cssi/SciSciGPT-SciSciNet huggingface dataset:
Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: CON

Immune checkpoint inhibitors (ICPis) have revolutionized the treatment of cancers by engaging the patient’s own immune system against the tumor (1⇓–3). Checkpoint pathways are innate mechanisms to put the brakes on immune activation. Approved agents target checkpoint pathways mediated by cytotoxic T lymphocyte–associated antigen 4 (CTLA4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PDL-1) (1,4⇓⇓–7). Releasing the breaks on the immune system enhances destruction of tumor cells, but can lead to immune-related adverse effects (8,9), including renal toxicity (1,2,10⇓⇓–13). The incidence of renal toxicity with ICPis ranges from 1% to 5% (12). This risk is higher in patients that are on combination therapy with both anti-CTLA4 and anti–PD-1/PD-L1 with an odds ratio of 3.88 (95% CI, 2.21 to 6.81) (14). Further, a lower baseline GFR before therapy increases risk of kidney injury with an odds ratio of 1.99 (95% CI, 1.43 to 2.76) for every 30 ml/min per 1.73 m2 decline (14). The time to prevent kidney injury starts at the time of ICPi initiation. Based on a recent multicenter review of 138 patients, risk of ICPi-associated AKI (ICPi-AKI) was higher with concomitant use of proton pump inhibitors (PPIs) with an odds ratio of 2.85 (95% CI, 1.81 to 4.48) (14). Cortazar et al. describe that 70% of patients with ICPi-AKI were on potential acute interstitial nephritis (AIN)–causing medications including PPIs (15,16), nonsteroidal anti-inflammatory drugs (NSAIDs) (17), and antibiotics (18) where PPI was present on >50% of patients’ medication lists. Baseline use of PPIs was also associated with ICPi-AKI in a large study by Seethapathy et al. (1), particularly 2.5 months after being on ICPi. Appropriate counseling to stop or substitute these medications …
LEFT BUNDLE BRANCH PACING IN CARDIAC AMYLOIDOSIS

Pacing options in cardiac amyloidosis (CA) are limited as criteria for biventricular pacing is often not met and RV pacing-induced dyskinesis with small left ventricle(LV) further reduces cardiac output. 75 year old white male was referred to our office for pacemaker placement with chronotropic
Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions.

The discovery and initial characterization 20 years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been considered as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these diseases. However, based on our current knowledge, it is not apparent that autoantibodies presenting the DFS IIF pattern fall into these categories. These antibodies invariably target a chromatin-associated protein designated as dense fine speckled protein of 70 kD (DFS70), also known as lens epithelium-derived growth factor protein of 75 kD (LEDGF/p75) and PC4 and SFRS1 Interacting protein 1 (PSIP1). This multi-functional protein, hereafter referred to as DFS70/LEDGF, plays important roles in the formation of transcription complexes in active chromatin, transcriptional activation of specific genes, regulation of mRNA splicing, DNA repair, and cellular survival against stress. Due to its multiple functions, it has emerged as a key protein contributing to several human pathologies, including acquired immunodeficiency syndrome (AIDS), leukemia, cancer, ocular diseases, and Rett syndrome. Unlike other ANAs, “monospecific” anti-DFS70/LEDGF autoantibodies (only detectable ANA in serum) are not associated with SARD and have been detected in healthy individuals and some patients with non-SARD inflammatory conditions. These observations have led to the hypotheses that these antibodies could be considered as negative biomarkers of SARD and might even play a protective or beneficial role. In spite of 20 years of research on this autoantibody-autoantigen system, its biological and clinical significance still remains enigmatic. Here we review the current state of knowledge of this system, focusing on the lessons learned and posing emerging questions that await further scrutiny as we continue our quest to unravel its significance and potential clinical and therapeutic utility.
Interpersonal vs. Non-Interpersonal Cumulative Traumas and Psychiatric Symptoms in Treatment-Seeking Incarcerated Women.

Incarcerated women are at elevated risk of lifetime trauma exposure. Prevalence rates of trauma exposure and how these events relate to specific domains of psychiatric symptomology among this group...
Coronavirus and Mass Incarceration

Despite claims by anti-mass-incarceration advocates attempting to use coronavirus to argue for early release, evidence shows that inmates are significantly more safe in prison than set free.
Hits and runs: Determinants of the cross-country variation in the severity of impact from the 2008–09 financial crisis

Abstract Recent empirical work on the 2008–09 financial crisis has found mixed results on the usefulness of indicators to explain the cross-country variation in the incidence of the crisis in non-originating countries. While some authors have found success with various indicators, Rose and Spiegel (2009a,b) find that almost no indicators are robust. We employ Bayesian model averaging (BMA) to verify Rose–Spiegel’s conclusions under model uncertainty, confirming their findings. We then employ latent class models (LCM) to check the data for parameter heterogeneity. We find that there is substantial evidence of heterogeneity in the relationship between various indicators and crisis impact, both across individual indicators as well as across financial crisis episodes. In particular, when using de-trended growth rates, a similar model fits the 1997 Asian financial crisis, although the coefficients change qualitatively in some cases. These results highlight the difficulty in employing simple linear models for early warning purposes, but demonstrate that there are robust indicators of cross-country variation in crisis impact across episodes, such as the pre-crisis growth in banking credit. A 2-class model explains the variation in crisis impact, where pre-crisis level of per-capita income assists in the prediction of membership in a particular class.
Minimizing indexicality

I critically examine Cappelen and Lepore’s definition of and tests for indexicality, and refine them to improve their adequacy. Indexicals cannot be defined as expressions with different referents in different contexts unless linguistic meaning and circumstances of evaluation are held constant. I show that despite Cappelen and Lepore’s claim that there are only a handful of indexical expressions, their “basic set” includes a number of large and open classes, and generates an infinity of indexical phrases. And while the tests can be used effectively to combat contextualism concerning ‘knows’ and ‘actual,’ many expressions not in their basic set test positive for indexicality, including quantifier nouns, weather reports, and comparative adjectives. I rebut their claim that context-shifting arguments inevitably lead to radical contextualism, and that if there were any indexicals beyond their basic set, communication would be impossible.
The influence of childhood trauma on aggression and violent behavior in first episode psychosis: A critical review

Abstract The association between childhood trauma and aggressive and violent behavior in chronic psychotic conditions (e.g., schizophrenia) is well-established. However, the impact of childhood trauma on aggression and violent behavior in first episode psychosis is unclear and comparatively understudied. To date, studies examining these relations in first episode psychosis have found that individuals experiencing early psychosis have high rates of both childhood trauma and aggressive and violent behavior compared to healthy controls prior to initial contact with mental health services. Childhood trauma is related to an increase in the prevalence and severity of aggression. These findings stress the importance and necessity of early detection and intervention in first episode psychosis, as both have been effective in reducing aggression in non-FEP samples with trauma histories. Incorporating trauma-focused interventions into treatment plans for individuals in the beginning phases of psychosis might reduce rates of aggression for individuals with a history of trauma and improve outcomes. Here, we review the literature on childhood trauma and aggression in first episode psychosis and discuss implications for future research.
Single virus assay reveals membrane determinants and mechanistic features of Sendai virus binding

Sendai virus (SeV, formally murine respirovirus) is a membrane-enveloped, negative sense RNA virus in the Paramyxoviridae family, and is closely related to human parainfluenza viruses. SeV has long been utilized as a model paramyxovirus and has recently gained attention as a viral vector candidate for both laboratory and clinical applications. To infect host cells, SeV must first bind to sialic-acid glycolipid or glycoprotein receptors on the host cell surface via its hemagglutinin-neuraminidase (HN) protein. Receptor binding induces a conformational change in HN, which allosterically triggers the viral fusion (F) protein to catalyze membrane fusion. While it is known that SeV binds to 2,3-linked sialic acid receptors, and there has been some study into the chemical requirements of those receptors, key mechanistic features of SeV binding remain unknown, in part because traditional approaches often convolve binding and fusion. Here, we develop and employ a fluorescence microscopy-based assay to observe SeV binding to supported lipid bilayers (SLBs) at the single particle level, which easily disentangles binding from fusion. Using this assay, we investigate mechanistic questions of SeV binding. We identify chemical structural features of ganglioside receptors that influence viral binding and demonstrate that binding is cooperative with respect to receptor density. We measure the characteristic decay time of unbinding and provide evidence supporting a "rolling" mechanism of viral mobility following receptor binding. We also study the dependence of binding on target cholesterol concentration. Interestingly, we find that while SeV binding shows striking parallels in cooperative binding with a prior report of Influenza A virus, it does not demonstrate a similar sensitivity to cholesterol concentration and receptor nano-cluster formation. STATEMENT OF SIGNIFICANCEParamyxoviruses are a family of membrane-enveloped viruses with many notable human and animal pathogens. In this study, we develop and use an assay to observe the initial step of infection - virus binding to the host membrane - for Sendai virus, the prototypical paramyxovirus, at the single virus level. This assay uses cell membrane mimics - supported lipid bilayers - as targets for virus binding to enable easy control of the membrane components with which the virus interacts. Using our assay, we gain insight into basic biophysical questions about Sendai virus binding, including the chemical characteristics of the receptor, the cooperative nature of binding, the influence of cholesterol, and the mechanism of viral mobility following binding.
Note on a Littlewood-Paley inequality

We show that a recent result of Littlewood-Paley type, due to the author, is essentially best-possible. In a recent paper [W], the author proved Littlewood-Paley inequalities for certain finite linear sums f = Z1 AIq(I), defined on Rd. The summation here is indexed over D, the family of dyadic cubes in Rd; the A, are complex numbers. The functions 0(I), assumed to be smooth, belong to a family F that is "almost-orthogonal" and satisfies a mild decay condition. Precisely, we assume that there is an M > d/2 such that for all x E Rd and all I E X (1) kt(i)(X)| ? ?(I)IVq(I)(X)I ? III1/2(1 + IX-xiI/1(I))M. The notation is more or less standard: XI denotes I's center, ?(I) is its sidelength, and III is its Lebesgue measure (per tradition, we shall use JEJ to mean the Lebesgue measure of any measurable set E). We assume in addition that, for any finite linear sum Zi VI0(I), (2) I2 I ZVI0(I)1 dx d. For every a E A,, as above and 0 < p < oc, there is a constant C = C(M, d, p, a, b, p) such that, for all finite linear sums f = ZI AIq(I) from F, 2 ~~~~~~~p/2 If <c Rd d E II (1 + Ix. II/gj)) +p VI ux<C I x Received by the editors August 24, 1998 and, in revised form, February 20, 1999. 2000 Mathematics Subject Classification. Primary 42B25.
Pediatric bone marrow transplantation: psychosocial issues for parents after a child's hospitalization

Bone marrow transplantation (BMT), once a highly experimental procedure performed in only a handful of medical centers, has become increasingly common and is now considered to be the treatment of choice for some diseases. Although a growing number of pediatric patients undergo this life-saving procedure, psychosocial research has focused primarily on adult BMT patients. This article presents data from an exploratory study of 73 parents whose children successfully completed the transplant. The study identified the major concerns and needs of this unique population as they coped with life after a child's transplant. The results indicated that although most parents coped adequately, certain problems such as financial strains and fears of relapse remained.
Host Effect on Arbovirus Replication: Appearance of Defective Interfering Particles in Murine Cells

Serial passage of Semliki Forest virus (SFV) in chicken embryo cells had little effect on SFV yield; however, high multiplicity infection of murine cells with one of the late passage pools (passage 9 SFV) resulted in a virus yield 10- to 20-fold lower than that obtained with earlier passage virus and 80-fold lower than the corresponding yield in chicken cells. This effect was accompanied by a striking decrease in the levels of 42S and 26S RNA and by increased proportions of a small single-stranded viral RNA (molecular weight, 9 x 10(5)) and of a low-molecular-weight replicative form. There was also a reduction in the number of specific membranous structures previously associated with the group A arbovirus replication complex. These results suggested that passage 9 SFV contained defective interfering particles which were detected more readily after one passage in a murine indicator host cell. Identical results were obtained with two different murine cell lines: one a leukemia virus-free clone of AKR cells and the other JLS-V9 cells chronically infected with Rauscher leukemia virus. Host production of RNA tumor virus particles apparently did not affect arbovirus replication.
Autonomic hyperreflexia in spinal cord injury associated with pulmonary embolism

Abstract Autonomic hyperreflexia results from a variety of noxious stimuli. A case of acute pulmonary embolism associated with severe autonomic hyperreflexia illustrates the importance of autonomic hyperreflexia in signaling the onset of serious medical complications in spinal cord injured patients. An episode of autonomic hyperreflexia not associated with the usual causes can be an important signal of serious visceral pathology.
Exemptions to the European Union Personal Data Privacy Directive: Will They Swallow the Directive?

This Note analyses the probable effectiveness of the European Union Data Protection Directive, which was passed in order to curtail the invasion of personal privacy that has accompanied the development of the Internet, in light of three potentially expansive exemptions contained within the Directive. The author concludes that the goals of the Directive will be achieved only if Member States interpret these exemptions restrictively when enacting legislation pursuant to the Directive.
An inclinometer based on free convective motion of a heated air mass

In this application a thick-film tilt sensor has been developed based on heat transfer by natural convection. The device measures internal changes in heat transfer caused by the inclination using the force of gravity as an input. The device is functionally equivalent to traditional proof-mass accelerometer. The proof mass in the new thick-film sensor is a gas. The gaseous proof-mass provides great advantages over the use of the traditional solid proof mass. A conditioning electronics amplifies the signal variation induced by the inclination compensating the deviation due to the initial asymmetrical values of the bridge arms and their slow variations. Preliminary tests on the first prototypes show an accuracy of about 2% fall scale output, repeatability of about 0.2/spl deg/ and resolution better than 0.1/spl deg/ over a /spl plusmn/20/spl deg/ range.
Shape Resonances in the Photoionization Spectra of Free and Chemisorbed Molecules

With the emergence of synchrotron radiation as a powerful spectroscopic tool, it has become possible to study in detail the photoionization cross sections immediately above the various ionization potentials, not only of core levels (which can also be done by x-ray absorption) but also of all the different valence levels (though the use of photoelectron spectroscopy). The most prominent features in these cross sections are in molecular physics known as shape resonances and constitute major modifications of a simple hydrogenic photoabsorption cross section. Essentially the same phenomenon is sometimes in the condensed matter literature referred to as XANES (x-ray absorption near edge structure), to contrast it with EXAFS (extended x-ray absorption fine structure). This very rich field has over the last five years developed into several different directions. The purpose of the present paper is to summarize some fairly recent experiments concerned with shape resonances in free diatomic molecules and to show how this knowledge can be used in surface physics to extract information otherwise difficult to obtain. Many of the properties of free molecules are retained after chemisorption. It is possible to perform much more accurate theoretical calculations for free molecules than for the molecule- surface complex. By cautiously extrapolating these calculations to the chemisorbed phase much new insight has been gained.
Laser-Induced Chemical Processes: Reactions with Oriented Reagents

To the chemist, the laser provides the ability to prepare molecules according to a precise prescription and to probe the subsequent chemical fate of this energized system. Mention is made here of but one class of experiments where use of the laser is allowing us not only to pose detailed questions about the nature of reaction dynamics but to receive in some instances even the beginnings of an intelligible answer.
Femtosecond Spectroscopy of Retinal Proteins

Recent advances in the generation of ultrashort light pulses1,2 have made possible the study of chemical and biological reactions with unprecedented time resolution. Two of the most rapid reactions that have been studied thus far occur in the biological pigments rhodopsin and bacteriorhodopsin. Both are intrinsic membrane proteins which contain visible absorbing, retinal prosthetic groups. Rhodopsin contains 11-cis retinal which is converted to the all-trans isomer following absorption of a photon (Fig. 1).3,4 Bacteriorhodopsin contains all-trans retinal which photoisomerizes to the 13-cis form (Fig. 2). The protein stores a portion of the energy of the absorbed photon and uses it to drive subsequent ground state conformational changes.5,6 In rhodopsin, this process leads ultimately to visual excitation,7–10 while in bacteriorhodopsin, a proton is pumped across the membrane forming an electrochemical potential gradient that is used to synthesize ATP.11 Both isomerization reactions are very rapid, occurring on timescales equal to or more rapid than the isomerization rates of small organic molecules in solution.12,13
Prolonged Complete Response in a Pediatric Patient With Primary Peripheral T-Cell Lymphoma of the Central Nervous System

We describe a child with a 2-week history of progressive headaches, blurry vision, and intermittent vomiting. Magnetic resonance imaging (MRI) of the brain showed a deep left hemispheric lesion with extension into the corpus callosum. Histology and immunophenotyping of the lesion was consistent with peripheral T-cell lymphoma, not otherwise specified. Chemotherapy was initiated and a complete remission was achieved. This case illustrates that a chemotherapeutic regimen used in adults with central nervous system (CNS) lymphoma can achieve durable remissions in pediatric patients with peripheral T-cell lymphoma, not otherwise specified of the CNS.
Validation of a watershed model without calibration

[1] Traditional approaches for the validation of watershed models focus on the “goodness of fit” between model predictions and observations. It is possible for a watershed model to exhibit a “good” fit, yet not accurately represent hydrologic processes; hence “goodness of fit” can be misleading. Instead, we introduce an approach which evaluates the ability of a model to represent the observed covariance structure of the input (climate) and output (streamflow) without ever calibrating the model. An advantage of this approach is that it is not confounded by model error introduced during the calibration process. We illustrate that once a watershed model is calibrated, the unavoidable model error can cloud our ability to validate (or invalidate) the model. We emphasize that model hypothesis testing (validation) should be performed prior to, and independent of, parameter estimation (calibration), contrary to traditional practice in which watershed models are usually validated after calibrating the model. Our approach is tested using two different watershed models at a number of different watersheds in the United States.
Algorithms for computating principal and minor invariant subspaces of large matrices

Computing all the eigenvalues and eigenvectors of a large matrix is a time-consuming operation. There are many applications in signal processing, control, and applied mathematics that require only the minimum and/or maximum eigenpairs. In this paper, new methods for computing the smallest and largest eigenvalues of symmetric matrix are developed. These methods are modifications of the Rayleigh quotient iteration aimed at circumventing some drawbacks of that method such as its non or slow convergence. In this approach, the Rayleigh quotient is sequentially minimized over several orthogonal vectors. At each iterate, a vector is formed from a linear combination of the current iterate and an orthogonal vector that is derived from a gradient of a Ritz functional. The proposed methods have global and cubic convergence rate. These methods are also generalized to solve high resolution temporal and spatial frequency tracking problems. The eigenstructure tracking algorithm has update complexity O(n/sup 2/ p), when n is the data dimension and p is the dimension of the minor or major subspaces. The performance of these algorithms is tested with several examples. Simulations involving large matrices have shown that the convergence behavior is independent of the size of the matrices.
Analysis of flow changes in side branches jailed by flow diverters in rabbit models

Purpose to investigate the relationship between hemodynamic conditions created immediately after flow diversion and subsequent occlusion of experimental aneurysms in rabbits.
A Life In and Out of Anthropology An Interview with Jack Sargent Harris

■ This article presents an interview with Jack Sargent Harris (1912—2008), an anthropologist who earned his PhD at Columbia University in 1940 and was one of the first US anthropologists to do fieldwork in Africa, showing an interest in materialistic theoretical approaches. As a merchant seaman before becoming an anthropologist he traveled the globe, including trips to the Soviet Union, Africa, Asia, the Caribbean, and Latin America. During the Second World War, Harris became a clandestine operative engaged in counter-espionage for the United States' Office of Strategic Services in West Africa and in South Africa. Returning to the United States, he was hired by the fledgling United Nations as part of its decolonization efforts. However, Harris fell victim to the McCarthy-era witch hunt and was purged from the United Nations. He moved to Costa Rica in 1954 where he became a successful entrepreneur.
Ab initio calculations of the rotational barrier in dimethyl diselenide

The heights of the rotational barriers of the diselenide bridge in dimethyl diselenide have been calculated at the Hartree-Fock level with the 3-21G basis set. The minimum in the rotational potential energy function occurs at a torsional angle of 85.64°. The barriers were determined by complete geometry optimization at each point along the potential surface. The results are compared with other calculations and with the available experimental results. © 1996 John Wiley & Sons, Inc.
Aging and olfactory and taste function

This article focuses on the change in olfaction and taste with aging. It discusses histopathology with an emphasis on age-related changes, causes of chemosensory dysfunction in the elderly, how to evaluate a patient with dysfunction, useful tests and imaging, clinical consequences of chemosensory impairments, and available treatment options.
Dielectronic recombination rates for ions of the magnesium sequence at low energies

The dielectronic recombination (DR) rate coefficient αDR is explicitly calculated for the Si, Ar, Fe and Mo target ions of the Mg isoelectronic sequence with twelve electrons. Both the 3s, Δn ≠ 0 and 3s, Δn = 0 transitions are considered in detail. An explicit LS coupling scheme was applied to all the dominant transitions of these ions. Results of αDR with different free electron temperatures are also discussed
Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonists: Characterization of 6-[125I]methyl-8-iodo-1, 3-dichlorodibenzofuran-Ah receptor complexes☆

Abstract 6-Methyl-8-iodo-1,3,-dichlorodibenzofuran (I-MCDF) and its radiolabeled analog [125I]MCDF have been synthesized and used to investigate the mechanism of action of 1,3,6,8-substituted dibenzofurans as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) antagonists. Like 6-methyl-1, 3,8-trichlorodibenzofuran (MCDF), I-MCDF partially antagonized the induction by TCDD of microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities in rat hepatoma H-4-II E cells and male Long-Evans rat liver. Incubation of rat liver cytosol with [125I]MCDF followed by velocity sedimentation analysis on sucrose gradients gave a specifically bound peak which sedimented at 9.6 S. This radioactive peak was displaced by coincubation with a 200-fold excess of unlabeled I-MCDF, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and benzo [a]pyrene. Based on the velocity sedimentation results and the elution profile from a Sephacryl S-300 gel permeation column, the Stokes radius and apparent molecular weights of the cytosolic [125I]MCDF-Ah receptor complex were 6.5 nm and 259,200, respectively. In addition, the nuclear [125I]MCDF-receptor complex eluted at a salt concentration of 0.29 m KCl from a DNA-Sepharose column. Velocity sediment analysis of the nuclear [125I]MCDF-Ah receptor complex from rat hepatoma H-4-II E cells gave a specifically bound peak at 5.6 ± 0.8 S. All of these properties were similar to those observed using [3H]-TCDD as the radioligand. In addition, there were several ligand-dependent differences observed in the properties of the I-MCDF and TCDD receptor complexes; for example, the [125I]MCDF rat cytosolic receptor complex was unstable in high salt buffer and was poorly transformed into a form with increased binding affinity on DNA-Sepharose columns; Scatchard plot analysis of the saturation binding of [3H]TCDD and [125I]MCDF with rat hepatic cytosol gave KD values of 1.07 and 0.13 n m and Bmax values of 137 and 2.05 fmol/mg protein, respectively. The nuclear extract from rat hepatoma H-4-II E cells treated with I-MCDF or TCDD interacted with a dioxin-responsive element in a gel retardation assay. These results suggest that the mechanism of antagonism may be associated with competition of the antagonist receptor complex for nuclear binding sites.
Ultrafast Dynamics in Complex Materials

I will discuss the development and application of novel optical spectroscopic techniques to study ultrafast dynamics in complex materials, emphasizing the investigation of correlated electron materials such as heavy fermions, superconductors and magnetic materials.
Is my network module preserved and reproducible

In many applications, one is interested in determining which of the properties of a network module change across conditions. For example, to validate the existence of a module, it is desirable to show that it is reproducible (or preserved) in an independent test network. Here we study several types of network preservation statistics that do not require a module assignment in the test network. We distinguish network preservation statistics by the type of the underlying network. Some preservation statistics are defined for a general network (defined by an adjacency matrix) while others are only defined for a correlation network (constructed on the basis of pairwise correlations between numeric variables). Our applications show that the correlation structure facilitates the definition of particularly powerful module preservation statistics. We illustrate that evaluating module preservation is in general different from evaluating cluster preservation. We find that it is advantageous to aggregate multiple preservation statistics into summary preservation statistics. We illustrate the use of these methods in six gene co-expression network applications including 1) preservation of cholesterol biosynthesis pathway in mouse tissues, 2) comparison of human and chimpanzee brain networks, 3) preservation of selected KEGG pathways between human and chimpanzee brain networks, 4) sex differences in human cortical networks, 5) sex differences in mouse liver networks. While we find no evidence for sex specific modules in human cortical networks, we find that several human cortical modules are less preserved in chimpanzees. In particular, apoptosis genes are differentially co-expressed between humans and chimpanzees. Our simulation studies and applications show that module preservation statistics are useful for studying differences between the modular structure of networks. Data, R software and accompanying tutorials can be downloaded from the following webpage: http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/ModulePreservation.
Enhancing depression screening to identify college students at risk for persistent depressive symptoms.

Abstract Background Depressive symptoms in college students are prevalent and are associated with considerable academic impairment. Many universities have implemented depressive symptom screening programs and the number of students identified as in need of services following screening greatly exceeds available mental health resources. The present study sought to refine depressive symptom screening programs by identifying predictors of a persistent course of depressive symptoms and developing cut-scores for accurately identifying students who will experience a persistent symptom course. Method Students ( n =262) who reported elevated depressive symptoms both an initial screening and baseline assessment ( n =150) were invited to participate in telephone-based follow-up assessments 4, 8, and 12 months post-baseline. Results Two depressive symptom courses were identified: a persistently elevated depressive symptoms course and a decreasing depressive symptoms course. Baseline social disconnection and negative feedback-seeking both significantly predicted membership in the persistently elevated depressive symptoms course. Cut-scores that robustly discriminated between the two symptom courses were identified. Limitations The present sample was predominantly female and Hispanic; the four-month spacing of assessments may have resulted in a failure to identify individuals who experience brief, yet impairing, recurrent depressive episodes. Conclusion These findings can inform approaches to identifying college students most in need of mental health services for depressive symptoms based on the presence of social disconnection and/or negative feedback-seeking. Screening cut-points on social disconnection and negative feedback-seeking measures can reduce the number of cases identified as needing mental health services while retaining the majority of cases who will experience a persistent depressive symptom course.
Isolation of atrial fibrillation to a pulmonary vein.

This is a 37-year-old woman with paroxysmal atrial fibrillation (AF) for 1.5 years. She has had symptomatic recurrences (palpitations and syncope) despite flecainide ± beta blockers and sotalol. An electrophysiological study elsewhere found AF initiated by atrial tachyarrhythmias originating …
Wildfire burn-intensity mapping using high-altitude reconnaissance photography

In 1994, wildfires burned over 117,360 hectares (290,000 acres) of forest land on the Payette National Forest in central Idaho. To assess the impact of the fires on the timber resource, a special mission was planned for NASA's Earth Resources-2 high altitude reconnaissance aircraft. For this project, the aircraft carried a 12 inch lens Wild- Heerbrugg RC-10 aerial mapping camera loaded with Kodak SO- 060 Aerochrome Infrared film. The 1:60,000 scale photography was used to map burn intensity within the gross fire perimeter in high, medium, low and not-burned classes. Polygons were digitized and the digital information was used in the ARC-INFO environment to determine the gross effects of the wildfires on the timber resource. An accuracy assessment was performed by comparing the interpretation to data collected from plots established within the burned area. In this paper, we review the need for the information, the mission parameters, the image exploitation phase, the results of the accuracy assessment and the application of the data to forest management.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Vomitoxin (deoxynivalenol)-mediated inhibition of nuclear protein binding to NRE-A, an IL-2 promoter negative regulatory element, in EL-4 cells.

Abstract Interleukin-2 (IL-2) gene expression is superinduced by the trichothecene mycotoxin vomitoxin (VT, deoxynivalenol) in primary and cloned murine T cells—an activity that relates to this toxin's capacity to inhibit protein synthesis. Binding of the transcription factor ZEB (NIL-2-a) to the negative regulatory element NRE-A plays a critical role in silencing IL-2 expression in the EL-4 cell line, a murine Th1-like lymphoma. The objective of this study was to test the hypothesis that VT impairs NRE-A-binding activity in the EL-4 T cells model. Electrophoretic mobility shift assay (EMSA) in control EL-4 cells revealed a slower migrating band, previously identified as ZEB, and a faster migrating band. VT inhibited NRE-A binding activity in unstimulated EL-4 cells as evidenced by the concentration-dependent reduction of both bands with as little as 50 ng/ml of the toxin being inhibitory. Specificity of NRE-A binding for the two bands was verified by demonstrating (1) competition with excess unlabeled NRE-A probe and absence of competition with mutant NRE-A or unrelated (NF-κB) probes and (2) EMSA supershift using antibody specific for ZEB. NRE-A binding activity was also reduced when cells were treated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (ION). Cotreatment of VT potentiated PMA+ION-mediated reduction of the NRE-A binding activity in concentration-dependent fashion. VT-mediated reduction of NRE-A binding was observed in PMA+ION-stimulated cells as early as 2 h and was still detectable after 24 h. Competitive RT-PCR analysis of mRNA indicated that VT did not reduce ZEB transcript levels. Western analysis of nuclear extracts revealed that, although VT exposure decreased ZEB protein expression, the effects were minimal, required high VT concentrations (500–1000 ng/ml) and were not qualitatively consistent with large concomitant decreases in NRE-A binding activity. Furthermore, VT at levels up to 1000 ng/ml had no effect on ZEB expression in whole cell lysates, suggesting that VT did not selectively inhibit translation of this negative transcription factor. Taken together, these data indicate that the capacity of VT to up-regulate IL-2 expression may relate, in part, to its capacity to decrease ZEB binding to the negative regulatory element within this cytokine's promoter. The inability to associate decreased NRE-A binding with impaired ZEB transcription or translation suggests that post-translational modification of this negative transcription factor may be requisite for VT's down-regulatory effects.
Our Growing Problem: Population

Several recent events have led sociologists to overlook population in an examination of social problems; 1) well-publicized declines in the U.S. crude birth rate may have led to a sense of complacency, 2) the complacency tends to be encouraged by a parochial rather than international approach to social problems, 3) the focus on environmental problems has tended to displace population, and 4) the study of “deviance” eliminates population concerns. This analysis notes that population growth rates for the world and for the poorer nations have never been higher. United States growth is very high among the more developed nations, and it faces a second wave from our earlier “baby boom.” Research results indicating trade-offs in the quantity and quality of population within the family, the community, the nation, and the world are reviewed. Without the neutralizing effects of rapid population growth the “Development Decade” of the 60's would have been a great success. Awareness of the many complications arising from population growth is clearly a prerequisite to intelligent action.
A DIRECT PROOF OF A RESULT OF SHELAH

Shelah has shown (see [1]) that the number d, the smallest cardinality of a dominating family, is less than or equal to the number i, the smallest cardinality of a maximal independent family on ω. This was done using a downward Lowenheim-Skolem argument. Thus it is interesting to find a direct “elementary” proof. Here we show that this can be done.
RETURNS ON PROJECT-FINANCED INVESTMENTS: EVOLUTION AND MANAGERIAL IMPLICATIONS

In the past, project finance was used primarily to fund relatively low-risk natural resource projects with highly predictable cash flows. Today project finance is used for a wide range of assets, such as satellite telecommunications systems, amusement parks, and microprocessor factories, and in developing as well as developed countries. The author explores how the evolution into riskier assets has changed expected returns on project-financed investments. Higher return variability and greater failure rates have caused project debt capacities to fall. What is notable about project-financed investments, however, is that the best returns are not very high. And because the nature of most projects limits the upside potential, a much higher fraction of project-financed investments must be successful for capital providers to earn acceptable returns on their investments. The move into riskier assets has also led to increased emphasis on the risk management role of project finance; that is, through careful structure and design, a firm can use project finance to reduce the collateral damage caused by a failing investment and also to limit sovereign risks. But even so, the author suggests that the original structures were never designed to handle projects with significant asset risk. For this reason, in cases of riskier projects, single-asset project loans are likely to be replaced by either traditional corporate financing vehicles or hybrid structures involving elements of both project and corporate finance. One example of such hybrid financing is Calpine's revolving construction facilities that are used to finance portfolios of merchant power plants.
A Success Course for Freshmen on Academic Probation: Persistence and Graduation Outcomes

Administrators at a large, public university launched a mandatory success course for freshmen placed on academic probation at the end of their first semester. We compared the rates of course participant and nonparticipant return to good academic standing; persistence to the 2nd, 3rd, and 4th years; and graduation (within 4 to 5 years). The chi-square test for independence revealed significant differences across all measures of persistence and graduation between the control and treatment groups. We call for an increase in credit-bearing success courses using applied retention theories in the curriculum for students on academic probation.
The Origin of the P3 Pattern of Sylvilagus, Caprolagus, Oryctolagus and Lepus

An Upper Pliocene population of Nekrolagus progressus (Hibbard) represented by 178 P3s from the Rexroad fauna has 11.8% of the individuals with a P3 enamel pattern that is like the Ps pattern of Sylvilagus, Caprolagus, Oryctolagus and Lepus . For the first time in the fossil record there is evidence for the time and place of the variation (mutation) within a population that produced a character of generic grade. It is proposed that this pattern developed in North America and gave rise to that now found in Sylvilagus, Caprolagus, Oryctolagus and Lepus . Cenozoic faunas of Eurasia that contain remains of Oryctolagus and Lepus are younger than the Rexroad fauna. Over 2,000 Recent Lepus, Oryctolagus and Sylvilagus dentitions were examined. Twelve Recent specimens of these three genera were found that contained the Nekrolagus pattern. The genera are quite recent in origin. These rabbits provide an excellent group for comparative study with the late Pliocene Nekrolagus to establish the rate of generic development. A phylogenetic summary is given to show the relationship of the Leporinae as based upon the development of P2 and P3.
Decrease in [3H]flunitrazepam receptor binding in rats tolerant to the effects of nitrazepam.

Studies were performed to evaluate the binding of [3H]flunitrazepam to cell membranes from the brain cortex of rats that were made tolerant, by the i.p. administration of nitrazepam once daily, to the anxiolytic and sedative effects (after 14 days) and the anticonvulsant action (electroshock, after 28 days) of nitrazepam. A significant decrease in the number of specific [3H]flunitrazepam binding sites was found only in the group that was tolerant to the anticonvulsant effect. The same experiments were also carried out with oxazepam. Since there were no signs of tolerance, the administration of the drug, 10 mg/kg once daily i.p., was continued for 6 weeks. No tolerance occurred and there were no changes in [3H]flunitrazepam binding site density. We conclude that tolerance to the anticonvulsant effect of nitrazepam could be related to the down-regulation of the benzodiazepine receptors.
Structure−Reactivity Effects on Primary Deuterium Isotope Effects on Protonation of Ring-Substituted α-Methoxystyrenes

Primary product isotope effects (PIEs) on L+ and carboxylic acid catalyzed protonation of ring-substituted α-methoxystyrenes (X-1) to form oxocarbenium ions X-2+ in 50/50 (v/v) HOH/DOD were calculated from the yields of the α-CH3 and α-CH2D labeled ketone products, determined by 1H NMR. A plot of PIE against reaction driving force shows a maximum PIE of 8.7 for protonation of 4-MeO-1 by Cl2CHCOOH (ΔG° = 1.0 kcal/mol). The PIE decreases to 8.1 for protonation of 4-MeO-1 by L3O+ (ΔG° = −2.8 kcal/mol) and to 5.1 for protonation of 3,5-di-NO2-1 by MeOCH2COOH (ΔG° = 13.1 kcal/mol). The PIE maximum is around ΔG° = 0. Arrhenius-type plots of PIEs on protonation of 4-MeO-1 and 3,5-di-NO2-1 by L3O+ and on protonation of X-1 by MeOCH2COOH in 50/50 (v/v) HOH/DOD give similar slopes and intercepts. These were used to calculate values of [(Ea)H − (Ea)D] = −1.2 kcal/mol and (AH/AD) = 1.0 for the difference in activation energy for reactions of A−H and A−D and for the limiting PIE at infinite temperature, respectively. ...
Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations

Mutations in the Aristaless-related homeobox gene (ARX) are associated with a wide variety of neurologic disorders including lissencephaly, hydrocephaly, West syndrome, Partington syndrome, and X-linked intellectual disability with or without epilepsy. A genotype–phenotype correlation exists for ARX mutations; however, the molecular basis for this association has not been investigated. To begin understanding the molecular basis for ARX mutations, we tested the DNA binding sequence preference and transcriptional repression activity for Arx, deletion mutants and mutants associated with various neurologic disorders. We found DNA binding preferences of Arx are influenced by the amino acid sequences adjacent to the homeodomain. Mutations in the homeodomain show a loss of DNA binding activity, while the T333N and P353R homeodomain mutants still possess DNA binding activities, although less than the wild type. Transcription repression activity, the primary function of ARX, is reduced in all mutants except the L343Q, which has no DNA binding activity and does not functionally repress Arx targets. These data indicate that mutations in the homeodomain result in not only a loss of DNA binding activity but also loss of transcriptional repression activity. Our results provide novel insights into the pathogenesis of ARX-related disorders and possible directions to pursue potential therapeutic interventions.
Hydrogen-bonding interaction in molecular complexes and clusters of aerosol nucleation precursors.

Complexes and clusters bridge the gap between molecular and macroscopic levels by linking individual gaseous molecules to newly formed nanoparticles but the driving forces and mechanism for the formation of complexes and clusters in the atmosphere are not well understood. We have performed ab initio and density functional quantum chemical calculations to elucidate the role of organic acids in the formation of complexes with common atmospheric nucleating precursors such as sulfuric acid, water, and ammonia. A central feature of the complexes is the presence of two hydrogen bonds. Organic acid−sulfuric acid complexes show one strong and one medium-strength hydrogen bond whereas the corresponding hydrogen bonds in organic acid−ammonia complexes are characterized as medium-strength and weak. The formation of strong hydrogen bonds in organic acid−sulfuric acid complexes is explained by the well-established resonance-assisted hydrogen bonding theory. Organic acid−sulfuric acid and organic acid−organic acid comp...