cssi/SciSciGPT-SciSciNet huggingface dataset:
Bayesian hierarchical error model for analysis of gene expression data

Motivation: Analysis of genome-wide microarray data requires the estimation of a large number of genetic parameters for individual genes and their interaction expression patterns under multiple biological conditions. The sources of microarray error variability comprises various biological and experimental factors, such as biological and individual replication, sample preparation, hybridization and image processing. Moreover, the same gene often shows quite heterogeneous error variability under different biological and experimental conditions, which must be estimated separately for evaluating the statistical significance of differential expression patterns. Widely used linear modeling approaches are limited because they do not allow simultaneous modeling and inference on the large number of these genetic parameters and heterogeneous error components on different genes, different biological and experimental conditions, and varying intensity ranges in microarray data. Results: We propose a Bayesian hierarchical error model (HEM) to overcome the above restrictions. HEM accounts for heterogeneous error variability in an oligonucleotide microarray experiment. The error variability is decomposed into two components (experimental and biological errors) when both biological and experimental replicates are available. Our HEM inference is based on Markov chain Monte Carlo to estimate a large number of parameters from a single-likelihood function for all genes. An F-like summary statistic is proposed to identify differentially expressed genes under multiple conditions based on the HEM estimation. The performance of HEM and its F-like statistic was examined with simulated data and two published microarray datasets---primate brain data and mouse B-cell development data. HEM was also compared with ANOVA using simulated data. Availability: The software for the HEM is available from the authors upon request.
Dynamic factor graphs: A novel framework for multiple features data fusion

The Dynamic Tree [1] (DT) Bayesian Network is a powerful analytical tool for image segmentation and object segmentation tasks. Its hierarchical nature makes it possible to analyze and incorporate information from different scales, which is desirable in many applications. Having a flexible structure enables model selection, concurrent with parameter inference. In this paper, we propose a novel framework, dynamic factor graphs (DFG), where data segmentation and fusion tasks are combined in the same framework. Factor graphs (FGs) enable us to have a broader range of modeling applications than Bayesian networks (BNs) since FGs include both directed acyclic and undirected graphs in the same setting. The example in this paper will focus on segmentation and fusion of 2D image features with a linear Gaussian model assumption.
Far Infrared Sealed Liquid Cell with Polyethylene Windows

Liquid cells of constant path length with high density polyethylene windows for the it region are generally difficult to obtain. Most commercially available 1 polyethylene cells are sufficient only for survey spectra and cannot be used for careful measurements during long or repeated scans since repeatability and adequate absorbance measurements 2 are difficult to obtain. Moreover, the measurement of air sensitive solutions is often unsuccessful because air leaks develop and because determining the actual cell thickness is not easy.
Learning Time-Intensity Profiles of Human Activity using Non-Parametric Bayesian Models

Data sets that characterize human activity over time through collections of time-stamped events or counts are of increasing interest in application areas as human-computer interaction, video surveillance, and Web data analysis. We propose a non-parametric Bayesian framework for modeling collections of such data. In particular, we use a Dirichlet process framework for learning a set of intensity functions corresponding to different categories, which form a basis set for representing individual time-periods (e.g., several days) depending on which categories the time-periods are assigned to. This allows the model to learn in a data-driven fashion what "factors" are generating the observations on a particular day, including (for example) weekday versus weekend effects or day-specific effects corresponding to unique (single-day) occurrences of unusual behavior, sharing information where appropriate to obtain improved estimates of the behavior associated with each category. Applications to real-world data sets of count data involving both vehicles and people are used to illustrate the technique.
Microsatellite DNA in genomic survey sequences and UniGenes of loblolly pine

Genomic DNA sequence databases are a potential and growing resource for simple sequence repeat (SSR) marker development in loblolly pine (Pinus taeda L.). Loblolly pine also has many expressed sequence tags (ESTs) available for microsatellite (SSR) marker development. We compared loblolly pine SSR densities in genome survey sequences (GSSs) to those in non-redundant EST and cDNA sequences (UniGenes) and designed SSR primer pairs from both sequence types. Overall SSR densities were 96 SSR/Mb in GSSs and 38 SSR/Mb in UniGenes. Loblolly pine had the lowest transcriptome SSR density when compared to 49 other species in the NCBI UniGene database. Among the five different GSS genome fractions of loblolly pine analyzed, methylation-filtered DNA had the highest SSR density at 145 SSR/Mb. The most abundant loblolly pine SSR motif was AT in both GSSs (34 SSR/Mb) and UniGenes (7.6 SSR/Mb). Among the trinucleotide SSR motifs, the most abundant was AAT (9.5 SSR/Mb) in GSSs and AGC (4.9 SSR/Mb) in UniGenes. We designed PCR primer pairs for 120 genomic SSRs and 315 EST-SSRs and evaluated PCR amplification for 108 (25%). We identified 21 primer pairs that reliably amplified polymorphic loci from 31 loblolly pine individuals and estimated that at least 60 additional polymorphic marker loci could be developed from available P. taeda GSS and UniGene resources.
Balance testing and balance-testable design of logic circuits

We propose a low-cost method for testing logic circuits, termed balance testing, which is particularly suited to built-in self testing. Conceptually related to ones counting and syndrome testing, it detects faults by checking the difference between the number of ones and the number of zeros in the test response sequence. A key advantage of balance testing is that the testability of various fault types can be easily analyzed. We present a novel analysis technique which leads to necessary and sufficient conditions for the balance testability of the standard single stuck-line (SSL) faults. This analysis can be easily extended to multiple stuck-line and bridging faults. Balance testing also forms the basis for design for balance testability (DFBT), a systematic DFT technique that achieves full coverage of SSL faults. It places the unit under test in a low-cost framework circuit that guarantees complete balance testability. Unlike most existing DFT techniques, DFBT requires only one additional control input and no redesign of the underlying circuit is necessary. We present experimental results on applying balance testing to the ISCAS 85 benchmark circuits, which show that very high fault coverage is obtained for large circuits even with reduced deterministic test sets. This coverage can always be made 100% either by adding tests or applying DFBT.
Programmable analog device array (PANDA): a platform for transistor-level analog reconfigurability

The design and development of analog/mixed-signal (AMS) ICs is becoming increasingly expensive, complex, and lengthy. Lacking a reconfigurable platform, analog designers are denied the benefits of rapid prototyping, hardware emulation, and smooth migration to advanced technology nodes. To overcome these limitations, this work proposes a new approach that maps any AMS design problem to a transistor-level reconfigurable vehicle, thus enabling fast validation and a reduction in post-Silicon bugs, and minimizing design risk and costs. The unique features of the approach include: (1) transistor-level programmability that emulates each transistor behavior in an analog design, reproducing the system and achieving very fine granularity of reconfiguration; (2) programmable switches that are treated as a design component during analog transistor mapping, and optimized with the reconfiguration matrix; (3) parasitics reduction that leverages the aggressive scaling of CMOS technology. Based on these principles, a digitally controlled PANDA platform is designed at a 32nm node. Several 90nm analog blocks are successfully emulated with the 32nm platform, including a folded-cascode operational amplifier, a sample-and-hold module (S/H), and a voltage-controlled oscillator (VCO). A solid basis to future efforts on the architecture, hierarchical optimization, and related design automation tools is demonstrated.
EFFECTS OF TAXATION ON THE INVESTMENT POLICIES AND CAPACITIES OF INDIVIDUALS

THE CRYING NEED in a study of the effects of taxation on the investment capacity and policies of individuals-especially of individuals with large incomes and substantial wealth-is for empirical information.1 The theoretical aspects of the problem have been discussed at length in academic literature. Previous studies have also provided extensive aggregative analysis and a considerable amount of case material illustrating different types of investor reactions. But the available empirical information has been so limited that it has been difficult or impossible to draw even tentative generalizations as to how investors really think and act which were founded on fact rather than on hypothesis or assertion. In this paper we shall summarize the main conclusions of a research project which has attempted to obtain a broad base of empirical data bearing on this problem. In order to have time to touch on at least the highlights of our main findings we shall not stop to describe our methodology except to say that it has relied heavily on the "small sample" field survey techniques; our primary sources of information consist of Survey Research Center data and a sample of 750 interviews with private investors, mainly in the upper income and wealth percentiles of the population. The latter interviews were conducted by our staff as part of the empirical research underlying this study.
Selective Silicon-Germanium Source/Drain Technology for Nanoscale Cmos

Future CMOS technology nodes bring new challenges to formation of source/drain junctions and their contacts. To avoid MOSFET performance degradation with scaling, series resistance contribution of each junction must be limited to five percent of the device channel resistance. This requires ultra-shallow junctions with extremely low sheet, spreading and contact resistance. In this paper, we present an overview of the SiGe junction technology recently proposed by this laboratory for nanoscale CMOS. The technology is based on selective deposition of boron or phosphorus doped SiGe alloys in source/drain regions isotropically etched to the desired junction depth. Since the dopant atoms naturally occupy the substitutional sites during growth, the need for an activation anneal is completely eliminated limiting the maximum process temperature to 550°C for boron and 750°C for phosphorus. In this temperature range, dopant diffusion is virtually eliminated resulting in extremely abrupt doping profiles. Elimination of the high temperature implant anneal also makes the process compatible with the thermal stability needs of future high-K gate dielectrics. A key advantage of the technology is its potential to reduce the junction contact resistance. SiGe provides a smaller bandgap under the metal contact resulting in a smaller metal-semiconductor barrier height. Since the contact resistivity is an exponential function of the barrier height, the technology provides a significant advantage in reducing the contact resistivity. The results to date indicate that the technology is a promising alternative for nanoscale CMOS source/drain junctions and their contacts.
Influences of the paraventricular and suprachiasmatic nuclei and olfactory bulbs on melatonin responses in the golden hamster.

Removal of the pineal, or denervation of thisgland by superior cervical ganglionectomy, blocks testicular regressionin golden hamsters exposed to short photoperiods. Aspiration of the olfactory bulbs or lesions of the suprachiasmatic or paraventricularnuclei of the hypothalamus (SCNx or PVNx) have similareffects. We have examined the effects of these operations on pineal melatonin content and gonadal responses to various patterns of exogenous melatonin in order to examine the roles played by the olfactory bulbs, the SCN, and the PVN in hamster photoperiodism. SCNx and PVNx significantly reduced pineal melatonin content throughout the dark phase, while bulbectomy did not significantly affect melatonin concentrations at the time of the nocturnal peak. Bulbectomy significantlydelayed the nightly onset of locomotor activityin hamsters exposed to 14L: 1OD, but not that of animals housed in 1OL:14D. Although bulbectomy reduced the gonadal response to one or three daily injectionsof melatonin, these individuals exhibited significant testicular regression in response to melatonin as long as injections fell in the evening. In contrast, destruction of the PVN rendered hamsters unresponsive to one daily melatonin injection, but equally responsive to three injections, regardless of the time of day at which these injevtions were given. Whereas exposure of bulbectomized hamsters to 30 weeks of short days made them refractory to subsequent melatonin challenge, PVNx hamsters remained sensitive to appropriately timed melatonin treatments regardless of their photoperiodic history. Many, but not all hamsters that experienced complete SCN lesions remained sensitive to three daily melatonin injections. The results indicate that these operations differ fundamentally in their influence on hamster photoperiodism: destruction of the SCN or PVN intereferes with melatonin synthesis, and removal of the olfactory bulbs overrides reproductive responses to a normal melatonin signal.
A Critique of Instructional

The ‘objectives model’ of curriculum planning, predicated upon behavioural performances, has become the dominant form of curriculum planning in Europe and elsewhere in the world. This paper argues that the objectives model is satisfactory for training or instruction, but falls down when applied to a true sense of ‘education’. The paper outlines 13 limitations on the use of educational objectives. It is argued that those interested in using objectives are guided by evaluation as assessment rather than principles of procedure for education. Education is about the process of ‘travelling’ on an educational journey – not about ‘arriving’ at a destination. Keywords: instructional objectives, limitations of objectives, curriculum planning, process model. (Published: 1 March 2010) Citation: Education Inquiry Vol. 1, No. 1, March 2010, pp.57–67
Velocity modulation spectroscopy of molecular ions I: The pure rotational spectrum of TiCl+ (X3Φr)

The pure rotational spectrum of the TiCl + ion in its X 3 Ur ground state has been measured in the frequency range 323–424 GHz, using a combination of direct absorption and velocity modulation techniques. The ion was created in an AC discharge of TiCl4 and argon. Ten, eleven, and nine rotational transitions were recorded for the 48 Ti 35 Cl + , 48 Ti 37 Cl + , and 46 Ti 35 Cl + isotopomers, respectively; fine structure splittings were resolved in every transition. The rotational fine structure pattern was irregular with the X =4 component lying in between the X = 2 and 3 lines. This result is consistent with the presence of a nearby 3 Dr state, which perturbs the X = 2 and 3 sub-levels, shifting their energies relative to the X = 4 component. The data for each isotopomer were analyzed in a global fit, and rotational and fine structure parameters were determined. The value of the spin–spin constant was comparable to that of the spin–orbit parameter, indicating a large second-order spin–orbit contribution to this interaction. The bond length established for TiCl + , r0 = 2.18879 (7) A ˚ , is significantly shorter than that of TiCl, which has r0 = 2.26749 (4) A ˚ . The shorter bond length
A 100-MS/s 4-MHz Bandwidth 77.3-dB SNDR ΔΣ ADC with a Triple Sampling Technique

A new ΔΣ ADC architecture using a triple sampling technique and a two-step summation scheme is presented. A 4th-order switched-capacitor ΔΣ ADC with a 4-bit quantizer is designed for a low-power direct-conversion digital TV receiver SoC. It achieves a 77.3-dB SNDR over a 4-MHz bandwidth with a 100-MHz clock frequency. The chip, fabricated in a 0.18-mum CMOS process, occupies 1.57 mm2 and draws 15.3 mA from a 1.8-V supply. It achieves a 0.58-pJ/conversion FOM
Voluntary Choices in Concerted Deals: The Menu Approach to Debt Reduction in Developing Countries

This article examines the mechanics and attributes of concerted debt reduction agreements that offer creditors a choice between exit and relending options. The menu approach sets prices for different choices that implement a decentralized equilibrium. When banks can commit to choose from the menu and are not allowed to free ride, a menu can be designed that assures that the price paid for debt repurchased is equal to the marginal value of the debt claims. This can be achieved by taxing the gains that accrue to nonexiters witb a request for new money. The equilibrium amount of debt reduction rises when the new money request is increased. The importance of banks' heterogeneity for menus to dominate simple concerted buybacks and the case in which debt reduction can be financed by loans from international financial institutions are discussed.
The death watch: certifying death using cardiac criteria

In the past, inadequate diagnostic instruments sometimes led to incorrect diagnoses of death, so careful and prolonged observation--the "death watch"--was required. Diagnostic instruments are now accurate and determining the presence or absence of circulation and cerebral function is easy in virtually all cases. Still, ambiguity and controversy in diagnosing death persists because the current criteria, irreversible cessation of cardiac or whole brain function, are ambiguous. Recent reintroduction of non-heart-beating organ donation has highlighted the controversy. Data on the ability to achieve restoration of spontaneous circulation are quite consistent, but they support several different sets of reasonable death criteria. This article concludes with a rejection of a fixed notion of "irreversibility" because it does not conform to current practice, is potentially deleterious to social events at the time of death, and the reversibility of cardiopulmonary arrest is dependent on available means of resuscitation. Finally, the time required to ensure irreversible cessation of cardiac function despite potential intervention is too broad to be clinically applicable and is unreasonable. Diagnosis of death should be based on the context in which it occurs because the medical means available determine what is irreversible.
Biological correlates of prostate cancer perineural invasion diameter

Perineural invasion is a symbiotic relationship between cancer cells and nerves and is most frequently seen in "neurotropic" cancers such as prostate cancer. It results in increased perineural space cancer cell growth and decreased apoptosis and induces nerve growth. Tissue microarrays were constructed from 640 radical prostatectomy specimens with prostate cancer. The perineural diameter was measured as previously described. Multiple biomarkers have been previously performed on this tissue microarray cohort, and all data were kept in the same database. The biomarker results database was queried for correlations between perineural invasion diameter and tissue biomarkers. Increased perineural invasion diameter correlated with increased proliferation of prostate cancer cells and with apoptosis. It also correlated with proteins involved in survival pathways such as nuclear factor κB, c-Myc, phosphorylated AKT, and its downstream effector FHKR, but not with GSK. Unlike nerve density, it did not correlate with decreased PTEN expression. Increased perineural invasion diameter was associated with higher levels of hormonal receptors such as androgen receptor, but not estrogen receptor. Also associated with perineural invasion diameter were coregulators and corepressors including SRC1 and TIF2. Perineural invasion diameter had the strongest correlation with tumor volume (ρ = 0.579, P = .000), not identified with nerve density. These data demonstrate that perineural invasion has the same biologic correlations as neural density. However, we found a distinct and very strong correlation with increased tumor volume. These data confirm that perineural invasion is the ultimate and most successful interaction between cancer cells and nerve fibers, resulting in increased tumor growth.
Alcohol-induced protein hyperacetylation: Mechanisms and consequences

Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylation. This reversible, post-translational modification on the epsilon-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol-induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.
Simulations of Frontogenesis in a Moist Atmosphere Using Alternative Parameterizations of Condensation and Precipitation

Abstract Heat and moisture budgets are computed for the 40 km model simulations of moist frontogenesis described recently by Hsie and others. The apparent heat source and moisture sinks are dominated by the condensation term and have maxima in the middle troposphere. Both the large-scale (200 km) moisture convergence and the large-scale vertical motion are highly correlated with the mesoscale condensation rate. Four alternative schemes for treating the effects of moist convection in primitive equation models are tested, and the results compared with those from the explicit scheme for calculating condensation and precipitation. A scheme in which only water vapor is predicted yields results similar to the explicit simulation, which included prediction equations for water vapor, cloud water and rainwater. The neglect of two opposing effects-water loading and evaporation-is apparently responsible for the similarity to the control. However, when both cloud water and water vapor are predicted, the presence of e...
Linking Racial-Ethnic Socialization to Culture and Race-Specific Coping Among African American College Students:

In addition to the use of coping strategies generally shared by all Americans, research has shown that African Americans tend to make use of culture and race-specific coping styles that distinguish...
Of Diamonds and Rust: A New Look at Resources

The German philosopher Hegel told us that one can understand oneself better by understanding others. By seeing what one is not, one sees better what one is. In the stream of discussions at the Copenhagen conference, I gained a new perspective on the challenge of blending evolutionary and strategic theories of the firm: the biggest hurdles are not analytical but philosophical. Evolutionary theorists and business strategists have fundamentally different world views. Although our preconference paper (see Chapter 1) duly noted the different legacies of each tradition, we missed the enormity of the ideology, the deep-seated convictions and ways of seeing that underlie the respective streams of work.
Organizational Decision-Making - Aggregating Individuals' Incentives and Information

How organizations - systems in which multiple actors with private information and heterogeneous incentives work towards a joint goal - reach decisions, is a question of fundamental importance to sc...
DNP and PhD collaboration: Bringing together practice and research expertise as predegree and postdegree scholars

A deliberate course of predegree intraprofessional DNP and PhD student collaboration can yield relationships that will facilitate postdegree teamwork. Working together, DNP-prepared nurses can use their practice expertise, and PhD-prepared nurses can use their research expertise to improve and change health care. This article presents 3 contexts in which predegree collaboration can occur between DNP and PhD students. Postdegree DNP and PhD collaboration can occur in 2 contexts.
Growing Organic Heirloom Tomatoes in the Field and High Tunnels in North Carolina: Comparative Economic Analysis

In this study, we conducted an economic analysis of high tunnel and openfield production systems of heirloom tomato (Solanum lycopersicum) based on a twoyear study at the Center for Environmental Farming Systems (CEFS) located in Goldsboro, eastern North Carolina. The research site was transitional organic using organically certified inputs and practices on land not yet certified. Production costs and returns were documented in each system and provide a useful decision tool for growers. Climatic conditions varied dramatically in 2007 compared with 2008 and differentially affected total and marketable yields in each system. Profits were higher in the open-field system and the high tunnels in 2007 and 2008, respectively. Sensitivity analysis was conducted using a range of market prices from $1.60/lb to $3.60/lb and a range of fruit marketability levels from 35% to 80%. Both systems were profitable except at the lowest price point and the lowest percent marketability level in high tunnel in 2007. At $2.60/lb, seasonal average sale price reported by growers for this region, and depending on percent marketability levels, the payback period for high tunnels ranged from two to five years. Presented sensitivity tables will enable decision makers to knowledgably estimate economic potential of open-field and high tunnel systems based on expected local prices and fruit quality parameters.
Advantages of telepsychiatry in child and adolescent mental health

Introduction Telepsychiatry is increasingly utiilized to evaluate and treat diagnostically and geographically diverse youth. (Szeftel et al., 2012; Hilty et al., 2013). Important public health implications arise for US psychiatrically ill youth, most of whom receive no treatment, others depend on pediatricians without input from a child psychiatrist (Goldstein and Myers, 2014). Potential advantages of telepsychiatry include increased access to care from child psychiatrists directly, and through collaborations with pediatricians, and uniquely positive response in patients more communicative in this setting (Pakyrek et al., 2010). Objectives – To present the effectiveness of Telepsychiatry in psychiatrically ill youth, and specific subgroups who especially benefit. – To show increased access to psychiatric care occurs through collaborations between child psychiatrists and pediatricians. Aims To present the advantages of telepsychiatry for child and adolescent mental health and clinicians. Methods Review of selected published Telepsychiatric evidence-based research and best practice recommendations. Results – Psychiatrically ill youth are effectively evaluated and treated using Telepsychiatry (Myers et al. (2011), Hilty et al., 2013). – Very young children and youth with Autism Spectrum Disorders, or anxiety disorders respond particularly positively to Telepsychiatry (Szeftel et al., 2012; Pakyuerek et al., 2010: Myers et al., 2010). – Telepsychiatry provides increased access to care through collaborations between child psychiatrists and pediatricians (Goldstein and Myers, 2014; Myers et al., 2011). Conclusion Telepsychiatry is a promising advantageous modality for youth based on effectiveness, broad administration and unique benefit for very young and socially impaired youth. References not available.
Detection and analysis of influenza during 2009 in Xicheng network laborotary of state

Objective:Detection on throat swab specimens from patients suspected influenza of two hospital in Xicheng district in order to analyze the epidemic characteristics of Influenza in 2009.Methods:We have detected virus nucleic acid isolated from specimens on specific genes infA,SWinfA,SWH1 and control gene RNP by real-time RT-PCR,then identified the subtype on FluB,FluH1,Flu H3 genes.Results:In total 1220 specimens,there were 279 positive samples with influenza A(H1N1)virus subtype,moerover,the higest quantity emergered in October and November;in addition to the existence of the seasonal influenza subtypes,the positive of A(H3) subtypes were 113 which the higest quantity emergered in August and September,the positive of B subtypes were 28 which the higer quantity emergered in December,the positive of A1 subtypes were 7 which disapared after September A(H1),as well as 32 positive of A subtypes undentified.Conclusion:Influenza A(H1N1)virus were predominant strains strains in Xicheng district in 2009,as the same time,there were also exist the seasonal influenza strains with the differiential subtype and emergered in different time.
Acidic isoferritins and E-type prostaglandins in sources of colony stimulatory factors mask detection of cycling granulocyte-macrophage progenitor cells

The effect of granulocyte-macrophage colony stimulatory factors (GM- CSF), acidic isoferritins, and E-type prostaglandins on the detection of the cycle status of human granulocyte-macrophage progenitor cells (CFU-GM) was investigated. Bone marrow cells were pulse-treated with control medium or high specific activity tritiated thymidine [3HTdr) and subsequently plated over feeder layers containing mononuclear blood leukocytes prepared in the absence or presence of anti-acidic isoferritins and/or indomethacin, or plated in the presence of medium conditioned by placental cell or GCT-conditioned media free of acidic isoferritins and prostaglandin-E. The presence of anti-acidic isoferritins and/or indomethacin in the blood leukocyte feeder layers increased the detectable stimulatory capacity of these cells and permitted detection of a larger proportion of marrow CFU-GM in cycle than in control cultures. The cycle status was not influenced by GM-CSF in conditioned medium regardless of the dilution of conditioned medium used to stimulate colony formation. This suggests that GM-CSF, supplied to the cells after treatment with 3HTdr, does not itself influence the detection of CFU-GM in cycle, but using sources of GM-CSF that contain acidic isoferritins or prostaglandin-E will underestimate the actual number of CFU-GM in S-phase.
Deep Diving: Imagination, Intuition, and the Interpenetration of Minds

How do we help patients who come to us without access to feelings and without curiosity about themselves and others? The author suggests that the analyst’s imagination and intuition provide a channel or medium through which to apprehend aspects of the patient’s internal life, make contact and communicate with younger parts of the patient, and provide containment to these parts of the person. As the analyst engages her imagination in this way, communication channels open and shared states of consciousness between analyst and patient are created, thereby facilitating the interpenetration of minds and the opening up of previously closed object worlds. In the course of this work, compassion serves as a vehicle for truth, penetrating previously closed object relational systems. This kind of work poses risks for the analyst.
Leucine Metabolism in T Cell Activation: mTOR Signaling and Beyond

In connection with the increasing interest in metabolic regulation of the immune response, this review discusses current advances in understanding the role of leucine and leucine metabolism in T lymphocyte (T cell) activation. T cell activation during the development of an immune response depends on metabolic reprogramming to ensure that sufficient nutrients and energy are taken up by the highly proliferating T cells. Leucine has been described as an important essential amino acid and a nutrient signal that activates complex 1 of the mammalian target of rapamycin (mTORC1), which is a critical regulator of T cell proliferation, differentiation, and function. The role of leucine in these processes is further discussed in relation to amino acid transporters, leucine-degrading enzymes, and other metabolites of leucine metabolism. A new model of T cell regulation by leucine is proposed and outlines a chain of events that leads to the activation of mTORC1 in T cells.
CHAPTER 39 – Effects of Steroids on Mood/Depression

Modern studies have addressed the inconsistent methodology in menopause research. So far, several researchers report mood-enhancing effects of hormone replacement therapy (HRT), but others fail to demonstrate this pattern. Generalizations from data on HRT, such as biological outcomes and psychological variables, are difficult to make. Most studies included in the meta-analyses used adequate sample sizes, controlled research designs, random assignment, and valid, reliable outcome measures for depression. Overall results of the meta-analyses demonstrated that depressed mood scores decreased from pretreatment to post treatment for estrogen versus estrogen plus progesterone comparison treatment. Estrogen was a more effective treatment. Significant effect scores were associated with HRT. The average treatment subject had lower levels of depressed mood compared to control subjects. Estrogen plus progesterone reduced the effect of estrogen replacement therapy (ERT) on depressed mood. The androgen alone and androgen plus estrogen treatment yielded a large effect. The onset of mood and anxiety symptoms associated with HRT remains under diagnosed and undertreated. Because noncompliance with HRT may have serious implications for the postmenopausal woman, the prescribing physician should inquire about mood in women, who may hesitate to report depressive symptoms and who may therefore discontinue HRT in an attempt to self-treat.
Evaluation of Damping Ratios for the Seismic Analysis of Tall Buildings

AbstractThis paper examines damping ratios in tall buildings in California inferred from motions recorded in instrumented buildings during earthquake motions. A total of 41 measured seismic responses from 14 buildings with 20 or more stories are analyzed using a parametric least-squares system identification technique in the time domain. The reliability of the inferred damping ratios is first examined based on the sensitivity of the structural response to variations in modal damping ratios. Using only inferred damping ratios deemed reliable, it is found that the damping ratios of the fundamental mode decrease with increasing building height, reaching values lower than 2.5%—the damping value that is commonly recommended for seismic design in the United States for buildings taller than 150 m. The variation of damping of higher modes with frequency is then examined by studying the results of those buildings where damping ratios of at least the first three modes are reliably inferred. It is shown that the var...
ApoE e3 allele and DRS Outcome in Patients with Severe Traumatic Brain Injury (TBI) (S46.007)

Objective: ApoE e4 is associated with poor prognosis in patients with severe traumatic brain injury, other polymorphisms may confer protective or have no effect in outcome measure by DRS at hospital discharge, three and six months follow-up. Background: The ApoE protein exists in three major isoforms, denoted as apoE2, apoE3 and apoE4. Various combinations of any two of the three major alleles will give rise to one of six possible genotypes (APOE e2/e2, APOE e3/e3, APOE e4/e4, APOE e2/e3, APOE e3/e4 and APOE e2/e4). ApoE may be a requirement in the mobilization of cholesterol in the CNS, where it is required for neural plasticity. Poorer scores on the GCS, unfavorable outcome on the GOS 6 months post-TBI, and/or lower Functional Independence Measure (FIM) scores have been observed for ɛ4 carriers. Outcome following TBI is, however, highly variable. Design/Methods: 170 patients (White 22.9[percnt], Hispanic 48.2[percnt], Black 26.4[percnt], Asian 2.4[percnt]; Male 78.8[percnt]) with severe TBI, GCS ≤ 8 were included. A blood sample was collected for DNA analysis, and genotyping of the following variants of ApoE gene was performed: ɛ2-4. Other variables included age, injury severity score, race, gender. Functional outcome was measured by Disability Rating Scale at hospital discharge, 3 and 6 months. Generalized linear model and Elastic net regularization were used to select the important predictors. Results: Two variables came out as significant predicting outcome by DRS: age and ApoE e3 variant. ApoE3-containing genotypes (e2/e3, e3/3 or e3/e4) were associated with lower DRS scores (p < 0.05). Conclusions: The findings in this study support the importance of ApoE in predicting outcome in patients with severe traumatic brain injury. However, in our study ApoE e3-containg genotypes predict better outcome when compared to ApoE e4 allele as previously described. Further differences in outcome may be accounted by polymorphisms in promoter regions. Disclosure: Dr. Ponce Mejia has nothing to disclose. Dr. Cruz Navarro has nothing to disclose. Dr. Jerry has nothing to disclose. Dr. Robertson has nothing to disclose.
Using stories to instill an entrepreneurial mindset in engineers: The case study initiative

While the case method is not new to engineering education, what faculty mean when they say “case study” is wide-ranging. Building on previous guidelines for the writing of case studies and their use in the undergraduate engineering classroom, I have built a program to write, share, and teach faculty how to use case studies in core engineering classrooms. By building on the Kern Entrepreneurial Engineering Network's (KEEN) entrepreneurial mindset, I have refreshed previous case study method pedagogies to help students understand how they might use their technical skills in their careers.
Chemical Aspects of Equilibrium Segregation to Ceramic Interfaces

Equilibrium segregation to solid interfaces has been the subject of increasing scientific interest over the last few years. This has in large part been the result of a growing experimental capability for the chemical characterization of surfaces and interfaces. The segregation of embrittling impurities to grain boundaries in metals has been the most intensively studied interfacial segregation phenomenon1, 2 although significant work has also been performed on segregation to metal surfaces3, 4. In contrast, there has been relatively little work on the measurement of equilibrium segregation to other types of solid interfaces, such as grain boundaries in ceramics5, 6, surfaces of ionic solids7, 8, or interphase interfaces of any kind9.
The Land and Labor Market Impacts of the U.S. Shale Boom

The U.S. shale boom of the mid-2000s traded off possible environmental damage and negative quality-of-life impacts against income gains and rents captured by workers and property owners. This study measures the effect of local shale oil and gas extraction on local land prices and wages. Using the timing of the boom and variation in extraction rates as a treatment across 2,141 counties from 2000 to 2010, I find that counties with oil and gas activity experienced employment and wage increases of 4% and 3.8% respectively, while house values are no different relative to counties without shale energy resources. However, among the set of energy producers, high-output counties experience gains all three outcomes relative to low-output counties. My results imply a per-capita willingness to pay of approximately $425 for a 1% reduction in total energy produced in-county.
A lightweight framework for peer-to-peer programming

Peer-to-peer systems (P2P) have become one of the most popular Internet applications in use today. Implementing a P2P protocol requires the developer to manage a number of issues related to socket handling (both from a server and client perspective), threads, and message passing (or alternate means of communication between nodes). These infrastructure-related issues are often independent of the algorithmic details of the protocol itself. While there are frameworks available that encapsulate these low-level details for developers, they may not be suitable for students in an introductory networking course because of the overhead of having to learn the interface of a full-featured library. This paper presents the development of a lightweight, pedagogical framework for implementing and experimenting with P2P protocols and applications, aimed especially at students in introductory networking courses.
Molecular Determinants of Substrate Affinity and Enzyme Activity of a Cytochrome P450BM3 Variant

Cytochrome P450BM3 catalyzes the hydroxylation and/or epoxidation of fatty acids, fatty amides, and alcohols. Protein engineering has produced P450BM3 variants capable of accepting drug molecules normally metabolized by human P450 enzymes. The enhanced substrate promiscuity has been attributed to the greater flexibility of the lid of the substrate channel. However, it is not well understood how structurally different and highly polar drug molecules can stably bind in the active site nor how the activity and coupling efficiency of the enzyme may be affected by the lack of enzyme-substrate complementarity. To address these important aspects of non-native small molecule binding, this study investigated the binding of drug molecules with different size, charge, polar surface area, and human P450 affinity on the promiscuous R47L/F87V/L188Q/E267V/F81I pentuple mutant of P450BM3. Binding free energy data and energy decomposition analysis showed that pentuple mutant P450BM3 stably binds (i.e., negative ΔGb°) a broad range of substrate and inhibitor types because dispersion interactions with active site residues overcome unfavorable repulsive and electrostatic effects. Molecular dynamics simulations revealed that 1) acidic substrates tend to disrupt the heme propionate A-K69 salt bridge, which may reduce heme oxidizing ability, and 2) the lack of complementarity leads to high substrate mobility and water density in the active site, which may lead to uncoupling. These factors must be considered in future developments of P450BM3 as a biocatalyst in the large-scale production of drug metabolites.
Youth and the opioid epidemic

The current epidemic of opioid addiction has arguably been the most recalcitrant in the nation's history and the first to involve substantial numbers of adolescents. The country has embarked on a public health response, including increasing access to addiction treatment. However, the treatment infrastructure, which was initially created in the 1970s, is ill equipped for meeting the needs of adolescents and young adults, who are often cared for in pediatric primary care. In this article, I review the development of the current treatment system, examine shortfalls in regard to youth-specific needs, and propose suggestions for addressing the current crisis while simultaneously preparing to address future epidemics of addiction by enabling pediatricians to better manage substance use disorders in primary care.
Can Immune Checkpoint Inhibitors Keep JC Virus in Check

Three groups are now reporting in the Journal descriptions of the clinical course of 10 patients with progressive multifocal leukoencephalopathy (PML) who were treated with the immune checkpoint in...
In vivo longitudinal imaging of RNA interference-induced endocrine therapy resistance in breast cancer.

Endocrine therapy resistance in breast cancer is a major obstacle in the treatment of patients with estrogen receptor-positive (ER+) tumors. Herein, we demonstrate the feasibility of longitudinal, noninvasive and semiquantitative in vivo molecular imaging of resistance to three endocrine therapies by using an inducible fluorescence-labeled short hairpin RNA (shRNA) system in orthotopic mice xenograft tumors. We employed a dual fluorescent doxycycline (Dox)-regulated lentiviral inducer system to transfect ER+ MCF7L breast cancer cells, with green fluorescent protein (GFP) expression as a marker of transfection and red fluorescent protein (RFP) expression as a surrogate marker of Dox-induced tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown. Xenografted MCF7L tumor-bearing nude mice were randomized to therapies comprising estrogen deprivation, tamoxifen or an ER degrader (fulvestrant) and an estrogen-treated control group. Longitudinal imaging was performed by a home-built multispectral imaging system based on a cooled image intensified charge coupled device camera. The GFP signal, which corresponds to number of viable tumor cells, exhibited excellent correlation to caliper-measured tumor size (P << .05). RFP expression was substantially higher in mice exhibiting therapy resistance and strongly and significantly (P < 1e-7) correlated with the tumor size progression for the mice with shRNA-induced PTEN knockdown. PTEN loss was strongly correlated with resistance to estrogen deprivation, tamoxifen and fulvestrant therapies.
Financial Costs, Benefits, and Patient Risk Preferences in Node-Negative Breast Cancer: Insights from a Decision Analysis Model

Since the 1988 National Cancer Institute Clinical Alert [1], treating nodenegative breast cancer patients outside the context of a clinical trial has been actively debated. To address this controversial question, we developed a decision analysis model to explore the effectiveness of adjuvant therapy in node-negative women at different levels of recurrence risk [2]. Decision analysis is one of a variety of techniques used to gather, analyze, and synthesize information. Other tools include randomized clinical trials, metaanalysis, database analysis, expert reviews of the literature, and consensus panels. Using these methods, a physician or policy maker ideally reaches a conclusion that will be translated into a clinical care or health care policy recommendation. Where does decision analysis fit into this hierarchy? It is an analytic tool that uses a decision tree which incorporates data from each of these sources to concurrently consider “apples and oranges,” for example, the trade-offs that must be made in the risks and benefits of any health care intervention [3]. Ideally, decision analysis “quantifies the qualifiers” and provides an integrated view of a specific question. Breast cancer is a fertile area for decision analysis since the key ingredients are identifiable and quantifiable: clear definitions of the disease and its natural history, definable benefits and risks with different modes of therapy, compet- ing alternative approaches, and controversy.