cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of fixation on bacterial cellular dimensions and integrity.

Summary Fixation facilitates imaging of subcellular localization and cell morphology, yet it remains unknown how fixation affects cellular dimensions and intracellular fluorescence patterns, particularly during long-term storage. Here, we characterized the effects of multiple fixatives on several bacterial species. Fixation generally reduced cell length by 5–15%; single-cell tracking in microfluidics revealed that the length decrease was an aggregate effect of many steps in the fixation protocol and that fluorescence of cytoplasmic GFP but not membrane-bound MreB-msfGFP was rapidly lost with formaldehyde-based fixatives. Cellular dimensions were preserved in formaldehyde-based fixatives for ≥4 days, but methanol caused length to decrease. Although methanol preserved cytoplasmic fluorescence better than formaldehyde-based fixatives, some Escherichia coli cells were able to grow directly after fixation. Moreover, methanol fixation caused lysis in a subpopulation of cells, with virtually all Bacillus subtilis cells lysing after one day. These findings highlight tradeoffs between maintenance of fluorescence and membrane integrity for future applications of fixation.
Transmission Mode 2D-IR Spectroelectrochemistry of In Situ Electrocatalytic Intermediates.

Unraveling electrocatalytic mechanisms, as well as fundamental structural dynamics of intermediates, requires spectroscopy with high time and frequency resolution that can account for nonequilibriu...
Service with a (Surgically-Induced) Smile: Gender Norms at Work

In this essay, the author explores the implications for women of robust social norms to perform "niceness" and the implications of this for economic equality.
Alien: The Experience of a Foreign Resident.

One night, I woke up in the pitch black to the deafening sound of a detonated bomb. The explosion killed dozens of people and shattered every window in our home, and in the dry heat of that disorienting night, all I sought was safety. I was 11 years old and living in Riyadh at the time, where my family had just relocated for my father’s job. That night, our quiet residential compound of mostly non-Saudi nationals was bombed by Islamic extremists against the Westernization of the country.1 Their message was clear: “We don’t want you here.” Miraculously unharmed, we left the country within days. Although grateful for the opportunities to experience different cultures during our frequent moves, I grew distanced from my birth country, Japan. I never lived anywhere long enough to feel like I could call it home. Then, in 2010, I came to the United States for college. Maybe I would find a home here, I hoped. Over the ensuing decade, as a foreigner, I became versed in the alphabet and number soup of visas on which my education and career would come to rely: F-1, J-1, OPT, H-1B. My visa status was a source of constant stress. The bureaucracy of the US Citizenship and Immigration Services was difficult to navigate. Worse, at every step of the way, I felt bluntly reminded of my status as deemed by the US government: officially, an “alien.” I felt alien … Address correspondence to Jamie Lim, MD, Department of Pediatrics, Boston Medical Center, 801 Albany St, 2nd Floor, Boston, MA 02119. E-mail: jamie.lim2{at}bmc.org
Spatially explicit life cycle assessment of fish: comparison of local vs. imported provision in Wisconsin

The global fish supply chain handles ~179 million tons of product annually (as in 2018). Transportation and distribution is an important part of fish supply chain, as fish and shellfish is the one of the largest globally traded food commodities with a trading value of ~$153 billion in 2017. Here we show that disregarding the environmental impacts of fish transportation, either land transit or flight, neglects a noteworthy portion of total fish provisioning environmental impacts. We identified that local fish provision, considering (1) all Wisconsin counties as production points, (2) cities of Chicago, Milwaukee, and Minneapolis as consumption points, and (3) effective, semi-effective, and ineffective space heating approaches, has significantly lower environmental impacts than imported fish provision, considering flight transportation from offshore production points. Meaning the necessity to elevate local fish production capacity to enhance the environmental sustainability of fish provision is essential, despite potential elevated heating demands for cold-weather aquaculture.
Boundary transformation representation of attractor shape deformation.

Detecting parameter changes in chaotic systems depends on characterizing the deformation of the strange attractor. Here, we present a new method for comparing the geometry of two attractors by examining their boundaries in 2D via shape context analysis. Poincare sections for each attractor are sampled along their outer limits, and a boundary transformation is computed that warps one set of points into the other. This boundary transformation is a rich descriptor of the attractor deformation and approximately proportional to a system parameter change in specific regions. Both simulated and experimental data with various levels of noise are used to demonstrate the effectiveness of this method.
Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice.

Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein that is highly expressed in odontoblasts, but only transiently expressed in presecretory ameloblasts during tooth development. We previously generated a knockin mouse model expressing a mouse equivalent (DSPP, p.P19L) of human mutant DSPP (p.P17L; referred to as "DsppP19L/+ "), and reported that DsppP19L/+ and DsppP19L/P19L mice manifested a dentin phenotype resembling human dentinogenesis imperfecta (DGI). In this study, we analyzed pathogenic effects of mutant P19L-DSPP on enamel development in DsppP19L/+ and DsppP19L/P19L mice. Micro-Computed Tomography (μCT) analyses of 7-week-old mouse mandibular incisors showed that DsppP19L/P19L mice had significantly decreased enamel volume and/or enamel density at different stages of amelogenesis examined. Acid-etched scanning electron microscopy (SEM) analyses of mouse incisors demonstrated that, at the mid-late maturation stage of amelogenesis, the enamel of wild-type mice already had apparent decussating pattern of enamel rods, whereas only minute particulates were found in DsppP19L/+ mice, and no discernible structures in DsppP19L/P19L mouse enamel. However, by the time that incisor enamel was about to erupt into oral cavity, distinct decussating enamel rods were evident in DsppP19L/+ mice, but only poorly-defined enamel rods were revealed in DsppP19L/P19L mice. Moreover, μCT analyses of the mandibular first molars showed that DsppP19L/+ and DsppP19L/P19L mice had a significant reduction in enamel volume and enamel density at the ages of 2, 3, and 24weeks after birth. Backscattered and acid-etched SEM analyses revealed that while 3-week-old DsppP19L/+ mice had similar pattern of enamel rods in the mandibular first molars as age-matched wild-type mice, no distinct enamel rods were observed in DsppP19L/P19L mice. Yet neither DsppP19L/+ nor DsppP19L/P19L mice showed well-defined enamel rods in the mandibular first molars by the age of 24weeks, as judged by backscattered and acid-etched SEM. In situ hybridization showed that DSPP mRNA level was markedly reduced in the presecretory ameloblasts, but immunohistochemistry revealed that DSP/DSPP immunostaining signals were much stronger within the presecretory ameloblasts in Dspp mutant mice than in wild-type mice. These results suggest that mutant P19L-DSPP protein caused developmental enamel defects in mice, which may be associated with intracellular retention of mutant DSPP in the presecretory ameloblasts.
Trips and public health: solutions for ensuring global access to essential AIDS medication in the wake of the Paragraph 6 Waiver.

In 2003 the World Trade Organization (WTO) proposed a waiver to the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) known as the "Paragraph 6 Waiver" in order to create flexibility for developing countries and to allow easier importation of cheap generic medication. ... To the companies who own pharmaceutical patents the notion that a government can use their product without the permission of the patent holder seems unfair and counterproductive. ... Canada was one of the first countries to enact legislation for the sole purpose of exporting generic drugs to developing countries and its experience is indicative of the problems presented by compulsory licensing and the Paragraph 6 Waiver. ... Exact amounts and methods for determining remuneration vary but presumably a fair system would compensate patent holders for the loss of their patent rights while maintaining the systems cost effectiveness for countries issuing the compulsory licenses. (excerpt)
Structural Compartmentation of the Cytosol: Zones of Exclusion, Zones of Adhesion, Cytoskeletal and Intercisternal Elements

Compartmentation of eukaryotic cells by systems of internal membranes is a familiar concept. Yet, membrane-bounded compartments are only one of several possible mechanisms for the separation of functional activities and the control of interactions. Less familiar are examples where the nonmembranous components of the cell, i.e., portions of the cytosol or so-called “soluble cytoplasm,” also seem to be compartmentalized. The cytosol is defined as that portion of the cytoplasm that occupies the space between the membrane-bounded compartments of the cell. It is a colloidal sol capable of sol-gel transformations (Wolman, 1955). Electron microscopy shows that the cytosol contains discrete cellular components such as ribosomes, glycogen particles, microtubules, and microfilaments. These components of the cytosol frequently are located in specific cellular regions and impart to the cytosol a degree of microorganization. Our interest is in how such microorganization is established and maintained and how microorganization is reflected by more familiar aspects of macroorganization and the control of growth and development. By and large, the organizing regions of the cytosol lack means of ready visualization, even by electron microscopy. Therefore, their properties and even their presence must sometimes be inferred from the response of other structures to regions of cytosol organization or deduced from comparative studies.
Thermogravimetric Analysis of Lubricants

A novel thermogravimetric analysis test method has been developed for the evaluation of lubricants. It involves superimposing the thermogravimetric trace of the sample in argon over the trace produced in oxygen atmosphere. The difference of the two traces indicates the oxidative influence on volatility as well as on the formation tendencies of high boiling (high molecular weight) oxidation products. The method was illustrated with a base oil with and without a catalyst package and an additive package. The test method is potentially useful for lubricant screening, quality control, and base oil composition effects on thermal oxidative stability.
Quilt packaging: a new paradigm for interchip communication

"Quilt packaging," (QP) a new paradigm for interchip communication, is presented. QP uses conducting modules that protrude from the sides of integrated circuits to affect an enhanced-speed, reduced-power method of interfacing multiple die together within a package or on a multichip module. The concept of QP is introduced along with a discussion of advantages over traditional system-on-chip and system-in-package technologies. Details of a process flow and preliminary results are presented. Simulations show expected signal propagation between adjacent die of greater than 150 GHz
Economic Incentives in Representing Publicly-Funded Criminal Defendants in England's Crown Court

The flux now engulfing the way in which the defenders of indigent criminal defendants are compensated in England’s Crown Court provides a sober lesson for U.S. lawyers. Once, U.S. lawyers, who themselves are appointed to represent indigent defendants, could have cited English practice to support a hefty increase in the meager compensation they receive in many jurisdictions. Spiraling costs in England, however, have brought dramatic changes, and have occurred in a rush. This essay explores compensatory schemes, incentives to reduce the cost of case resolution, and methods to ensure adequate advocacy. ECONOMIC INCENTIVES IN REPRESENTING PUBLICLY-FUNDED CRIMINAL DEFENDANTS IN ENGLAND'S CROWN COURT
Tilting at Windmills

Any educator will tell you that teaching is hard; it is exhausting, painful, frustrating and, at times, seemingly thankless. The difficulty of being a critical democratic educator who teaches with the desire of furthering social justice is tenfold. In previous articles (see Kress, 2010 and Kress, 2012) I have described the process of being and becoming a critical democratic educator as similar to playing a perpetual game of pinball.
Gastroschisis: can sonography of the fetal bowel accurately predict postnatal outcome?

To determine whether prenatal sonographic features of the small bowel can accurately predict postnatal outcome in fetuses with gastroschisis, the sonograms of 24 fetuses with prenatally detected gastroschisis were retrospectively reviewed for fetal bowel features including small bowel dilatation and bowel wall thickening. To identify a relationship between the sonographic features and neonatal outcome, each feature was analyzed against eight adverse clinical outcome measures including bowel obstruction or atresia, necrosis, and need for bowel resection, using chi-square analysis and Kendall's taub correlation. When a relationship was identified, the sensitivity and specificity of the sonographic feature for predicting adverse outcome were determined. Only maximum small bowel diameter was related to postnatal bowel complications. Significantly more fetuses with a maximum small bowel diameter of greater than 11 mm (7/12) had bowel complications than did fetuses with MBD 11 mm or less (2/12) P 11 mm). Although a maximum small bowel diameter of 11 mm stratified our fetuses, this measurement may not be clinically meaningful.
Characterization of mutants with single and multiple defects in the tryptophan biosynthetic pathway in Bacillus subtilis.

Abstract Sixty-five tryptophan auxotrophs which map in a cluster on the genome of Bacillus subtilis were characterized on the basis of (i) growth response, (ii) accumulation of intermediate compounds, and (iii) determination of enzymatic defects. They could be placed into six phenotypic classes. Certain of the mutants exhibited pleiotropic effects on more than one enzymatic activity in a manner different from those effects reported for the tryptophan pathway in other organisms. Invariably, mutations in the second gene, that coding for phosphoribosyl transferase activity, were found to lack the indoleglycerol phosphate synthase activity specified by the third gene in the cluster; however, this polarity did not extend to genes more distal in the cluster. Furthermore, mutations in the gene which codes for phosphoribosyl-anthranilate isomerase not only led to a loss of this enzyme but also to a loss of phosphoribosyl transferase and indoleglycerol phosphate synthase. In contrast, mutations in either of the loci coding for these latter functions had no apparent effect on isomerase activity. No polarity of the conventional type was found, e.g., none of the mutations in any gene led to polarized effects on the levels of the enzymes specified by the other genes of the cluster. These observations indicated a possible in vivo aggregation involving the transferase, isomerase, and synthase enzymes, with the isomerase acting as the “key” enzyme in the aggregate.
Stimulation of the subthalamic vasodilator area and fastigial nucleus independently protects the brain against focal ischemia.

Abstract We investigated whether stimulation of the functionally discrete subthalamic region, subthalamic cerebrovasodilator area (SVA), which increases cerebral blood flow (CBF) when excited, would, like stimulation of cerebellar fastigial nucleus (FN), produce central neurogenic neuroprotection. A 1-h electrical stimulation of SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral artery (MCA) by 48–55% in Sprague–Dawley rats and by 59% in Fisher rats. The salvaging effect of SVA stimulation, similar to FN, was long lasting and reduced the volume of infarctions placed 72 h or 10 days later by 58 and 26%, respectively, in Fisher rats. Bilateral lesioning of FN neurons by the microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA-evoked neuroprotection. Bilateral lesions of SVA neurons administered 5 days before FN stimulation had no effect on FN-induced neuroprotection but reversed the stimulus-locked increase in CBF accompanying FN stimulation. This study demonstrates that (1) excitation of neurons and/or fibers projecting through the SVA reduces ischemic infarctions as substantially as excitation of FN neurons; (2) the effects are long-lasting and not attributable to increases in cerebral blood flow, changes in blood gases or brain temperature, or rat strain; (3) the neuroprotective effects of SVA and FN stimulation are mutually independent and (4) FN-evoked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are part of a neuronal system in CNS, which is distributed and, when excited, acts to protect the brain from ischemic injury.
A road extraction method using beamlet transform

Synthetic Aperture Radar (SAR) systems have been widely used to estimate the various features on the ground. However, the images are often corrupted by noise that can impede further investigation of SAR images. Therefore, the extraction of features from SAR images with noisy backgrounds becomes a challenging issue in SAR image processing. The goal of this paper is to develop and implement a more robust method based on a beamlet transform to extract linear features such as roads from SAR images. The proposed method consists of three steps: First, an image pre-processing technique is used to offset the noise and low-contrast problems by recalculating the pixel values. Second, linear features such as road networks are then extracted by applying a beamlet transform based algorithm. In the third step, a post-processing algorithm is developed to analyze and link the discontinuities in order to connect the road networks in the image. Experimental results have demonstrated the effectiveness of this method.
A Framework for Studying Patterns of Effective Medication Adherence

Medication adherence has been studied extensively in the healthcare literature. Most of the studies focus on improving medication adherence using interventions, including those based on wireless and mobile technologies, and measure average medication adherence level. This is useful in differentiating between patients with high and low levels of adherence. In practice, the same average medication adherence could be achieved by patients with widely different adherence patterns. In this paper, the authors propose that in addition to average medication adherence level, the patterns of adherence should also be studied. The patterns of adherence can be obtained using wireless medication systems and set of actions/decisions can be communicated to these systems or mobile applications for medication management. The authors present a framework, some metrics including Effective Medication Adherence, and results related to the patterns of adherence. Their results show that pattern of adherence has significant impact on the effective medication adherence. Also, higher levels of effective adherence can be achieved for more flexible medication regimen, such as those with higher values of maximum inter-dose time. It is also possible for a patient with lower average adherence but a desirable pattern of adherence to have higher effective medication adherence than a patient with higher average adherence with less desirable pattern.
Loss ratio simulation method of MMPP/D/1/K using statistical techniques

For network planning and the operation of video streaming multicast services, it is very important to grasp the characteristics of packet loss against traffic type and buffer size because multicast uses UDP, not TCP, so packet recovery is not assured in this layer. This is possible by using Monte Carlo simulations (MCS), one of the most effective techniques. Although approximate methods have also been proposed as alternatives, in most cases, MCS results are provided to validate the proposal. However, there is no obvious way of determining when MCS should be terminated. This paper proposes a new obvious termination method for embedding in the MMPP/D/1/K MCS program that focuses on loss interval; it employs statistical techniques that allow loss ratios to be accurately estimated in the shortest possible time. The simulation is terminated when the χ2-statistic becomes less than or equal to a critical value, and the loss ratio is calculated from the number of all losses up to that time. A method of determining the parameters needed to calculate the χ2-statistic is also proposed to reduce the calculation time in MCS. To evaluate the proposed method, confidence intervals are obtained by applying the proposed method to six cases. Long-term loss ratios for the six cases are within 95 percent confidence intervals. 95 percent confidence intervals for the six cases are near approximate loss ratios. Embedding the proposed method in the MCS program imposes a time penalty of only 3.6 percent at most. The proposed method is thus very useful and usable.
Religion and Delinquency: Cutting Through the Maze

Research on the relationship between religion and delinquency has produced contradictory results, with some investigators uncovering a positive association, others a negative one, and still others none. Recent attempts to reconcile these findings have involved arguments that where, or in what social context, we measure the religion-delinquency association can affect our results. Herein, we show that how we measure that association can have an even more basic impact on our findings. When PRE-variety measures and chi-square statistics with multiple degrees of freedom are used to describe and test the significance of religion-delinquency associations, we find weak associations for some offenses but not others and even these vary according to how religion is measured. When odds ratios and more sensitive tests of significance are employed, we find strong effects of religion on all offenses regardless of how we measure it. In his recent presidential address to the Association for the Sociology of Religion, Stark announced his conversion to the belief that "religion has truly potent effects [on delinquency]" (1984, p. 273). This is the same Stark who in 1969, with Hirschi, published a brief article entitled "Hellfire and Delinquency" which suggested that it made no difference how often children attended church, how often their parents did the same, or how feverishly they believed that hell awaited sinners; religious youngsters were no less likely to be delinquent than their irreligious counterparts. "The church is irrelevant to delinquency," they concluded at that time, "because it fails to instill in its members love for their neighbors and because belief *Support for this research was provided by the Center for the Study of Youth Development at the Catholic University of America. We thank Travis Hirschi for providing some of the data for this report, Robert D. Ketterlinus for his help in analyzing the data, and the anonymous referees for their useful comments on an earlier draft. Address correspondence to Douglas M. Sloane, Center for the Study of Youth Development, Catholic University of America, Washington, DC 20064. ? 1986 The University of North Carolina Press
Characterizing the Locality of Diabatic States for Electronic Excitation Transfer By Decomposing the Diabatic Coupling

A common strategy to calculate electronic coupling matrix elements for charge or energy transfer is to take the adiabatic states generated by electronic structure computations and rotate them to form localized diabatic states. In this paper, we show that, for intermolecular transfer of singlet electronic excitation, usually we cannot fully localize the electronic excitations in this way. Instead, we calculate putative initial and final states with small excitation tails caused by weak interactions with high energy excited states in the electronic manifold. These tails do not lead to substantial changes in the total diabatic coupling between states, but they do lead to a different partitioning of the total coupling between Coulomb (Forster), exchange (Dexter), and one-electron components. The tails may be reduced by using a multistate diabatic model or eliminated entirely by truncation (denoted as “chopping”). Without more information, we are unable to conclude with certainty whether the observed diabatic tails are a physical reality or a computational artifact. This research suggests that decomposition of the diabatic coupling between chromophores into Coulomb, exchange, and one-electron components may depend strongly on the number of states considered, and such results should be treated with caution.
Two-dimensional infrared measurements of the coupling between amide modes of an α-helix

The 2D IR spectra of doubly isotopically substituted a-helices with 13 C@ 16 O and 13 C@ 18 O labels enabled the couplings between amide-I modes separated by one, two and three residues to be measured. The magnitudes and signs of couplings between the isotopomers and between them and the helix exciton band states confirm that the states of the helix and isotopomers are delocalized. The results are compared with simulations. The off-diagonal anharmonicities agree reasonably with a set of couplings that derive from transition charge interactions except for nearest neighbors for which the coupling is modified by through bond interactions. 2003 Published by Elsevier B.V.
Intra Placental Gene Transfer of Ad-hIGF-1 in a Mouse Model of Placental Insufficiency (PI) Corrects Liver Growth Factor Expression (IGFBP-1)

s / Placenta 34 (2013) A1–A99 A7 Conclusion: In conclusion, the YS in Necromys is able to generate MSCs with satisfactory characteristics of growth, expansion, freezing and in vitro differentiation. These cells resulted as potential stem cells with promising therapeutic values for cell therapy. Supported by FAPESP (Proc.09/53392-8).
Negative Regulation of VEGF Signaling in Human Coronary Artery Endothelial Cells by G Protein-Coupled Receptor Kinase 5

G protein-coupled receptor kinase 5 (GRK5) is present in endothelial cells (ECs) and has the potential to regulate EC function through seven transmembrane-spanning receptor (7TMR) signaling. Recently, it has been appreciated that GRKs can affect receptor tyrosine kinases (RTKs). VEGF, an RTK, is one of the most potent mediators for EC function and angiogenesis; therefore, we determined the role GRK5 plays in VEGF signaling in human coronary artery ECs (HCAECs). GRK5 levels were increased by VEGF treatment in HCAECs. Adenoviral overexpression of GRK5 inhibited migration and proliferation of HCAECs in response to VEGF. GRK5 overexpression in HCAECs significantly suppressed both acute and late activation of Akt and extracellular signal-related kinase (ERKs) as well as the phosphorylation of GSK-3beta, an endogenous substrate of Akt. Coimmunoprecipitations revealed that GRK5 is physically associated with Akt. This study shows for the first time that GRK5 negatively regulates VEGF signaling in HCAECs and suggests that targeted intervention of GRK5 in ECs might be a novel therapeutic strategy to prevent and treat disorders involving altered EC function.
Independent study in secondary schools

This paper reviews research and other publications on independent study in secondary schools in the United States appearing subsequent to the Alexander-Hines survey of the field in 1965–66. Particular attention is given to the rationale of independent study, types, characteristic features, independent study students and teachers, schedules, facilities, and outcomes. To the extent possible in the absence of another, more recent, comprehensive national survey, comparisons are made with the findings of the Alexander-Hines study. The state of the field, burgeoning but somewhat confused by the use of “independent study” as time rather than process, is summarized in a final section.
Knowing the unknowable and contested terrains in accounting

Abstract Creating visibilities and breaking silences are powerful legacies of critical accounting research and education. This paper, promoting that we further develop our understandings of how ideas are created, reveals how language is nuanced, power is embed in accounting technology, and accounting education crafts and restricts meaning. Particular ways of knowing in accounting education are appraised as well as emerging approaches to critical and ethical accounting education in order to deliberate: how can we foster a truly critical framework by which educators and students can “think different” and what can be done to promote sustainable, principled, and nuanced business practices? Our views of the morality of our world, how social structures affect ways of knowing, and what disrupts and challenges the status quo are particularly of concern to promote social transformation and justice.
eThread: A Highly Optimized Machine Learning-Based Approach to Meta-Threading and the Modeling of Protein Tertiary Structures

Template-based modeling that employs various meta-threading techniques is currently the most accurate, and consequently the most commonly used, approach for protein structure prediction. Despite the evident progress in this field, accurate structure models cannot be constructed for a significant fraction of gene products, thus the development of new algorithms is required. Here, we describe the development, optimization and large-scale benchmarking of eThread, a highly accurate meta-threading procedure for the identification of structural templates and the construction of corresponding target-to-template alignments. eThread integrates ten state-of-the-art threading/fold recognition algorithms in a local environment and extensively uses various machine learning techniques to carry out fully automated template-based protein structure modeling. Tertiary structure prediction employs two protocols based on widely used modeling algorithms: Modeller and TASSER-Lite. As a part of eThread, we also developed eContact, which is a Bayesian classifier for the prediction of inter-residue contacts and eRank, which effectively ranks generated multiple protein models and provides reliable confidence estimates as structure quality assessment. Excluding closely related templates from the modeling process, eThread generates models, which are correct at the fold level, for >80% of the targets; 40–50% of the constructed models are of a very high quality, which would be considered accurate at the family level. Furthermore, in large-scale benchmarking, we compare the performance of eThread to several alternative methods commonly used in protein structure prediction. Finally, we estimate the upper bound for this type of approach and discuss the directions towards further improvements.
Cell Culture Techniques

Publisher Summary This chapter surveys the cell culture approach to studying the brain. There are various equipment and reagents that are necessary to maintain cells outside their endogenous environments including biosafety hood, cell incubator, treated cell culture flasks/plates, and water bath. Further, growth media is also critical to cell culture experiments, supplying nutrients (amino acids and vitamins), and a source of energy (glucose) for cells. There are three categories of cells used in culture experiments: immortalized cell lines, primary cell cultures, and stem cells. Immortalized cell lines are the cells that have been manipulated to proliferate indefinitely and can thus be cultured for long periods of time. These are derived from a variety of sources that have chromosomal abnormalities or mutations that permit them to continually divide, such as tumors. Primary cell and tissue culture uses tissue removed directly from a living animal rather than immortalized cells that continuously divide in a dish. Primary tissue culture allows scientists to directly investigate cells of interest, probing the functions of specific neuronal or glial subtypes and the cellular and molecular dynamics specific to certain cell types. They are like immortalized cell lines in that they should theoretically be able to be propagated in culture continuously, but they are also primary cells derived directly from a living organism. Stem cells are characterized through gene and protein marker expression as well as function.
SENSITIVITY ANALYSIS OF THE STOCHASTIC GROWTH RATE: THREE EXTENSIONS†

Summary The perturbation analysis of population growth rate plays an important role in population biology. The sensitivity and/or elasticity (proportional sensitivity) of population growth rate to changes in the vital rates are regularly used (i) to predict the effects of environmental perturbations, (ii) to characterize selection gradients on life-history traits, (iii) to evaluate management tactics, (iv) to analyse life table response experiments, and (v) to calculate the sampling variance in population growth rate. In a stochastic environment, population growth is described by the stochastic growth rate, which gives, with probability 1, the asymptotic time-averaged growth rate of any realization. Tuljapurkar derived the sensitivity and elasticity of the stochastic growth rate to changes in the entries of the stochastic matrices. This paper extends his result to cover three cases, each of which has arisen recently in applications. The first gives the response of the stochastic growth rate to environment-specific perturbations, applied only in a specified subset of the possible environments. The second gives the sensitivity and elasticity of the stochastic growth rate to changes in lower-level parameters. The third applies to stochastic seasonal models, in which the projection matrix for each year is a periodic product of matrices describing seasonal transitions. In this case interest focuses on the sensitivity of the stochastic growth rate to changes in the entries of the seasonal matrices, not entries in the annual matrices. The paper describes examples of problems where each of these extensions is needed, and the algorithms for each of the new calculations.
Who gets the best sleep? Ethnic and socioeconomic factors related to sleep complaints

Objectives Lower socioeconomic status is associated with short or long sleep duration and sleep disturbance (e.g., sleep apnea), which are all related to increased mortality risk. General sleep complaints, however, which may better approximate symptoms as they are experienced, have not been examined in a large population sample.
Amrinone and the Pulmonary Vascular Pressure–Flow Relationship in Conscious Control Dogs and Following Left Lung Autotransplantation

Background: Amrinone, a bipyridine compound, is known to improve left ventricular function via its positive inotropic and afterload-reducing effects. The goal of this study was to assess the efficacy of amrinone as a pulmonary vasodilator, an effect that could be beneficial in the setting of right heart failure associated with pulmonary hypertension. Methods: investigated were the effects of intravenous amrinone (750 μg/kg loading dose plus 1-20 μg.kg -1 .min -1 maintenance dose) on the left pulmonary vascular pressure-flow (LPQ) relationship in chronically instrumented, conscious dogs
Tokamak start-up with electron-cyclotron heating

Experiments are described in which the startup voltage in a tokamak is reduced by approx. 60% by the use of a modest amount of electron cyclotron resonance heating power for preionization. A 50% reduction in volt-second requirement and impurity reflux are also observed.
Testicular neoplasms in children

Six cases of testicular tumors in children are presented: 3 patients had teratoma, 1 embryonal carcinoma, 1 orchioblastoma, and 1 paratesticular rhabdomyosarcoma. Three of the 6 patients presented with hydroceles. The treatment consisted of orchiectomy alone. All patients were alive and free of disease one and one-half to eight and one-half years after orchiectomy. It is suggested that orchiectomy alone is curative in most children with testicular tumors under the age of two years.
An interview with Dan L. Longo, Section Editor of the Malignant hematological diseases section

Dan L. Longo is professor of medicine at Harvard Medical School in the division of hematology at Brigham and Women’s Hospital and Deputy Editor of the New England Journal of Medicine. He is a Master of the American College of Physicians and is a member of the American Society of Clinical Investigation and the Association of American Physicians. He has been active in research on the treatment of malignant lymphoma including new treatments targeting CD30, CD40, HLA Class II molecules and immunoglobulin idiotype. His laboratory work has focused in part on the regulation of lymphocyte proliferation, NK cell effects on hematopoiesis, and tumor-induced immunosuppression. He is the Section Editor of the Malignant hematological diseases section for BMC Hematology. In this interview, he explains how he first became interested in hematology and gives his personal view on the recent progress and future challenges of the hematological cancer field in particular.
Market and Non-Market Failures: Comparison and Assessment

This paper aims to redress the asymmetry in the standard economic treatment of the shortcomings of markets and governments by developing and applying a theory of ‘nonmarket’ failure– that is, of government failure – so that the comparison between markets and governments can be made more systematically, and choices between them arrived at more intelligently. Several conclusions are drawn. First, the choice between markets and governments is not a pure one, actual systems inevitably involve combinations between markets and governments. Second, with respect to both static and dynamic efficiency criteria, markets generally do better than governments. Third, there are various ways in which government can contribute to improving the functioning of markets. Fourth, market forces can play a useful role in improving the functioning of government and reducing the incidence of nonmarket failures.
Modeled biogeochemical responses to mesoscale eddies in the South China Sea

[1] Mesoscale eddies are observed each year in the South China Sea (SCS); however, their contributions to the biogeochemical cycles have never been systematically quantified. Here, we use a coupled three-dimensional physical-biogeochemical model to evaluate the eddy impact. We first track the modeled mesoscale eddies in the SCS and then analyze the biogeochemical responses to these eddies individually. Compared with the SCS basin mean, modeled depth-integrated (0–125 m) chlorophyll, zooplankton, new production, and silicate uptake are significantly enhanced in the cyclonic eddies and reduced in the anticyclonic eddies. Following the movements of the eddy center, temporal variations of phytoplankton community structure suggest that diatoms respond to cyclonic eddies strongly first and the responses last longer; then picoplankton grow after the diatoms. In the cyclonic eddies, modeled new production is 1.87 ± 0.37 mmol N m−2 d−1, which is 28% higher than the SCS basin-averaged value, while in the anticyclonic eddies, modeled new production is about 32% lower than the SCS basin mean. As a consequence, modeled detrital nitrogen export for cyclonic eddies is 41% higher than the SCS basin mean, and that for anticyclonic eddies is 31% lower than the SCS basin mean. These values experience strong interannual variations with anomalously low magnitudes found during El Nino conditions for both of the eddies and the SCS basin mean. Our results indicate that cyclonic eddies in the SCS are important sources of nutrients to the euphotic zone and therefore play a significant role in regulating biological productivity and the carbon cycle.
Assessing health care use and cost consequences of a new screening modality: the case of digital mammography.

BACKGROUND Full-field digital mammography (FFDM) has largely replaced screen-film mammography (SFM) for breast cancer screening, but how this affects downstream breast-related use and costs is unknown. OBJECTIVES To compare breast-related health care use and costs among Medicare beneficiaries undergoing SFM versus FFDM from 1999 to 2005. DESIGN Retrospective cohort study. SUBJECTS Medicare-enrolled women aged 66 and older with mammograms in Breast Cancer Surveillance Consortium registries. MEASURES Subsequent follow-up with additional imaging or breast biopsy within 12 months was ascertained through Medicare claims. Associated mean costs were estimated by screening modality and year, adjusting for confounding factors, and clustering within mammography facilities using Generalized Estimating Equations. RESULTS Among 138,199 women, 332,324 SFM and 22,407 FFDM mammograms were analyzed. Approximately 6.5% of SFM and 9.0% of FFDM had positive findings. In 2001, subsequent imaging was higher among FFDM versus SFM (127.5 vs. 97.4 follow-up mammography claims per 1000 index mammograms), whereas subsequent biopsy was lower among FFDM versus SFM (19.2 vs. 24.9 per 1000 index mammograms) with differences decreasing over time. From 2001 to 2004, mammography subsequent to FFDM had higher mean costs than SFM ($82.60 vs. $64.31 in 2001). The only cost differences between SFM and FFDM for ultrasound or biopsy were in 2001. CONCLUSIONS Subsequent breast-related health care use differed early in FFDM introduction, but diminished over time with differences attributable to higher recall rates for additional imaging and lower rates of biopsy in those undergoing FFDM versus SFM. Remaining cost differences are because of higher reimbursement rates for FFDM versus SFM.
Neural substrates of the cognitive processes underlying spelling: Evidence from MR diffusion and perfusion imaging

Background: Despite a rich literature on the cognitive processes underlying spelling, there is little known about the neural substrates of these processes. Aims: The study aimed to identify regions of brain dysfunction associated with impairment of each cognitive process underlying spelling. It was hypothesised that impairments of distinct components of the spelling task would be associated with different areas of low blood flow or infarction in acute stroke patients. Methods & Procedures: Associations between impairment of each component of the spelling process and hypoperfusion and/or infarct of any of 11 Brodmann's areas (BAs) were identified in a consecutive series of 80 patients studied within 24 hours of onset of left hemisphere stroke. Impairment of each component of spelling was identified with tests of written naming, word comprehension, spelling words and pseudowords to dictation, direct and delayed copying, and case transcoding. Infarct and/or hypoperfusion in each BA was identified with MR dif...
Immunoassay readout method using extrinsic Raman labels adsorbed on immunogold colloids

An immunoassay readout method based on surface-enhanced Raman scattering (SERS) is described. The method exploits the SERS-derived signal from reporter molecules that are coimmobilized with biospecific species on gold colloids. This concept is demonstrated in a dualanalyte sandwich assay, in which two different antibodies covalently bound to a solid substrate specifically capture two different antigens from an aqueous sample. The captured antigens in turn bind selectively to their corresponding detection antibodies. The detection antibodies are conjugated with gold colloids that are labeled with different Raman reporter molecules, which serve as extrinsic labels for each type of antibody. The presence of a specific antigen is established by the characteristic SERS spectrum of the reporter molecule. A near-infrared diode laser was used to excite efficiently the SERS signal while minimizing fluorescence interference. We show that, by using different labels with little spectral overlap, two different antigenic species can be detected simultaneously. The potential of this concept to function as a readout strategy for multiple analytes is briefly discussed.
Perturbation in connexin 43 and connexin 26 gap‐junction expression in mouse skin hyperplasia and neoplasia

To examine the possible role of gap junctions in mouse skin tumor progression, we generated a panel of mouse skin tissue samples exhibiting normal, hyperplastic, or neoplastic changes and characterized the expression of the gap-junction genes connexin 43 (Cx43) and connexin 26 (Cx26) by in situ hybridization and immunohistochemical analyses. In normal skin, these two gap junction genes were differentially expressed; Cx43 was found predominantly in the less differentiated lower spinous layers, whereas Cx26 was found in terminally differentiating upper spinous and granular layers. In hyperplastic epidermis exhibiting an expansion of the differentiated upper layer, i.e., epidermis with a thickened granular layer or in which the granular layer was replaced with keratinocytes exhibiting tricholemmal differentiation, expression of Cx43 and Cx26 remained segregated in the lower and upper spinous layers, respectively. However, in papillomas, Cx26 was localized in the lower but not upper spinous layer, an expression pattern identical to that of Cx43. In addition, the overall expression levels of both Cx43 and Cx26 appeared to be greatly elevated in the papillomas. It is interesting that such marked alteration in the pattern of Cx26 expression occurred within the context of hyperplastic changes histologically identical to those seen in the nonpapillomous hyperplasias. Interestingly, in neoplastic skin lesions containing a squamous cell carcinoma, Cx43 and Cx26 expression was extinguished. Moreover, expression of Cx43 was also significantly reduced in adjacent apparently nonneoplastic tissues. Overall, these observations show that perturbations in gap-junction gene expression are associated with skin hyperplasia and neoplasia. Such findings suggest a possible role for gap junctions in the malignant conversion of mouse epidermal cells.
Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway

Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-kappaB signaling pathway, we investigated the effects of GA on NF-kappaB-mediated cellular responses and NF-kappaB-regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-x(L), and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-kappaB. GA suppressed NF-kappaB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IkappaBalpha phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-kappaB-dependent reporter gene expression. The NF-kappaB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKbeta was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-kappaB and apoptosis. Overall our results demonstrate that GA inhibits NF-kappaB signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor.