cssi/SciSciGPT-SciSciNet huggingface dataset:
Convective delivery of glial cell line-derived neurotrophic factor in the human putamen.

Object The authors conducted an analysis of the distribution of glial cell line–derived neurotrophic factor in the human striatum following convection-enhanced delivery. Methods Computational examinations of the effects of differing catheters, infusion rates, infusate concentrations, and target placement on distribution were completed based on the protocols of three recent clinical trials. Results Similar drug distributions around on-target end-hole catheters were predicted in two of the trials (AmgenUT study and Bristol study), although there was slightly deeper penetration for one of the trials (Bristol) due to a higher infusate concentration. However, when positioning uncertainly located catheter tips close to gray–white matter interfaces, backflow could diminish delivery, shunting infusate across the interfaces. For delivery via a multiport catheter at a constant base infusion rate plus a periodic bolus inflow rate (Kentucky study), base inflow alone generated a somewhat smaller distribution volume re...
Wada memory asymmetry scores and postoperative memory outcome in left temporal epilepsy

Summary Background Memory asymmetry scores are used in intracarotid amobarbital procedure (IAP) to predict memory outcome after anterior temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE). Reversed asymmetry (RA) of memory scores occurs in a minority of patients, with better memory performance observed following contralateral injection. Left ATL patients with RA are reported to have poorer postoperative verbal memory outcome. Studies also suggest that dysphasia during language dominant left hemisphere injection may contribute to lower right-sided memory scores seen in RA. Purpose To examine the role of dysphasia in RA and investigate the relationship between RA scores and memory outcome after ATL. Method IAP asymmetry scores and duration of speech arrest following bilateral IAP injection were examined in 50 patients with unilateral left TLE. Postoperative memory outcome was examined in a subset of patients ( n =31). Results Thirty-nine percent of patients had RA on IAP. The duration of speech arrest after left injection was significantly longer in the RA group compared to the expected asymmetry (EA) group. RA was not associated with negative postoperative memory outcome. Conclusions In left TLE patients, RA of IAP memory scores does not preclude good postoperative memory outcome. Prolonged speech arrest after left injection may lower right side memory scores contributing to misleading RA. Memory asymmetry patterns are sensitive to IAP protocol effects; therefore, RA may not be a robust predictor of memory outcome following left ATL.
Distance computation in the space of phylogenetic trees

A phylogenetic tree represents the evolutionary history of a set of organisms. There are many different methods to construct phylogenetic trees from biological data. To either compare one such algorithm with another, or to find the likelihood that a certain tree is generated from the data, researchers need to be able to compute the distance between trees. In 2001, Billera, Holmes, and Vogtmann introduced a space of phylogenetic trees, and defined the distance between two trees to be the length of the shortest path between them in that space. We use the combinatorial and geometric properties of the tree space to develop two algorithms for computing this geodesic distance. In doing so, we show that the possible shortest paths between two trees can be compactly represented by a partially ordered set. We calculate the shortest distance between the start and target trees for each potential path by converting the problem into one of finding the shortest path through a certain subspace of Euclidean space. In particular, we show there is a linear time algorithm for finding the shortest path between a point in the all positive orthant and a point in the all negative orthant of Rk contained in the subspace of Rk consisting of all orthants with the first i coordinates non-positive and the remaining coordinates non-negative for 0 < i < k. This case is of interest, because the general problem of finding a shortest path through higher dimensional Euclidean space with obstacles is NP-hard. The resulting algorithms for computing the geodesic distance appear to be the best available to date.
Mandating and Standardizing the Teaching of Critical Literacy Skills: A Cautionary Tale

In this article, I critique a component of the highly structured Open Court Reading curriculum designed to teach elementary children “inquiry and higher-order thinking” skills. The intended outcome of this component is, I argue, the production of critically literate and informed consumers of information. However, both the critical thinking skills the inquiry process purports to engender and the potential for critical literacy development it advertises are lost in the standardized, step-by-step implementation characteristic of the entire language arts curriculum itself. The article ends with implications and descriptions of promising alternatives that promote both critical thinking skills and critical literacy practices.
EFFECT OF SUXAMETHONIUM ON THE ICP OF CATS WITH AND WITHOUT THIOPENTONE PRETREATMENT

Twelve cats were assigned equally to two groups, one with normal, and the other with artificially-increased intracranial pressure. When suxamethonium was administered to these animals, the intracranial pressure increased in both groups, irrespective of their baseline intracranial pressure. When the same dose of suxamethonium was administered after pretreatment with thiopentone in both groups of animals, the intracranial pressure again increased from the control values.
Relationships Between Rate of Growth, Catheptic Enzymes and Meat Palatability in Young Bulls

Relationships between rate of growth, endogenous muscle enzymes and meat palatability were investigated in 48 young (13 mo) Angus bulls. After backgrounding for 4 mo, bulls were placed on a high-energy diet for 30 d, at which time they were assigned randomly to one of three feeding treatments: 1) high energy (ad libitum-fed), 2) maintenance energy (restriction-fed to maintain body weight) or 3) sub-mahtenance energy (restriction-fed to lose .68 kgld). Cattle were slaughtered after 30 or 60 d on trial. Cathepsins B and H and p-glucuronidase in the longissimus muscle were quantitated at slaughter. Serum hydroxyproline, longissimus muscle collagen, taste-panel ratings and peak load for shear were obtained. Rate of growth did not influence enzyme or palatability traits and, although differences were noted for plasma hydroxyproline, muscle collagen amount and solubility were unchanged. Overall, about one-half of the variation in serum hydroxyproline, muscle collagen, taste-panel ratings and shear-force value could be explained by collective differences in selected enzyme traits. These data indicate that a significant relationship exists between proteolytic activity of longissimus muscle and meat tenderness.
Comparison of unique hue stimuli determined by two different methods using Munsell color chips

Unique hue stimuli were determined by male and female observers using two different visual experimental procedures involving Munsell color chips of varying hue but identical chroma and value. The hypothesis was that unique hues can be more reliably established by explicit selection from a series of ordered stimuli than implicitly by hue scaling a series of stimuli in terms of neighboring UHs and this was statistically confirmed. The implicit selections based on long term memory of UHs appears to have been more challenging to observers since variability was increased by nearly 50% compared to when UHs were explicitly selected. The ranges of unique hues selected in the two methods were, however, comparable and no statistically significant difference was found between the results of females and males. The intra-observer variability in picking a stimulus to represent a unique hue, for all observers and averaged for all hues, was approximately 12% of the mean spread of unique hues, confirming that the large inter-observer variability is driven by differences in color vision and perhaps cognitive processes. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2010
Engineering Active Interfaces between Cells and Electronics

This paper introduces a strategy for integrating the functions of mammalian cells with electrodes. The strategy is based on the use of self-assembled monolayers of alkanethiolates on gold that present ligands for the adhesion of cells. The monolayers have been engineered such that applied potentials result in the modulation of ligand activities at the substrate and a corresponding influence over the behavior of attached cells. Early examples have demonstrated electroactive substrates that can turn on the migration of cells and that can release adherent cells. These examples represent a general route to integrating electrical processes with cellular processes.
Primary groups and the political system: simulation and reality.

In the preceding Article (“The Relevance of the Behavioral Sciences to the Study of International Relations”) Singer urged an interdisciplinary approach to the study of political science. In this paper he discusses Sidney Verba's Small Groups and Political Behavior, which suggests ways of “bridging the gap between the political and the scientific” and discusses the advantages and disadvantages of attempting to apply sociological and social-psychological materials and methods to the political process.
A Troublesome Statistic: Traders and Coastal Shipments in the Westward Movement of Slaves

We analyze all slave manifests housed at the National Archives—some 24,400 documents involving approximately 135,000 slaves who were transported in the coastwise trade from 1810 to 1861. The manifests list the name of the owner or shipper, which allows us to match names with traders found in other sources. We also utilize demographic characteristics of the manifests to estimate the probability that a trader organized the shipment. Commercial transactions increased over the antebellum period, and on average were responsible for approximately 55 percent of slaves who migrated from Atlantic to Gulf coast ports. “No one has ever suggested a method for finding what proportion of the slaves transported from one state to another were taken by their original masters or their heirs for their own use.”Bancroft 1931, p. 397
Discrimination of globally unpolarized fields through Stokes vector element correlations

In a previous publication [ J. Opt. Soc. Am. A21, 988 ( 2004)], we examined theoretically joint probability distributions of Stokes vector elements and suggested the existence of various types of globally unpolarized light that could be discriminated through measurement of the Stokes vector element correlations. We now study the joint distribution of the degree of polarization and the three Stokes parameters as it relates to material properties in highly scattering, depolarizing random media. We describe numerical and experimental results of second-order Stokes vector element correlations, demonstrating the existence of various types of nonclassical, globally unpolarized light, and we suggest experimental means for discriminating between such field distributions. We also discuss the usefulness of the Stokes vector element correlations as an experimental tool for discriminating between different globally unpolarized fields and for verifying the assumption of Gaussian statistics usually invoked in the context of multiple light scattering.
Relationship between abnormal fetal testing and adverse perinatal outcomes in intrauterine growth restriction.

Objective This study was undertaken to compare the efficacy of nonstress test, biophysical profile, or abnormal Dopplers in predicting adverse perinatal outcomes in intrauterine growth restriction. Study Design Retrospective cohort study of intrauterine growth restriction (birthweight Results We identified 151 singleton pregnancies with intrauterine growth restriction meeting the inclusion criteria. On bivariate analysis significant variables associated with adverse outcomes were as follows: history of chronic hypertension, corticosteroid administration, and gestational age of delivery. These were adjusted by using logistic regression. The positive predictive values of abnormal Doppler for respiratory distress syndrome and the composite of adverse outcomes were 36% and 42% respectively. Of the testing modalities compared, only abnormal Doppler significantly predicted respiratory distress syndrome and the composite of adverse outcome. Conclusion In cases of intrauterine growth restriction, the presence of abnormal Doppler is the best predictor of adverse perinatal outcome.
Parafascicular thalamic nucleus activity in a rat model of Parkinson's disease

Parkinson's disease is associated with increased oscillatory firing patterns in basal ganglia output, which are thought to disrupt thalamocortical activity. However, it is unclear how specific thalamic nuclei are affected by these changes in basal ganglia activity. The thalamic parafascicular nucleus (PFN) receives input from basal ganglia output nuclei and directly projects to the subthalamic nucleus (STN), striatum and cortex; thus basal ganglia-mediated changes on PFN activity may further impact basal ganglia and cortical functions. To investigate the impact of increased oscillatory activity in basal ganglia output on PFN activity after dopamine cell lesion, PFN single-unit and local field potential activities were recorded in neurologically intact (control) rats and in both non-lesioned and dopamine lesioned hemispheres of unilateral 6-hydroxydopamine lesioned rats anesthetized with urethane. Firing rates were unchanged 1-2 weeks after lesion; however, significantly fewer spontaneously active PFN neurons were evident. Firing pattern assessments after lesion showed that a larger proportion of PFN spike trains had 0.3-2.5 Hz oscillatory activity and significantly fewer spike trains exhibited low threshold calcium spike (LTS) bursts. In paired recordings, more PFN-STN spike oscillations were significantly correlated, but as these oscillations were in-phase, results are inconsistent with feedforward control of PFN activity by inhibitory oscillatory basal ganglia output. Furthermore, the decreased incidence of LTS bursts is incompatible with inhibitory basal ganglia output inducing rebound bursting in PFN after dopamine lesion. Together, results show that robust oscillatory activity observed in basal ganglia output nuclei after dopamine cell lesion does not directly drive changes in PFN oscillatory activity.
Melting and flowing of viscous volumes

We present a simple, linear 3D cellular automata approach for animating the melting process of solid volumetric models. Accurate modelling of object melting usually requires complicated physical simulations of heat transfer and phase transition from solid to liquid. Instead, we propose a simplified model to describe the melting behaviors of highly viscous objects, such as wax, lava, plastic, metal and chocolate. We simulate the process by which a volumetric solid transforms into a viscous liquid as the amount of heat it accumulates on its surface reaches a certain temperature. We then animate smooth fluid behavior using a cellular automata. The dynamic volume data is rendered directly on texture mapping hardware to achieve an interactive speed.
Personalizing medicine: a systems biology perspective.

Mol Syst Biol. 5: 249 According to the SEER Cancer Statistics Review, between 1975 and 2005, the deaths from heart disease in the United States declined from 37.8 to 26.6%, whereas over the same period those from cancer increased from 19.2 to 22.8% (Ries et al , 2008). In the US alone, it is estimated that in 2008 a total of 565,650 patients will have died from cancer, whereas 1,437,180 will have been newly diagnosed (Jemal et al , 2008). Thus, despite undeniable advancements in early diagnostics and progress in reducing morbidity through therapeutic efforts, it appears that after spending billions of dollars on oncology research since 1971, more than three decades later the ‘war on cancer’ is still far from being won (http://dtp.nci.nih.gov/timeline/noflash/milestones/M4_Nixon.htm). Although pressure from patients, advocacy groups and funding agencies is mounting, the conventional population‐based approach for therapeutic developments in clinics still relies on passing a series of randomized controlled trials that depend on enrollment of many patients in search for favorable yet averaged outcome patterns that statistically document safety and efficacy. Research and development (RD rather, it argues for incorporating also the molecular fingerprint, or signature, and associated growth kinetics of …
Mobile learning: A framework and evaluation

Wireless data communications in form of Short Message Service (SMS) and Wireless Access Protocols (WAP) browsers have gained global popularity, yet, not much has been done to extend the usage of these devices in electronic learning (e-learning). This project explores the extension of e-learning into wireless/handheld (W/H) computing devices with the help of a mobile learning (m-learning) framework. This framework provides the requirements to develop m-learning applications that can be used to complement classroom or distance learning. A prototype application was developed to link W/H devices to three course websites. The m-learning applications were pilot-tested for two semesters with a total of 63 students from undergraduate and graduate courses at our university. The students used the m-learning environment with a variety of W/H devices and reported their experiences through a survey and interviews at the end of the semester. The results from this exploratory study provide a better understanding on the role of mobile technology in higher education.
Human vergence eye movements to oblique disparity stimuli: Evidence for an anisotropy favoring horizontal disparities

Binocular disparities applied to large-field patterns elicit vergence eye movements at ultra-short latencies. We used the electromagnetic search coil technique to record the horizontal and vertical positions of both eyes while subjects briefly viewed (150 ms) large patterns that were identical at the two eyes except for a difference in position (binocular disparity) that was varied in direction from trial to trial. For accurate alignment with the stimuli, the horizontal and vertical disparity vergence responses (HDVRs, VDVRs) should vary as the sine and cosine, respectively, of the direction of the disparity stimulus vector. In a first experiment, using random-dots patterns (RDs) with a binocular disparity of 0.2, this was indeed the case. In a second experiment, using 1-D sine-wave gratings with a binocular phase difference (disparity) of 1/4-wavelength, it was not the case: HDVRs were maximal when the grating was vertical and showed little decrement until the grating was oriented more than � 65 away from vertical, whereas VDVRs were maximal when the grating was horizontal and began to decrement roughly linearly when the grating was oriented away from the horizontal. We attribute these complex directional dependencies with gratings to the aperture problem, and the HDVR data strongly resemble the stereothresholds for 1-D gratings, which are minimal when the gratings are vertical and remain constant for orientations up to � 80 away from the vertical when expressed as spatial phase disparities [Morgan, M. J., & Castet, E. (1997). The aperture problem in stereopsis. Vision Research, 37, 2737–2744.]. To explain this constancy of stereothresholds, Morgan and Castet (1997) postulated detectors sensitive to the phase disparity of the gratings seen by the two eyes (rather than their linear separation along some fixed axis, such as the horizontal). However, because (1) our VDVR data with gratings did not show this constancy and (2) the available evidence strongly suggests that there are no major differences in the disparity detectors mediating the initial HDVR and VDVR, we sought an alternative explanation for our data. We show that the dependence of the initial HDVR and VDVR on grating orientation can be successfully modeled by a bias in the number and/or efficacy of the detectors that favors horizontal disparities. 2008 Published by Elsevier Ltd.
Neurodegeneration in Diabetic Retinopathy

Neurodegeneration can be defined as a chronic, progressive loss of neuronal function and structural integrity, which usually includes the death and removal of neurons at an accelerated rate. In neurodegenerative diseases, the loss of neurons occurs gradually over a protracted period of time, such as the kind of neural loss that occurs in Parkinson’s or Alzheimer’s disease. The term neurodegeneration is used frequently in discussions of many disease pathologies that primarily affect neurons; however, neurodegenerative diseases have been more accurately defined as, “…neurological disorders with heterogeneous clinical and pathological expressions affecting specific subsets of neurons in specific functional anatomic systems; they arise for unknown reasons and progress in a relentless fashion.”
Real-time Photo-Realistic Physically Based Rendering of Fine Scale Human Skin Structure

Skin is noticeably bumpy in character, which is clearly visible in close-up shots in a film or game. Methods that rely on simple texture-mapping of faces lack such high frequency shape detail, which makes them look non-realistic. More specifically, this detail is usually ignored in real-time applications, or is drawn in manually by an artist. In this paper, we present techniques for capturing and rendering the fine scale structure of human skin. First, we present a method for creating normal maps of skin with a high degree of accuracy from physical data. We also present techniques inspired by texture synthesis to "grow" skin normal maps to cover the face. Finally, we demonstrate how such skin models can be rendered in real-time on consumer-end graphics hardware.
Angiotensin II stimulates internalization and degradation of arterial myocyte plasma membrane BK channels to induce vasoconstriction.

Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated K+ (BK) channel α and auxiliary β1 subunits that modulate arterial contractility. In arterial myocytes, β1 subunits ...
The distribution of P-element sequences in Drosophila: the willistoni and saltans species groups.

This report describes the distribution of P-element sequences among members of the closely relatedwillistoni andsaltans species groups of the subgenusSophophora. Gel-blotting analyses showed that many, but not all, species from each of these groups possess sequences with homology to the P transposable element ofDrosophila melanogaster, a sophophoran species belonging to themelanogaster species group. Furthermore, P-homologous fragments are present in lower numbers inwillistoni- andsaltans-group species than inD. melanogaster P strains, and, in some species of those two groups, exhibit species-characteristic hybridization patterns. On the basis of these results, it is proposed that P elements have had a long evolutionary history in thewillistoni andsaltans lineages.
New Venture Organization Personality and Recruitment: Understanding the Job Seeker's Perspective

New firms often have difficulties recruiting key employees, impacting the growth and viability of the firm. The majority of the literature has examined this difficulty from the hiring firm’s perspe...
HYPOXIA ATTENUATES METABOLISM OF PLATELET ACTIVATING FACTOR BY FETAL AND NEWBORN LAMB LUNGS

The metabolism of platelet activating factor (PAF) by lungs of near-term fetal and 5- to 9-day-old lambs was studied during normoxia and hypoxia at 37 degrees C in 30 mM Tris buffer. PAF synthesis was studied in lung cytosol and membrane using 250 microM [3H]acetyl CoA, 40 microM lyso-PAF, and 50 micrograms protein. PAF catabolism was studied in lung homogenate (LH) using 50 microM [3H]alkyl-PAF. PAF was extracted and assayed by thin-layer chromatography (TLC) and liquid scintillation spectrometry. Levels of PAF synthesized (nmol/min per mg protein) by fetal lung membrane versus cytosol were 1.35 +/- 0.07 versus 0.61 +/- 0.08, which were greater than those by newborn which were 0.33 +/- 0.07 versus 0.17 +/- 0.03. Hypoxia did not alter PAF synthesis by the lungs. PAF catabolism (nmol lyso-PAF/min per mg protein) by fetal LH was 0.07 +/- 0.01, which increased to 0.24 +/- 0.02 during normoxia. In newborn LH, the rate was 0.24 +/- 0.04 and increased to 0.33 +/- 0.01 during normoxia. PAF catabolism was higher in newborn than in fetal LH. An increase in pO2 augmented PAF catabolism, more in fetal than in newborn LH. Thus rate of PAF synthesis decreases from fetus to newborn, but PAF catabolism increases from fetus to newborn. The higher rate of PAF synthesis coupled with a low rate of PAF catabolism in the hypoxic environment of fetal lungs may predispose the fetus to a high PAF level, which may contribute to the high basal vasomotor tone in fetal lungs. A fall in PAF level with oxygenation, due to increased PAF catabolism, may facilitate the normal fall in pulmonary vascular resistance at birth.
“This is for the Brown Kids!” Racialization and the Formation of “Muslim” Punk Rock

Recent research shows that non-Muslims “read” Muslim and non-Muslim Others through an Islamophobic lens, whether the victims of Islamophobia are practitioners of Islam or not. Yet how Muslims and non-Muslims band together against anti-Muslim racism in nonreligious ways and venues is less understood. The author draws on a wide range of qualitative data to show how “Taqwacore” punks (taqwa means “God consciousness” in Arabic and core comes from hardcore punk) create a racial identity as “brown kids” that is panethnic and opposed to the major racial frames used to vilify Muslims and brown-bodied Others. Taqwacore punks do this by (1) using punk rock attitudes to call out whiteness and keep it out of their punk and (2) redefining punk in favor of “brown kids.” These findings expand a new body of scholarship that shows how marginalized youth are using popular culture to create new racial identities against whiteness.
Probe into the Development of CMCC Business Analysis System Construction

This article introduces the enterprise business idea of the CRM customer relations management and the construction background and the core idea of CMCC business analysis system.This article ana- lyzes the problems in the primary construction period and elaborates how to construct the CRM system effectively so as to assist enterprises to change the operation process and be adapted to such operating model.
On the Analysis of the Un-World Historical Socialism Feature of Traditional Socialism

Socialism should be a world historical cause in the era of the world history,but the long-period curbed environments and subjective mistakes made the traditional socialism own distinct Un-world historical socialism features.The closed and conservative features made traditional socialism lost its development direction,and then socialism cause steep plunge.
Configuring European Archives: Spaces, Materials and Practices in the Differentiation of Repositories from the Late Middle Ages to 1700:

While recordkeeping and record-using were important in Classical societies and early medieval Europe, rapid evolution and change characterized recordkeeping practices from the late Middle Ages throughout the early modern period. This paper recasts changes in Western European recordkeeping from the fourteenth to eighteenth century in terms of the differentiation of spaces and practices, thus challenging older literature that sees increasing accumulation around a foundational archivum as the primary mode of expansion. Empirically, the argument concentrates on developments in the German lands that produced highly sophisticated Registratur (practices that tracked and indexed a wide variety of circulating records) across the German sphere after 1400. As first argued by Ernst Pitz, early modern German archivists began differentiating conceptual and physical spaces for recordkeeping in the fifteenth century, thus producing both archives of charters and registries of informational records of many kinds. A close e...
The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen.

The breadth of the expressed T cell repertoire to antigens under Ir gene regulation is central to the understanding of Ir gene function. While major histocompatibility complex (MHC)-related differences in the elicited T cell repertoire are readily demonstrated, the reasons for the choice of particular determinants are not clear. It is commonly assumed that the Ia molecules as the sole products of Ir genes somehow influence the choice of determinants selected for response. That this choice can be severely restricted in the C57BL/6 mice to hen egg-white lysozyme (HEL) was shown earlier with L2 (a.a. 13-105) immunization. L2, as the major cyanogen bromide cleavage fragment of HEL represents about 70% of the whole molecule and contains all the determinants recognize by proliferative T cells induced with HEL in this strain. All clones obtained from L2-immunized B6 mice recognized HEL and determinants available only within the T11 peptide (a.a. 74-96), suggesting that the entire T cell repertoire was restricted to determinants within the T11 region for HEL [1]. To test this hypothesis, long-term T cell lines were derived from HEL-immunized B6 mice. Bulk HEL- and L2-induced T cell lines showed similar L2-specific responses. However, in contrast to clones from the L2-lines, which were all specific for T11, the large majority of clones from the HEL-induced lines were specific for "non-T11" determinants. Antigen recognition of all clones was restricted by a similar restriction element on the I-Ab molecule. Thus, T cells directed against "non-T11" determinants available on the L2 fragment were not induced by L2 itself but required the whole molecule. The evidence clearly shows that within the T cell repertoire, the selection of clones is dramatically changed by the context in which the determinants are available. In fact, a hierarchy of T cells specific for T11 and "non-T11" determinants results. Structural differences between HEL and L2 lead to an inversion of this hierarchy. As both the HEL- and L2-induced lines were maintained and cloned under identical conditions, this appears to reflect the cellular interplay that occurs during the early in vivo selection period, rather than during the later in vitro activation and propagation of the lines and clones derived from them. The direct implications of these findings relate to interpretations of Ir gene phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)
Clinical applications of advances in the genetics of IBD

Our rapidly expanding understanding of the genetics of inflammatory bowel disease (IBD) has led to important clinical applications. It is becoming apparent that genes help determine the clinical phenotype, intestinal and extraintestinal complications, response to treatment, and drug toxicities in these disorders. For example, NOD2/CARD15 mutations are associated with ileal Crohn's disease, possibly with a fibrosing/obstructing phenotype, but do not influence responses to infliximab treatment. Similarly, certain human leukocyte antigen (HLA) haplotypes are associated with aggressive, extensive ulcerative colitis and strongly influence extraintestinal manifestations of IBD, including uveitis and various forms of arthritis. Expression of the glucocorticoid receptor b determines the clinical response to corticosteroids, whereas genetically regulated levels of enzymes metabolizing 6-mercaptopurine/azathioprine may determine clinical responses and toxicities to these important immunosuppressive agents. Once we have a more sophisticated understanding of the mechanisms of genetic defects in IBD, it may be feasible to restore physiologic function to prevent the onset of disease in susceptible individuals. However, because we do not have the ability to prevent disease at the present time, it is premature to screen offspring and first-degree relatives of IBD patients for the NOD2/CARD15 genotype. One can anticipate that it will become feasible to prospectively determine a patient's genotype and to individualize a drug regimen, leading to highly effective, safe treatments for IBD patients on a rational, rather than empiric, basis.
Exciton Transport in Naphthalene-Doped Poly (Methylmethyl-Acrylate): Spatial and Energetic Disorder

A novel method is presented for the study of spatially and/or energetically disordered domains in a photoactivated polymeric material. Long-lived phosphorescence and delayed fluorescence spectra and their decay dynamics are studied in a “plexiglass” sample that is both mechanically improved and optically activated via doping with aromatic molecules (naphthalene, anthracene). The dopants are aggregated in sub-microscopic domains (“cavities”, “pores”). Fractal-like energy transport and exciton recombination (fusion, annihilation) are observed and related to the structural aspects and the energetic disorder. Energy trapping is studied for samples doped heavily with naphthalene and lightly with anthracene. Exciton fusion is studied on samples with naphthalene dopant (and photo-products: excimer, radial, etc.). While the spectra reveal only the high degree of energetic disorder, the decay dynamics characterize the geometric disorder. The naphthalene singlet exciton transport is about three orders of magnitude slower than in crystalline naphthalene and obeys Stern-Volmer kinetics. This corresponds to normal (non-fractal, non-dispersive) diffusion of the excitation (due, in part, to longer-range transitiondipole-transition-dipole interactions). However, the triplet exciton motion and reaction (fusion) clearly show anomalous (dispersive) diffusion and non-classical (fractal-like) recombination kinetics. The effective spectral dimension is about 1.5 over a wide temperature range (77–165K), indicating that the geometrical disorder (“fractal nature of the cavities”) appears to dominate (for the short-range, exchange-like interactions). The triplet exciton transport and kinetics are at least two orders of magnitude slower than in perfectly crystalline naphthalene domains (and all exciton motion is frozen at about 4.2K). Large inhomogeneous fluorescence line-broadening is observed (~100 cm−1), as well as spectral diffusion (due to triplet exciton energy relaxation).
Abstract 2655: Oncogenic chromatin factors drive cell type-specific transcription within megadomains in NUT midline carcinoma

NUT midline carcinoma (NMC), a subtype of squamous cell cancer, is one of the most aggressive human solid malignancies known. NMC is driven by the creation of a translocation oncoprotein, BRD4-NUT, which blocks differentiation and drives growth of NMC cells. BRD4-NUT forms distinctive nuclear foci in patient tumors, which we find correlate with ∼100 unprecedented, hyperacetylated expanses of chromatin that reach up to 2 Mb in size. These ‘megadomains’ appear to be the result of aberrant, feed-forward loops of acetylation and binding of acetylated histones. Megadomains drive transcription of underlying DNA in NMC patient cells and in naive cells induced to express BRD4-NUT. Here we characterize the constituents of BRD4-NUT chromatin complexes using a crosslinking approach, BioTAP-XL. We find many transcriptional activating proteins known to associate with BRD4, along with novel interactors including p300/CBP and a previously uncharacterized BRD4-NUT Megadomain Associated Protein (BMAP1). BMAP1 is expressed in primary NMC tissue and a subset of more common head and neck squamous cell carcinomas (HNSQC). Concurrently, we discovered a patient-derived NMC harboring a novel BMAP1-NUT fusion. BMAP-NUT blocks differentiation, and like BRD4-NUT recruits p300 to form hyperacetylated megadomains, including at the MYC locus. Thus, our proteomic and genetic approaches have converged on a novel mechanism that involves reprogramming very large regulatory regions to drive oncogenic transcription. Citation Format: Mitzi I. Kuroda, Artyom A. Alekseyenko, Erica M. Walsh, Xin Wang, Adlai Grayson, Peter T. Hsi, Peter V. Kharchenko, Christopher A. French. Oncogenic chromatin factors drive cell type-specific transcription within megadomains in NUT midline carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2655.
Late Archaic bison hunters in northern Colorado : 1997-1999 excavations at the Kaplan-Hoover bison bonebed (5LR3953)

Limited excavations at a Late Plains Archaic arroyo trap along the Cache la Poudre River near Windsor in northern Colorado have exposed the remains of an estimated 200 bison. The bonebed was uncovered during construction activities, which removed an estimated 4 m of sediment from above the upper surface of the bonebed. Partial excavation of an 18.5 m2 cross-sectional portion of the arroyo has produced an assemblage of over 4000 bison bones. An AMS date on wood charcoal and a standard radiometric age from bone collagen provided statistically similar dates and yield an averaged uncalibrated radiocarbon age of 2724±35 RCYBP. The number of stone tools recovered is low, with only nine corner-notched projectile points and point fragments, several scrapers and flake tools, and over 120 resharpening flakes. Patterns of mandibular molar eruption and wear indicate a single early fall kill. Human utilization of many of the carcasses was limited, with very few of the marrow bones fractured or removed from the kill site. Based on skeletal element counts, the carcass segments most frequently taken from the kill were rib slabs, thoracic vertebrae, scapulae, femora, and lumbar-sacral units. Cutmark frequencies support this interpretation. The most common locations for butchering marks are on the thoracic spines, rib blades, and mandibular symphyses. After humans abandoned the site, carnivores extensively modified the remaining carcass segments. Subsequent burial of the bonebed included fluvial transport and re-orientation of many of the bones within the old arroyo. The project has emphasized incorporating public interaction and education into the research program.
Resistivities of curing epoxy systems II. Bisphenol-A diglycidyl ether/poly amide

This paper is part of a continuing study of several common epoxide/ hardener systems. Previous work1,2 is extended to the epoxide/ polyamide system, an example of which is bisphenol-A diglycidyl ether/General Mills' Versamid 140.
Innovation Factors for Reasonable Royalties

Patentees who are successful in litigation are entitled to no less than a “reasonable royalty” for the infringing use of the patent. Currently, reasonable royalties are assessed by the fact-finder using the cumbersome, difficult-to-apply fifteen-factor Georgia Pacific test. The Georgia Pacific test has been widely and roundly criticized, and there is general agreement that it too often hinders patent law’s central goal: promoting technological innovation. To improve the reasonable royalty analysis, this Article proposes adding innovation-centric factors to the Georgia Pacific test, including the total amount spent on research & development and commercialization of the invention, taking into account opportunity costs and project-specific risk. Additionally, the Article suggests emphasizing a slightly modified version of one existing innovation-centric, Georgia Pacific factor: the technological benefits offered by the invention when compared to alternative approaches. Like the “objective” factors used to make determinations of whether a patent is obvious, these innovation factors will help fact-finders to make more accurate and more consistent reasonable royalty determinations while more ably advancing patent law’s goal of spurring innovation.
Percolation blockage: A process that enables melt pond formation on first year Arctic Sea ice

Melt pond formation atop Arctic sea ice is a primary control of shortwave energy balance in the Arctic Ocean. During late spring and summer, the ponds determine sea ice albedo and how much solar radiation is transmitted into the upper ocean through the sea ice. The initial formation of ponds requires that melt water be retained above sea level on the ice surface. Both theory and observations, however, show that first year sea ice is so highly porous prior to the formation of melt ponds that multi-day retention of water above hydraulic equilibrium should not be possible. Here we present results of percolation experiments that identify and directly demonstrate a mechanism allowing melt pond formation. The infiltration of fresh water into the pore structure of sea ice is responsible for blocking percolation pathways with ice, sealing the ice against water percolation, and allowing water to pool above sea level. We demonstrate that this mechanism is dependent on fresh water availability, known to be predominantly from snowmelt, and ice temperature at melt onset. We argue that the blockage process has the potential to exert significant control over inter-annual variability in ice albedo. Finally, we suggest that incorporating the mechanism into models would enhance their physical realism. Full treatment would be complex. We provide a simple temperature threshold-based scheme that maybe used to incorporate percolation blockage behavior into existing model frameworks. This article is protected by copyright. All rights reserved.
The Distance of Heaven: An Analysis of the Guodian Wu Xing

This paper argues that the Guodian Wu Xing consists of two interrelated sections that reflect its distinction between goodness (a characteristic of humans) and virtue (a trait of Heaven). Individually, each section emphasizes different aspects of self-cultivation. When read against one another, they articulate the text’s main argument that Heaven is a distant figure and that the sage, a figure who understands the Way of Heaven, is almost unreachable. As such, the text focuses on the gentleman, a figure who achieves virtue (defined as timeliness) within a dispositional context by emulating Heaven in accordance with the Way of the Gentleman.
Financial Relationships between Urologists and Industry: An Analysis of Open Payments Data

Abstract Introduction The Open Payments Program was enacted to increase transparency of financial relationships between physicians and the medical device and pharmaceutical industry. We examined nonresearch related financial relationships between urologists and industry in the United States using the latest Open Payments data. Methods We performed a descriptive analysis of Open Payments data released by the Centers for Medicare and Medicaid Services for 2014. Total payment amounts associated with various urological drug and device categories were calculated. We then examined for correlations between payments and prescribing at the national level using Medicare Part D prescribing data. Results There were 232,207 payments totaling $32,418,618 made to 8,618 urologists (73.6% of practicing urologists in the United States) during calendar year 2014. Median payment was $15 (IQR $11 to $24). While the majority of individual payments (68%) were $20 or less, 82% of the urologists in the database received more than $100 from industry during 2014. The frequency of industry payments was positively correlated with Medicare Part D prescribing frequency as well as the sum of claims (r = 0.726, p = 0.005 and r = 0.755, p = 0.003, respectively). Conclusions Nearly 75% of urologists in United States received nonresearch payments from industry in 2014. Most individual payments were for less than $20 but the majority of urologists received more than $100 in aggregate during the study year, with most of the money going toward speaker fees. Payments were positively correlated with Part D prescribing, yet confounding variables make it difficult to establish a cause and effect relationship.
Abstract 084: Significant Roles of Hyperglycemia and Obesity in the Disruption of Blood Pressure Circadian Rhythm in Leptin-receptor Mutant Db/db Mice

Blood pressure (BP) exhibits 24-hour rhythm. Loss of BP oscillation has been found in up to 75% diabetic patients and is associated with increased risks of target organ injuries. However, the mechanisms underlying the disruption of BP circadian rhythm in diabetes remain poorly understood. We and others have demonstrated that type 2 diabetic db/db mice in C57/KsJ background have hypertension and severely disrupted BP circadian rhythm. Since these db/db mice were severely hyperglycemic (>600 mg/dL) as well as obese, it is unclear which factor or both contribute to the disruption of BP oscillation. Moreover, it is unclear whether clock genes are involved in the diabetes associated disruption of BP circadian rhythm. To address these specific questions, we cross bred the leptin receptor mutated db/db mice in the C57BL/KsJ background with PERIOD2::LUCIFERASE knock in mice in C57BL/6J background. At 4-5 months old, the blood glucose in these db/db -Per2 mice was higher than controls (320.3 vs 153 mg/dL) but was significantly lower than the C57/KsJ - db/db mice (608.5 mg/dL). However, the body weight of these db/db -per2 mice was significantly higher than both the C57/KsJ- db/db (66.4 vs 44.8 g) as well as control mice (33.9 g). The metabolic flexibility, which is represented by respiratory exchange ratio and measured using TSE LabMaster Indirect Calorimetry System, was significantly compromised in the db/db -per2 mice when compared to controls. We then determined the BP in the db/db -per2 mice using radiotelemetry under 12: 12 light: dark cycle. The circadian parameters of BP, including period length, amplitude and acrophase were calculated using Chronos-fit software. The results demonstrated that db/db -per2 mice have normal BP value but disrupted BP circadian rhythm, with decreased power of 24h oscillation, diminished amplitude and shifted acrophase. However, the extent of the disruption was significantly less than that we have reported in the C57/KsJ- db/db mice. By using LumiCycle, we are currently investigating the clock gene functions in various tissues including SCN, aorta, liver, and etc isolated from db/db -Per2 mice. In summary, we demonstrated that both hyperglycemia and obesity significantly contribute to the disruption in BP circadian rhythm in db/db mice.
Should we treat acute hepatitis C? A decision and cost-effectiveness analysis.

It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re-evaluate acute HCV management in the era of direct-acting antiviral agents (DAAs). In this study a microsimulation model was developed to analyze the tradeoffs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long-term outcomes such as quality-adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost effectiveness ratio (ICER) was $19,991 per QALY, demonstrating that treatment of acute HCV was cost-effective using a willingness-to-pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost-saving, increasing QALYs by 0.03 and decreasing costs by $3655. Conclusion: Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6 week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. This article is protected by copyright. All rights reserved.