cssi/SciSciGPT-SciSciNet huggingface dataset:
Frequency of actionable somatic alterations with genomic profiling: the Columbia University experience.

e23132Background: Personalized medicine in oncology is increasingly available due to the development of more targeted therapies as well as the decreasing expense and rapid results of next generation sequencing (NGS). At Columbia University Medical Center, patients undergo genomic profiling with a NGS assay called the Columbia Combined Cancer Panel (CCCP). We sought to assess the frequency of actionable alterations identified across tumor types. Methods: The CCCP can detect alterations in 467 tumor-specific genes and exons. The results are categorized into 4 tiers: tier 1 variants are actionable alterations associated with tumor type and tier 2 variants are alterations in targeted pathways, actionable alterations in other tumor types, or alterations in well-established cancer genes. Tier 3 and 4 variants do not currently have potential to be targeted. We retrospectively reviewed 219 consecutive adult oncology patients who underwent CCCP testing between 07/10/2014 and 12/15/2015. We examined clinical charac...
Recovery high schools may be a key component of youth recovery support services.

Peer group associations are an important part of an adolescent’s identity that can be difficult to shift without significant support and positive reinforcement for change. Youth with substance use ...
Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

Abstract Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. Perspective NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress.
Context cameras for the Orbiting Carbon Observatory 3 (OCO-3) instrument

We have developed an adaptable camera platform that takes advantage of screened and qualified commercial off the shelf (COTS) components (CMOS sensor, rad-tolerant microcircuits, lenses) to significantly shorten development time of space-borne visible imaging systems while reducing the overall cost and risk of the development. This modular camera platform is implemented as a suite of two visible-light cameras for the Orbiting Carbon Observatory 3 (OCO-3) instrument at NASA's Jet Propulsion Laboratory (JPL). The Internal Context Camera (ICC) and External Context Camera (ECC) provide contextual engineering imaging support for the calibration of the OCO-3 instrument, intended to significantly reduce the duration of the mission's calibration campaign. The OCO-3 mission has taken advantage of the design and qualification work performed by JPL's Mars 2020 Enhanced Engineering Camera (EECam) team in reusing the qualified COTS CMOS imaging sensor, proven electronic designs, and scalable field-programmable gate array (FPGA) firmware to meet OCO-3's mission requirements and resource availability. We will be presenting the steps taken by JPL to design, build, and test the Context Cameras for the OCO-3 mission. We will highlight the design deviations from the Mars2020 EECams and discuss the methodology of tailoring the EECam design for the OCO-3 requirements. Camera imaging capabilities, including focal plane and optical performance, will be presented, as well as a summary of the calibration and environmental test results. Finally, we will discuss the potential for future applications for the Context Cameras.
Sustainable Notebooks: Who Carries the Cost?

The portable computer or notebook has become an integral and even essential aspect of modern life. Year-in-year its price to the consumer falls while its performance grows, yet recent analysis suggest that pound-for-pound its environmental costs are amongst the highest of any product on the planet. In this paper we explore the market price of “sustainable” notebooks. Drawing on the framework of the ‘tragedy of the commons’ we postulate that as manufacturers shift costs away from the commons to comply with sustainability standards, the cost to the consumer will inevitably rise. We test our hypothesis by comparing the prices of EPEAT Gold certified notebooks with uncertified portable computers. The results are discussed, alternative hypotheses explored and further research outlined.
Systems of Ordinary Differential Equations

In this chapter we discuss systems of first order ordinary differential equations and methods for their solutions. The importance of such systems stems from the following observations: 1. A coupled system of differential equations of any order can always be rewritten as a system of first order equations.
Disconjugacy and Higher Order Dynamic Equations

In this chapter, we introduce the study of disconjugacy of nth order dynamic equations on time scales. Disconjugacy of ordinary differential equations is thoroughly studied and has a rich history. Much of what we develop in this chapter has been presented for ordinary differential equations in Coppel’s often cited monograph [100]. The analogous theory for forward difference equations was developed by Philip Hartman [154] in a landmark paper which has generated so much activity in the study of difference equations.
Using Mediation and Moderation Analyses to Enhance Prevention Research

Integrating mediating and moderating variables into prevention research can refine interventions and guide program evaluation by demonstrating how and for whom programs work, as well as lending insight into the construct validity of an intervention. In this way, program development and evaluation strategies that incorporate mediation and moderation analyses contribute to our ability to affect behavioral change. This chapter aims to illustrate how mediation and moderation analyses enhance and inform prevention and intervention work. To that end we define and differentiate the models, discuss their application to prevention programming and research, and provide information on their estimation for individuals seeking to implement these analyses.
Moments of Insight

No, life is not always steady and predictable. We can become increasingly sensitive to a world of creative tipping points. Included are, from Chaos Theory, the “Butterfly Effects” of our lives. Creative insight itself is likely one of these. With some of the background flickers of our days, we may not even notice. Others can be larger, a rare one momentous, shifting lives, even changing worlds. A vignette provides an example of the latter. Like a martial artist, the creator can work with this flux, sensing energies and balance, at times to tweak, advance, divert, or even to transform events.
A Human-Centered Control Framework for Robotic Sit-to-Stand Assistance

In this research, we propose a human-centered control framework for the Sit-To-Stand (STS) assistance by using a robot manipulator. The framework is designed to assist those with weak knees and feeble muscles to get out of a seated position. Compared to previous work on STS assistance, we develop a novel human-centered strategy that explicitly optimizes the human joint loads under the human body dynamics while taking care of the constantly-changing intention of the human during the actual STS assistance. Simulations and experiments are conducted to validate the proposed control framework.
“Looking Back” to Solve Differently: Familiarity, Fluency, and Flexibility

The present study focuses on a specific step of Polya’s problem-solving process, namely, “looking back” to solve a problem differently. In particular, it examines the extent to which the practice of “looking back” to solve differently has been integrated into mathematics classroom instruction in the United States. The findings of the present study indicate, to a certain degree, that this practice is little known to high school students, even those from some very selective schools. Moreover, it demonstrates that a high level of mathematical preparation might not be a sufficient condition for a student’s inclination to search for (let alone consider the need for) more than one solution method. Pedagogical implications of emphasizing the importance of connections between different mathematical topics are discussed.
FuseLoc: A CCA Based Information Fusion for Indoor Localization Using CSI Phase and Amplitude of Wifi Signals

With the growth of location based services, indoor localization is attracting great interests as it facilitates further ubiquitous environments. In this paper, we propose FuseLoc, the first information fusion based indoor localization using multiple features extracted from Channel State Information (CSI). In FuseLoc, the localization problem is modelled as a pattern matching problem, where the location of a subject is predicted based on the similarity measure of the CSI features of the unknown location with those of the training locations. The system exploits both the amplitude and phase information of CSI over multiple antennas from Orthogonal Frequency Division Multiplexing (OFDM) system for localization. Specifically, Fuse-Loc implements a discriminative feature extraction from measured CSI for pattern matching, where an effective feature fusion is performed using Canonical Correlation Analysis (CCA) by maximizing the pairwise correlations across the feature sets. Finally a similarity measure is performed to find the best match to localize a subject. Experimental results show that FuseLoc can estimate location with high accuracy which outperforms other state-of-the-art approaches.
Adsorption and Electrochemistry of Carbon Monoxide at the Ionic Liquid-Pt Interface.

In this work, CO adsorption and oxidation processes were studied with cyclic voltammetry and anodic adsorptive stripping chronoamperometry in two structural different ionic liquids (ILs) (i.e., 1-b...
Purinergic receptor expression and function in rat vagal sensory neurons innervating the stomach.

Abstract The nodose ganglion (NG) is the main parasympathetic ganglion conveying sensory signals to the CNS from numerous visceral organs including digestive signals such as gastric distension or the release the gastrointestinal peptides. The response characteristics of NG neurons to ATP and ADP and pharmacological interrogation of purinergic receptor subtypes have been previously investigated but often in NG cells of undetermined visceral origin. In this study, we confirmed the presence of P2X3 and P2Y1 receptors and characterized P2X and P2Y responses in gastric-innervating NG neurons. Application of ATP-evoked large inward currents and cytosolic Ca2+ increases in gastric-innervating NG neurons. Despite the expression of P2Y1 receptors, ADP elicited only minor modulation of voltage-gated Ca2+ channels. Considering the sensitivity of NG neurons to comorbidities associated with disease or neural injury, purinergic modulation of gastric NG neurons in disease- or injury-states is worthy of further investigation.
Embracing machine learning and digital health technology for precision dermatology.

Involvement from the dermatology community in the current revolution in sensors, personal health devices, computing, and machine learning algorithms can enable us to reach the promise of precision ...
Anthropology and Rural Economic Development

Anthropologists have usually studied rural peoples and have often been concerned with problems of economic development and social change. Such a concern goes back at least to the period between the wars, when colonial governments began to realize that anthropological knowledge could be of use to them, both in their everyday administration and in their development schemes. Initially, anthropologists who were interested in problems of social and economic development were involved in promoting development; more recently there has been interest in the process itself as a subject of pure anthropological inquiry. This paper describes and comments on some of the approaches that anthropologists have followed in the analysis of economic development and social change in rural Africa. Such research is important in post-colonial Africa for both practical and theoretical reasons, as new social and economic institutions are being created in Africa's rural areas that will bear importantly on future economic development. Most modern anthropology is carried out within the context of a community such as a village, an ethnic group, or a district. The anthropologist aims at understanding in depth; he also follows a self-consciously holistic approach. He assumes that there is a connection between the social organization of a group, its belief system and ritual, its conceptions of time and space, its technology, its economic organization, and its physical environment. Most anthropological analyses, even when focussed elsewhere, include sections on the environment in which people live and the ways in which they exploit that environment. Evans-Pritchard's, The Nuer', one of the classical anthropological monographs on an African society, includes a detailed section on ecology in which he shows how the annual cycle of migration forced on the Nuer by their habitat in the marshes of the southern Sudan has all-important implications for their social structure. In Africa as elsewhere, social organization is one aspect of technology, and the particular form that exploitation of the environment takes is a reflex of the social organization. Economic organization and social organization are analytically separate, but interdependent, abstractions.
Density-stable yield-stress displacement flow of immiscible fluids in inclined pipes

Abstract We experimentally study the displacement flow of a non-Newtonian yield-stress fluid by an immiscible Newtonian one in an inclined pipe. The pipe has a small diameter-to-length ratio. The less dense displacing fluid is placed above the denser displaced fluid i.e. a density-stable configuration. The displacing and displaced solutions are oil and water-based respectively. The flow between the Newtonian and non-Newtonian fluids has been studied over a wide range of controlling parameters, namely imposed flow rate, inclination angle, density difference, yield stress, viscosity, and surface tension. Compared to the previously studied miscible limit, we observe novel fracturing behavior at the interface between the two fluids; this fracture pattern is preserved in the non-Newtonian gel as the advancing oil flows through. Instead of both slump and center-type flows observed in the miscible case, we primarily observe center-type flows, which maintain similar flow profiles across mean imposed flow rates V ^ 0 in the study. Similarly to the miscible case, the inclination angle β is not found to have an effect on the velocity of the advancing frontal region of the displacing fluid, V ^ f . The average thickness of the residual yield-stress layer in this study was found to be 0.14 of the radius, decreasing to 0.12 of the radius when higher viscosity oils are used as the displacing fluid. The residual layer thickness slightly increases with Reynolds number, Re, but shows no dependency on the density difference between the two fluids captured by the Atwood number, At. Finally, the unevenness in the yield-stress residual layer for immiscible fluids is found to be significantly less than that of the miscible case.
Atomic-scale patterning in two-dimensional van der waals superlattices

Two-dimensional (2D) van der Waals superlattices comprised of two stacked monolayer materials have attracted significant interest as platforms for novel optoelectronic and structural behavior. Although studies are focused on superlattice fabrication, less effort has been given to the nanoscale patterning and structural modification of these systems. In this report, we demonstrate the localized layer-by-layer thinning and formation of nanopores/defects in 2D superlattices, such as stacked MoS2-WS2 van der Waals heterostructures and chemical vapor deposited bilayer WSe2, using aberration-corrected scanning transmission electron microscopy (STEM). Controlled electron beam irradiation is used to locally thin superlattices by removing the bottom layer of atoms, followed by defect formation through ablation of the second layer of atoms. The resulting defects exhibit atomically-sharp pore edges with tunable diameters down to 0.6 nm. Structural periodicities and focused STEM irradiation are also utilized to form close-packed nanopore arrays in superlattices with varying twist angles and commensurability. Applying these methods and mechanisms provides a forward approach in the atomic-scale patterning of stacked 2D nanodevices.
Viral Surrogates in Potable Reuse Applications: Evaluation of a Membrane Bioreactor and Full Advanced Treatment

AbstractThis study employed quantitative polymerase chain reaction (qPCR) to evaluate the occurrence and removal of five microbial surrogates at two water reuse facilities. The surrogates were (1) ...
Modeling human disease: a mouse model of acute kidney injury to chronic kidney disease progression after cardiac arrest.

Matsushita et al. describe a model of acute kidney injury to chronic kidney disease progression in mice surviving cardiac arrest: mice develop severe acute kidney injury that initially recovers but is followed by the onset of impaired renal function on longer-term follow-up. These findings suggest that distinct cardiorenal toxicities and/or injury dynamics are operative in this cardiac arrest model that do not occur in traditional models of acute kidney injury, providing new opportunities for therapeutic and biomarker discovery for an important clinical problem.
Social Entrepreneurship: Research as Disciplined Exploration

Social enterprises address social problem by means of markets. Over the last two decades they have become increasingly popular across geographies. During this time open contestation and ideological debates over the promise, intention and meaning of social entrepreneurship have dominated public discourse but also inhibited the development of a solid knowledge base on social enterprises as a form of organizing in the spectrum of private action for public purpose. The dominant way of seeing social enterprises as pursuing dual – commercial and social – goals and as ideal sites to study the battle of logics confines our way of looking and limit the theorizing potential around social enterprise. In this chapter I advocate for disciplined exploration approach to study social enterprises to expose this potential. I draw from a collaborative research project involving 1,045 social enterprises across nine countries and show patterns and common features of social enterprises regarding their choice of legal form, their participation in the market for public purpose, their social footprint, and their role in changing local institutional arrangements. I argue that embracing rather than taming the diversity of social enterprises opens opportunities for developing new but more importantly for recasting, refining and connecting existing theories.
ASD, Trauma, and Coordinated Care

This chapter explores issues related to trauma in youth with Autism Spectrum Disorder (ASD) and how trauma and its sequelae can be identified and addressed through interdisciplinary coordinated care. Foundational information on trauma-informed care (TIC) and intervention strategies are provided to help guide professionals and families in better understanding common experiences of trauma in youth with ASD and effective ways to offer support and promote healing.
What Does Financial Heterogeneity Say About the Transmission of Monetary Policy

Do financial constraints determine the transmission of monetary policy? I examine this question using the staggered enactment of anti-recharacterization legislation as a source of exogenous variation in creditor rights that loosens firm financial constraints. Treatment effect estimates indicate constraints matter. A 25 basis-point expansionary monetary policy shock results in a 2 percentage-point higher investment growth among treated (unconstrained) firms, reflecting their flatter marginal cost curves for financing which amplifies responses to shifts in the marginal benefit curve. This relationship reverses during economic downturns when investment opportunities are scarce. I rationalize these findings in a static model with convex financing costs.
Cost Minimization Analysis of a Teledermatology Triage System in a Managed Care Setting.

Importance Teledermatology (TD) enables remote triage and management of dermatology patients. Previous analyses of TD systems have demonstrated improved access to care but an inconsistent fiscal impact. Objective To compare the organizationwide cost of managing newly referred dermatology patients within a TD triage system vs a conventional dermatology care model at the Zuckerberg San Francisco General Hospital and Trauma Center (hereafter referred to as the ZSFG) in California. Design, setting, and participants A retrospective cost minimization analysis was conducted of 2098 patients referred to the dermatology department at the ZSFG between June 1 and December 31, 2017. Intervention Implementation of the TD triage system in January 2015. Main outcomes and measures The main outcome was mean cost to the health care organization to manage newly referred dermatology patients with or without TD triage. To estimate costs, decision-tree models were constructed to characterize possible care paths with TD triage and within a conventional dermatology care model. Costs associated with primary care visits, dermatology visits, and TD visits were then applied to the decision-tree models to estimate the mean cost of managing patients following each care path for 6 months. The mean cost for each visit type incorporated personnel costs, with the mean cost per TD consultation also incorporating software implementation and maintenance costs. Finally, ZSFG patient data were applied within the models to evaluate branch probabilities, enabling calculation of mean cost per patient within each model. Results The analysis captured 2098 patients (1154 men [55.0%]; mean [SD] age, 53.4 [16.8] years), with 1099 (52.4%) having Medi-Cal insurance and 879 (41.9%) identifying as non-White. In the decision-tree model with TD triage, the mean (SD) cost per patient to the health care organization was $559.84 ($319.29). In the decision-tree model for conventional dermatology care, the mean (SD) cost per patient was $699.96 ($390.24). Therefore, the TD model demonstrated a statistically significant mean (SE) cost savings of $140.12 ($11.01) per patient. Given an annual dermatology referral volume of 3150 patients, the analysis estimates an annual savings of $441 378. Conclusions and relevance Implementation of a TD triage system within the dermatology department at the ZSFG was associated with cost savings, suggesting that managed health care settings may experience significant cost savings from using TD to triage and manage patients.
Supported Palladium Catalysts: A Facile Preparation Method and Implications to Reductive Catalysis Technology for Water Treatment

Supported palladium (Pd) catalysts have been extensively studied for water purification applications. However, this technology is primarily challenged by the high cost of Pd and the lack of optimiz...
3134 – CHARACTERIZATION OF THE HEMATOPOIETIC STEM CELLS AND BONE MARROW MICROENVIRONMENT IN SICKLE CELL DISEASE PATIENTS

Little is known about the status of the bone marrow (BM) in Sickle Cell Disease (SCD) patients. In this study, we characterized the hematopoietic stem and progenitors (HSPC) and the stromal cells from BM aspirates of eight SCD patients before transplant in comparison with age-matched BM aspirates from healthy individuals. By using multiparametric flow analysis, we observed a group of SCD patients (n=4) with characteristics similar to controls, and a distinct group of SCD patients (n=4) that exhibited lower average frequency of CD34+ cells, HSCs, multipotent and lymphoid progenitors. Methylcellulose colony assays showed a decreased ability of the BM cells of these patients to form colonies compared to control BM. scRNA-seq analysis of sorted BM CD34+ cells from SCD patients indicated changes in the DNA damage and cell cycle regulatory pathways compared to controls. Interestingly, all SCD patients displayed an increase in the BM non-hematopoietic cells including CD45-/CD31+ and CD45-/CD105+ subsets compared to controls, suggesting a change in their BM stromal niche. In vitro, SCD BM-derived stromal cells revealed distinct gene expression patterns including an increase in inflammatory cytokine (IL-6) & cell death-related genes (p16 and Bax) but decrease expression of a pluripotent gene (Oct4). We also detected an increase of inflammatory regulators, miR-155, and miR-146 in all BM-derived stromal cells from SCD patients, which correlates with increased inflammatory gene expression in these cells. Finally, analysis of the BM biopsies revealed alterations in the stromal components as evidenced by an overall decrease in cellularity in some patients, and increased iron deposits and activated macrophages. Taken together, these preliminary data suggest that the BM cells and BM microenvironment of SCD patients are phenotypically & molecularly different from control BM. Further studies will clarify whether there are correlations between the severity of the disease and BM alterations and whether the BM status at pre-transplant may help in predicting engraftment and outcomes of BM transplants in SCD patients.
Donor race has no role in predicting allograft and patient survival among kidney transplant recipients

Abstract A heated debate in creatinine-based estimated glomerular filtration rate (eGFR) calculation is the inclusion of race alongside biological factors, such as age and gender. Similarly, the race variable was included in the calculation of the Kidney Donor Risk Index (KDRI) as deceased donor kidneys from black donors have historically been shown to be associated with lower allograft or patient survival. Given the current climate of uncertainty with the use of race in nephrology, we sought to answer the question of whether removing the donor race variable from the KDRI would alter its validity to assess allograft and patient survival. Our modeling and analysis showed that removing donor race from the original KDRI did not alter the overall model predictability of allograft failure or patient mortality. Clinical risk factors included in the KDRI have largely accounted for differential risk between black and other donors. Adding donor race into the KDRI only shifts how risk is attributed to these clinical risk factors, without yielding better prediction of outcomes than the model without race.
Integrating Thermal Analysis and Reaction Modeling for Rational Design of Pyrolytic Processes to Remediate Soils Contaminated with Heavy Crude Oil

We developed a novel methodology that combines thermo-analytical measurements and mathematical methods to inform the reliable pyrolytic treatment of specific soil/contaminant systems. Our approach improves upon current "black-box" design methods that may overestimate the required treatment intensity and hinder cost efficacy. We used thermogravimetry and evolved gas analysis to characterize the complex network of soil mineral transformations, contaminant desorption, and pyrolytic reactions occurring when contaminated soils are heated in an anoxic atmosphere. The kinetics of these reactions were quantified using a distributed activation energy (DAE) approach with six pseudocomponents and used in a mathematical model for continuous-flow reactors to predict the removal of hydrocarbon contaminants without other fitting parameters. This model was tested with pilot-scale data from pyrolytic treatment of soils contaminated with crude oil and found to be a good predictor of the total petroleum hydrocarbon (TPH) removal for temperatures between 370 and 470 °C and residence times from 15 to 60 min. The light hydrocarbon fraction desorbed quickly, and over 99.7% removal was achieved at 420 °C and 15 min residence time. However, 95% removal of the heavy hydrocarbon fraction, which is a good proxy for polyaromatic hydrocarbons (PAHs), required 470 °C with 15 min residence time. This model can be employed to select operating conditions (e.g., reactor size, treatment time, and temperature) to reliably achieve remediation objectives for specific hydrocarbon/soil mixtures without inflating energy requirements, which would lower operating costs and decrease the process carbon footprint on a system-specific basis.
Position Masking for Improved Layout-Aware Document Understanding.

Natural language processing for document scans and PDFs has the potential to enormously improve the efficiency of business processes. Layout-aware word embeddings such as LayoutLM have shown promise for classification of and information extraction from such documents. This paper proposes a new pre-training task called that can improve performance of layout-aware word embeddings that incorporate 2-D position embeddings. We compare models pre-trained with only language masking against models pre-trained with both language masking and position masking, and we find that position masking improves performance by over 5% on a form understanding task.
Emerging roles of N-linked glycosylation in brain physiology and disorders

N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.
Obesity and Labor Market Performance

Obesity is the most pressing public health problem in developed countries and is rapidly becoming so in developing countries. Obesity is associated with a host of comorbidities and strains health care systems around the globe. Obesity is also associated with poor labor market outcomes such as lower wages and a lower probability of employment. While this negative correlation between obesity and wages/employment is well documented across numerous countries, sorting out causality from correlation has been challenging. Most studies that credibly disentangle correlation from causation find a negative and significant causal effect of obesity on wages and employment, particularly for women.
The Importance of Phospholipid-Protein Interactions for Regulation of the Activities of Membrane-Bound Enzymes

Soluble enzymes have been shown to undergo changes in conformation which result in modification of their kinetic properties. These changes can result from alterations in the enzyme’s environment or from the binding of soluble ligands. Both of these well-known phenomena are useful for the dynamic regulation of rates of substrate flux in various metabolic pathways (Atkinson, 1966; Stadtman, 1966; Koshland, 1970). Interest in this type of regulatory mechanism has focused on the properties of soluble proteins and enzymes, but the same general principles are likely to apply also to proteins which are bound to membrane structures. In fact, the number of parameters which potentially can alter protein structure—and thereby protein function—is greater for membrane-bound enzymes than for soluble enzymes, since particulate enzymes are likely to be in contact with or partially embedded in the hydrophobic portion of the membrane bilayer and exposed to an aqueous environment (Singer and Nicolsen, 1972). Furthermore, besides the binding of soluble ligands, changes in the gross composition or structure of the lipid bilayer could alter the properties of proteins which interact with it.
Evaluation of the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in fed and fasted Greyhound dogs

This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24 h after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline CMAX for the remaining fasted dogs (n = 3) was 22.8-64.5 ng/mL compared to 30.6-127 ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUCINF for the three fasted dogs was 167-720 h·ng/mL compared to 287-1146 h·ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69-91% (n = 3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R(2) = 0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs.
Crustal noble gases in deep brines as natural tracers of vertical transport processes in the Michigan Basin

4 He, 21 Ne, 40 Ar, and 136 Xe. Both 40 Arcrust and 136 Xecrust display the presence of a strong vertical gradient along the sedimentary strata of the basin. We show that the in situ production for these two gases within the sedimentary strata is insufficient to account for the observed crustal component in the Michigan brines. These point to the presence of a deep, external source for crustal noble gases, likely the Precambrian crystalline basement beneath the Michigan Basin. Furthermore, observed elemental ratios of crustal noble gases ( 4 He/ 40 Ar, 21 Ne/ 40 Ar, 4 He/ 136 Xe, and 21 Ne/ 136 Xe) in these brines vary over several orders of magnitude with respect to the expected production ratios from the crystalline basement rocks and display a systematic pattern within the basin. Specifically, samples above the Salina Group (shallow formations) are relatively enriched in 4 Hecrust and 21 Necrust with respect to 40 Arcrust and 136 Xecrust, as opposed to those below the massive Salina evaporite layer (deeper formations) which exhibit complementary patterns. We show that such a general trend is best explained by a Rayleigh-type elemental fractionation model involving upward transport of crustal noble gases and associated elemental fractionation processes, controlled by both diffusion- and solubility-related mechanisms. As previously indicated by the mantle and atmospheric noble gas signatures in these same Michigan brine samples, release of deep crustal noble gases into the basin is yet another independent indicator pointing to the occurrence of a past thermal event in the basin. We suggest that recent reactivation of the ancient midcontinent rift system underneath the Michigan Basin is likely responsible for the upward transport of heat and loss of the atmospheric noble gas component, as well as release of crustal (still ongoing) and mantle noble gases into the basin via deepseated faults and fracture zones. Such a model also supports an internal heat source hypothesis as being largely responsible for the existence of past high temperatures in the basin without involvement of largescale brine migration from peripheral forming orogenic fold belts.
Reflections on Client Perjury

This article discusses the extent to which a criminal defense attorney legally and ethically may cooperate with his or her client in concealing the truth.
First results from experiment NA49 at the CERN SPS with 158 GeV/nucleon Pb on Pb collisions

CERN experiment NA49 had its first beam time in November/December 1994 with a {sup 208}Pb beam of 158 GeV/nucleon. The experimental setup to study Pb+Pb collisions is described and first results on two particle correlations and transverse energy production are discussed.
Making Way and Making Sense: Including Newcomers in Interaction:

In our everyday interactions as they unfold in real time, how do we do including? This article examines a specific set of interactional moments when the potential to be included (or not) recurs: when a newcomer arrives to some social scene where two or more already-present persons are actively engaged in some activity and that newcomer displays interest in joining into their activity. I show how arriving newcomers bodily display that they want to join into the pre-present party’s interaction, and I analyze a key utterance-based practice that pre-present speakers use to include newcomers into their interaction—the practice of previous activity formulating. Through this practice, speakers summarize the activities or conversational topics in which they were engaged before establishing copresence with arrivers, thereby making way and making sense for them so they can join into their interaction. By showing that participants treat pre-present speakers’ offers of formulations as preferred over arrivers’ request...
Changes in mRNA Levels of the Myoc/Tigr Gene in the Rat Eye after Experimental Elevation of Intraocular Pressure or Optic Nerve Transection

PURPOSE. To isolate the rat Myoc/Tigr gene and investigate changes in its expression pattern in normal eyes and in eyes with either pressure-induced optic nerve damage or optic nerve transection. METHODS. Expression pattern of the rat Myoc/Tigr gene was investigated by Northern blot hybridization. Optic nerve damage and death of ganglion cells in the retina were induced unilaterally, by injection of hypertonic saline solution, episcleral vein cauterization, or optic nerve transection. The levels of mRNA for Myoc/Tigr were compared between several tissues of the control and surgically altered eyes, by using semiquantitative RT-PCR, real-time PCR, and Northern blot analysis. RESULTS. The rat Myoc/Tigr gene is 10 kb long and contains three exons. Among the eye tissues analyzed, Myoc/Tigr mRNA was detected in the combined tissues of the eye angle, sclera, cornea, retina, and optic nerve head. With pressure-induced optic nerve degeneration, the level of Myoc/Tigr mRNA decreased in the retina and the combined tissues of the eye angle, but increased in the optic nerve head. After optic nerve transection, the level of Myoc/Tigr mRNA increased in the retina, hut did not change in the combined tissues of the eye angle. CONCLUSIONS. The decreased level of Myoc/Tigr mRNA in the retina after induction of elevated intraocular pressure compared with that in the control retina cannot be explained by ganglion cell death alone. Differences in Myoc/Tigr mRNA levels in eye tissues after elevation of intraocular pressure or optic nerve transection may reflect the activation of different signaling pathways involved in regulation of this gene.
Following Their Instincts

Patterns of Behavior . Konrad Lorenz, Niko Tinbergen, and the Founding of Ethology. By Richard W. Burkhardt Jr. . University of Chicago Press, Chicago, 2005. 648 pp. $80. ISBN 0-226-08089-7. Paper, $29, £20.50. ISBN 0-226-08090-0. This history of ethology examines how theory, practice, place, and politics interacted to shape the developing discipline.
Adaptive Metamorphs model for 3D medical image segmentation

In this paper, we introduce an adaptive model-based segmentation framework, in which edge and region information are integrated and used adaptively while a solid model deforms toward the object boundary. Our 3D segmentation method stems from Metamorphs deformable models [1]. The main novelty of our work is in that, instead of performing segmentation in an entire 3D volume, we propose model-based segmentation in an adaptively changing subvolume of interest. The subvolume is determined based on appearance statistics of the evolving object model, and within the subvolume, more accurate and object-specific edge and region information can be obtained. This local and adaptive scheme for computing edges and object region information makes our segmentation solution more efficient and more robust to image noise, artifacts and intensity inhomogeneity. External forces for model deformation are derived in a variational framework that consists of both edge-based and region-based energy terms, taking into account the adaptively changing environment. We demonstrate the performance of our method through extensive experiments using cardiac MR and liver CT images.
Drug metabolism in the nasal mucosa.

Nasal delivery is a potential alternative for systemic availability of drugs restricted to intravenous administration, such as peptide and protein drugs. Although nasal delivery avoids the hepatic first-pass effect, the enzymatic barrier of the nasal mucosa creates a pseudo-first-pass effect. The xenobiotic metabolic activity in the nasal epithelium has been investigated in several species including humans. The Phase I, cytochrome P-450 enzymes have been studied extensively for their toxicological significance, since these enzymes metabolize inhaled pollutants into reactive metabolites which may induce nasal tumors. The cytochrome P-450 activity in the olfactory region of the nasal epithelium is higher even than in the liver, mainly because of a three- to fourfold higher NADPH-cytochrome P-450 reductase content. Phase II activity has also been found in the nasal epithelium. The delivery of peptides and proteins has been hindered by the peptidase and protease activity in the nasal mucosa. The predominant enzyme appears to be aminopeptidase among other exopeptidases and endopeptidases. The absorption of peptide drugs can be improved by using aminoboronic acid derivatives, amastatin, and other enzyme inhibitors as absorption enhancers. It is possible that some of the surfactants, e.g., bile salts, increase absorption by inhibiting the proteolytic enzymes. Thus, in addition to the permeation barriers, there also exists an enzymatic barrier to nasal drug delivery, which is created by metabolic enzymes in the nasal epithelium.
Induction of Red Color Formation in Cabbage Juice by Lactobacillus brevis and Its Relationship to Pink Sauerkraut

Membrane-filtered cabbage juice, when fermented by Lactobacillus brevis under conditions of controlled pH, frequently produced a water-soluble red pigment. The pigment, presumably responsible for imparting a highly objectionable discoloration to sauerkraut, was formed during the post logarithmic phase of growth. Color development is pH dependent (5.2 to 6.3) and can be suppressed by chemical reductants or anaerobic conditions of growth. The compound responsible for discoloration was purified and partially characterized.
Nature of the Ethylenediaminetetraacetic acid Requirement for Transformation of Bacillus subtilis with Single-Stranded Deoxyribonucleic Acid

The ethylenediaminetetraacetate (EDTA) requirement for transformation of Bacillus subtilis with single-stranded deoxyribonucleic acid (DNA) was examined. The results indicate that a chelating agent such as EDTA is a stringent requirement for transformation with single DNA strands only at nonsaturating DNA concentrations, and that EDTA, when required, must be present during several steps in the transformation process and appears to insure the survival of single-stranded DNA by rendering a nuclease in competent populations inactive.
Expression of the human spermidine/spermine N1-acetyltransferase in spermidine acetylation-deficient Escherichia coli

A cDNA encoding the human spermidine/spermine N1-acetyltransferase (N1SSAT) was conditionally expressed in a strain of Escherichia coli deficient in spermidine-acetylating activity. Conditional expression of this cDNA was performed under the control of the lac promoter, by addition of the non-hydrolysable lactose analogue isopropyl beta-D-thiogalactoside. Expression of the N1SSAT cDNA oriented in the sense direction resulted in the acetylation of spermidine at the N1 but not the N8 position and a decrease in endogenous spermidine contents and growth rates in these bacteria. When this cDNA was expressed in the antisense orientation, spermidine acetylation was not detected and endogenous spermidine contents and growth rates were unaffected. Increasing the endogenous N1-acetylspermidine concentration by addition of this amine to the culture medium did not suppress growth, and increasing endogenous spermidine pools by exogenous addition was not sufficient to restore optimal growth in cells expressing the human N1SSAT. Exogenous spermidine, but neither N1- nor N8-acetylspermidine, stimulated cell growth in strains unable to synthesize spermidine. These results suggest that one physiological consequence of spermidine acetylation in E. coli is growth inhibition. The mechanism of this inhibition seems to involve the formation of acetylspermidine, and is not simply due to a decrease in the intracellular concentration of non-acetylated spermidine.
Human Hemoglobin: Identification of a Key Intermediate

Human hemoglobin binds four oxygen molecules with positive cooperativity in a binding cascade of eight partially ligated intermediates whose oxygen ligands are distributed in different combinations between the hemoglobin's two αβ dimers. Traditionally, it had been assumed that, given their close association in forming the hemoglobin tetramer, the two αβ dimers would always respond to oxygen binding in a synchronous and symmetric manner. Using linkage thermodynamics, the intermediate binding constants are evaluated via dimer–tetramer assembly with ligand configurations within the tetramer fixed through the use of hemesite analogs. It is observed that the free energy contribution of the asymmetrically ligated intermediate composed of one fully oxygenated αβ dimer plus one unoxygenated dimer is not the same as other doubly ligated intermediates, which contain at least one bound oxygen on both dimers. Therefore, the dimers within the tetramer respond to oxygenation differently, and cooperativity is dependent on the distribution of ligands between the two αβ dimers.