets thresholds, and detects and diagnoses performance problems on a network of Unix computers. Key to the success and scalability of this system are the time series models we developed to model the variations in workload on each host. Analysis of the load average records of 50 machines yielded models which show, for workstations with simulated problem injection, false positive and negative rates of less than 1%. The server machines most difficult to model still gave average false positive/negative rates of only 6%/32%. Observed values exceeding the expected range for a particular host cause the expert system to focus on that machine. There it applies tools with finer resolution and more discrimination, including per-command profiles gleaned from process accounting records. It makes one of 18 specific diagnoses and notifies the administrator, and optionally the user [a].
Exonuclease VII of Escherichia coli PURIFICATION AND PROPERTIES

Abstract A new deoxyribonuclease, exonuclease VII, has been identified and purified 1,700-fold from Escherichia coli K12. The enzyme is an exonuclease specific for single-stranded DNA or duplex DNA containing single-stranded termini. The purified enzyme is active in the presence of EDTA, but is stimulated 25% by MgCl2. Optimal activity occurs at pH 7.9 in potassium phosphate buffer. The molecular weight, as determined by gel filtration and sedimentation analysis, is 88,000; the Stokes radius is 89 A. The friction coefficient of the enzyme is 3.07, suggesting an asymmetric structure. In the accompanying paper (Chase, J. W., and Richardson, C. C. (1974) J. Biol. Chem. 249, 4553–4561) we show that the enzyme is an exonuclease which can initiate hydrolysis at both 3' and 5' termini to yield products which are exclusively oligonucleotides.
Synchronized Swimming--The Training at Squaw Valley.

(1979). Synchronized Swimming—The Training at Squaw Valley. Journal of Physical Education and Recreation: Vol. 50, No. 5, pp. 45-47.
Nanoprobes for intracellular and single cell surface-enhanced Raman spectroscopy (SERS)

Surface-enhanced Raman spectroscopy (SERS) is a promising and powerful label free technique for high resolution analysis of single cells. For intracellular analysis, there is a need for SERS-active nanoprobes that are minimally invasive to cells, do not affect cell viability, and provide reproducible signals. This work reviews the state-of-the-art tools currently available for intracellular SERS. Various types of SERS probes are considered, including colloidal gold and silver nanoparticles, metallized optical fibers, and tip-enhanced Raman probes. We also discuss recently developed SERS-active nanopipettes implemented on the basis of pulled glass microcapillaries. Finally, the critical aspects of selecting an optimal SERS nanoprobe for single-cell analysis depending on a particular application are summarized. Copyright © 2012 John Wiley & Sons, Ltd.
Diagnostic Evaluation and Staging of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) frequently presents at an advanced and incurable stage of the disease. Common signs and symptoms of PDA include abdominal or back pain, jaundice, weight loss, pruritus, and nausea/vomiting. Diagnostic workup includes serum chemistries and CA19-9, primarily to monitor disease status and response to treatment. Imaging studies are performed to assess resectability and stage disease, and pancreatic protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) are the preferred imaging studies for this purpose. Conventional staging is based on the American Joint Cancer Committee (AJCC) Staging System, 7th Edition and informs prognosis, while surgical staging systems focus specifically on assessing the likelihood of a complete (negative margins) resection with operative management. Herein, we review the presenting signs and symptoms, the diagnostic evaluation, and staging of PDA.
Moral reasoning and moral character: Relationships between the Kohlberg and the Hogan models.

The empirical relationships between Kohlberg's model of moral reasoning and Hogan's model of moral character were examined in 132 college students to test the hypothesis that moral judgments are a reflection of the structure of moral character. No relationships were found between measures of moral reasoning and measures of moral character. Kohlberg's measure of moral reasoning, however, was related to an alternative measure of moral reasoning (r = .51, p < .01); moral character measures of empathy (r = .40, p < .01) and socialization (r = −.44, p < .01) were related to the use of marijuana as predicted. It was concluded that moral reasoning and moral character are empirically independent domains.
GENERATING TEXT WITHOUT TREES

In this paper, I present an architecture for generating extended text. This architecture is implemented in a system, Salix, which incrementally generates natural language texts whose structure is derived from the domain structure of the subject matter. The architecture is composed of data-driven, domain-independent strategies for producing increments of text. The strategies include metastrategies that combine or choose among all strategies that are applicable at each increment or decide what to do if no strategy applies. Salix's capabilities are demonstrated in generating texts, in the domains of houses and families, that are comparable to descriptions elicited from human speakers. Salix has also been utilized to generate texts about text style (Germain 1991). The approach to text generation presented here is compared to others in the literature along the dimensions of local organization, coherence, focusing, and domain independence. An argument is made for the approach presented here that locally organizes and incrementally generates coherent text.
Kindergarteners’ Self-Reported Social Inhibition and Observed Social Reticence: Moderation by Adult-Reported Social Inhibition and Social Anxiety Disorder Symptoms

Prevention of later anxiety problems would best be accomplished by identifying at-risk children early in development. For example, children who develop Social Anxiety Disorder (SAD) may show social withdrawal in the form of social inhibition (i.e., shyness with unfamiliar adults and peers) at school entry. Although the use of children’s perceptions of their own social inhibition would provide insight into early risk, the utility of young children’s self-reports remains unclear. The current study examined whether children deemed more extreme on social inhibition or social anxiety by adult report provided self-report of social inhibition that related to observed social reticence in the laboratory. Participants included 85 kindergarten children (36 female, 49 male), their parents, and their teachers. Moderation analyses revealed that children’s self-reported social inhibition related significantly to observed social reticence under the conditions of high parent-reported social inhibition, high teacher-reported social inhibition, and high SAD symptoms. These results suggest that the most inhibited children are aware of their behavior and can report it in a meaningfully way as young as kindergarten age.
Flexible pixel compositor for autostereoscopic displays

Autostereoscopic displays in fact show many views of the object of interest simultaneously. These individual views have to be re-shuffled to fit the final display. This composition task is usually done as an off-line process. We present in this paper a flexible pixel compositor that bridges the image generator (e.g., a rendering cluster) and the final display devices (such as a set of over-lapping projectors to form an ultra-high-resolution display). Our compositor is capable of performing an arbitrary mapping of pixels from any input frame to any output frame, and executing typical composition operations (e.g., blending) at the same time. To the best of our knowledge, our design is the only compositor that allows non-block based per-pixel warping and composition. This is particularly important for lenticular displays in which the different views have to be interleaved in the frame buffer. In this paper, we present an initial hardware prototype and some preliminary results in the firmware development.
The problem of identification of parameters by the distribution of the maximum random variable: solution for the trivariate normal case

Abstract Let ( X i , Y i , Z i ), i = 1, 2, …, m , be a number of independent random vectors each with a non-singular trivariate normal distribution function with non-zero correlations and zero means. Let ( X , Y , Z ) be their maximum, i.e., X = max i X i , Y = max i Y i , and Z = max i Z i . In this paper, we show that the distribution of ( X , Y , Z ) uniquely determines the parameters of the distributions of ( X i , Y i , Z i ), 1 ≤ i ≤ m .