cssi/SciSciGPT-SciSciNet huggingface dataset:
Linear-array-based photoacoustic tomography for label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters

Circulating tumor cell (CTC) clusters arise from multicellular grouping in the primary tumor and elevate the metastatic potential by 23 to 50 fold compared to single CTCs. High throughout detection and quantification of CTC clusters is critical for understanding the tumor metastasis process and improving cancer therapy. In this work, we report a linear-array-based photoacoustic tomography (LA-PAT) system capable of label-free high-throughput CTC cluster detection and quantification in vivo. LA-PAT detects CTC clusters and quantifies the number of cells in them based on the contrast-to-noise ratios (CNRs) of photoacoustic signals. The feasibility of LA-PAT was first demonstrated by imaging CTC clusters ex vivo. LA-PAT detected CTC clusters in the blood-filled microtubes and computed the number of cells in the clusters. The size distribution of the CTC clusters measured by LA-PAT agreed well with that obtained by optical microscopy. We demonstrated the ability of LA-PAT to detect and quantify CTC clusters in vivo by imaging injected CTC clusters in rat tail veins. LA-PAT detected CTC clusters immediately after injection as well as when they were circulating in the rat bloodstreams. Similarly, the numbers of cells in the clusters were computed based on the CNRs of the photoacoustic signals. The data showed that larger CTC clusters disappear faster than the smaller ones. The results prove the potential of LA-PAT as a promising tool for both preclinical tumor metastasis studies and clinical cancer therapy evaluation.
Abstract 145: Apelin Reduces Myocardial Infarction Size and Promotes Angiogenesis by Increasing SDF-1/CXCR4 and AKT/eNOS/VEGF Pathways

Background: Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and is emerging as a key player in the regulation of angiogenesis as well as ischemia/reperfusion injury. So far, little is known about the functional role of apelin in myocardial ischemia. We investigated the potential intracellular molecular mechanisms and protective role of apelin during myocardial ischemic injury. Methods and Results: Myocardial ischemia was achieved by ligation of the left anterior descending coronary artery (LAD) for 24 hours and 14 days. Myocardial apoptosis was detected by TUNEL staining. Akt, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), SDF-1 and CXCR4 expression were measured by western blot. The CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells were determined by immunostaining. Myocardial capillary and arteriole densities were analyzed in the border zone of infarcted myocardium at 14 d of ischemia. Treatment of C57BL/6J mice with apelin-13 (1 mg/Kg.d) by i.p. injection for 3 days before surgery results in significant decreases in TUNEL positive cells and myocardial infarct size at 24 hours of ischemia. Treatment with apelin increases the phosphorylation of AKT and eNOS and upregulates VEGF expression in the ischemic heart. Furthermore, treatment with apelin leads to the expression of SDF-1 and CXCR4 and increases in the number of CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells in ischemic hearts. Treatment with apelin also significantly increases myocardial capillary densities and arteriole formation together with a significant decrease in the ratio of heart weight to body weight at 14 days of ischemia. This is accompanied by a significant improvement of cardiac function after 14 days of ischemia. Conclusions: Our data demonstrate that apelin contributes to the protection of myocardial infarction and angiogenesis by the mechanisms involving in upregulation of SDF-1/CXCR4 and AKT/eNOS/VEGF pathways.
Consolidation settlement of Salt Lake County tailings impoundment revealed by time-series InSAR observations from multiple radar satellites

Abstract Tailings impoundment failures may lead to catastrophically fatal, environmental and financial consequences. Monitoring the stability of tailings facility is therefore indispensable for sustainable mining development. Particularly, tailings experience gradual consolidation settlement as the pore pressure dissipates and the terrain subsides. However, field investigations and geotechnical analysis at tailings impoundment are limited by sparse field instrumentation due to high cost. Interferometric Synthetic Aperture Radar (InSAR) can provide a full spatial view of settlement rate at millimeter-scale precision with bi-weekly or monthly updates. Here we integrate big remotely sensed data including multi-temporal and multi-spaceborne SAR images of ENVISAT, ALOS PALSAR-1, and Sentinel-1A, and SRTM DEM and LIDAR DEM, as well as water level data, to investigate the dynamics of consolidation settlement over the tailings impoundment area in the vicinity of Great Salt Lake, Utah. We show that the reclaimed south pond is experiencing enormous quasi-linear settlements with the largest rate of 200 + mm/yr around the low-permeable decant pond clay at the northeast corner during 2004–2011, and the rate decreases to 100 + mm/yr during 2015–2016. The nearly decadal InSAR measurements can be well-explained by geotechnical consolidation model, which reveals the long-term exponentially decaying settlement and predicts the settlement process in the near future. InSAR-derived displacement maps also highlight active motions of surrounding infrastructures, such as some highway segments. There is no clear evidence that the fluctuating deformation at those locations and seasonal varied water level are correlated. Our results demonstrate that high-resolution surface displacement measurements from InSAR can significantly improve our understanding of tailings settlement process and facilitate the monitoring of dams/infrastructures stability.
Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004–2014

Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004–2014
Sidgwickian Objectivity and Ordinary Morality

1. Two strands of discussion concerning the word “good” can be traced through the Anglo-American moral philosophy of the past century. The first begins with G. E. Moore’s claim that “good” names a simple non-natural property, known by intuition, and common to all acts, objects, and states of affairs that we call good. 1 The claim is implausible: “good” does not seem to be applied univocally to pies, knives, persons, or sunsets. The response to Moore, however, has led to an increasingly sophisticated awareness of the complexity of “good.” For example, a number of thinkers, cognitivist and non-cognitivist alike, have recognized that “good” has a variety of criteria of application. 2 In a functional context, “good” may be used to guide choices, as in other areas, but things will be good insofar as they possess the qualities necessary to achieve the purpose of the relevant object. 3 As the properties, and the standards, will differ from object to object, so will the meaning of “good” differ in part. But this implies that goodness is not a simple property, whether non-natural or natural. The second strand of discourse about “good” starts, not with Moore, but with Sidgwick. Much of the post-Moorian discussion focuses on questions of the meaning of “good” in certain limited types of contexts, such as functional contexts. But the analysis of “good” as applied to functional objects allows us to speak with equal ease of a good knife and a good chef, on the one hand, and a good instrument of sado-masochism and a good robber on the other. An account of “good” would seem necessary which could provide a wider context for moral assessment of robbers who, while admirably fulfilling their purposes, are nonetheless morally despicable. This demand would seem to indicate the need for an account of the objective goodness which is good regardless of any agent’s particular interests, purposes, or wants. In The Methods of Ethics, Henry Sidgwick addresses this problem. In doing so, he proposes a formal condition which must be met by any reason or good-making characteristic which is, as objective, to constitute the basis
Instructor Perspectives on Comparative Heatmap Visualizations of Student Engagement with Lecture Video

The use of online video in learning environments is prevalent -- serving in a variety of roles, such as multimedia textbook, video lecture, or medium for documenting student coursework. For instructors who employ video as a learning material, it is becoming increasingly important to gain a deeper understanding of the fit of video content across student cohorts, as well as the impact on student engagement, learning, and success. In order to better understand instructor interests and needs in this regard, we developed a learning analytics visualization tool that links data on student viewing and video interactions with student demographics and performance measures. Instructors can use the tool to generate and compare correlated heatmap visualizations representing student engagement across segments of the video. This paper describes an initial user study conducted with instructors in an HCI course context to understand how this kind of feedback can inform their use of video in the classroom. Results show that instructors find such feedback very useful across a variety of use cases.
Central Nervous System Manifestations of Mycoplasma Pneumoniae, Systematic Review of the Literature with Regard to Pathogenosis and Treatment in Adult Subjects, with First Case Report of Successful Treatment with Intravenous Immunoglobulin in an Adult (P5.092)

Objective: NA Background: Central nervous system manifestations of Mycoplasma pneumoniae (CNSMP) are well recognized in the pediatric population. However, the pathogenesis, diagnosis, and treatment of CNSMP in adult subjects remains poorly understood. Design/Methods: We present a young adult patient with CNSMP successfully treated with intravenous immunoglobulin (IVIG), in addition to a systematic review of the literature conducted for studies reporting CNSMP (January 1984 to October 2017). This review utilized pre-specified Medical Subject Headings (MeSH) terms, Boolean logic, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A 19-year-old man presented with seven days of flu-like illness, followed by diffuse paresthesias, diplopia, dysarthria, facial droop, and ataxia. His level of consciousness progressively worsened. Brain MRI revealed prominent T2-hyperintensity spanning the medulla and pons, post-contrast enhancement, and scattered supratentorial T2-hyperintensities. CSF was notable for lymphocytic-predominant cells (141 mm 3 ) and mild protein elevation (69 mg/dL). Despite empiric treatment (antibacterials (not sensitive to M. Pneumonia), antiviral, high-dose steroid), deterioration continued. IVIG introduced on hospital day four led to dramatic improvement within four days, and complete recovery at six months. CSF PCR resulted positive for Mycoplasma pneumoniae (absence of alternative etiologies). Abstract review identified 153 potential articles (32 excluded; insufficient data). Of the remaining 121 studies: 15 (12%) reported CNSMP in adults, while 6 (5%) reported treatment with IVIG (pediatric cases only). In total 46 adult cases were identified (none using IVIG). Including our patient, all 47 adult cases were entered into a database detailing clinical, radiological, and prognostic features. Conclusions: To our knowledge, this is the largest review on adult CNSMP and the first reported case of IVIG treatment in an adult patient. IVIG has potential value in treatment of this disorder. Our case supports that a co-infectious autoimmune mechanism may be involved, if not primarily responsible, to explain cases refractory to standard treatment. Study Supported by: NA Disclosure: Dr. Piran has nothing to disclose. Dr. Mathew has nothing to disclose. Dr. Linn has nothing to disclose. Dr. Lu has nothing to disclose. Dr. Salgado has nothing to disclose.
Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1–Mediated Cholesterol Removal

CYP46A1 is the cytochrome P450 enzyme that converts cholesterol to 24-hydroxycholesterol, a cholesterol elimination product and a potent liver X receptor (LXR) ligand. We conducted retinal characterizations of Cyp46a1-/- mice that had normal fasting blood glucose levels but up to a 1.8-fold increase in retinal cholesterol. The retina of Cyp46a1-/- mice exhibited venous beading and tortuosity, microglia/macrophage activation, and increased vascular permeability, features commonly associated with diabetic retinopathy. The expression of Lxrα and Lxrβ was increased in both the whole Cyp46a1-/- retina and retinal macroglia/macrophages. The LXR-target genes were affected as well, primarily in activated microglial cells and macrophages. In the latter, the LXR-transactivated genes (Abca1, Abcg1, Apod, Apoe, Mylip, and Arg2) were up-regulated; similarly, there was an up-regulation of the LXR-transrepressed genes (Ccl2, Ptgs2, Cxcl1, Il1b, Il6, Nos2, and Tnfa). For comparison, gene expression was investigated in bone marrow-derived macrophages from Cyp46a1-/- mice as well as retinal and bone marrow-derived macrophages from Cyp27a1-/- and Cyp27a1-/-Cyp46a1-/- mice. CYP46A1 expression was detected in retinal endothelial cells, and this expression was increased in the proinflammatory environment. Retinal Cyp46a1-/- phosphoproteome revealed altered phosphorylation of 30 different proteins, including tight junction protein zonula occludens 1 and aquaporin 4. Collectively, the data obtained establish metabolic and regulatory significance of CYP46A1 for the retina and suggest pharmacologic activation of CYP46A1 as a potential therapeutic approach to dyslipidemia-induced retinal damage.
Weather-driven malaria transmission model with gonotrophic and sporogonic cycles

Malaria is mainly a tropical disease and its transmission cycle is heavily influenced by environment: The life-cycles of the Anopheles mosquito vector and Plasmodium parasite are both strongly affe...
Relevance, vision, and career development: Thinking about the next generation of professionals in sociology

The commentary seeks to differentiate sociology as a discipline and as a profession. The concepts of relevance, vision, and professional development are suggested as necessary building blocks to more intentionally develop the profession of sociology. Finally, a program of local professional development is offered as a step in positively influencing the next generation of practicing sociologists.
Concordance between a U.S. Educational Autism Classification and the Autism Diagnostic Observation Schedule.

States in the United States differ in how they determine special education eligibility for autism services. Few states include an autism-specific diagnostic tool in their evaluation. In research, t...
Cage Isomers of N14 and N16: Nitrogen Molecules That Are Not a Multiple of Six

Molecules consisting entirely or predominantly of nitrogen are the focus of much research for their potential as high energy density materials (HEDM). Recent theoretical predictions on cage stability for N12, N18, N24, N30, and N36 indicate that the most thermodynamically stable isomer has 3-fold symmetry (D3h or D3d symmetry point group). Such molecules have a triangle−pentagon bonding group on each end with a band of hexagons around the midsection. However, the existence of this symmetric isomer depends on the number of nitrogen atoms being a multiple of six. In the current study stability trends are addressed for two molecule sizes where this symmetric option does not exist, namely, N14 and N16. Isomer energies for these molecules are calculated using Hartree−Fock theory, density functional theory (B3LYP), and perturbation theory (MP4) along with the correlation-consistent basis sets of Dunning. At each molecule size the most stable cage is identified, and the structural features leading to cage stabil...
let-7g counteracts endothelial dysfunction and ameliorating neurological functions in mouse ischemia/reperfusion stroke model

Abstract Stroke is a debilitating disease, accounting for almost 20% of all hospital visits, and 8% of all fatalities in the United States in 2017. Following an ischemic attack, inflammatory processes originating from endothelial cells within the brain microvasculature can induce many toxic effects into the impacted area, from both sides of the blood brain barrier (BBB). In addition to increased BBB permeability, impacted brain microvascular endothelial cells can recruit macrophages and other immune cells from the periphery and can also trigger the activation of microglia and astrocytes within the brain. We have identified a key microRNA, let-7g, which levels were drastically diminished as consequence of transient middle cerebral artery occlusion (tMCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro ischemia/reperfusion conditions, respectively. We have observed that let-7g* liposome-based delivery is capable of attenuating inflammation after stroke, reducing BBB permeability, limiting brain infiltration by CD3+CD4+ T-cells and Ly6G+ neutrophils, lessening microglia activation and neuronal death. These effects consequently improved clinical outcomes, shown by mitigating post-stroke gait asymmetry and extremity motor function. Due to the role of the endothelium in propagating the effects of stroke and other inflammation, treatments which can reduce endothelial inflammation and limit ischemic damage and improving recovery after a stroke are required. Our findings demonstrate a critical link between the CNS inflammation and the immune system reaction and lay important groundwork for future stroke pharmacotherapies.
Bringing Inter-Thread Cache Benefits to Federated Scheduling

Multiprocessor scheduling of hard real-time tasks modeled by directed acyclic graphs (DAGs) exploits the inherent parallelism presented by the model. For DAG tasks, a node represents a request to execute an object on one of the available processors. In one DAG task, there may be multiple execution requests for one object, each represented by a distinct node. These distinct execution requests offer an opportunity to reduce their combined cache overhead through coordinated scheduling of objects as threads within a parallel task. The goal of this work is to realize this opportunity by incorporating the cache-aware BUNDLE-scheduling algorithm into federated scheduling of sporadic DAG task sets.This is the first work to incorporate instruction cache sharing into federated scheduling. The result is a modification of the DAG model named the DAG with objects and threads (DAG-OT). Under the DAG-OT model, descriptions of nodes explicitly include their underlying executable object and number of threads. When possible, nodes assigned the same executable object are collapsed into a single node; joining their threads when BUNDLE-scheduled. Compared to the DAG model, the DAG-OT model with cache-aware scheduling reduces the number of cores allocated to individual tasks by approximately 20 percent in the synthetic evaluation and up to 50 percent on a novel parallel computing platform implementation. By reducing the number of allocated cores, the DAG-OT model is able to schedule a subset of previously infeasible task sets.
Quantitative Analysis of the Cerebral Vasculature on Magnetic Resonance Angiography

The arterial connections in the Circle of Willis are a central source of collateral blood flow and play an important role in pathologies such as stroke and mental illness. Analysis of the Circle of Willis and its variants can shed light on optimal methods of diagnosis, treatment planning, surgery, and quantification of outcomes. We developed an automated, standardized, objective, and high-throughput approach for categorizing and quantifying the Circle of Willis vascular anatomy using magnetic resonance angiography images. This automated algorithm for processing of MRA images isolates and automatically identifies key features of the cerebral vasculature such as branching of the internal intracranial internal carotid artery and the basilar artery. Subsequently, physical features of the segments of the anterior cerebral artery were acquired on a sample and intra-patient comparisons were made. We demonstrate the feasibility of using our approach to automatically classify important structures of the Circle of Willis and extract biomarkers from cerebrovasculature. Automated image analysis can provide clinically-relevant vascular features such as aplastic arteries, stenosis, aneurysms, and vessel caliper for endovascular procedures. The developed algorithm could facilitate clinical studies by supporting high-throughput automated analysis of the cerebral vasculature.
Concept Drift Monitoring and Diagnostics of Supervised Learning Models via Score Vectors.

Supervised learning models are one of the most fundamental classes of models. Viewing supervised learning from a probabilistic perspective, the set of training data to which the model is fitted is usually assumed to follow a stationary distribution. However, this stationarity assumption is often violated in a phenomenon called concept drift, which refers to changes over time in the predictive relationship between covariates $\mathbf{X}$ and a response variable $Y$ and can render trained models suboptimal or obsolete. We develop a comprehensive and computationally efficient framework for detecting, monitoring, and diagnosing concept drift. Specifically, we monitor the Fisher score vector, defined as the gradient of the log-likelihood for the fitted model, using a form of multivariate exponentially weighted moving average, which monitors for general changes in the mean of a random vector. In spite of the substantial performance advantages that we demonstrate over popular error-based methods, a score-based approach has not been previously considered for concept drift monitoring. Advantages of the proposed score-based framework include applicability to any parametric model, more powerful detection of changes as shown in theory and experiments, and inherent diagnostic capabilities for helping to identify the nature of the changes.
Leveraging Demand Data as a Proxy for Understanding Large-scale Events

Although, the internet opens an exceptional possibility for researchers conducting empirical studies on large-scale events by lowering the cost of collecting data and increasing the amount of information, there is a need to be cautious about not breaching the privacy of the users involved. Some types of internet data such as demand on networked systems (demand data) alleviate privacy concerns to some degree. To gauge the utility of demand data in understanding community behaviors during large scale events, we investigate its use in understanding quarantine compliance during Covid-19 pandemic. We analyse CDN demand data, google mobility data, and daily infection cases to see the pattern of correlation, and degree of influence of one variable on the others.
A rat model of ischemic osteonecrosis for investigating local therapeutics using biomaterials

Osteonecrosis is one of the most disabling diseases affecting pediatric and adult populations. Local application of biomaterials is a promising therapeutic strategy for osteonecrosis. Currently, there is a lack of low-cost animal models of osteonecrosis for testing and developing biomaterials-driven therapeutics. To develop a rat model of ischemic osteonecrosis (IO), the distal femoral epiphysis was selected due to its size 7.7 folds larger than the proximal femoral epiphysis (p<0.0001). The feasibility of intraosseous drillings and the local application of biomaterials were determined. Four model biomaterials were successfully applied: injectable hydrogel, microsphere, bone cement, and implant. The IO was induced by surgically cauterizing the blood vessels supplying the distal femoral epiphysis. Osteonecrosis of the whole epiphysis was achieved with a complete absence of blood flow and near 100% of apoptotic osteocytes. At eight weeks after IO, severe bone deformity and osteoarthritis developed in the affected epiphysis. The histological analysis showed 50% lacunae empty in the IO group compared to 2% in the control group (p<0.0001). The μCT analysis showed the epiphyseal quotient decreased to 0.46 in the IO group compared to 0.53 in the control group (p<0.0001), and the distal femoral epiphysis in the IO group was 19% smaller than the control group (p<0.01). The Safranin O stained sections showed articular cartilage erosions and subchondral bone fractures in the IO group. In summary, we established a clinically relevant IO model on rats that is compatible with the application of biomaterials for treatment. STATEMENT OF SIGNIFICANCE: Osteonecrosis is one of the most serious orthopedic conditions, leading to permanent joint deformity and end-stage osteoarthritis. An efficient and low-cost animal model is essential for development and testing of new treatment strategies for osteonecrosis. This is the first study to develop a clinically relevant model of osteonecrosis on the distal femoral epiphysis of rats. The model is highly efficient in developing osteonecrosis with relatively low cost and it provides suitable skeletal size to apply various forms of biomaterials. More importantly, it mimicked the pathological features and progression of osteonecrosis in humans. The study is expected to have an important impact on the development and testing of innovative biological therapeutics for osteonecrosis.
Epigallocatechin Is Eliminated Faster From Plasma Than Epigallocatechin Gallate: Mathematical Modeling of Green Tea Catechin Metabolism in Healthy Adults

Objectives The predominant catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)] in green tea extract (GTE) vary in bioactivity. Our objective was to develop a physiologically relevant mathematical model of catechin metabolism and assess their fractional catabolic rates relative to their structural attributes, which may influence their bioactivities.
Anonymous Living Liver Donation: Literature Review and Case Series Report.

Background Anonymous living liver donations (ALLDs) raise ethical concerns regarding the donors' motivations. Thus, ALLDs are not as widely accepted as directed donations from friends and family. Literature on ALLDs is limited. Understanding this particular group of individuals is crucial, as they could further help mitigate the shortage of liver grafts worldwide. Methods A literature review was performed to identify current definitions, ethical considerations, different approaches, and barriers to ALLD worldwide. Furthermore, we present our current experience after the establishment of a protocol to enable an ALLD program in our center and surveyed potential donors to better understand their motives throughout the process. Results Literature regarding ALLD is scarce. Canada leads the experience with the majority of case reports published to date. Survey-based evaluation of this unique group of individuals reflects the selflessness nature of anonymous living donors and shows that most of them experience the donation as a positive and life-changing event. In our experience, 41 individuals initiated the process of ALLD during the study period. Most were lost to follow-up or deemed ineligible. Five candidates fully completed the donation process and successfully underwent living liver donation. Given that 2 candidates have a follow-up period <3 mo from donation, we have only included data on the first 3 donors in this analysis. Eight individuals (19.5%) responded to the survey with respondents sharing similar reasons for initiating ALLD but varied and multifactorial reasons for terminating. Conclusions Different institutional protocols can be used to accomplish ALLD, including the one utilized by our institution. Adopting policies to allow for ALLDs and reducing modifiable factors that contribute to ending donation has the potential to increase grafts and decrease wait times.Supplemental Visual Abstract: http://links.lww.com/TP/C251.
Scleroderma esophagus

Scleroderma (systemic sclerosis) is a connective tissue disorder characterized by thickening and fibrosis of the skin and visceral involvement that may include the heart, lungs, kidneys, and gastrointestinal tract. At least 40–50% of patients with scleroderma experience esophageal symptoms such as heartburn and dysphagia, while up to 90% of patients have esophageal dysfunction on objective testing at some point in their disease. The disease results in smooth muscle dysfunction that causes esophageal aperistalsis and reduced lower esophageal sphincter pressures. Gastroesophageal reflux with poor acid clearance results with an increased incidence of complications such as peptic stricture and Barrett's esophagus. Aggressive medical therapy is necessary to prevent these and other complications of gastroesophageal reflux.
Techniques and Tools of Modern Plant Breeding

Field and vegetable crops are primary source of food. Field crops are also a rich source of cellulosic biomass and carbohydrates for biofuels. One of the major challenges facing agriculture today is improving the productivity of crops in an environmentally sustainable manner. Annual climate variation causes temperature extremes, floods, and droughts which all exacerbate the vulnerability of crops to pests and diseases. Conventional plant breeding has evolved and molecular and modern breeding methods have enhanced the pace of crop improvement work. Plant breeders now use molecular and genetic techniques to selectively identify phenotypes and genotypes that are associated with traits of interest. Such functional genomics studies help plant breeders efficiently utilize the germplasm. Cutting edge molecular tools are now available in economically important crops as well as model plant systems. Gene expression techniques have been combined with forward and reverse genetic methods for isolation and introgression of desirable alleles into breeding populations that are used to develop hybrid crops. This chapter focuses on modern techniques and resources that field and vegetable crop scientists use to generate genetic information and efficient breeding strategies.
The Concept of Constituency: Origins, Part 1: What Territorial Representation Was Not Meant To Do

The history of representation in England, from which we have taken our model of legislation, is briefly this[:] before the institution of legislating by deputies, the whole free part of the community usually met for that purpose; when this became impossible, by the increase of numbers the community was divided into districts, from each of which was sent such a number of deputies as was a complete representation of the various numbers and orders of citizens within them; but can it be asserted with truth, that six men can be a complete and full representation of the numbers and various orders of the people in this state? – Cato, no. 5, Fall 1787 At the founding of the United States, territorial electoral constituencies were an institutional habit of mind so ingrained in thought and practice that almost no argument about them appears in the literature. Further, territory was the basis (often paired with wealth, religion, or literacy) of representation in all colonial charters and their subsequent state constitutions at the founding. It is not discussed in any depth by those authors who influenced the writers and “ratifiers” of the Constitution: James Harrington, David Hume, Algernon Sidney, John Locke, or Montesquieu. Nor does it appear in the writings of the era, those of Edmund Burke, James Madison, Alexander Hamilton, Thomas Jefferson, or Thomas Paine, in other prominent primary sources nor in the writings of the Anti-Federalists. In only one place is another method of constituency definition even hinted at: professional class.
Two-Dimensional Tables

It is not our primary intention to provide a rigorous account of log-linear model theory. Such a treatment demands extensive use of advanced calculus and asymptotic theory. On the other hand, some knowledge of the basic issues is necessary for a correct understanding of applications of log-linear models. In this chapter we address these basic issues for the simple case of two-dimensional tables.
Hyporheic flow and residence time distributions in heterogeneous cross-bedded sediment

[1] The permeability heterogeneity of cross-bedded sediment increases path lengths of river-groundwater mixing (hyporheic exchange) in riverbeds and modifies the distribution of residence times. For two case studies, we numerically simulated fluid flow and solute transport through immobile bed forms composed of heterogeneous sediment and equivalent homogeneous sediment in order to clarify how cross-bedded permeability structures impact hyporheic exchange. The two permeability fields are from the cross-bedded Massillon Sandstone and modern climbing ripple deposits of the Brazos River (Texas). In both cases, permeability heterogeneity creates long hyporheic exchange paths but only slightly increases the depth of exchange relative to equivalent homogeneous sediment. In the Massillon example, permeability heterogeneity increases the proportion of long hyporheic residence times (>3 days). In the Brazos example, permeability heterogeneity increases the proportion of short residence times (<17 h). We attribute the different responses in residence time distributions to differences in permeability patterns near the sediment-water interface. The tails of residence time distributions extend for tens of years and conform to a power law in both heterogeneous and homogeneous sediment. Current–bed form interactions are responsible for the long tails, as opposed to permeability heterogeneity.
Patient understanding of drug risks: an evaluation of medication guide assessments

PURPOSE: When a Medication Guide (MG) is part of Risk Evaluation and Mitigation Strategy (REMS), manufacturers assess the effectiveness of MGs through patient surveys, which have not undergone systematic evaluation. We aimed to characterize knowledge rates from these patient surveys, describe their design and respondent characteristics, and explore predictors of acceptable knowledge rates. METHODS: We analyzed MG assessments submitted to the Food and Drug Administration from September 2008 through June 2012. We evaluated the prevalence of specific characteristics, and calculated knowledge rates, whereby we defined "acceptable knowledge" when ≥ 80% of respondents correctly answered questions about the primary drug risk. Univariate logistic models were used to investigate the predictors of acceptable knowledge rates. RESULTS: We analyzed the first completed MG assessment for each drug with a patient survey, resulting in 66 unique MG assessments. The mean knowledge rate was 63.8%, with 20 MG assessments (30.3%) achieving the 80% threshold. Compared to assessments that did not reach acceptable knowledge rates, those that did were more likely associated with additional REMS elements (e.g. Elements to Assure Safe Use or Communication Plans). Other factors, including mean age, reading or understanding the MG, and being offered or accepting counseling were not associated with knowledge rates. There was considerable variation in the design of MG assessments. CONCLUSIONS: Most MG assessments did not reach the 80% knowledge threshold, but those associated with additional interventions were more likely to achieve it. Our study highlights the need to improve patient-directed information and the methods of assessing it. Copyright © 2015 John Wiley & Sons, Ltd. Language: en
Differential encoding of spatial information among retinal on cone bipolar cells

The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina.
“There Is More to Life than a Glass of Water”: Immigration in the Contemporary United States

Buddha Is Hiding: Refugees, Citizenship, the New America. Aiwha Ong. California Series in Public Anthropology. Berkeley: University of California Press, 2003. 333 pp. Immigrants, Welfare Reform, and the Poverty of Policy. Philip Kretsedemas and Ana Aparacio, eds. Westport, CT: Praeger Publishers, 2004. 303 pp. Remaking the American Mainstream: Assimilation and Contemporary Immigration. Richard Alba and Victor Nee. Cambridge, MA: Harvard University Press, 2003. 359 pp.
Application of machine learning in SNP discovery

Single nucleotide polymorphisms (SNP) constitute more than 90% of the genetic variation, and hence can account for most trait differences among individuals in a given species. Polymorphism detection software PolyBayes and PolyPhred give high false positive SNP predictions even with stringent parameter values. We developed a machine learning (ML) method to augment PolyBayes to improve its prediction accuracy. ML methods have also been successfully applied to other bioinformatics problems in predicting genes, promoters, transcription factor binding sites and protein structures. The ML program C4.5 was applied to a set of features in order to build a SNP classifier from training data based on human expert decisions (True/False). The training data were 27,275 candidate SNP generated by sequencing 1973 STS (sequence tag sites) (12 Mb) in both directions from 6 diverse homozygous soybean cultivars and PolyBayes analysis. Test data of 18,390 candidate SNP were generated similarly from 1359 additional STS (8 Mb). SNP from both sets were classified by experts. After training the ML classifier, it agreed with the experts on 97.3% of test data compared with 7.8% agreement between PolyBayes and experts. The PolyBayes positive predictive values (PPV) (i.e., fraction of candidate SNP being real) were 7.8% for all predictions and 16.7% for those with 100% posterior probability of being real. Using ML improved the PPV to 84.8%, a 5- to 10-fold increase. While both ML and PolyBayes produced a similar number of true positives, the ML program generated only 249 false positives as compared to 16,955 for PolyBayes. The complexity of the soybean genome may have contributed to high false SNP predictions by PolyBayes and hence results may differ for other genomes. A machine learning (ML) method was developed as a supplementary feature to the polymorphism detection software for improving prediction accuracies. The results from this study indicate that a trained ML classifier can significantly reduce human intervention and in this case achieved a 5–10 fold enhanced productivity. The optimized feature set and ML framework can also be applied to all polymorphism discovery software. ML support software is written in Perl and can be easily integrated into an existing SNP discovery pipeline.
An alternative explanation of the semiarid urban area “oasis effect”

[1] This research evaluates the climatic summertime representation of the diurnal cycle of near-surface temperature using the Weather Research and Forecasting System (WRF) over the rapidly urbanizing and water-vulnerable Phoenix metropolitan area. A suite of monthly, high-resolution (2 km grid spacing) simulations are conducted during the month of July with both a contemporary landscape and a hypothetical presettlement scenario. WRF demonstrates excellent agreement in the representation of the daily to monthly diurnal cycle of near-surface temperatures, including the accurate simulation of maximum daytime temperature timing. Thermal sensitivity to anthropogenic land use and land cover change (LULCC), assessed via replacement of the modern-day landscape with natural shrubland, is small on the regional scale. The WRF-simulated characterization of the diurnal cycle, supported by previous observational analyses, illustrates two distinct and opposing impacts on the urbanized diurnal cycle of the Phoenix metro area, with evening and nighttime warming partially offset by daytime cooling. The simulated nighttime urban heat island (UHI) over this semiarid urban complex is explained by well-known mechanisms (slow release of heat from within the urban fabric stored during daytime and increased emission of longwave radiation from the urban canopy toward the surface). During daylight hours, the limited vegetation and dry semidesert region surrounding metro Phoenix warms at greater rates than the urban complex. Although prior work has suggested that daytime temperatures are lower within the urban complex owing to the addition of residential and agricultural irrigation (i.e., “oasis effect”) we show that modification of Phoenix's surrounding environment to a biome more representative of temperate regions eliminates the daytime urban cooling. Our results indicate that surrounding environmental conditions, including land cover and availability of soil moisture, play a principal role in establishing the nature and evolution of the diurnal cycle of near-surface temperature for the greater Phoenix, Arizona, metropolitan area relative to its rural and undeveloped counterpart.
Interaction among Gsk-3, Gbp, Axin, and APC in Xenopus Axis Specification

Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that negatively regulates its substrates, one of which is b -catenin, a downstream ef- fector of the Wnt signaling pathway that is required for dorsal-ventral axis specification in the Xenopus em- bryo. GSK-3 activity is regulated through the opposing activities of multiple proteins. Axin, GSK-3, and b -cate- nin form a complex that promotes the GSK-3-medi- ated phosphorylation and subsequent degradation of b -catenin. Adenomatous polyposis coli (APC) joins the complex and downregulates b -catenin in mammalian cells, but its role in Xenopus is less clear. In contrast, GBP, which is required for axis formation in Xenopus , binds and inhibits GSK-3. We show here that GSK-3 binding protein (GBP) inhibits GSK-3, in part, by preventing Axin from binding GSK-3. Similarly, we present evidence that a dominant-negative GSK-3 mu- tant, which causes the same effects as GBP, keeps en- dogenous GSK-3 from binding to Axin. We show that GBP also functions by preventing the GSK-3-mediated phosphorylation of a protein substrate without elimi- nating its catalytic activity. Finally, we show that the previously demonstrated axis-inducing property of overexpressed APC is attributable to its ability to stabi- lize cytoplasmic b -catenin levels, demonstrating that APC is impinging upon the canonical Wnt pathway in this model system. These results contribute to our growing understanding of how GSK-3 regulation in the early embryo leads to regional differences in b -catenin levels and establishment of the dorsal axis.
Current Concepts in Cervical Pathology

Abstract Context.—The correct diagnosis and reporting of cervical in situ and invasive carcinoma are essential for the appropriate clinical management of patients with human papillomavirus–associated disease. Objectives.—To review common mistakes made in the diagnosis of cervical dysplasia and invasive carcinoma, describe variants and benign mimics of high-grade squamous intraepithelial lesion and adenocarcinoma in situ, and discuss available ancillary studies that can be useful in making the distinctions as well as to review important factors related to prognosis that should be included in the pathology report. Data Sources.—Review of current literature. Conclusions.—There are many mimics and variants of cervical squamous and glandular lesions that can be resolved with ancillary studies and careful histologic examination. Prognostically important features, such as tumor size, presence of vascular invasion, and margin status, should always be included in the pathology report.
Steady-state creep of metal-ceramic multilayered materials

Abstract A general approach is presented for analyzing the steady-state creep response and its underlying mechanisms in metal-ceramic multilayers subjected to monotonic or cyclic variations in temperature. This approach combines the plate or beam theories of continuum mechanics with the mechanism-based classical constitutive equations for steady-state creep. The method is capable of predicting the evolution of overall curvature in the layered solid, the generation of thermal stresses within each layer, and the dominant deformation mechanisms at any through-thickness location of each layer at any instant of time or temperature for prescribed layer geometries, thermo-mechanical properties of the constituent layers, and the applied thermal history. Simulations are presented for AlAl 2 O 3 bilayer and Al 2 O 3 AlAl 2 O 3 trilayer model systems. The predicted results are compared with appropriate experimental measurements for the bilayers subjected to thermal cycling up to 450°C. It is found that the multilayer creep calculations capture the essential features of cyclic thermal response; the extent of stress relaxation in the Al layer, however, is somewhat overestimated, especially at higher temperatures. Possible reasons for such discrepancy are discussed, and the significance and limitations of the overall approach are highlighted. The effects of the rate of heating or cooling on deformation, and the correlations between the present creep analyses and rate-independent elastoplastic formulations for multilayers are also considered. The influence of layer thickness on the evolution of creep mechanisms is also examined from thick multilayers to the limiting case of a thin metallic film on a brittle substrate.
The association of bloody nipple discharge with breast pathology

(2005). The association of bloody nipple discharge with breast pathology. The Women's Oncology Review: Vol. 5, No. 2, pp. 123-124.
Mechanical and Myocardial Factors in Chronic Constrictive Pericarditis

The hemodynamic findings in five patients are presented in order to demonstrate the variability in the clinical and physiologic patterns that may be encountered in restrictive disease of the pericardium. The mechanical effects of pericardial encasement previously described were confirmed. Furthermore, it was found that myocardial insufficiency and hypervolemia were not only important causative agents in the circulatory dysfunction but were in some measure reversible, thus permitting resolution of the congestive state and disappearance of the "typical" hemodynamic findings of constrictive pericarditis.
A Stereospecific Synthesis of Pyrimidine β-D-2′-Deoxyribonucleosides

Abstract A stereospecific route for the synthesis of pyrimidine 2′-β-D-deoxyribonucleosides has been developed using suitably modified methyl 2-deoxy-D-ribofuranosides. The stereochemistry of the nucleoside bond is dictated by the chirality at C-4 of the pentofuranose. A novel palladium hydroxide catalyzed alcholysis of a nucleoside bond has been discovered. Preliminary studies of the mechanism and limitations of this reaction are described.