cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of Progression From Impaired Glucose Tolerance to Diabetes on Cardiovascular Risk Factors and Its Amelioration by Lifestyle and Metformin Intervention: The Diabetes Prevention Program randomized trial by the Diabetes Prevention Program Research Group

OBJECTIVE Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as pre-diabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglycerides, HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program. RESEARCH DESIGN AND METHODS A total of 3,234 participants with impaired glucose tolerance (IGT) were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin, or placebo. Using repeated-measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status. RESULTS CVD risk factor values and changes from baseline became more unfavorable as glucose tolerance status deteriorated but improved with reversion to normal glucose tolerance (NGT), especially in the ILS intervention group (trend test P P = 0.02] in ILS and HDL cholesterol [ P = 0.02] in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia. CONCLUSIONS Progression from IGT to diabetes is associated with mild deterioration, whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS, but less so with metformin, in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously.
‘Latin lebensraum’: the geopolitics of Ibero-American Antarctica

Abstract Geopolitical thinking has exerted, and continues to exert, a significant influence upon the approaches towards Antarctica taken by the principal nations of South America. During the 1980s the concept of an ‘Ibero-American quadrant’ of Antarctica, located between 0° and 90°W, has acquired growing acceptance in Latin America and Spain. Within this quadrant Argentina and Chile possess long-standing sovereignty claims, while more recently other Latin countries (Brazil, Cuba, Ecuador, Peru, Spain and Uruguay) have established presences therein. The long-standing geopolitical tradition in South America provides the foundation for the contemporary and future geopolitical perceptions held about Antarctica by individual South American countries. A significant trend relates to the emergence of a cooperative and integrative form of geopolitical thought in place of a more traditional nationalist and aggressive approach. Nevertheless, the concept of Ibero-American cooperation, though possessing the potential of enhancing the effectiveness of individual Antarctic programmes, raises the possibility of ranging Ibero-Latin American countries against other states involved in Antarctica.
Scale-based approach for image quality evaluation

In images, anomalies such as edges or object boundaries take on a perceptual significance that is far greater than their numerical energy contribution to the image. Wavelet transform highlights these anomalies by representing them with significant coefficients. The contribution of a wavelet coefficient to the perceptual quality of the image is related to its magnitude. Degradation in image quality due to image compression reflects in the form of reduction in the magnitude of the wavelet coefficients. Since, significant wavelet coefficients appear across different scales and orientations, it is important to observe the wavelet transform at different scales and orientations. In this paper, the wavelet transform of a given image and the reconstructed images at various quality levels are represented in the form of energy density plots suggested in reference one. A quality metric is proposed based on the absolute difference between the energy densities corresponding to the original and reconstructed images. Preliminary results obtained using the scale-based image quality evaluation strategy are reported.
Heterogeneity of Coarse Particles in an Urban Area

The variation in composition and concentration of coarse particles in Rochester, a medium-sized city in western New York, was studied using UNC passive samplers and computer-controlled scanning ele...
Hepatitis B Screening in Asian and Pacific Islanders: New Guidelines, Old Barriers

Chronic hepatitis B virus (HBV) infection is a serious liver disease that disproportionately affects Asian and Pacific Islander immigrants. In May 2014, the U.S. Preventive Services Task Force released new HBV screening guidelines that expanded screening to non-pregnant adolescents and adults who were born in Asia and the Pacific Islands, and U.S.-born persons not vaccinated as infants whose parents were born in Central or Southeast Asia. Although the guidelines empower health care providers and community health workers to expand their screening efforts, old barriers to screening remain deeply rooted in this population. These barriers include cultural beliefs about wellness, myths and misconceptions about HBV, and lack of access to appropriate, culturally sensitive care. Through a combination of strategies—retooling the current health care workforce to be more culturally sensitive providers, involving oriental medicine practitioners in patient education, and engaging grassroots organizations—we can overcome barriers and take full advantage of the new HBV screening guidelines.
Do the cognitive and behavioral sciences need each other

Game theory provides a descriptive or a normative account of an important class of decisions. Given the cognitive sciences' emphasis on explanation, unification with the behavioral sciences under a descriptive model would constitute a step backwards in their development. I argue for the interdependence of the cognitive and behavioral sciences and suggest that meaningful integration is already occurring through problem-based interdisciplinary research programs.
Turning in circles: the neuropharmacology of rotation.

Abstract Animals with unilateral lesions of the nigrostrial system rotate when administered dopaminergic agents. The same agents also induce rotation, though at lower rates, in normal animals. Despite the apparent simplicity of the rotatory response, variations in methodology among studies may alter the kind and/or magnitude of rotation data obtained. In some cases, due to insufficient control procedures, inaccurate or erroneous interpretations may be reached. The importance of considering several testing parameters is discussed. It is concluded that rotation is primarily due to asymmetric dopaminergic nigrostriatal function, although other pathways mediated by norepinephrine, serotonin, acetylcholine and GABA appear to have modulatory roles.
The implantable cardioverter–defibrillator: An update

The implantable cardioverter-defibrillator (ICD) provides life-saving therapy to prevent sudden cardiac death. ICDs have been implanted in millions of patients worldwide since the first human implant in 1980. Clinical trials have helped establish guidelines for ICD implantation in primary and secondary prevention of sudden cardiac death. Recent trials have also tested and compared various programing strategies to avoid unnecessary shocks and improve survival among ICD recipients. ICDs may also assist with monitoring for heart failure management. In this review, we discuss the clinical science to date that has helped define the role of ICDs in current practice.
Argon transition probabilities revisited

In a paper by P. Baessler and M. Kock (J. Phys. B, vol.13, p.1351, 1980), a 2 lambda interferometric technique is used to determine the electron number density, n/sub e/, in a pure argon plasma generated in a wall stabilized arc. Hydrogen is then added to obtain the reduced linewidth of the Balmer line H/sub beta /. Baessler and Kock then use an electron density correction factor to correct the transition probabilities obtained from experiments using hydrogen for n/sub e/ determination. Their result neglects the temperature change due to the modification to the electron density. The present author has shown that their correction factor is invalid and results in transition probability corrections that are in error by 30-200%. >
Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture.
Scaling of submaximal oxygen uptake with body mass and combined mass during uphill treadmill bicycling

This study examined the scaling relationships of net O2 uptake [V˙o 2(net)= V˙o 2 − restingV˙o 2] to body mass (M B) and combined mass (M C= M B + bicycle) during uphill treadmill bicycling. It was...
Experimental study on advanced underwater robot control

The control issue of underwater robots is very challenging due to the nonlinearity, time variance, unpredictable external disturbances, such as the sea current fluctuation, and the difficulty in accurately modeling the hydrodynamic effect. Conventional linear controllers may fail in satisfying performance requirements, especially when changes in the system and environment occur during the operation since it is almost impossible to manually retune the control parameters in water. Therefore, it is highly desirable to have an underwater robot controller capable of self-adjusting control parameters when the overall performance degrades. This paper presents the theory and experimental work of the adaptive plus disturbance observer (ADOB) controller for underwater robots, which is robust with respect to external disturbance and uncertainties in the system. This control scheme consists of disturbance observer (DOB) as the inner-loop controller and a nonregressor based adaptive controller as the outer-loop controller. The effectiveness of the ADOB was experimentally investigated by implementing three controllers: PID, PID plus DOB, and ADOB on an autonomous underwater robot, ODIN III.
Validity and composition of the Silurian trilobite genera Borealarges and Dicranogmus, with new species from the Canadian Arctic

New silicified material from Arctic Canada demonstrates that the lichid trilobite genera Borealarges and Dicranogmus, recently claimed to be synonyms, are independent groups with no close phylogenetic connection to one another. Dicranogmus has been known mainly from cranidia alone; prior association of librigenae and pygidia with the Arctic Canadian species D. skinneri has been queried. This association is correct beyond reasonable doubt, based on description of new material of both D. skinneri and a new species. Three new species of Borealarges are related to B. tuckerae Adrain 1994. Cladistic analysis supports the monophyly of this species group. Pending further new information, however, the group is retained within the genus Borealarges. The stratigraphic range of the species group is extended from the lower Wenlock (Sheinwoodian) to upper Ludlow (Ludfordian) by the discovery of a rare species in the Douro Formation of Cornwallis Island, Arctic Canada. New taxa from the Wenlock of the Cape Phillips Formation, Arctic Canada, include Dicranogmus wynni, Borealarges nicoae, B. warholi, and B. yulei. Resume : Du materiel silicifie nouvellement recolte de l'Arctique canadien demontre que les genres lichides Borealaspis et Dicranogmus sont des groupes independants sans lien phylogenetique proche, a l'encontre de l'assertion recente qu'ils etaient synonymes. Dicranogmus n'etait connu auparavant que de cranidiums isoles; l'association de librigenes et pygidiums referes a l'espece de l'Arctique canadien D. skinneri a ete mise en doute. Cette association est exacte au-dela de tout doute raisonnable, en se basant sur la description de nouveau materiel de D. skinneri et d'une autre espece. Trois nouvelles especes de Borealaspis sont apparentees a B. tuckerae Adrain, 1994. L'analyse cladistique supporte la monophylie de ce groupe d'especes. Par contre, dans l'attente de nouvelles informations, ce groupe est maintenu dans le genre Borealaspis. La duree stratigraphique de ce groupe d'especes est prolongee du Wenlock inferieur (Sheinwoodien) au Ludlow superieur (Ludfordien) suite a la decouverte d'une espece rare dans la Formation de Douro de l'Ile Cornwallis de l'Arctique canadien. Des taxons nouveaux du Wenlock de la Formation de Cape Phillips, Arctique canadien, comprennent Dicranogmus wynni, Borealarges nicoae, B. warholi et B. yulei. (Traduit par la Redaction) Adrain 763
Science for Students with Disabilities

The purposes of this paper are to introduce this special series and to present a framework for science for students with disabilities. The paper reviews curriculum and instructional perspectives and proposes consideration of a thematic scheme for the organization and development of science programs to meet the needs of students with disabilities.
Development of locomotion toward home nesting material in neonatal rats

Neonatal rats were individually placed in a narrow choice zone between home and fresh nesting materials. At Day 2 postpartum the pups made significantly more home-choosing responses (vs responses for fresh nesting material). At a mean of 5.6 days (range, 4 to 9 days) the pups reached a criterion of 2 consecutive days of responses all for home nesting material. The number of head contacts increased abruptly upon reaching the criterion. In a 2nd experiment we observed that the pups which were repeatedly tested performed no better than those which were tested for the 1st or the 2nd time. Thus, (a) home-seeking responses appear to emerge substantially earlier than previously reported by other investigators, (b) head-contact responses appear to be related to successful home-chossing, and (c) some maturational rather than experiential factors are important for the development of both head-contact and home-choosing responses.
Applications of a Numbering Scheme for Polygonal Obstacles in the Plane

We present efficient algorithms for the problems of matching red and blue disjoint geometric obstacles in the plane and connecting the matched obstacle pairs with mutually nonintersecting paths that have useful geometric properties. We first consider matching n red and n blue disjoint isothetic rectangles and connecting the n matched rectangle pairs with nonintersecting monotone rectilinear paths; each such path consists of O(n) segments and is not allowed to touch any rectangle other than the matched pair that it is linking. Based on a numbering scheme for certain geometric objects and on several useful geometric observations, we develop an O(n log n) time, O(n) space algorithm that produces a desired matching for isothetic rectangles. If an explicit printing of all the n paths is required, then our algorithm takes O(n log n+λ) time and O(n) space, where λ is the total size of the desired output. We then extend these matching algorithms to other classes of red/blue polygonal obstacles. The numbering scheme also finds applications to other problems.
How stroke survivors and primary support persons experience nurses in rehabilitation.

The role of nursing in rehabilitation has been studied from various perspectives. This study explored experiences with nursing care in rehabilitation from the perspective of stroke survivors and their primary support persons (PSP). The sample consisted of six stroke survivors and seven primary support persons. Through in-depth phenomenological interviews, participants related the experiences with nursing care that stood out for them. The experience was conceptualized as a two-dimensional continuum from helpful to adversarial, with none of the participants articulating a therapeutic presence from nurses. Implications for nursing are explored
Office Techniques for Detecting Optic Neuropathies Brightness Sense Compared to Traditional Screening Tests

This Study Evaluated Relationships Between Brightness Sense And Visual Acuity, Optic Disc Changes, Afferent Pupillary Defect, And Color Vision In 88 Patients With Optic Neuropathies. To Assess Screening Sensitivity, Patients In Four Disease Categories (Optic Neuritis, n=47; Ischemic Optic Neuropathy, N = 23; Compressive Lesions, N = 8; Other Neuropathies, N = 10) Were Classified As Normal Or Abnormal On Each Measure. Overall, Brightness Sense Was The Most Sensitive Measure In Detecting Optic Neuropathies And Color Vision Was The Least Sensitive Measure. Only Optic Disc Changes Differentiated Significantly Between Disease Groups (P < 0.001). For Patients With Ischemic Optic Neuropathy Optic Disc Changes And Visual Acuity Were The Most Sensitive Measures. Brightness Sense Was Significantly Decreased From Normal In All Groups (P < 0.0001), But Did Not Vary Significantly Between Groups. In Patients With Optic Neuritis, Brightness Sense Was Significantly Correlated With The Afferent Pupillary Defect (r=−0.47),...
Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer.

Background: Platelet-derived microparticles (MPs) are believed to play an important role in coagulation and inflammatory disorders. Unfortunately, MP size renders them difficult to study and analyze by conventional flow cytometry. Methods: We analyzed and characterized platelet-derived MPs, using antibodies against the major surface glycoproteins (GP), the platelet activation antigen P-selectin (CD62P), and a marker of procoagulant activity (phosphatidylserine exposure). MPs were generated by exposure of platelets to thrombin receptor activating peptide (TRAP) or ionophore. Both agonists induced significant microvesiculation of platelets, and the resulting MPs were analyzed by a new digital flow cytometer: Becton-Dickinson FACSAria™. Results: Membrane GPs were equally well represented in MPs generated by either reagent. In contrast, P-selectin was more intensely expressed in TRAP-MPs, while phosphatidylserine (PS) expression was markedly increased in ionophore-MPs. Two distinct populations of TRAP-MPs (one PS-positive and another PS-negative) were apparent. The latter characteristic facilitated sorting of MPs according to their PS exposure. Conclusions: The data presented herein show a significant improvement in the methodology applied until now to the characterization of MPs. The ability to characterize and sort MP subpopulations may help to resolve their contributions to normal and pathological functions. © 2007 International Society for Analytical Cytology
Vibrational population distributions in infrared multiple-photon excitation probed by coherent anti-stokes Raman spectroscopy

Coherent anti-stokes Raman spectroscopy has been used as a probe for molecules pumped by high-intensity CO2 laser radiation. Ozone, sulfur hexafluoride, and chloroethane have been investigated. The intensity of the ground-state CARS signal is decreased by IR multiphoton excitation, but signals at new vibrational origins do not appear. The observations on chloroethane are interpreted in terms of a rate-equation model for IRMPE, modified to take vibrational redistribution into account.
An area-efficient router for the Data-Intensive Architecture (DIVA) system

A key component of the Data-Intensive Architecture (DIVA) is the Processing-In-Memory (PIM) Routing Component (PiRC) that is responsible for efficient communication between PIM chips. This paper presents the design of a low area, delay and power router for DIVA. A 58.5% saving in area and 86% reduction in load on the clock as compared to an earlier PIM router design makes the presented design ideal for use in the second version of DIVA, with low area being a critical design requirement for DIVA. This paper also gives a comparison of the presented design with an earlier PIM router design in terms of delay and power to justify the new design choice.
Biological effects of heavy ions from the standpoint of target theory.

Abstract The biological effect of heavy ions is best described through the action cross section, as a function of the end-point of interest and the charge and speed of the ion. In tract theory this is called the “ion-kill” cross section, for it is the effect produced by a single heavy ion and its delta rays. As with nuclear emulsions the biological track structure passes from the grain count regime to the track width regime to the thindown region with an increase in LET. With biological cells, as with any detector capable of storing sub-lethal damage, with low LET irradiation the action cross section (in the ion-kill mode) is increasingly obscured by the effect of “gamma-kill”, by the influence of overlapping delta rays from neighboring heavy ions. Thus at low LET response is dominated by the gamma-kill mode, so that the RBE approaches 1. The theory requires 4 radiosensitivity parameters for biological detectors, extracted from survival curves at several high LET bombardments passing through the grain count regime, and at high doses. Once these are known the systematic response of biological detectors to all high LET bombardments can be unfolded separating ion kill from gamma kill, predicting the response to a mixed radiation environment, and predicting low dose response even at the level of a single heavy ion. Cell killing parameters are now available for a variety of cell lines. Newly added is a set of parameters for cell transformation.
T Cell-Deficiency Exacerbates Diacetyl-Induced Obliterative Bronchiolitis

Purpose RATIONALE: Obliterative bronchiolitis (OB) is the major graft-limiting complication after lung transplantation. OB also occurs in manufacturing workers exposed to compounds such as diacetyl (DA), an artificial butter flavoring. We recently established a novel OB model in rats using intratracheal instillation (ITI) of DA. Given the importance of adaptive immunity in post-transplant OB, we hypothesized that T cells are necessary for the development of DA-induced OB. Methods and Materials Athymic nude rats and wild-type (WT) Sprague Dawley controls received one ITI dose of DA (125mg/kg) and were euthanized 7 days later. Lung OB was semi-quantitatively graded in a blinded fashion. Lung cell suspensions were assessed for RNA transcripts and also analyzed by flow cytometry using antibodies against CD3, CD4, CD25, intracellular FOXP3, and neutrophils. Results Unexpectedly, DA-exposed nude rats had significantly more severe airway obliteration and an increased percentage of airways affected by OB, compared to DA-exposed controls ( Fig. 1 ). A significant reduction in overall T cells and CD4+CD25+FOXP3+ regulatory T cells (Tregs) was confirmed in nude rats vs. WT controls after DA exposure. Lungs of DA-treated nude rats further demonstrated increased neutrophils and upregulation of IL-8, a neutrophil chemoattractant, compared to WT. Conclusions T cell-deficiency leads to exacerbation of DA-induced OB in rats. A potential mechanism may involve decreased regulation by Tregs of IL-8 expression, with a resulting increase in neutrophilic inflammation. Given the limited small animal models that reflect OB pathology, further study of mechanisms that lead to DA-induced OB could be useful to understand basic mechanisms of disease pathogenesis.
Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport

Neutrophil elastase is a serine protease that is abundant in the airways of individuals with cystic fibrosis (CF), a genetic disease manifested by excessive airway Na+ absorption and consequent dep...
Covalent binding of a selective agonist irreversibly activates guinea pig coronary artery A2 adenosine receptors.

Experiments employing guinea pig heart Langendorff preparations compared the coronary vasoactivity of a functionalized congener of adenosine, 2-[(2-aminoethyl-aminocarbonylethyl)phenylethylamino]-5′-N-ethylcarboxamidoadenosine, APEC, with the vasoactivity of the product of the reaction of APEC with 1,4-phenylenediisothiocyanate, 4-isothiocyanatophenylaminothiocarbonyl-APEC (DITC-APEC). Previous experiments showed that whereas APEC binds reversibly to the A2A adenosine receptor of brain striatum, DITC-APEC binds irreversibly. APEC caused concentration-dependent coronary vasodilation that persisted unchanged when agonist administration continued for up to 165 min, but promptly faded when the agent was withdrawn. The unselective adenosine receptor antagonist 8-(4-sulfophenyl)theophyline (8-SPT) antagonized the vasoactivity of APEC. By contrast, DITC-APEC1 (0.125 -1.0 nM) caused progressive, concentration-independent vasodilation that persisted unchanged for as long as 120 min after the agent was stopped and that was insensitive to antagonism by subsequently applied 8-SPT. However, perfusion of the heart with buffer containing 0.1 mM 8-SPT strongly antagonized the coronary vasodilatory action of DITC-APEC1 given subsequently. Such observations indicate that the covalent binding of DITC-APEC1 causes irreversible activation of the guinea pig coronary artery A2A adenosine receptor. Neither APEC nor DITC-APEC appeared to desensitize the coronary adenosine receptor during two or more hours of exposure to either agonist.
Chronic chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose

To determine the effect of chronic sulfonylurea therapy on islet function in noninsulin-dependent diabetes mellitus (NIDDM), studies were performed in 18 untreated NIDDM patients before and after 12-16 weeks of chlorpropamide therapy. Fasting plasma glucose (FPG) fell with chlorpropamide therapy from 249 +/- 16 to 157 +/- 8 mg/dl (mean +/- SEM; P less than 0.001), and basal insulin increased from 17 +/- 2 to 24 +/- 3 microU/ml (P less than 0.001). The percent change in basal insulin correlated with the pretreatment FPG (r = 0.62; P less than 0.01) and inversely with the change in FPG during chlorpropamide (r = -0.57; P less than 0.025). Thus, patients with the highest pretreatment FPG showed the largest relative increase in basal insulin and the largest fall of FPG with chlorpropamide therapy. In nine patients, arginine-stimulated acute insulin responses (AIR) were studied at each of three plasma glucose (PG) levels both before and during chlorpropamide treatment. AIR at FPG was not different before and during treatment. However, when PG during treatment was matched by glucose infusion to the pretreatment FPG, the AIR was clearly increased during chlorpropamide therapy (176 +/- 65 vs. 49 +/- 11 microU/ml; P less than 0.02). When AIR is plotted against PG for each individual, the slope of the regression line generated (slope of glucose potentiation) is a measure of that patient's islet sensitivity to glucose. The logarithm of the slope of glucose potentiation correlated inversely with FPG (r = -0.92; P less than 0.001). Chlorpropamide treatment increased the slopes of potentiation from 0.26 +/- 0.11 to 1.47 +/- 0.70 (P less than 0.01). We conclude that chronic chlorpropamide therapy augments both basal and stimulated insulin secretion in NIDDM and that this may be an important mechanism of the drug's hypoglycemic effect. The data support the hypothesis that the hyperglycemia of NIDDM is related to islet insensitivity to glucose and that chlorpropamide treatment improves this impairment.
The role of alpha1-fetoprotein transcription factor/LRH-1 in bile acid biosynthesis : A known nuclear receptor activator that can act as a suppressor of bile acid biosynthesis

Two key regulatory enzymes in the bile acid biosynthesis pathway are cholesterol 7alpha-hydroxylase/CYP7A1 (7alpha-hydroxylase) and sterol 12alpha-hydroxylase/CYP8B1 (12alpha-hydroxylase). It has been shown previously that hepatocyte nuclear factor-4alpha (HNF-4) and the alpha(1)-fetoprotein transcription factor (FTF) are activators of 7alpha-and 12alpha-hydroxylase transcription and that the small heterodimer partner (SHP) suppresses bile acid biosynthesis by heterodimerizing with FTF. However, the role of FTF in bile acid biosynthesis has been studied only in tissue culture systems. In heterozygous FTF knockout mice, 7alpha- and 12alpha-hydroxylase genes were expressed at 5-7-fold higher levels than in wild-type mice, an apparent direct contradiction to previous in vitro observations. This higher expression of the 7alpha- and 12alpha-hydroxylase genes resulted in a 33% higher bile acid pool in their gallbladders, bile more enriched in cholic acid, and a 13% decrease in plasma cholesterol levels. Adenovirus-mediated FTF overexpression in wild-type mice resulted in 10-fold lower expression of the 7alpha- and 12alpha-hydroxylase genes and up to 8-fold higher SHP expression, highlighting the dual role that FTF plays in different promoters. Shorter overexpression times still resulted in lower 7alpha- and 12alpha-hydroxylase expression, but unchanged SHP expression, suggesting that two different mechanisms are involved in the FTF-mediated suppression of 7alpha- and 12alpha-hydroxylase expression. This FTF-mediated suppression of the expression of two bile acid biosynthesis genes resulted in a 3-fold lower rate of bile acid synthesis in a rat bile fistula animal model. Based on these observations and on protein binding studies performed in vitro and by chromatin immunoprecipitation, we hypothesize that FTF has two synergetic effects that contribute to its role in bile acid biosynthesis: 1) it has the ability to activate the expression of SHP, which in turn heterodimerizes and suppresses FTF transactivation activity; and 2) it occupies the FTF/HNF-4 recognition site within the 7alpha- and 12alpha-hydroxylase promoters, which can otherwise be occupied by a factor (HNF-4) that cannot be suppressed by SHP.
Phaeohyphomycosis in Transplant Patients

Phaeohyphomycosis is caused by a large, heterogenous group of darkly pigmented fungi. The presence of melanin in their cell walls is characteristic, and is likely an important virulence factor. These infections are being increasingly seen in a variety of clinical syndromes in both immunocompromised and normal individuals. Transplant patients are especially at risk due their prolonged immunosuppression. There are no specific diagnostic tests for these fungi, though the Fontana-Masson stain is relatively specific in tissue. They are generally seen in a worldwide distribution, though a few species are only found in specific geographic regions. Management of these infections is not standardized due to lack of clinical trials, though recommendations are available based on clinical experience from case reports and series and animal models. Superficial infections may be treated without systemic therapy. Central nervous system infections are unique in that they often affect otherwise normal individuals, and are difficult to treat. Disseminated infections carry a high mortality despite aggressive therapy, usually with multiple antifungal drugs. Considerable work is needed to determine optimal diagnostic and treatment strategies for these infections.
Ability of Lithium to Accelerate the Recovery of Granulopoiesis after Subacute Radiation Injury

Lithium stimulates granulopoietic recovery after mice are exposed to 2 Gy. By examining the hematopoietic inductive microenvironment (HIM) using the stromal colony assay, we demonstrate here that lithium, during the two weeks after irradiation, produced less stromal colony suppression than was observed from the irradiated controls. Recovery peaked by day 19 and returned to normal by day 28. This response was also observed in splenic derived stroma. Furthermore, stroma from lithium-irradiated animals supported the in vitro growth of granulocyte-macrophage colonies (CFU-GM) greater than observed from irradiated controls. These data suggest lithium accelerates granulopoietic recovery by first providing for a completely reconstituted and functional HIM.
The New Judicial Federalism: Where We are Now

This essay comments on the interesting Burger Court case of Pennhurst State School & Hospital v. Halderman. In that case, having construed the applicable federal statute as inapplicable, and after ten additional years of litigation required by the Court itself, the Court launched a simultaneous attack on ex parte Young, federal jurisdiction, forum selection options, and the Civil Rights Act. To carve these holes in national legislative and judicial powers, the Court, in effect, overruled the venerable Siler case, by Justice Peckham, the author of ex parte Young. Siler itself was an ex parte Young action. Thus the Court without good reason after a decade of litigation, left without recourse the continuing condition of suffering children in what the courts below characterized as "a snakepit."
The reactionπ+p→foΔ++ at 13.1 GeV/c

Data for the reactionπ+p→foΔ++ at 13.1 GeV/c is presented and discussed within a Reggeized pion exchange model with absorption.
Abnormalities of Cerebellar Structure and Function in Alcoholism and Other Substance Use Disorders

Substance use disorders (SUDs) are associated with cognitive and behavioral dysfunction as well as abnormalities of brain structure and function. Functional impairments associated with SUD may be partially explained by cerebellar dysfunction. Individuals with abuse of and/or dependence on alcohol, marijuana, stimulants, opioids, and tobacco have atypical cerebellar volume, differential patterns of cerebellar activation during cognitive tasks, and abnormal structural and functional connectivity between the cerebellum and other brain regions. Cerebellar abnormalities are associated with impaired executive function in individuals with drug and alcohol use disorders, as well as SUD duration, severity, and treatment outcomes. Interestingly, children and adolescents with a family history of SUD, who are at increased risk for drug and alcohol problems, also show structural and functional abnormalities of the cerebellum. Consequently, cerebellar dysfunction in individuals with SUD may reflect both premorbid risk factors for addiction and the neurotoxic consequences of drugs and alcohol on the brain.
A multi-channel thermally reconfigurable SiN spectral shaper

We demonstrate a 4-channel SiN spectral shaper capable of 2π-phase tuning and 30dB-amplitude control in each frequency channel. The phase tuning efficiency of 410mW/2π is measured using both optical intensity autocorrelation and RF beat notes.
Stance width and angle at sea: Effects of sea state and body orientation

BACKGROUND On land, the distance and angle between the feet in side-by-side stance tend to have characteristic values. Ship motion mandates changes in the control of stance, but there have been no direct assessments of how stance width and angle are controlled at sea. We predicted that participants would adopt a wider stance at sea. METHOD On two ships, we measured experienced crewmembers' stance width and stance angle during quiet stance when facing forward and when facing athwartship. Each ship was 84 m long and displaced 3500 tons. Measurements were repeated over consecutive days at sea. For one ship, we tested crew-members on land prior to the cruise. RESULTS On land, stance width (mean = 19.0 cm) and stance angle (mean = 16.19 degrees) were similar to previous reports. At sea, stance width tended to be greater than on land. When facing athwartship on Ship B, changes in stance width across days were correlated with changes in motion of the ship in its surge axis (r = 0.968). Stance angle at sea did not differ from stance angle on land. CONCLUSIONS The results suggest that preferred stance width is influenced by the fact of being at sea and by the sea state. These variations may be related to the efficiency of postural control on land and at sea. Future research should examine changes in stance width as novices acclimate to life at sea.
Quantum beats in crystalline tetracene delayed fluorescence due to triplet pair coherences produced by direct singlet fission.

A detailed analysis of the oscillations seen in the delayed fluorescence of crystalline tetracene is presented in order to study the mechanism of singlet fission. Three quantum beat frequencies of 1.06 ± 0.05, 1.82 ± 0.05, and 2.92 ± 0.06 GHz are resolved, which are damped on a time scale of 20 ns. The effects of sample morphology, excitation wavelength, and temperature are examined. A density matrix model for singlet fission is developed that quantitatively describes the frequencies, amplitudes, and damping of the oscillations. The model assumes a direct coupling of the initially excited singlet exciton to the triplet pair manifold. There is no electronic coherence between the singlet and triplet pair states, but the rapid singlet decay time of ∼200 ps in solution-grown single crystals provides the impulsive population transfer necessary to create a coherent superposition of three zero-field triplet pair states |xx⟩, |yy⟩, and |zz⟩ with overall singlet character. This superposition of the three states gi...
Abstract IA30: How cells survive: Single cell analysis reveals properties of non-genetic apoptosis resistance.

The mechanism of non-genetic resistance to TRAIL-induced apoptosis remains unresolved as the regulatory pathways involved are interconnected and complex. Single-cell mass cytometry was used to profile functional changes in regulatory factors while simultaneously monitoring apoptotic progression in TRAIL-treated cells. Cells resistant to TRAIL possessed diverse signaling states, however only cells within a subset of these states, termed “essential persisters” (EPs), were able to survive long-term and replicate. Constriction of the EP signaling states with kinase perturbagens decreased cell survival, however, the EPs occupied unique signaling states for each cell line tested. In order to overcome cell-type specific resistance, single peturbogen data was used to predict the effects of perturbagen combinations on survival. The level of EP signaling state constriction by a single perturbagen was a more robust predictor of combinatorial effects than extrapolating from single perturbogen cell survival data directly. These findings provide a population-level understanding of non-genetic resistance and explain the shortcoming of previous ‘bulk’ methods for identifying mechanisms of TRAIL-resistance. The use of signaling space constriction in persisters may guide design of therapies against non-genetic resistance in the future. Citation Format: Douglas R. Green. How cells survive: Single cell analysis reveals properties of non-genetic apoptosis resistance. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA30.
483 LIGAMENT ENGINEERING: THE RESPONSE OF BONE MARROW STROMAL CELLS TO HIGH-FREQUENCY STIMULATION AND UNIAXIAL STRETCH.

Rupture of the anterior cruciate ligament (ACL) is one of the most common ligament injuries of the knee. Current ACL surgical strategies consist of using a local autograft or allograft to replace the native ligament. Decreased range of motion and weakness has been commonly associated with autografts. Allografts are associated with immunogenic rejection and a lack of available donors. Previous studies have shown that human bone marrow stromal cells (BMSCs) can be stimulated toward a fibroblast-like lineage. Although the exact mechanism underlying differentiation in response to mechanical stimulation remains unclear, these cells hold a great potential for use in ACL engineering. The aim of this project was to determine the effects of mechanically stimulating BMSCs under controlled frequency during in vitro cultivation. Specifically, we wanted to determine the potential synergistic effects of high-frequency mechanical stimulation to “prime” BMSCs prior to low-frequency uniaxial stretch. A high-frequency 60 Hz stimulation system was developed and characterized. Microporous scaffolds were constructed from biodegradable polycaprolactone polymer. BMSCs were harvested from Lewis rats, expanded in culture, and seeded at 1 × 106 cells per scaffold. The seeded cells were then exposed to a 10-minute regiment of sine-shaped vibration (60 Hz) with a peak-to-peak acceleration of 1.8 ± 0.1 m/sec2 and a displacement amplitude of 67 ± 5 μm during a period of 7 days. The cells were then placed in a bioreactor cultivated for 7 days during which low-frequency (0.125 Hz) uniaxial strain (6%) was applied. Initial qRT-PCR data revealed that at 1 × 106 cell density, no up-regulation in gene expression was observed in stress-resistant biomarkers collagen I, collagen III, and tenascin C. Cell-seeding density was independently confirmed by cryosections stained with hematoxylin and eosin. Using higher cell density in this model system, future experiments will investigate the role of high-frequency stimulation independently and synergistically with other means of biomechanical stimulation.
Too Little Oxygen: Ventilation, Prone Positioning, and Extracorporeal Membrane Oxygenation for Severe Hypoxemia

Severe hypoxemia is associated with untoward outcomes in acute respiratory distress syndrome patients. Nevertheless, in and of itself, correction of hypoxemia is not an adequate surrogate outcome for mortality and clear evidence-based targets for correction of hypoxemia remain to be determined. At present, clinical management is directed toward achieving sufficient oxygenation while minimizing toxicity of ventilator-induced lung injury. The gold standard remains lung-protective mechanical ventilation, using lower-tidal volumes and pressure-limited ventilator titration. Notable progress in care includes further refinements in mechanical ventilation, consideration of salutatory effects of early prone positioning and neuromuscular blockade, and exploration of adjunctive extrapulmonary support with extracorporeal membrane oxygenation. This review focuses on three specific aspects: the evolving trend toward open lung ventilation, tempered by the recent cautionary experience with high-frequency oscillation ventilation; the evolution of prone positioning as a treatment for the most hypoxemic patients; and the continued future promise of extracorporeal support as a true rescue therapy.
Gravity's Rainbow, Operation Crossbow and the Culture of Containment

Since its publication in 1973, Gravity's Rainbow has attracted critics interested in the representation of film in Pynchon's third novel. The novel contains numerous allusions to actual films and film actors and a fictional film community directed by Gerhardt von Goll and starring Greta Erdmann and Max Schlepzig. In one of the novel's more memorable moments, Slothrop and Greta re-enact a scene from von Goll's masterpiece, Alpdrucken, which re-enactment dissolves into the experience Franz Pokier had of viewing Alpdrucken when it was first released. Pynchon shows a special interest in film and in the play between the real and the reel. For some readers, the closing scene in the Orpheus Theatre signifies that we have always been at the movies in Gravity's Rainbow. Nonetheless, most of the previous critical work on film in Gravity's Rainbow has focused primarily on the films alluded to and on their relation to the thematic arguments in the novel. In this essay, I explore a different cinematic path and suggest some ways Gravity's Rainbow relates to a film released during the time of its writing, the 1965 film Operation Crossbow.
Effects of dried sewage sludge on wheat cultivars in the southwestern United States

An experiment was conducted at Mesa, Arizona in 1981, 1982 and 1983 to compare the growth and grain yield of six wheat ( Triticum aestivum L.) cultivars when fertilized with dried sewage sludge and inorganic fertilizers from commercial sources. The soil type was a Laveen loam soil, which is a member of the coarse–loamy, mixed, hyperthermic Typic Calciorthids. At planting, in December of each year, three fertilizer treatments were applied: (1) recommended rates of nitrogen (N), phosphorus (P) and potassium (K) for wheat in Arizona; (2) 10 metric tonnes/ha of dried sewage sludge: and (3) inorganic fertilizers to provide N, P and K in amounts equal to those applied in the sewage sludge. Wheat cultivars grown with recommended rates of N, P and K from commercial fertilizer required a shorter period from planting to flowering, grew shorter plants and produced lower grain yields than did the same cultivars grown with sewage sludge in amounts necessary to provide the recommended amount of N, with no additional commercial fertilizer. Wheat grain from all fertilizer treatments contained very low concentrations of cadmium, zinc, copper, lead and nickel; however, grain grown with sewage sludge contained more zinc, lead and nickel than did grain produced with conventional culture. Cultivars differed in number of days from planting to flowering, plant height, lodging, number of heads per unit area, number of seeds per head, seed weight and grain yield, within each fertilizer treatment. Future wheat breeders should be able to develop new cultivars that can utilize the plant nutrients in dried municipal sewage sludge more effectively than present cultivars in the southwestern United States and in similar environments throughout the world.
Abstract WP431: Acute Stroke in Right Anterior Insula and Frontal Operculum Impair Empathy

Introduction: Emotional empathy includes emotional contagion (sharing another’s feelings) and perspective-taking (inferring another’s feelings). Earlier studies show that right hemisphere stroke (R...
Uncertainty in perceptual representations

How are perceptual decisions made? The answer to this seemingly simple question necessitates that we specify the nature of perceptual representations on which decisions are based. Some traditional models postulate that the perceptual representation consists of a simple point estimate of the stimulus. Such models do not allow the estimation of sensory uncertainty. On the other hand, recent models have proposed that the perceptual representation involves a full probability distribution over the possible stimulus values. Such models allow a precise estimation of sensory uncertainty. These two possibilities -- point estimates vs. full distributions -- are often seen as the only alternatives but they are not. Here I present five possible perceptual representation schemes that allow the extraction of different levels of sensory uncertainty. I explain where popular models fall within the five schemes and explore the relevant empirical evidence and theoretical arguments. The overwhelming evidence is at odds with both point estimates vs. full distributions. This conclusion is in stark contrast with current popular models in computational neuroscience built on such distributions. Instead, the most likely scheme appears to be one in which the perceptual representation features a point estimate coupled with a strength-of-evidence value.