cssi/SciSciGPT-SciSciNet huggingface dataset:
Supporting handheld technologies in a medical school curriculum: lessons from three years of design, development and implementation

As PDA's becomes increasingly accepted in clinical settings, medical schools are following suit by requiring or recommending PDA's to enhance students' clinical knowledge and skills. This paper examines the implementation of a PDA requirement at a leading US based medical school over three years. It explicates the complexity of diffusing a nomadic technology even in an educational environment generally receptive to new technologies. The outcomes of three years of specialized design and development for PDA's illustrate the uniqueness of handheld technologies, requiring a much needed theory of mobile computing. The authors conclude that while PDA's are successfully integrated in clinical settings, their value in medical education is less unambiguous.
Theory of the self-similar laser oscillator

Similariton laser oscillators support much higher pulse energies. Despite experimental and numerical studies, there is no analytic theory to date. We present a semi-analytic theory based on the variational approach and a novel trial function.
Optical resonators with ten million finesse.

We report a significant improvement of the finesse and quality factor of a calcium fluoride whispering gallery mode optical resonator achieved with iterative thermal annealing. The initial and final values of the resonator finesse are ℱi ≈ 5 × 105 and ℱf ≥ 107 respectively. The measurements are conducted at room temperature in the laboratory atmosphere.
Comparing the Quality of Confinement and Cost-Effectiveness of Public Versus Private Prisons: What We Know, Why We Do Not Know More, and Where to Go from Here:

The movement to privatize correctional institutions has gained considerable momentum as the need to reduce the costs of incarceration to public agencies has become more critical. The empirical evidence regarding whether private prisons are more cost-effective and whether they provide a higher quality of confinement to inmates, however, is inconclusive. To help clarify this portion of the prison privatization debate, this article contains a systematic review of the evaluation literature comparing the costs and quality of confinement of public versus private prisons. In doing so, three issues are highlighted: (a) the conclusions that can be reached based on the existing literature,(b) the major methodological inconsistencies that have hindered researchers' ability to draw firm conclusions from the body of empirical studies thus far, and (c) the direction that future research in this area may take to advance a better understanding of the potential advantages and disadvantages of prison privatization.
Polarimetric calibration of SIR-C using point and distributed targets

In preparation for the Shuttle Imaging Radar-C/XSAR (SIR-C/XSAR) flights, the University of Michigan has been involved in the development of calibration procedures and precision calibration devices to quantify the complex radar images with an accuracy of 0.5 dB in magnitude and 5 degrees in phase. In this paper, the preliminary results of the SIR-C calibration and a summary of the University of Michigan's activity in the Raco calibration super-site is presented. In this calibration campaign an array of point calibration targets including trihedral corner reflectors and polarimetric active radar calibrators (PARCs) in addition to a uniform distributed target were used for characterizing the radiometric calibration constant and the distortion parameters of the C-band SAR. Two different calibration methods, one based on the application of point targets and the other based on the application of the distributed target, are used to calibrate the SIR-C data and the results are compared with calibrated images provided by JPL. The distributed target used in this experiment was a field of grass, sometimes covered with snow, whose differential Mueller matrix was measured immediately after the SIR-C overpass using The University of Michigan polarimetric scatterometer systems. The scatterometers were calibrated against a precision metallic sphere and measured 100 independent spatial samples for characterizing the differential Mueller matrix of the distributed target to achieve the desired calibration accuracy. The L-band SAR has not yet been adequately calibrated for inclusion here. >
Psychotropic adjuvant analgesics for pain in cancer and AIDS

The 'WHO Analgesic Ladder' is a well validated approach for the selection of appropriate analgesic therapy for cancer pain as well as pain in AIDS. The mainstay of analgesic intervention for cancer and AIDS pain of moderate to severe intensity continues to be the appropriate use of opioid analgesics. There is, however, a growing appreciation for the role of adjuvant analgesics, such as antidepressants and other psychotropic medications, at each step of the WHO Analgesic Ladder, particularly in the treatment of neuropathic pain. Knowledge of the indications and usefulness of psychotropic analgesic drugs in cancer and AIDS pain populations will be most important to clinicians practicing in psycho-oncology/AIDS settings, particularly since these drugs are useful not only in the treatment of psychiatric complications of cancer and AIDS, but also as adjuvant analgesic agents in the management of pain. This paper reviews the literature on the use of antidepressants, psychostimulants, neuroleptics, anticonvulsants and other psychotropic analgesics in the management of cancer and AIDS pain. Mechanisms of analgesia, drug selection, and recommendations for clinical usage are discussed. The appropriate and timely use of psychotropic adjuvant analgesic drugs represents an opportunity for active psychiatric contribution to the multidisciplinary management of cancer and AIDS pain.
Human endometriotic xenografts in immunodeficient RAG-2/γ(c)KO mice

Abstract Objective The purpose of this study was to create a novel animal model for studies of endometriosis. Study design To facilitate the study of the transplantation of endometriosis into immunodeficient RAG-2/γ(c)KO mice, endometriosis biopsy specimens were collected from 19 women by laparoscopic surgery and grafted subcutaneously into the mice, which were treated subsequently with estradiol and progesterone to create 28-day artificial cycles. The grafts were collected during the first, second, and fourth cycles and were evaluated histologically for evidence of bleeding and immunocytochemically for estrogen receptor and progesterone receptor. Results Biopsy specimens that contained endometrium-like glands were well accepted (>90% success). These grafts maintained glandular morphologic condition, estrogen receptor, and progesterone receptor; bled after progesterone withdrawal; and formed chocolate cysts. However, biopsy specimens that lacked glands or that consisted of peritoneal adhesions and stroma were accepted poorly Conclusion Human endometriosis transplanted into RAG-2/γ(c)KO mice can provide a model for endometriotic bleeding.
Single point vs. mapping approach for spectral cytopathology (SCP)

In this paper we describe the advantages of collecting infrared microspectral data in imaging mode opposed to point mode. Imaging data are processed using the PapMap algorithm, which co-adds pixel spectra that have been scrutinized for R-Mie scattering effects as well as other constraints. The signal-to-noise quality of PapMap spectra will be compared to point spectra for oral mucosa cells deposited onto low-e slides. Also the effects of software atmospheric correction will be discussed. Combined with the PapMap algorithm, data collection in imaging mode proves to be a superior method for spectral cytopathology.
Physical activity and quality of life in older adults: an 18-month panel analysis.

Although physical activity has been associated with quality of life (QOL), the empirical evidence regarding the mechanisms underlying this relationship is limited. In the present study, we examined the mediating roles played by self-efficacy and health status in the physical activity–QOL relationship from baseline to 18-month follow-up in a sample of community-dwelling older adults. Community-dwelling adults (N = 321, M age = 63.8 years) were recruited to participate in a cross-sectional study and were later contacted to participate in an 18-month follow-up. Individuals completed a battery of questionnaires assessing physical activity, self-efficacy, physical self-worth, disability limitations, and quality of life. A panel analysis within a covariance modeling framework was used to analyze the data. Overall, the model was a good fit to the data (χ2 = 61.00, df = 29, p < 0.001, standardized root mean residual = 0.05, Comparative Fit Index = 0.97) with changes in physical activity indirectly influencing change in life satisfaction from baseline to 18 months via changes in exercise self-efficacy, physical self-worth, and disability limitations independent of baseline relationships and demographic factors. Specifically, increases in physical activity were associated with increases in exercise self-efficacy which, in turn, was associated with higher physical self-worth and fewer disability limitations which were associated with greater life satisfaction. The findings from this study suggest the relationship between physical activity and global QOL in older adults may be mediated by more proximal modifiable outcomes that can be targeted in physical activity programs and interventions.
Multiple drug resistance in osteosarcoma.

Osteosarcoma is a mesenchymal neoplasm in which the malignant cells produce an osteoid matrix. Morphologic classification of these tumors is based on the degree of osteoid production, the presence of coexisting cartilaginous or fibrous stroma, the presence of a round cell component, and the degree of vascularity" 2. Although the histologic appearance of osteogenic sarcoma can vary extensively, diagnosis usually is not difficult"2. With the exception of parosteal and well differentiated variants, osteogenic sarcomas are aggressive malignancies and without aggressive chemotherapy and ablative surgery, prognosis is very poor3. With ablative surgery alone, long term survival has been approximately 10%; however, with the advent of neoadjuvant chemotherapy and modem surgical approaches, survival has increased to 52-87%4,5. Despite progress in the treatment of this tumor, approximately 25% of patients do not respond to aggressive therapy, and most of those succumb to distant metastatic disease6. The strongest predictor of clinical outcome with current therapeutic modalities is the degree of necrosis induced by preoperative chemotherapy, as identified histologically in the surgical resection specimen4,5. At present, factors which reliably predict therapeutic response are lacking, although some authors believe that chondroblastic tumors and tumors which occupy more than a third of the bone require more aggressive chemotherapy7. Many of the ongoing investigations of osteosarcoma have therefore focused on the identification of factors which are predictive of poor response to current preoperative treatments with the aim of developing alternative protocols and improving response. Recent evidence suggests that one mechanism of chemotheraputic resistance in many tumor types is nonspecific removal of cytotoxic drugs from tumor cells by the membrane pump known as P-glycoprotein8. This ATPdependent membrane protein has broad specificity, and
Wastewater Contaminants and Treatment

With the utilization of irrigation systems for wastewater treatment and disposal, engineers should be aware of common contaminants, methods of on-farm wastewater treatment, and methods of risk evaluation. The primary concerns with wastewater treatment and reuse are prevention of disease and prevention of nutrient contamination and eutrophication of surface and subsurface water resources. Regulations and treatment processes have been set up as a barrier between contaminants and people. In addition, best management practices have been established for optimal and safe utilization of waste. Epidemiological studies and quantitative risk assessment methods can help to establish the risk to human health of wastewater treatment, containment, and reuse practices. Based on risk assessment, regulators establish rules for wastewater treatment and disposal. The last wall of defense against disease and death is the immune system.
Analysis of user-generated multimedia data on medication management and consumption behavior using data mining techniques

Technology-enabled tools have been suggested as a solution to assist older adults in the management and consumption of medications. However, existing systems and studies are often limited by incomplete understanding of the potential users' behaviors. This study uses a web-based survey and photo submission system to collect and analyze user profiles and behavioral characteristics. Various data mining techniques, including association rules, clustering and classification, are used on quantified data to find important behavioral patterns, group users with similar characteristics, and discern factors related to risky medication management behaviors. This paper presents the process and results of analysis, including a detailed description of coding scheme and model development. Practical and methodological implications are also discussed.
The Need for Fundamental Reform in Public Safety Spectrum and Communications Policy

The events surrounding Hurricane Katrina and the 9/11 attacks demonstrated that the communications systems used by first responders in the United States are not adequate to meet the challenges of a post-9/11 world. The U.S. system is based on assumptions that local agencies should have maximal flexibility at the expense of standardization and regional coordination, that commercial carriers and municipal systems have little role to play, that public safety should not share spectrum or network infrastructure, and that narrowband voice applications should dominate. Many programs have been proposed to incrementally improve public safety communications systems, but without any fundamental changes to these policies, such incremental changes are likely to have limited impact. However, a tremendous opportunity is coming thanks to the transition to digital television; 24 MHz of spectrum has been identified for reallocation from TV to public safety in 2009, roughly doubling the public safety spectrum below 2 GHz. Unless policymakers act, this new spectrum will be managed under these same old policies. This paper explains why it is time for fundamental reform. Policy reforms should include some combination of: shifting some responsibility and authority for decisions about public safety communications infrastructure from many independent local government agencies to the federal government; further expanding the role of commercial service providers, municipal Wi-Fi networks, and other systems that serve the public; allowing public safety to share spectrum, and possibly multi-purpose network infrastructure as well, with other users; and further expanding capabilities beyond traditional voice communications. Since the TV band spectrum reallocated to public safety has few legacy systems that must be accommodated or moved, it is an excellent place to launch a new policy.
Tending to Change: Toward a Situated Model of Affinity Spaces.

The concept of affinity spaces, a theoretical construct used to analyze literate activity from a spatial perspective, has gained popularity among scholars of literacy studies and, particularly, videogame studies. This article seeks to expand current notions of affinity spaces by identifying key assumptions that have limited researchers' ability to interrogate the processes of deliberation and change within affinity spaces. Drawing on insights from recent empirical research, this study theorizes an expanded model of affinity spaces, which can aid researchers in their continued investigations of affinity spaces, as well as educators interested in creating such spaces in traditional school settings.
An Improvement to COSMO-SAC for Predicting Thermodynamic Properties

A modified COSMO-SAC model is presented to calculate thermodynamic properties of pure fluids and mixtures using statistical thermodynamics and the surface charge density of each compound obtained from a quantum mechanics (QM) calculation. The main differences from the previous models are that the new model includes a dispersion contribution in the mixture interaction, and is reparametrized using measured pure and mixture thermodynamic data simultaneously. With a single set of universal parameters, the new model provides higher accuracy than our previous models for predicting mixture thermodynamic properties while maintaining the same accuracy for pure compound thermodynamic properties. The overall root-mean-square deviation (RMSD) in the logarithms of partition coefficients for 992 octanol–water partitioning systems and 829 other solvent–water partitioning systems with this new model is reduced by about 10% compared to the results from previous models. Also, the agreement between the predicted and measure...
Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts

Renal glomerular capillary tufts have been believed to arise from angiogenic ingrowth of extrinsic vessels. We found, however, that when embryonic day 12 (E12) mouse kidneys were maintained in culture for 6 days and then grafted into anterior eye chambers of adult transgenic ROSA26 host mice (which carry the beta-galactosidase transgene), glomerular endothelial cells within the grafts were predominantly of intrinsic, kidney origin. To identify potential endothelial precursors, we immunolabled kidneys with antibodies against the vascular endothelial growth factor receptor, flk-1. Numerous discrete cells expressing flk-1 were scattered throughout the nephrogenic mesenchyme of both E12 and newborn kidneys, and with development these cells became concentrated in microvessels, glomerular vascular clefts, and glomerular tufts. In adults, flk-1 was weakly expressed in glomeruli but absent elsewhere. To examine abilities of flk-1-positive cells to establish glomeruli, E12 kidneys were grafted into kidney cortices of adult and newborn ROSA26 hosts. Grafts into adults resulted in few glomeruli containing host-derived endothelium, whereas a majority of glomeruli grafted into newborns contained host cells. Cells of graft origin were found in vessels forming in renal cortices of newborn hosts, but not in adults. Our findings indicate that embryonic kidney cells expressing flk-1 are angioblasts that create microvessels and glomeruli by vasculogenesis.
Motivation for the DEN-ng Policy Model

This chapter discusses the motivation for developing a new policy model. The most important of these are—building a model that mapped a detailed architecture; ensuring that the policy information model is tightly integrated with other information models that described the managed objects that the policy model is managing and controlling; developing interfaces among the business, system, and implementation views; and defining policy in a dynamic as well as a static sense. There are three main policy models in the industry—the DEN model, the IETF model, and the DMTF model. DEN is used as the basis for both IETF and DMTF models. A TMF NGOSS program is briefly described and characterized as a blueprint from which the DEN-ng (Directory Enabled Networks new generation) policy model was built. Special emphasis is laid to the catalyst programs of the TMF, since they are a perfect way for vendors to get used to the power of the SID and DEN-ng models.
Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model

Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD.
Gaussian measures on Lp spaces, 1 ≤ p < ∞☆

This paper contains the following three types of results: First, a 1-1 correspondence is established between Gaussian measures on Lp, 1 ≤ p < ∞, and Gaussian processes with paths in Lp. Second, a 0–1 law for Gaussian measures on Frechet spaces is proved, which is subsequently applied to obtain two other 0–1 laws. In the first, it is shown that the paths of a measurable Gaussian process belong to Lp with probability 0 or 1, and in the second, it is shown that a certain random series converges uniformly on any Borel subset of the real line with probability 0 or 1. Third, a Gaussian measure on Lp is characterized in terms of the characteristic function; and its topological support is obtained in terms of its mean and covariance operator.
Draft Genome Sequences of 14 Staphylococcus aureus Sequence Type 5 Isolates from California, USA.

ABSTRACT Staphylococcus aureus is part of the human epithelial microbiota; however, it is also a pathogen. The acquisition of mobile genetic elements plays a role in the virulence of S. aureus isolates and contributes to treatment failures. This report details the draft genome sequences of 14 clinical S. aureus isolates.
Learning About Ethics: Analogical Encoding Increases Moral Awareness

Making ethical decisions presumably requires knowledge about ethics. If so, then one reason that people might make unethical decisions is that they have limited understandings of ethical principles. Deepening people’s understanding of ethical principles then might enable them to make more ethical decisions. As drawing analogies can foster deeper understandings of principles, the current study tested whether comparing two analogous examples of an ethical principle, the conflict of interest principle, improves people’s understanding of that principle, and found that it did. The study also showed that, as a result, drawing analogies promoted higher levels of moral awareness for a new situation in which the principle was at stake. Finally, the study found that drawing analogies also promoted making an ethical choice. Thus, the study supports the possibility that one reason people make poor ethical choices might be that they have limited understanding of ethical principles, which decreases moral awareness.
Mixed-integer nonlinear programming formulation of a UAV path optimization problem

We present a mixed-integer nonlinear programming (MINLP) formulation of a UAV path optimization problem, and attempt to find the global optimum solution. As objective functions in UAV path optimization problems tend to be non-convex, traditional optimization solvers (typically local solvers) are prone to local optima, which lead to severely sub-optimal controls. For the purpose of this study, we choose a target tracking application, where the goal is to optimize the kinematic controls of UAVs while maximizing the target tracking performance. First, we compare the performance of two traditional solvers numerically - MATLAB's fmincon and knitro. Second, we formulate this UAV path optimization problem as a mixed-integer nonlinear program (MINLP). As this MINLP tends to be computationally expensive, we present two pruning methods to make this MINLP tractable. We also present numerical results to demonstrate the performance of these methods.
Marriage and the economic status of women with children

Marriage is positively correlated with income, and women with children are much less likely to be in poverty if they are married. Selection into marriage makes it difficult to assess whether these correlations represent a causal effect of marriage. One instrument for marriage proposed in past research is the gender of a woman’s first child. We find that women who have a boy first are about 0.33 percentage points more likely to be married at any point in time. This effect operates through both increasing the probability that unmarried mothers marry the child’s father and reducing the probability of divorce. We also find that women whose first child is a boy experience higher levels of family income and are less likely to receive welfare income, be below the poverty line, and receive food stamps. Estimates using child gender as an instrumental variable for marriage suggest that marriage plays a large causal role in improving the economic well-being of women with children and that these effects are largest among women at the lower end of the income distribution.
Designing for immunity to power input audio frequency conducted susceptibility (AFCS)

• Designing for AFCS starts with identifying – AFCS limits … Voltage and current or power – Test setup details – Pass fail criteria … Voltage at loads • For AC inputs – May need to consider non-continuous input current – Concerns are typically rectifier filter capacitor current and AFCS voltage presented to DC-DC converter • Typically cannot do much at EMI filter to reduce threat • For the DC-DC converter – AFCS immunity — combination of EMI filter and control loop • Power input filter must be designed with the power converter
Statin use and mortality in gout: A general population-based cohort study.

Abstract Objectives Gout is associated with a higher risk of cardiovascular disease and premature mortality. We examined the potential survival benefit of statin use among gout patients in the general population. Methods We performed an incident user cohort study with time-stratified propensity score matching using a database representative of the UK general population between January 1999 and December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators within 1-year cohort accrual blocks. We estimated the hazard ratio (HR) for mortality using a Cox proportional hazard model and the mortality rate difference using an additive hazard model. We examined potential subgroup effects stratified by key factors, including circulatory disease history. Results Among 17,018 statin initiators, 2025 deaths occurred during the follow-up (mean = 5.0 years) with a mortality rate of 24.0/1000 person-years (PY). The number of deaths and all-cause mortality rate among matched comparators during the follow-up (mean = 4.6 years) were 2503 and 31.7/1000 PY respectively. Compared with non-initiators, statin initiators experienced a 16% lower relative risk of all-cause mortality (HR = 0.84, 95% CI: 0.79–0.89) and 7.7 (95% CI: 6.1–9.3) fewer deaths per 1000 PY. This protective association was stronger among those without prior circulatory disease (HRs = 0.65 vs. 0.85; p for interaction = 0.02). Conclusion In this general population-based cohort study, statin initiation was associated with a lower risk of mortality in gout, potentially with greater benefits among those without prior circulatory disease. The proper use of statins may help to substantially improve the premature mortality in gout.
Vascular deficiency of Smad4 causes arteriovenous malformations: a mouse model of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that leads to abnormal connections between arteries and veins termed arteriovenous malformations (AVM). Mutations in TGFβ pathway members ALK1, ENG and SMAD4 lead to HHT. However, a Smad4 mouse model of HHT does not currently exist. We aimed to create and characterize a Smad4 endothelial cell (EC)-specific, inducible knockout mouse (Smad4f/f;Cdh5-CreERT2) that could be used to study AVM development in HHT. We found that postnatal ablation of Smad4 caused various vascular defects, including the formation of distinct AVMs in the neonate retina. Our analyses demonstrated that increased EC proliferation and size, altered mural cell coverage and distorted artery–vein gene expression are associated with Smad4 deficiency in the vasculature. Furthermore, we show that depletion of Smad4 leads to decreased Vegfr2 expression, and concurrent loss of endothelial Smad4 and Vegfr2 in vivo leads to AVM enlargement. Our work provides a new model in which to study HHT-associated phenotypes and links the TGFβ and VEGF signaling pathways in AVM pathogenesis.
Method of Characteristics

This chapter elaborates method of characteristics applicable to systems of quasi-linear partial differential equations. Systems of quasi-linear partial differential equations are one or more partial differential equations linear in the first derivatives of the dependent variables, with no higher order derivatives present. If the initial data is not given along a characteristic, then an exact solution can be obtained (generally implicit). A quasi-linear partial differential equation can be transformed into a set of ordinary differential equations that define the characteristics, and a set of ordinary differential equations that describe how the solution changes along any specific characteristic. This technique extends naturally to systems of partial differential equations, with virtually no increase in complexity. This allows a single partial differential equation of higher order (and hyperbolic type) to be analyzed.
COGNITIVE STRUCTURE AND AFFECT IN LANGUAGE

Publisher Summary This chapter discusses the cognitive structure and affect in language. One of the basic principles in linguistic analysis is that of minimal contrast. Minimal contrast occurs at any linguistic level when two elements differ by a single feature and that feature is relevant to a linguistic distinction. There appears to be an inherent correlation between the principles of marking and a negative affective component in lexical entries. Semantic structures would have to be paired with the specific lexical items inserted into syntactic structures. One of the most ubiquitous of the cognitive categories derives from the perceptual experience of space. A variety of interpretations placed upon abstract, symbolic, and even personal events requires the use of space as a model or metaphor. Explicit spatial imagery represents the obvious case. But there is implicit application of spatial models and metaphors. A careful analysis of any conceptual category into which semantic or lexical information is encoded reveals that one can find cases in which affective dimensions inherently are a part of the cognitive structure formed within the conceptual category.
Role of the H subunit C-terminal domain in the assembly of the vacuolar H+-ATPase

The vacuolar H+-ATPase (V-ATPase) is regulated by reversible disassembly into autoinhibited V1-ATPase and Vo proton channel sectors, a process that is poorly understood on the molecular level. V-ATPase is a rotary motor and recent structural analysis revealed that disassembled V1 and Vo are in different rotary states, a mismatch that is likely responsible for the inability to reconstitute holo V-ATPase from its functional sectors in vitro. Here, using the model organism S. cerevisiae, we show that a key impediment for binding of autoinhibited V1 to Vo is the conformation of the inhibitory C-terminus of subunit H (HCT). Using biolayer interferometry and biochemical analysis, we show that selective disruption of HCT's binding site on V1 allows in vitro assembly of a structurally and functionally coupled V-ATPase complex. The resultant mutant V-ATPase, however, does not disassemble as readily as the wild type enzyme, highlighting the importance of HCT's conformation in the mechanism of reversible disassembly. These findings pave the way for identifying molecules that allow for therapeutic modulation of aberrant V-ATPase activity in the disease state.
The Global Need for Water Sustainability

This chapter looks at some of the ways water suppliers are reacting to the growing scarcity of clean, safe water. The focus is on descriptions of the innovative water management practices and process implemented by municipalities and other public water suppliers. It begins with a review of innovative policy changes in organizations and closes with a look at some of the management and governance changes taking place in the industry.
The efficacy of the secondary Extension Technique in the management of arterio-venous fistula-associated steal syndrome:

Background:Dialysis-associated steal syndrome remains a difficult clinical scenario for vascular access surgeons. The ideal treatment would improve blood flow to the hand without compromising the f...
The structural arrangement at intersubunit interfaces in homomeric kainate receptors

Kainate receptors are glutamate-gated cation-selective channels involved in excitatory synaptic signaling and are known to be modulated by ions. Prior functional and structural studies suggest that the dimer interface at the agonist-binding domain plays a key role in activation, desensitization, and ion modulation in kainate receptors. Here we have used fluorescence-based methods to investigate the changes and conformational heterogeneity at these interfaces associated with the resting, antagonist-bound, active, desensitized, and ion-modulated states of the receptor. These studies show that in the presence of Na+ ions the interfaces exist primarily in the coupled state in the apo, antagonist-bound and activated (open channel) states. Under desensitizing conditions, the largely decoupled dimer interface at the agonist-binding domain as seen in the cryo-EM structure is one of the states observed. However, in addition to this state there are several additional states with lower levels of decoupling. Replacing Na+ with Cs+ does not alter the FRET efficiencies of the states significantly, but shifts the population to the more decoupled states in both resting and desensitized states, which can be correlated with the lower activation seen in the presence of Cs+.
Novel Tools for Plant Genome Annotation and Applications to Arabidopsis and Rice

Our conference title, “Genome Exploitation: Data Mining”, is equally evocative and provocative. The combined use of the terms “exploitation” and “mining” conjures up images of the industrial process of exploiting natural resources by mining the earth for precious metals. Such parallels are not accidental but reflect a widely accepted paradigm of modern genetics. This paradigm is evident in many other terms that have become common in our field, including biotechnology, genetic engineering, high-throughput approaches, etc. It may be a bit too early to circumscribe this paradigm precisely. Undoubtedly, this will be done in the introductory chapters of forthcoming textbooks. But the dominant theme can be pinpointed as the industrialization of molecular biology and genetics. In this article I shall raise concerns about eager acceptance of this paradigm and argue for a more balanced approach. Personally, I would have preferred a conference title like “Genome Exploration:New Frontiers”. Such title would place emphasis on discovery and learning, and it may suggest a more measured pace towards applications. In the technical part of this article I review my research group’s efforts to provide
Association of Filaggrin Loss-of-Function Variants With Race in Children With Atopic Dermatitis

Importance Atopic dermatitis (AD) is a common chronic illness that has been associated with variation in the filaggrin gene (FLG). Four variants are most often evaluated. Objectives To comprehensively describe and compare results from targeted sequencing of FLG loss-of-function (LoF) variants in children of African and European ancestry and the association of these variants with onset and persistence of AD. Design, Setting, and Participants This prospective US cohort study assessed the genetic subcohort of the Pediatric Eczema Elective Registry (PEER). Children with mild to moderate AD were included in the analysis. Massively parallel sequencing (MPS) was used to focus on FLG LoF variation in white and African American children. Patients were enrolled from June 2005 through July 2017. Data were analyzed from January 25 through May 10, 2019. Main Outcomes and Measures Associations of FLG LoF variation with white and African American ancestry and with the risk and persistence of AD. Results A total of 741 children were included in the analysis (394 [53.2%] female and 347 [46.8%] male; mean [SD] age at onset, 1.97 [2.72] years); of these, 394 (53.2%) were white, 326 (44.0%) were African American, and 21 (2.8%) were of other ancestries. Using MPS technology, 23 FLG LoF variants were found in children with AD. The prevalence of FLG LoF variants was 177 participants (23.9%) in the full cohort, 124 white participants (31.5%), and 50 African American participants (15.3%). The odds ratio for carrying any FLG LoF variant in a white child compared with an African American child with AD was 2.44 (95% CI, 1.76-3.39). Some FLG LoF variants are only found in children of a specific ancestry (eg, p.S3316* and p.R826* were not seen in white patients). Children with an FLG LoF were more likely to have persistent AD (odds ratio, 0.67; 95% CI, 0.56-0.80). Conclusions and Relevance The FLG LoF variants in a US cohort of children with mild to moderate AD differ significantly by race and their association with the persistence of AD. Conventional testing of the 4 frequently evaluated variants is inadequate. Any planned genetic diagnostic test for AD based on FLG LoF variants must be inclusive and not rely on the most frequently studied variants.
Drug-Induced Liver Injury Due to Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a heterogeneous group of medications intended to treat a variety of inflammatory diseases. While they are generally regarded as safe and most known for their potential gastrointestinal and renal side effects, cases of hepatotoxicity have been reported. This review summarizes the US and international literature regarding the incidence of NSAID-induced DILI and the biochemical signature of specific NSAIDs. Multiple studies have identified diclofenac as one of the more common culprits of NSAID-induced DILI. A genetic predisposition to DILI has been identified with diclofenac and lumiracoxib. While NSAID-induced hepatotoxicity is rare, the potential for serious hepatotoxicity exists especially with certain agents such as diclofenac. An improved understanding of pharmacogenomics and post-marketing surveillance/monitoring is needed to reduce the risk of this DILI.
Differentiation of progressive disease from pseudoprogression using 3D PCASL and DSC perfusion MRI in patients with glioblastoma.

To use 3D pseudocontinuous arterial spin labeling (3D PCASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion MRI to differentiate progressive disease from pseudoprogression in patients with glioblastoma (GBM). Thirty-two patients with GBM who developed progressively enhancing lesions within the radiation field following resection and chemoradiation were included in this retrospective, single-institution study. The updated modified RANO criteria were used to establish progressive disease or pseudoprogression. Following 3D PCASL and DSC MR imaging, perfusion parameter estimates of cerebral blood flow (ASL-nCBF and DSC-nrCBF) and cerebral blood volume (DSC-nrCBV) were calculated. Additionally, contrast enhanced volumes were measured. Mann–Whitney U tests were used to compare groups. Linear discriminant analysis (LDA) and area under receiver operator characteristic curve (AUC) analyses were used to evaluate performance of each perfusion parameter and to determine optimal cut-off points. All perfusion parameter measurements were higher in patients with progressive disease (mean, 95% CI ASL-nCBF 2.48, [2.03, 2.93]; DSC-nrCBF = 2.27, [1.85, 2.69]; DSC-nrCBV = 3.51, [2.37, 4.66]) compared to pseudoprogression (mean, 95% CI ASL-nCBF 0.99, [0.47, 1.52]; DSC-nrCBF = 1.05, [0.36, 1.74]; DSC-nCBV = 1.19, [0.34, 2.05]), and findings were significant at the p 0.447). All perfusion parameters demonstrated high AUC (0.954 for ASL-nCBF, 0.867 for DSC-nrCBF, and 0.891 for DSC-nrCBV), however, ASL-nCBF demonstrated the highest AUC and misclassified the fewest cases (N = 6). Lesions correctly classified by ASL but misclassified by DSC were located along the skull base or adjacent to large resection cavities with residual blood products, at areas of increased susceptibility. Both 3D PCASL and DSC perfusion MRI techniques have nearly equivalent performance for the differentiation of progressive disease from pseudoprogression in patients with GBM. However, 3D PCASL is less sensitive to susceptibility artifact and may allow for improved classification in select cases.
Demand for Online News Under Government Control: Evidence from Russia

We examine the nature of consumer demand for government-controlled online news outlets in Russia, testing whether such demand reflects a preference for pro-government ideological coverage, or other factors unrelated to outlets' ideological positions. We detect government-sensitive topics and measure outlets' news reporting decisions from news article texts, and estimate a structural model of demand for news using detailed browsing data that traces individual-level consumption. The average consumer has a distaste for pro-government ideology but a strong persistent taste for state-owned outlets, primarily driven by third-party referrals and non-sensitive news content. We discuss implications for online media control and media power.
Pupil-linked arousal biases evidence accumulation towards desirable percepts during perceptual decision-making

People are biased towards seeing outcomes they are motivated to see. The arousal system coordinates the body9s response to motivationally significant events, and is well positioned to regulate motivational effects on sensory perception. However, it remains unclear whether arousal would enhance or reduce motivational biases. Here we measured pupil dilation as a measure of arousal while participants performed a visual categorization task. We used monetary bonuses to motivate participants to see one category over another. Even though the reward-maximizing strategy was to perform the task accurately, participants were more likely to report seeing the motivationally desirable category. Furthermore, higher arousal levels were associated with making motivationally biased responses. Analyses using computational models indicated that arousal enhanced motivational effects by biasing evidence accumulation in favor of motivationally desirable percepts. These results suggest heightened arousal biases people towards what they want to see and away from an objective representation of the environment.
LOW COST LIMESTONE TREATMENT OF ACID SENSITIVE TROUT STREAMS IN THE APPALACHIAN MOUNTAINS OF VIRGINIA

The method of single point, single application liming has been studied as a means of mitigating anthropogenic acid in trout streams in Virginia. Three critically acid sensitive streams were dosed with a total of five applications of limestone sand and monitored before, during and after the treatments to assess changes in water chemistry and biota. Limestone treatments of 8 to 50 tons (particle sizes 150–1000 μm), with the amounts based on sulfate deposition loading and existent stream water chemistry, were used to restore ‘lost’ acid neutralizing capacity (ANC). Contact time between the limestone bed in the stream bottom and the water was the limiting factor affecting the degree of treatment with bed length primarily controlled by the gradient of the stream at the dosing site. A single site application was able to restore approximately 2/3 of the ANC. Exponential fits of limestone consumption data were used to predict that treaments of similar streams would last from two five years before reliming was necessary. Both total and monomeric aluminum levels were reduced up to 50%, and aquatic biota increased below the treatment sites. Post-liming average values for the three streams were pH 6.66, 82.7 μeq L−1 ANC and 2.63 mg L−1 Ca. The average ANC improvement suggests that some 88% of the native trout streams in Virginia, which average 29 μeq L−1 ANC reduction from acid deposition, could be temporarily restored using single application liming.
THU0040 Anaemia of chronic disease (acd) in a rodent model is similar to human acd and can be alleviated by aranesp treatment

Background We previously reported that ARANESP™ alleviates ACD in a rodent model of peptidoglycan-polysaccharide polymer (PG-APS) mediated inflammation. We report here the further characterisation of this model and the effects of ARANESP™ treatment on ACD. Objectives Methods Immunisation of Lewis rats with PG-APS induces chronic systemic inflammation characterised by relapsing arthritis and hepatic granulomas. Associated with the inflammation is acute, severe anaemia followed by chronic, moderately severe anaemia. As previously established, a 30 μg/kg dose of ARANESP™ every 2 weeks starting day 36 normalised peripheral blood (PB) haemoglobin levels by day 64. Results Acutely anaemic rats had greatly enhanced mean PB reticulocyte counts and greatly reduced mean RBC counts. Mean PB reticulocyte and RBC counts normalised during chronic anaemia, but RBC remained hypochromic and microcytic. Individual anaemic rats had transient increases in serum erythropoietin (EPO) concentrations. However, there was no significant difference in mean EPO concentrations compared to controls, which suggests EPO production was blunted. Histology of day 36 and day 112 anaemic rat spleen sections revealed greatly enhanced iron retention by splenic macrophages. In contrast, bone marrow (BM) macrophages were nearly devoid of iron. Serum iron concentratioans were significantly reduced by day 7 and remained low throughout the study. Interestingly, ARANESP™ treated rats showed decreased iron retention in macrophages and increased serum iron starting day 98. To identify which cytokines may contribute to the chronic anaemia of this model, peritoneal exudate cells (PEC) were isolated and challenged with PG-APS in vitro. Unstimulated PEC produced little or no cytokines. PG-APS challenged PEC from anaemic rats produced IL-1α, TNF-α, and IFN-γ. PG-APS challenged PEC from ARANESP™ treated anaemic rats trended towards reduced levels of these cytokines relative to anaemic PEC cultures. Conclusion In summary, we have shown this ACD model is similar to human ACD. Importantly, ARANESP™ treatment alleviates ACD in this model, thus indicating its potential therapeutic utility for human ACD.
Affectivation: Life-Giving Signs

Affectivation is a Janus-faced phenomenon. It is a permanent feature of our life in signs and of the life of signs and not just of a specific use of them. Human beings give life to themselves in multiple dimensions by giving life to signs, including the apprehension of the symbolic pregnance of natural objects taken as signs, and thereby giving life to their worlds. Cultural psychology and the philosophical analyses of cultures study these processes in intersecting and complementary ways, focusing on the felt sense of being affectivated. This giving of life to signs not only challenges and reveals us to ourselves but in the very processes of their creation or apprehension shapes, develops, and mirrors us. They stand over against us, interrupt and resist us, and make us present us to ourselves and to others in our multiple modes of existing. The production and interpretation of signs—and of the institutions and material frames they inform—is by its very nature a work of affectivation understood as processes and events of self-activation and self-affecting.