cssi/SciSciGPT-SciSciNet huggingface dataset:
Is vision continuous with cognition? The case for cognitive impenetrability of visual perception

Although the study of visual perception has made more progress in the past 40 years than any other area of cognitive science, there remain major disagreements as to how closely vision is tied to cognition. This target article sets out some of the arguments for both sides (arguments from computer vision, neuroscience, psychophysics, perceptual learning, and other areas of vision science) and defends the position that an important part of visual perception, corresponding to what some people have called early vision, is prohibited from accessing relevant expectations, knowledge, and utilities in determining the function it computes - in other words, it is cognitively im- penetrable. That part of vision is complex and involves top-down interactions that are internal to the early vision system. Its function is to provide a structured representation of the 3-D surfaces of objects sufficient to serve as an index into memory, with somewhat differ- ent outputs being made available to other systems such as those dealing with motor control. The paper also addresses certain concep- tual and methodological issues raised by this claim, such as whether signal detection theory and event-related potentials can be used to assess cognitive penetration of vision. A distinction is made among several stages in visual processing, including, in addition to the inflexible early-vision stage, a pre-per- ceptual attention-allocation stage and a post-perceptual evaluation, selection, and inference stage, which accesses long-term memory. These two stages provide the primary ways in which cognition can affect the outcome of visual perception. The paper discusses argu- ments from computer vision and psychology showing that vision is "intelligent" and involves elements of "problem solving." The cases of apparently intelligent interpretation sometimes cited in support of this claim do not show cognitive penetration; rather, they show that certain natural constraints on interpretation, concerned primarily with optical and geometrical properties of the world, have been com- piled into the visual system. The paper also examines a number of examples where instructions and "hints" are alleged to affect what is seen. In each case it is concluded that the evidence is more readily assimilated to the view that when cognitive effects are found, they have a locus outside early vision, in such processes as the allocation of focal attention and the identification of the stimulus.
Medicare readmission rates showed meaningful decline in 2012

Objective Descriptive analysis of 30-day, all-cause hospital readmission rate patterns from 2007-2012. Population Medicare FFS beneficiaries experiencing at least one acute inpatient hospital stay. Methods Using Chronic Condition Data Warehouse claims, we estimate unadjusted, monthly, readmission rates for the nation, within the Dartmouth Hospital Referral Regions (HRR), and compare participating and non-participating hospitals in the Partnership for Patients (P4P) program (overall and by number of inpatient beds at each facility). Results From 2007 through 2011, the national 30-day, all-cause, hospital readmission rate averaged 19 percent. During calendar year 2012, the readmission rate averaged 18.4 percent. Of the 306 HRRs, rates in 166 HRRs fell by between 1 and 5 percent, while rates dropped by more than 5 percent in 73 HRRs, with the largest reduction in Longview, Texas. Rates increased by more than 1 percent in only 30 HRRs, with the largest increase in Bloomington, Illinois. Readmission rates at hospitals participating in the P4P program have been, on average, consistently lower than the rates at non-participating hospitals within all size categories except for the very smallest and largest hospitals, but rates at both participant and non-participant hospitals fell in 2012. Discussion Although claims data are not yet final for 2012, our analysis indicates that hospital readmission rates for all Medicare FFS beneficiaries dropped noticeably during the year. The reasons behind the apparent reduction are not yet clear and merit further investigation.
Coordination strategies for multi-robot exploration and mapping

Situational awareness in rescue operations can be provided by teams of autonomous mobile robots. Human operators are required to teleoperate the current generation of mobile robots for such applications; however, teleoperation is increasingly difficult as the number of robots is expanded. As the number of robots is increased, each robot may also interfere with one another and eventually decrease mapping performance. As presented here, through careful consideration of robot team coordination and exploration strategy, large numbers of mobile robots can be allocated to accomplish the mapping task more quickly and accurately. We present both the coordination and exploration strategies and present results from experiments in simulation as well as with up to nine mobile platforms.
The pharmacology of calcium channel blockers

Ca2+-Antagonisten sind eine chemisch und pharmakologisch sehr divergente Wirkstoffklasse. Die hauptsachlich therapierelevanten 1, 4-Dihydropyridine, Phenykalkylamine und Benzothiazepine binden an drei unterschiedlichen Bindungsorten an der die Kanalpore bildenden α1c-Untereinheit des Typ-L-Ca2+-Kanals. Die Interaktionen mit dem Ca2+-Kanal sind gut charakterisiert. Die Stoffklassen unterscheiden sich in ihrer Gewebespezifitat und damit in ihrer Wirkcharakteristik: 1, 4-Dihydropyridine sind vornehmlich peripher vasodilatierend, die Vertreter der beiden anderen haben eine starkere kardiodepressive Wirkung. Die groste Wirkstoffgruppe, die 1, 4-Dihydropyridine, finden die breiteste Anwendung in der Behandlung des Bluthochdrucks. Verapamil wird vor allem fur die Therapie der supraventrikularen Arrhythmien eingesetzt. Weitere Einsatzgebiete sind die Behandlung der stabilen Angina pectoris und subarachnoidale Blutungen (nur Nimodipin).
Causality and Subjectivity in the Religious Quest

The dynamics of seeking causation and the dynamics of subjectivity are presented and then brought together in a consideration of the three core components of the religious quest: the search for and experience of ultimate explanations, the interiority of religious experience (“spirituality”), and the empathic experience of religious fellowship.
Efficient algorithm for the computation of on-chip capacitance sensitivities with respect to a large set of parameters

Recent CAD methodologies of design-for-manufacturability (DFM) have naturally led to a significant increase in the number of process and layout parameters that have to be taken into account in design-rule checking. Methodological consistency requires that a similar number of parameters be taken into account during layout parasitic extraction. Because of the inherent variability of these parameters, the issue of efficiently extracting deterministic parasitic sensitivities with respect to such a large number of parameters must be addressed. In this paper, we tackle this very issue in the context of capacitance sensitivity extraction. In particular, we show how the adjoint sensitivity method can be efficiently integrated within a finite-difference (FD) scheme to compute the sensitivity of the capacitance with respect to a large set of BEOL parameters. If np is the number of parameters, the speedup of the adjoint method is shown to be a factor of np/2 with respect to direct FD sensitivity techniques. The proposed method has been implemented and verified on a 65 nm BEOL cross section having 10 metal layers and a total number of 59 parameters. Because of its speed, the method can be advantageously used to prune out of the CAD flow those BEOL parameters that yield a capacitance sensitivity less than a given threshold.
A sociable robotic aide for medication adherence

In the United States, approximately 125,000 people die each year due to complications related to medication adherence, which costs the country approximately $100 - $300 billion dollars annually. The problem of medication adherence stems largely from people either having too many medications, causing confusion and making management harder, or taking larger dosages than prescribed. We propose a solution for improving medication adherence using a physically embodied social robot as a motivating factor. In particular, the robot's interaction will be similar to that of a digital pet game, except users will care for the pet by caring for themselves (i.e., taking their medication.) The robot will also leverage social-network support factors to promote the emotional and positive affective behaviors of patients.
Quantitative trait loci analysis of human event-related brain potentials: P3 voltage

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.
Examining the Impact of Integrating Physical Activity on Fluid Intelligence and Academic Performance in an Elementary School Setting: A Preliminary Investigation

Purpose:To examine the impact of integrating physical activity with elementary curricula on fluid intelligence and academic achievement. Methods:A random sample of 3rd grade teachers integrated physical activity into their core curricula approximately 30 minutes a day, 3 days a week from January 2008 to April 2008. Noninvasive fluid intelligence cognitive measures were used along with State-mandated academic achievement tests. Results:Experimental Group children averaged close to 1200 pedometer steps per integration day, thus averaging 3600 steps per week. Children in the Experimental Group performed significantly better on the SPM Fluid Intelligence Test. Children in the Experimental Group also performed significantly better on the Social Studies State mandated academic achievement test. Experimental Group children also received higher scores on the English/Language Arts, Math and Science achievements tests, but were not statistically significant compared with Control Group children. Children classified ...
An array-compensated spherical reflector antenna for a very large number of scanned beams

There are many stringent demands imposed on the applications of spaceborne antenna systems. One of the most challenging demands is the generation of multiple beams with the ability to scan a very large number of beamwidths. Since the parabolic reflectors have limitations in this application, a 35-m spherical reflector antenna is proposed for a geostationary radar antenna at Ka-band (35.6 GHz) due to its inherent capability of scanning the beams to very large number of beamwidths. The utility of using planar array feeds for correcting spherical phase aberrations is investigated to overcome the performance degradation effects. Two different methodologies are developed for the array excitation coefficients determination based on phase conjugate matching and the results are compared. Using the compensating feed array, the radiation characteristics of the compensated spherical reflector are simulated for no scan and large scan cases and the results are compared with the uncompensated case to show performance improvement. In order to demonstrate the technological readiness of the concept a 1.5-m breadboard model is designed to be built for experimental measurements. Some important mechanical design tolerances and realistic array feed topologies are investigated. The antenna concept developed in this paper is advocated to be used in the next generation of geostationary satellite antenna systems for remote sensing radar applications.
External Cooling in the Management of Fever

Although physical methods of cooling are the treatment of choice for hyperthermia, their value in the treatment of fever remains uncertain. Methods involving convection and evaporation are more effective than those involving conduction for the treatment of hyperthermia. These same methods, combined with antipyretic medication, are preferable to immersion as treatment for fever in young children but are generally not practical in adults. Febrile children treated with tepid-water sponging plus antipyretic drugs are more uncomfortable that those treated with antipyretic drugs alone, although they exhibit slightly more rapid reductions in temperature. When febrile, seriously ill patients are externally cooled and are sedated or paralyzed with drugs that suppress shivering, they may have a more rapid reduction of fever and reduced energy expenditure than if treated with antipyretic drugs alone. A risk/benefit assessment of the consequences of such treatment is not yet possible.
An algebraic approach to line-drawing analysis in the presence of uncertainty

Following the work of K. Sugihara (1984), the authors represent the geometric constraints imposed by the line-drawing of a polyhedron as a set of linear equalities and inequalities. They, however, explicitly take into account the uncertainty in the vertex position. This allows the circumvention of the superstrictness of the constraints without deleting any constraints. For a given error bound, the condition whether a line-drawing is the correct projection of a polyhedron is reduced to linear programing, and the 3D shape recovery is reduced to optimization under linear constraints. The approach has been implemented, and examples are presented. >
Optimal bus sequencing for escape routing in dense PCBs

The PCB routing problem has become so difficult that no commercial CAD software can provide an automatic solution for high-end boards. Existing algorithms for escape routing, an important step in PCB routing, are net-centric. Directly applying these algorithms will result in mixing nets of different buses together. But in practice, it is preferred to bundle together nets in a bus. Thus the bus-centric escape routing problem can be naturally divided into two subproblems: (1) finding a subset of buses that can be routed on the same layer without net mixings and crossings, which we refer to as the bus sequencing problem, and (2) finding the escape routing solutions for each chosen bus, which can be solved by a net-centric escape router. In this paper, we solve the bus sequencing problem. We introduce a new optimization problem called the longest common interval Sequence (LCIS) problem and model the bus sequencing problem as an LCIS problem. By using dynamic programming and balanced search tree data structure, we present an LCIS algorithm which can find an optimal solution in O(n log n) time. We also show that O(n log n) is a lower-bound for this problem and thus the time complexity of our algorithm is also the best possible.
Capital income taxation in growing open economies

Abstract This paper studies how alternative capital mobility assumptions affect the incidence and efficiency of capital income taxation. The study uses a two-country intertemporal equilibrium model in which imperfectly elastic investment captures the notion of imperfectly mobile physical capital. If home goods and foreign goods are perfect substitutes and investment is inelastic, the tax effects in open and closed economies are similar. Only if physical capital is perfectly mobile are capital income taxes completely shifted in small open economies. Only then, and if significant terms of trade effects are absent, do open economy efficiency losses substantially exceed the closed economy losses.
Can mature patch constraints mitigate the fragmenting effects of harvest opening size restrictions

Growing timber is not the primary management objective for many landowners. For example, the national forests must be managed to maintain the populations of all native and desired nonnative plants, fish, and wildlife under the National Forest Management Act. Similarly, only a small percentage of private landowners own land primarily for income generation from timber production (Birch 1996). As the emphasis on ecosystem management goals increases, harvest scheduling models must be modified to incorporate new objectives. When forest ecologists discuss ecosystem management, they are interested in things such as age distribution, patch size distribution, the amount of edge, the amount of interior forest, and the connectivity of the forest (Hunter 1990). With the exception of age distribution, these things are difficult to model directly in a mixed-integer harvest scheduling model. Models have been developed that incorporate a variety of spatial factors such as wildlife dispersal and amount of edge (Hof and Bevers 1998), maximum harvest opening size (Thompson et al. 1973, McDill et al. in press, Barrett et al. 1998, Borges and Hoganson 2000), and minimum habitat patch size constraints (Bettinger et al. 1997 and 2000, Hof and Joyce 1992, Sessions et al. 2000), which require large patches of mature forest to be present at all times. Often, incorporating these factors results in complex models that are difficult to solve to optimality. However, methods for modeling two factors in a spatially-explicit, mixed-integer harvest scheduling model – maximum harvest opening size and minimum patch size – have been proposed that can give optimal solutions to small problems (McDill et al. (in press), Rebain and McDill (in review)). This paper considers how controlling these two factors indirectly affects factors that are not directly controlled, including the age distribution, patch size distribution, and the amount of edge of a forest. The general model used in the study was a mixed-integer harvest scheduling model, with maximizing net present value as the objective. The planning horizon is 60 years, consisting of three 20-year periods. Four possible prescriptions were considered for each stand—harvest in period 1, 2, or 3, or not harvested at all. Flow constraints limit fluctuations in the harvest level from period to period, and ending age constraints are imposed to ensure that a desirable forest will be left at the end of the planning horizon. The yield and economic information used in the model is loosely based on a Pennsylvania oak forest. Ten variants on this general model were developed. One version of the model includes no maximum harvest opening limit and no patch requirements. The remaining nine variants include maximum harvest opening constraints and, in some cases, habitat patch size
Do fairness and equity matter?: An examination of organizational justice among correctional officers in adult prisons.

The concepts of justice and fairness are commonly examined in the literature on criminal justice, except for the issues affecting organizational justice in the workplace. Organizational justice has...
Technical communique: Robust adaptive control for nonlinear uncertain systems

A direct robust adaptive control framework for nonlinear uncertain systems with constant linearly parameterized uncertainty and nonlinear state-dependent uncertainty is developed. The proposed framework is Lyapunov-based and guarantees partial asymptotic robust stability of the closed-loop system; that is, asymptotic robust stability with respect to part of the closed-loop system states associated with the plant. Finally, a numerical example is provided to demonstrate the efficacy of the proposed approach.
Natural resolution of alcohol-related problems.

The diverse research discussed here, ranging from surveys to RCTs to process-oriented naturalistic studies, converged to raise previously overlooked research questions about relations between patterns of help-seeking and drinking problem resolutions. Contrary to conventional views, treatment is neither a necessary nor a sufficient condition for resolution, which can occur through a number of pathways and is influenced by extratherapeutic contextual variables. Further research on the variable course of resolutions, the surrounding contexts, and relations with help-seeking holds promise for informing the development of a range of interventions for drinking problems across the continuum of severity and for increasing their appeal.
Temporally-Stiffening Hydrogel Regulates Cardiac Differentiation via Mechanosensitive Signaling

Stiffness of the extracellular matrix (ECM) surrounding cells plays an integral role in affecting how a cell spreads, migrates, and differentiates, in the case of stem cells. For mature cardiomyocytes, stiffness regulates myofibril striation, beating rate, and fiber alignment, but does not induce de-differentiation [1,2]. Despite improved myocyte function on materials which mimic the ∼10 kPa heart stiffness, the heart does not begin as a contractile ∼10 kPa material, but instead undergoes ∼10-fold myocardial stiffening during development [3]. Thiolated hyaluronic acid (HA) hydrogels have been used to mimic these stiffening dynamics by varying hydrogel functionality and component parameters. Recently, we have shown that pre-cardiac mesodermal cells plated on top of these stiffening HA hydrogels improves cardiomyocyte maturation compared to static, compliant polyacrylamide (PA) hydrogels [3]. While active mechanosensing causes maturation, the specific mechanisms responsible for responding to time-dependent stiffness remain unknown. Here we examined protein kinase signaling and mechanics in response to dynamic vs. static stiffness during the commitment process from embryonic stem cells (ESCs) through cardiomyocytes to better understand how developmentally-appropriate temporal changes in stiffness regulate cell commitment.Copyright © 2013 by ASME
Benefits of Hybrid-Electric Propulsion to Achieve 4x Cruise Efficiency for a VTOL UAV

Electric propulsion enables radical new vehicle concepts, particularly for Vertical Takeoff and Landing (VTOL) aircraft because of their significant mismatch between takeoff and cruise power conditions. However, electric propulsion does not merely provide the ability to normalize the power required across the phases of flight, in the way that automobiles also use hybrid electric technologies. The ability to distribute the thrust across the airframe, without mechanical complexity and with a scale-free propulsion system, is a new degree of freedom for aircraft designers. Electric propulsion is scale-free in terms of being able to achieve highly similar levels of motor power to weight and efficiency across a dramatic scaling range. Applying these combined principles of electric propulsion across a VTOL aircraft permits an improvement in aerodynamic efficiency that is approximately four times the state of the art of conventional helicopter configurations. Helicopters typically achieve a lift to drag ratio (L/D) of between 4 and 5, while the VTOL aircraft designed and developed in this research were designed to achieve an L/D of approximately 20. Fundamentally, the ability to eliminate the problem of advancing and retreating rotor blades is shown, without resorting to unacceptable prior solutions such as tail-sitters. This combination of concept and technology also enables a four times increase in range and endurance while maintaining the full VTOL and hover capability provided by a helicopter. Also important is the ability to achieve low disc-loading for low ground impingement velocities, low noise and hover power minimization (thus reducing energy consumption in VTOL phases). This combination of low noise and electric propulsion (i.e. zero emissions) will produce a much more community-friendly class of vehicles. This research provides a review of the concept brainstorming, configuration aerodynamic and mission analysis, as well as subscale prototype construction and flight testing that verifies transition flight control. A final down-selected vehicle is also presented.
Feeding Response of the Green Peach Aphid (Homoptera: Aphididae) to Potato Glandular Trichomes

Green peach aphid, Myzus persicae (Sulzer), feeding behavior on the resistant potato species Solanum berthaultii Hawkes is characterized by a delay in probing, probes of shorter duration, and a decrease in total feeding time compared with the susceptible S. tuberosum cultivar ‘Hudson,’ The causal factor is associated with type B glandular trichomes. Removal of type B droplets resulted in a decrease in preprobe time compared with that on intact S. berthraultii leaves. Foliage of an F3 inter specific hybrid lacking type B trichomes did not deter feeding, Transfer of type B exudate to leaves of cv. Hudson produced a delay in probing compared with untreated leaves. The deterrence of type B exudate may reduce vector efficiency of the green peach aphid by delaying probing beyond the retention period of nonpersistent viruses such as potato virus y.
Mean flow generation in a rotating homogeneous flow

The mean flow generated by an oscillatory (tidal) current normal to a long ridge of constant cross-section and finite height in a rotating homogeneous fluid is investigated analytically and by laboratory experiments. The geometry is characterized by constant fluid depths hs and hj in the shallow (shelf) and deep regions, respectively, with the sloping region between being smooth and having a characteristic width L. This physical system is characterized by the temporal Rossby number Rot = co/f, the Ekman number E, the geometric parameters hs/hd and hs/L and the normalized tidal excursion as/L (or, alternatively, the Rossby number); here CO is the forcing frequency of the oscillatory current, f the Coriolis parameter and as the characteristic tidal excursion. The analysis assumes Ro t~O(l), E « 1, hs/L«O(l), hs / h(j ~ O(l) (i.e., finite amplitude topography) and as / L ~ O(l) (i.e., finite amplitude tidal excursions). The analysis is based upon a spectral method' and predicts mean flows along the depth contours of the topography with the shallow region on the right, facing downstream, for verticallyupward, or Northern Hemisphere, rotation. The theoretical approaches used by other investigators using different frictional parameterizations for infinitesimal tidal excursions are also presented. The laboratory experiments were conducted in a 1.8 m diameter circular rotating test cell in which a continuous annular topography of constant crosssection was installed along the tank periphery. The various theories were in qualitative support of the laboratory observations with respect to (i) mean flow direction, (ii) location of most intense currents and (iii) dependence on the principal system parameters. Predictions from the various theories give reasonable estimates of mean Lagrangian displacements
THE VALUE OF N.TERMINAL PRO.BRAIN NATRIURETIC PEPTIDE AFTER LVAD IMPLANTATION

NT-pro-BNP is a well-studied biomarker in patients with heart failure not requiring mechanical circulatory support. The propose of the study is to assess the changes in NT-pro-BNP after LVAD implantation. We conducted a retrospective study of patients who had LVAD implantation at the University of
Split Flywheel Design with Attitude Jitter Minimization Through Flywheel Phase Control

Attitude jitter in satellites has degrading effects on the performance of onboard sensors and communication instruments. The effect of jitter is more pronounced in small satellites due to their low inertia and has to be minimized to be able to use instruments that require directional stability. The source of jitter is primarily due to rotational imbalance in devices like reaction wheels, gyroscopes and motors. This paper discusses a novel method of reducing the amplitude of jitter using a split flywheel design and also adds redundancy to the system. The feasibility of this technique is explored in this paper by analyzing the dynamics of the split flywheel, a probable control approach and considering a typical design of the system.
Influence on Decentralized Water Supplying in Rural Area ofDujiangyan Within One Week After 5.12 Earthquake

Objective To explore the influence on drinking-water in rural area of Dujiangyan city and provide reference for establishing safe assessment of the drinking water at emergency by analyzing relevant data before and after 5.12 Earthquake.Methods Randomized samples of decentralized drinking water were collected from rural areas of Dujiangyan city,and were determined concerning certain emergency indexes with a comparison of before and after the Quake.Results The qualified rate of the drinking water monitored after earthquake was statistically equivalent of that of before earthquake(χ2=3.62,P0.05)excluding the disinfectant residual;while the rate of single standard turbidity before earthquake was higher than that of after(χ2=16.61,P0.05).Conclusion The influence of earthquake on the drinking-water of rural area are mainly turbidity,smell and taste,which indicate that the color,turbidity,smell and taste should be screened at first in emergency,and then decided whether monitored at site or in laboratory.
Presbytis m. melalophus (Brown langur)

Two male and two female animals from Indonesia, presumably Western Sumatra, at San Diego Zoo were studied with skin biopsies, stock is frozen. The karyotype of the female is prepared with the ASG technique. A characteristic secondary constriction is found in one autosomal submetacentric, here placed as the last autosome.
Toward an Integrative Theory of Religious Conversion: A Review Essay of The Oxford Handbook of Religious Conversion by Lewis R. Rambo and Charles F. Farhadian (2014)

This paper, a review essay of The Oxford Handbook of Religious Conversion (2014), first summarizes some of its social scientific chapters and then attempts to begin building an integrative theory of religious conversion. This theory is based upon a critical realist perspective and draws on Paloutzian’s multi-level interdisciplinary paradigm of conversion research, recent developments in the cultural sociology of religion, and the language of conversion, and it could be extended to integrate additional levels. The paper ends with a brief discussion of human flourishing and the possible role of conversion in it.
Multiple lines of evidence for performance of the canister and waste form in long-term nuclear waste disposal: Reviews

Abstract The time scales required for nuclear waste disposal are very large compared with those for other engineering endeavors. Because of this, there are many uncertainties associated with the quantitative performance assessment of canisters containing high-level radioactive waste in a waste form. Multiple lines of evidence can be helpful in building confidence in the long-term behavior (corrosion and dissolution) of the canister and waste form. These lines of evidence are derived from long-term supports and probabilistic models and developed based on shorter term tests, bounding and conservative approaches, and available observations on natural analogs. This paper presents the progress made for important lines of evidence considered in quantitatively assessing radionuclide release behavior from canisters and waste forms. This paper considers risk-significant issues for canisters and waste forms (i.e., risk informed approach) in the probabilistic performance assessment of the disposal system which has also other components such as geology and hydrology.
'Pickle or a cucumber?' administrator and practitioner views of successful adolescent recovery.

Introduction: Adolescent substance use disorders often involve a recurring cycle of treatment and relapse. The academic and practical definition of addition recovery for adults has been debated; ye...
Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression

// Hang Gyeong Chin 1, 2 , V.K. Chaithanya Ponnaluri 1 , Guoqiang Zhang 1 , Pierre-Olivier Esteve 1 , Scott E. Schaus 3 , Ulla Hansen 2, 4 , Sriharsa Pradhan 1 1 New England Biolabs, Inc. Ipswich, MA 01938, USA 2 MCBB Graduate Program, Boston University, Boston, MA 02215, USA 3 Deptartment of Chemistry, Center for Molecular Discovery, Boston University, Boston, MA 02215, USA 4 Department of Biology, Boston University, Boston, MA 02215, USA Correspondence to: Ulla Hansen, email: uhansen@bu.edu Sriharsa Pradhan, email: pradhan@neb.com Keywords: DNA methylation, transcription factor LSF, gene expression, HCC Received: August 04, 2016 Accepted: October 13, 2016 Published: November 10, 2016 ABSTRACT The transcription factor LSF is highly expressed in hepatocellular carcinoma (HCC) and promotes oncogenesis. Factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity and exerts anti-proliferative activity. Here, we show that LSF binds directly to the maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1) and its accessory protein UHRF1 both in vivo and in vitro . Binding of LSF to DNMT1 stimulated DNMT1 activity and FQI1 negated the methyltransferase activation. Addition of FQI1 to the cell culture disrupted LSF bound DNMT1 and UHRF1 complexes, resulting in global aberrant CpG methylation. Differentially methylated regions (DMR) containing at least 3 CpGs, were significantly altered by FQI1 compared to control cells. The DMRs were mostly concentrated in CpG islands, proximal to transcription start sites, and in introns and known genes. These DMRs represented both hypo and hypermethylation, correlating with altered gene expression. FQI1 treatment elicits a cascade of effects promoting altered cell cycle progression. These findings demonstrate a novel mechanism of FQI1 mediated alteration of the epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression.
Ascorbic Acid Catalyzes Nitric Oxide Production from Nitrite Ions.

We have previously shown that nitrite ions can be reduced by hemoglobin to nitric oxide (NO), a ubiquitous signaling molecule and potent vasodilator. Nitrite serves as a stable tissue and vascular source for NO production; the reduction reaction is maximal at about 50% oxygen saturation values and is enhanced at low pH but little is known about other effectors of this reaction. In the current work, we studied the effect of ascorbic acid on nitrite reduction under physiological conditions using chemiluminescence to quantify NO production. In physiological buffer, this reaction has a rate constant of about 1×10−5 M−1.s−1. Thus, a significant production of NO would likely occur in plasma only at pharmacological levels of ascorbic acid (> 1 mM) although lowering pH below 7.0 markedly enhances this reaction. Loading human erythrocytes with 0.5 mM dehydroascorbic acid, which is in redox equilibrium with ascorbic acid and which can significantly raise intracellular ascorbic acid levels, increased basal levels of nitrite ions from 42±9.0 nM to 98±56 nM. Uptake of nitrite ions into erythrocytes by incubation in 10 μM nitrite was increased about 1.5 fold by dehydroascorbic acid and the half-time of nitrite loss was slowed to the same extent. Ascorbic acid also reduced free ferric heme in erythrocytes and plasma to ferrous heme which catalyzed the reduction of nitrite to NO with a rate constant of 2.3×103 M−1.s−1 under physiological conditions. However, free ferrous ions did not significantly produce NO in physiological buffer (rate constant = 1.8×10−2 M−1.s−1). The reaction of ferrous heme with nitrite was not affected by heme binding to proteins such as hemopexin and albumin, or erythrocyte membranes. These results suggest that physiological levels of ascorbic acid (20–80 μM in plasma and erythrocytes) may act to catalyze NO production in the blood by promoting the reduction of nitrite ions by free ferrous heme and by increasing intra-erythrocytic levels of nitrite ions which can be reduced to NO by deoxyhemoglobin.
What Arnold Gesell Would Advocate Today

The first issue of Childhood Education, published in 1924, included an article by the eminent physician, Arnold Gesell. In the article, “The Significance of the Nursery School” (reprinted on pp. 19...
Multi-energy CT decomposition using convolutional neural networks

Spectral CT can provide accurate tissue composition measurements by utilizing the energy dependence of x-ray attenuation in different materials. We have introduced image reconstruction and material decomposition algorithms for multi-energy CT data acquired either with energy integrating detectors (EID) or photon counting detectors (PCD); however, material decomposition is an ill-posed problem due to the potential overlap of spectral measurements and to noise. Recently, convolutional neural networks (CNN) have generated excitement in the field of machine learning and computer vision. The goal of this work is to develop CNN-based methods for material decomposition in spectral CT. The CNN for decomposition had a U-net structure and was trained with either five-energy PCD-CT or DE-CT. As targets for training, we used simulated phantoms constructed from random combinations of water and contrast agents (iodine, barium, and calcium for five-energy PCD-CT; iodine and gold for DE EID-based CT). The experimentally measured sensitivity matrix values for iodine, barium, and calcium or iodine and gold were used to recreate the CT images corresponding to both PCD and DE-CT cases. These CT images were used to train CNNs to generate material maps at each pixel location. After training, we tested the CNNs by applying them to experimentally acquired DE-EID and PCD-based micro-CT data in mice. The predicted material maps were compared to the absolute truth in simulations and to sensitivity-based decompositions for the in vivo mouse data. The CNN-based decomposition provided higher accuracy and lower noise. In conclusion, our U-net performed a more robust spectral micro-CT decomposition because it inherently better exploits spatial and spectral correlations.
Advancement of analytical modes in a multichannel, microfluidic droplet-based sample chopper employing phase-locked detection.

In this work, we expand upon our recently developed droplet-based sample chopping concepts by introducing a multiplexed fluidic micro-chopper device (μChopper). Six aqueous input channels were integrated with a single oil input, and each of these seven channels was controlled by a pneumatic valve for automated sampling through software control. This improved design, while maintaining high precision in valve-based droplet generation at bandwidths of 0.03 to 0.05 Hz, enabled a variety of analytical modes to be employed on-chip compared to previous devices limited to sample/reference alternations. The device was analytically validated for real-time, continuous calibration with a single sample and five standards; multiplexed analysis during calibration using a mixed mode; and standard addition through spiking of six sample droplets with varying amounts of standard. Finally, the standard addition mode was applied to protein quantification in human serum samples using on-chip, homogeneous fluorescence immunoassays. Ultimately, with only ∼1.2 μL of total analyzed solution volume—representing 100-fold and 75-fold reductions in reagent and serum volumes, respectively—we were able to generate full, six-point standard addition curves in only 1.5 min, and results correlated well with those from standard plate-reader equipment. This work thus exploited microfluidic valves for both their automation and droplet phase-locking capabilities, resulting in a micro-analytical tool capable of complex analytical interrogation modes on sub-microliter sample volumes while also leveraging drastic noise rejection via lock-in detection. The multichannel μChopper device should prove particularly useful in analyzing precious biological samples or for dynamic analyses at small volume scales.
The Effectiveness of Sex Therapy: A Review of the Literature

Sex therapy has never been a part of the mainstream of academic psychiatry and psychology. Rather, most sex therapists have been practicing clinicians with only tangential interest (or competence) in psychotherapy outcome research. In this chapter, an extremely thorough review of the clinical literature on sex therapy, Douglas Hogan offers a critique of the methodological problems inherent in much of the published literature. By closely examining this literature, the author identifies some consistent findings on both etiology and treatment that seem, therefore, to be firmly established. This article provides a framework against which many of the clinical chapters in later parts of this book can be better evaluated and understood.
Surgery on Patients on Antiplatelet Agents

Coronary artery stenting is becoming the most common procedure for coronary revascularization and requires long-term dual antiplatelet therapy (DAPT) to prevent acute stent thrombosis. Stent type (bare metal or drug eluting) will ultimately determine the duration of DAPT. However, at least 12 months of DAPT is the gold standard for most stent types. During the course of treatment, there are situations in which DAPT may need to be interrupted. If a patient requires a procedure while receiving DAPT, clinicians must consider the risk of bleeding if therapy is continued, the risk of stent thrombosis if antiplatelet therapy is discontinued or interrupted, and the timing of the procedure in the context of when the stent was placed. In general, if the procedure can be delayed beyond 12 months of DAPT this would be ideal. However, if the procedure must be done prior to the cessation of DAPT, then patients need to be evaluated for the benefits of the procedure versus the risks of thrombosis if DAPT were to be discontinued.
Abstract 4667: The use of fragment-based screening approaches to improve the specificity of inhibitors targeting malignant melanoma

S100B belongs to the S100 protein family of Ca2+-binding proteins. Prior studies have shown that S100B is a biological marker for malignant melanoma. Increases in S100B levels are predictive of disease progression, recurrence, and overall low survival in the patients. It was shown previously that S100B binds to p53 and down-regulates its tumor suppression activities including growth arrest and apoptosis. Chemical biology and structure-based drug design methods are underway to inhibit S100B and restore p53 function. However, highly specific S100B inhibitors are required, so S100B can be blocked in melanoma without impairing S100A1 function in skeletal and cardiac muscle. With this goal in mind, a fragment-based screening approach using NMR and computational approaches is being applied. Results to date indicate that these methods can be used to identify specific small molecule fragments that target S100B and not S100A1. The fragments that uniquely bind S100B will then be considered with structural data of existing S100B-SBiX complexes to improve their specificity for binding S100B (i.e. versus S100A1). The inhibitor design strategy will also include improving the stability of the compounds their cell permeability, and their overall drug-like properties. The most promising of these new inhibitors will ultimately be used to target high levels of S100B found in malignant and rescue p53-dependent tumor suppression pathways in vivo with the goal of them having therapeutic value for treating malignant melanoma. Citation Format: Sreya Mukherjee, Shardell Spriggs, Paul Wilder, Wenbo Yu, Kristen Varney, Alexander D. MacKerell, David J. Weber. The use of fragment-based screening approaches to improve the specificity of inhibitors targeting malignant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4667.
A systematic review of shunt-related extraneural metastases of primary central nervous system tumors

Extraneural metastasis (ENM) of primary central nervous system (CNS) tumors is an uncommon occurrence. Case reports and case series describe ENM after shunting, but this phenomenon has not been well characterized. In this review we aim to better understand the risk factors and clinical implications of ENM associated with shunting. A literature search of cases of ENM related to shunt placement in patients with primary CNS tumors reported through January 2018 was performed using PubMed and Google Scholar. We identified 106 cases of ENM of primary CNS tumors related to shunt placement. The three most common tumor histologies resulting in ENM were germinoma (24%), medulloblastoma (21%), and glioblastoma (11%). Of the patients with ENM, 48% had leptomeningeal spread and 37% had brain or spinal cord metastasis. Mean survival time from shunt placement was 13 months. Ventriculoatrial-shunted cases had higher rates of widespread metastasis and shorter average survival time from shunt placement (2 months) than the average of all types of shunts. Given the known association with ENM, careful consideration should be given to shunt placement in patients with primary CNS tumors, especially germinomas, medulloblastomas, and glioblastomas. Appropriate surveillance should be instituted after shunt placement, and leptomeningeal or neural metastasis should prompt the consideration of potential ENM. When considering distal shunt options, our review suggests that ventriculoatrial shunts should be avoided if possible. For truly obstructive pathologies, the risk of ENM is a further indication to consider other treatment options such as endoscopic third ventriculostomy rather than shunt placement.
Evaluation of the effect of 2′-O-methyl, fluoro hexitol, bicyclo and Morpholino nucleic acid modifications on potency of GalNAc conjugated antisense oligonucleotides in mice

The potency of antisense oligonucleotide (ASO) drugs has significantly improved in the clinic after exploiting asialoglycoprotein receptor (ASGR) mediated delivery to hepatocytes. To further this technology, we evaluated the structure-activity relationships of oligonucleotide chemistry on in vivo potency of GalNAc-conjugated Gapmer ASOs. GalNAc conjugation improved potency of ASOs containing 2'-O-methyl (2'-O-Me), 3'-fluoro hexitol nucleic acid (FHNA), locked nucleic acid (LNA), and constrained ethyl bicyclo nucleic acid (cEt BNA) 10-20-fold compared to unconjugated ASOs. We further demonstrate that GalNAc conjugation improves activity of 2'-O-(2-methoxyethyl) (2'-O-MOE) and Morpholino ASOs designed to correct splicing of survival motor neuron (SMN2) pre-mRNA in liver after subcutaneous administration. GalNAc modification thus represents a viable strategy for enhancing potency of ASO with diverse nucleic acid modifications and mechanisms of action for targets expressed in hepatocytes.
Identifying Structural Brain Networks from Functional Connectivity: A Network Deconvolution Approach

We address the problem of identifying structural brain networks from signals measured by resting-state functional magnetic resonance imaging (fMRI). To this end, we model functional brain activity as graph signals generated through a linear diffusion process on the unknown structural network. While this is admittedly an oversimplification of the complex mechanisms at work in the brain, recent studies have shown it is an accurate generative model for the second-order statistics of functional signals. We show the diffusion model implies that the signal covariance matrix (a.k.a. functional connectivity) is an unknown polynomial function of the structural network’s adjacency matrix. Accordingly, we advocate a network deconvolution approach whereby we: (i) use the fMRI signals to estimate the eigenvectors of the structural network from those of the empirical covariance; and (ii) solve a convex, sparsity-regularized inverse problem to recover the eigenvalues that were obscured by diffusion. The inferred structural networks capture some key patterns that match known pathology in attention deficit/hyper activity disorder. We also offer preliminary evidence supporting their role as potential biomarkers for subject diagnosis and classification.