cssi/SciSciGPT-SciSciNet huggingface dataset:
Cocaine and alcohol use preceding suicide in African American and white adolescents

The goal of this investigation was to determine whether cocaine and ethanol use was a differentiating factor between African American and white teenage suicide victims. This is a retrospective analysis of medical examiner's records of all completed suicides in Fulton County, GA from 01/1989 to 12/2003, and included 1296 cases. There were 79 suicide victims aged 19 and younger during the study interval, and of this group, 49 (62%) were African American, 26 (33%) were white, and 4 (5%) other race, compared to adults (20 years) where 28.5% were African American, 68.6% white and 2.9% other race (chi(2)=42.678, d.f.=2, p<0.0001). Of the black teenaged victims, 82.2% had no cocaine or alcohol detected at autopsy, while 41.7% of the white victims were positive for one or both substance (chi(2)=4.633, d.f.=1, p=0.04). Only 8.9% of the black teenage suicide victims had used cocaine prior to death compared to 28% of the whites (chi(2)=4.432; d.f.=1; p<0.04). The suicide rate (suicide/100,000/year) for black teens was 5.48 compared to 4.16 for whites, but the rate of cocaine positive teen suicides was 1.12 for whites and 0.45 for blacks. The pattern of cocaine use changes dramatically in the adult group, with 27% of African American suicide victims compared to 7.7% of whites being positive (chi(2)=73.272; d.f.=1; p<0.001). Use of intoxicating substances does differentiate teenage suicide victims, as only a small proportion of black teenagers had used cocaine or alcohol prior to death compared to almost half of all whites.
The evolution and stability of cooperative traits

Recent works in multi-agent systems have identified agent behaviors that can develop and sustain mutually beneficial cooperative relationships with like-minded agents and can resist exploitation from selfish agents. Researchers have proposed the use of a probabilistic reciprocity scheme that uses summary information from past interactions to decide whether or not to honor a request for help from another agent. This behavior has been found to be close to optimal in homogeneous groups and outperform exploiters in mixed groups. A major shortcoming of these experiments, however, is that the composition of the group in term of agent behaviors is fixed. We believe that real-life rational agents, on the contrary, will change their behaviors based on observed performances of different behavioral traits with the goal of maximizing performance. In this paper, we present results from experiments on two distinct domains with population groups whose behavioral composition changes based on the performance of the agents. Based on the experimental results, we identify ecological niches for variants of exploitative selfish agents and robust reciprocative agents.
Terminase and the recognition, cutting and packaging of λ chromosomes

Abstract Terminase is a phage λ enzyme that has multiple functions in λ DNA packaging: it binds to λ DNA and proheads, thereby insuring packaging of the proper DNA; it introduces the staggered nicks that generate the cohesive ends of virion DNA; and it acts processively during sequential packaging of λ chromosomes. Recent studies identify the terminase binding and nicking sites on λ DNA, and show that terminase consists of a linear array of functional domains.
EFFECT OF SULFONAMIDES AND THIOUREAS ON THE THYROID GLAND AND BASAL METABOLISM1 2

IN A PRELIMINARY paper (1) in 1941 we reported that sulfaguanidine, a sulfonamide employed to combat intestinal infections, produced a remarkable enlargement of the thyroid gland in rats, either in the presence or absence of paraaminobenzoic acid. The widespread use of sulfonamides,3 and the certainty of their ever-extending use in both therapy and prophylaxis, demanded an immediate and detailed investigation of this effect on the thyroid gland (and possibly on the basal metabolic rate) of the rat and other experimental animals to provide a basis for the search of a similar reaction in man. Furthermore, since this effect was not prevented in the rat by paraaminobenzoic acid, and therefore did not parallel the bacteriostatic activity of sulfaguanidine, the possibility of elucidating other biological reactions, and hence new therapeutic uses for sulfonamides, could not be overlooked.
The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism.

Objective Elevated plasma homocysteine (tHcy) and the MTHFR c.677C > T variant have been postulated to increase the risk of venous thromboembolism (VTE), although mechanisms and implications to pediatrics remain incompletely understood. The objectives of this study were to determine the prevalences of elevated tHcy and MTHFR variant in a pediatric population with VTE or arterial ischemic stroke (AIS), and to determine associations with thrombus outcomes.
Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B

RNA splicing plays a fundamental role in human biology. Its relevance in cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B in primary leukemia cells derived from patients with chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD-895 and pladienolide-B induce an early pattern of mRNA intron retention – spliceosome modulation. This process was associated with apoptosis preferentially in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of these compounds was observed regardless of poor prognostic factors such as Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect of culture conditions that resemble the tumor microenvironment. In addition, the activity of these compounds was observed not only in vitro but also in vivo using the A20 lymphoma murine model. Overall, these findings give evidence for the first time that spliceosome modulation is a valid target in chronic lymphocytic leukemia and provide an additional rationale for the development of spliceosome modulators for cancer therapy.
Power-aware data management for small devices

Pervasive computing devices such as Personal Digital Assistants (PDAs) and laptop computers are becoming increasingly ubiquitous. The future promises even more advanced devices such as digital watches, jewelry, and even clothing. However, as pervasive devices become more widely used for more advanced applications, their resource limitations are becoming more apparent. In this work, we focus on data management and power limitations. We investigate the benefit of using power-aware schemes to automatically manage content across a collection of devices and prolong data availability. We monitor the available energy supply on each device and migrate content from devices that are in danger of dying. In our simulated environment, we have found that, using intelligent techniques for data management can increase the amount of time a collection of devices remains usable by over 2 times. Furthermore, our techniques can perform autonomously, independent of user intervention.
Sources of Law in Ghana

In January 1993, Ghana's Fourth Republic was inaugurated after a 12-year military interregnum. The Fourth Republic was ushered in by a new constitution promulgated in October, 1992, yet another signal to the resumption of legal normalcy. In the present discussion I examine the sources of law in Ghana. I begin with a consideration of the introduction of colonial law in Ghana, and its impact on the preexisting customary law system. I discuss the nature and classification of laws in Ghana as well as the concomitant choice of law problems. I describe the role played by statutory law and also the court system and case law. I undertake a synoptic survey of the main branches of law in Ghana and conclude with certain tasks for law reform in Ghana and the continent of Africa. A remarkable fact is how little the legal system in Ghana has changed over the years.
Spoken word frequency counts based on 1.6 million words in American English.

Written word frequency (e.g., Francis & Kucera, 1982; Kucera & Francis, 1967) constitutes a popular measure of word familiarity, which is highly predictive of word recognition. Far less often, researchers employ spoken frequency counts in their studies. This discrepancy can be attributed most readily to the conspicuous absence of a sizeable spoken frequency count for American English. The present article reports the construction of a 1.6-million-word spoken frequency database derived from the Michigan Corpus of Academic Spoken English (Simpson, Swales, & Briggs, 2002). We generated spoken frequency counts for 34,922 words and extracted speaker attributes from the source material to generate relative frequencies of words spoken by each speaker category. We assess the predictive validity of these counts, and discuss some possible applications outside of word recognition studies.
Effect of type and location of oil groove on the performance of journal bearings

A numerical study is performed of oil groove type (circumferential and axial), groove number (single and double) and groove location on journal bearing performance. The analysis involves the use of a cavitation algorithm. The interaction between cavitation phenomena and grooving is determined. Quantitative information is provided which will aid designers to better locate oil feed grooves.
Modification of the cysteine residues of cytochrome P-450cam with 2-bromoacetamido-4-nitrophenol

Abstract The Pseudomonas putida cytochrome P-450 was alkylated with the SH-reagent, 2-bromoacetamido-4-nitrophenol. One out of eight cysteine residues present in the enzyme reacted rapidly while another 3 ∼ 4 cysteine residues were gradually alkylated at longer reaction times. The derivative in which the most reactive cysteine residue was labeled with this reagent was hydrolyzed with trypsin and a tryptic peptide isolated. From the amino acid composition and end group analysis of the peptide, the rapidly reacting cysteine residue was shown to be Cys 355. This cysteine residue is probably exposed on the surface and is involved in the dimerization of the enzyme. The amino acid sequence about cysteine 355 shows sequence homology with residues 429–445 of the rat liver cytochrome P-450-LM-2.
Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study.

Summary The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men.
Comparative effectiveness and child health

Comparative effectiveness research is expected to play an important role in future clinical and policy decision making in the US; however, the application of comparative effectiveness methodologies to child health requires special attention to aspects of health and healthcare that are specific to children. These special considerations include the role of parent/caregiver as joint decision maker and co-participant in many types of interventions, how the effectiveness of an intervention varies by age and developmental stage, and the difficulties in translating short-term data from childhood into projected effectiveness over the lifespan. Each aspect of comparative effectiveness, such as conducting new studies, synthesizing existing evidence, emphasizing real-world settings, considering multiple decision makers, and measuring patient-relevant outcomes, will require expanded definitions when considered in the context of child health. This paper discusses how comparative effectiveness methods and concepts will differ when applied to child health and suggests a potential role for decision analysis as a method to synthesize data and project long-term outcomes. The initiation of comparative effectiveness studies for children represents an exciting opportunity to provide evidence that can guide clinical and policy decisions for child health.
FACTORS ASSOCIATED WITH 30-DAY READMISSIONS IN CONGESTIVE HEART FAILURE PATIENTS: ANALYSIS OF 2,536,439 ADMISSIONS

Congestive heart failure (CHF) is a major cause of morbidity and is associated with a high 30-day re-admission rate (RR) and economic burden on health care. This study was done to determine parameters associated with high 30-day RR secondary to CHF. Nationwide Inpatient Sample data was used to
Vehicle Sideslip Angle Estimation Using Two Single-Antenna GPS Receivers

Knowing vehicle sideslip angle accurately is critical for active safety systems such as Electronic Stability Control (ESC). Vehicle sideslip angle can be measured through optical speed sensors, or dual-antenna GPS. These measurement systems are costly (∼$5k to $100k), which prohibits wide adoption of such systems. This paper demonstrates that the vehicle sideslip angle can be estimated in real-time by using two low-cost single-antenna GPS receivers. Fast sampled signals from an Inertial Measurement Unit (IMU) compensate for the slow update rate of the GPS receivers through an Extended Kalman Filter (EKF). Bias errors of the IMU measurements are estimated through an EKF to improve the sideslip estimation accuracy. A key challenge of the proposed method lies in the synchronization of the two GPS receivers, which is achieved through an extrapolated update method. Analysis reveals that the estimation accuracy of the proposed method relies mainly on vehicle yaw rate and longitudinal velocity. Experimental results confirm the feasibility of the proposed method.Copyright © 2010 by ASME
Effect of polyalkyl polyphosphonates on bone development in young rats

Es wird gezeigt, dass Knochenentwicklung junger Ratten durch Behandlung mit Polyethylen-Polyphosphonat ohne toxische Wirkung verhindert wird. Die Polyphosphonate wirken direkt auf den Knochen und konnen eventuell verschiedene klinische Anwendungen finden.
The role of target vulnerabilities in high-technology protest movements: The nuclear establishment at Three Mile Island

Contemporary perspectives on social movements focus primarily upon challenging groups and political authorities, frequently ignoring the importance of vulnerabilities of the target of protest in shaping the outcomes of protracted struggles. The target's own human and technological weaknesses which emerge in the course of the conflict, however, are sometimes critical, as shown in this analysis of citizens' six-year endeavor to prevent the restart of Three Mile Island's Unit 1 reactor after the Unit 2 accident. If, as has been suggested (Perrow, 1984), modern industrial nations can expect an increase in such “system accidents,” they are likely to precipitate a new genre of social movements pitting local residents against high technology industries. Emergent target vulnerabilities are likely to figure prominently in some of these processes, and social movement analysts' explanatory models should allow for them.
A technique to improve the performance of a nonlinear filter with an application to satellite-aided aircraft navigation

This paper evaluates performance of a filter that transforms nonlinear measurements in the coordinate system of the state before using in the filter. The bias and computational performance of this mechanization are compared with the conventional extended Kalman (EK) filter. The bias in the EK filter is a function of the covariance of the estimation error, while in the state-coordinate-system (SCS) it depends on variance of the transformed measurement noise, which is independent of the estimation error and depends only on the nonlinearity. Thus when the initial covariance of the state is large, the SCS filter has less bias than the EK filter. This reduction in the bias is achieved at a cost of additional computations required to implement the transformation. The improved performance of the filter due to the coordinate transformation is then demonstrated with an example of satellite-aided aircraft navigation.
The Carapace and Crustacean Evolution—Arebuttal

ABSTRACT Professor Dahl purports to overthrow the long-standing premise that the primitive malacostracan carapace extends freely from the back of the cephalon. If the premise were overthrown, a number of serious difficulties would develop in long accepted hypotheses concerned with evolution within the Malacostraca as well as with the affinities of malacostracans with other crustacean taxa. However, we reaffirm that the free carapace is cephalic in the most primitive of the living malacostracans, the leptostracan phyllocarids, and in the ontogeny of the eucarids having the most anamorphic development known to the malacostracans, the Dendrobranchiata. These facts allow the formulation of hypotheses concerning (1) the loss of the carapace without the necessity of "resegmentation" in various malacostracans, and (2) the origin of the Maxillopoda from a malacostracan-like ancestor.
Resource balancing control allocation

Next generation aircraft with a large number of actuators will require advanced control allocation methods to compute the actuator commands needed to follow desired trajectories while respecting system constraints. Previously, algorithms were proposed to minimize the l 1 or l 2 norms of the tracking error and of the control effort. The paper discusses the alternative choice of using the l 1 norm for minimization of the tracking error and a normalized l 221E; norm, or sup norm, for minimization of the control effort. The algorithm computes the norm of the actuator deflections scaled by the actuator limits. Minimization of the control effort then translates into the minimization of the maximum actuator deflection as a percentage of its range of motion. The paper shows how the problem can be solved effectively by converting it into a linear program and solving it using a simplex algorithm. Properties of the algorithm are investigated through examples. In particular, the min-max criterion results in a type of resource balancing, where the resources are the control surfaces and the algorithm balances these resources to achieve the desired command. A study of the sensitivity of the algorithms to the data is presented, which shows that the normalized l 221E; algorithm has the lowest sensitivity, although high sensitivities are observed whenever the limits of performance are reached.
Genetic population structure of the southern oyster drill Stramonita (= Thais ) haemostoma

Nine collections in the southeastern USA of the thaidid molluscStramonita haemastoma, comprising 963 individuals, were made between June 1988 and November 1989, and examined for allozyme variation at 18 electrophoretically-detected loci. Two genetically-differentiated groups were identified and are referred to ascanaliculata-like andfloridana-like snails, based on previously-described subspecies ofS. haemastoma. The two groups were differentiated genetically at a level that is characteristic of congeneric species in other molluscan taxa. The two groups maintained their genetic differences in areas of sympatry, although rare hybrid individuals occurred (about 1.2% of the total set). Shell and radular characters showed little variation within or between the two groups. Within each group, allozyme allele frequencies showed little geographic variation across distances as great as 1 500 km. This result is consistent with the suggestion that species with planktonic larvae (such asS. haemastoma) should have higher rates of gene flow than related brooding species.
SU-FF-T-60: A Simplified Frame Work Using Deep Inspiration Breath-Hold (DIBH) for the Treatment of Left Breast Cancer with Improved Heart Sparing

Purpose: To develop a simplified frame work using deep inspiration breath‐hold (DIBH) for left breast treatment. Materials and Methods: The current version of Varian's RPM system was rarely used in amplitude gating mode, especially with breath hold. The major reason is that the breathing amplitude is much less reproducible than breathing phase. Further, the same signal captured by the infrared camera in simulation room and that in treatment room could be different in amplitude. In this study, we presented a simplified frame work to improve the reproducibility of patient's breathing amplitude. First, an aqua‐plastic body mask of 1.0–1.5 in wide was made right before patient's simulation while the patient is in DIBH. The body mask was set at umbilicus right superior to the marker box. It will then be used to guide the patient herself for DIBH. The DIBH signal is also displayed on a computer monitor set close to patient, which is a duplicate display of the DIBH signal in the RPM computer. The patient can see her own signal and can therefore guide her breath such that relatively constant amplitude can be achieved. Results: The frame work was tested by a few volunteers and all agree that the system is feasible for left breast treatment. The DIBH can last 15–35s with good constant amplitude. In case the captured amplitude is different in treatment room, the two gating threshold lines set in simulation can be adjusted overlay to the DIBH signal before treatment. Conclusion: The system is feasible for the treatment of left breast cancer with DIBH. Further improvement can be made by wiring the gating cable through patient using two electrodes; one on patient's body and the other on the guiding mask so that the amplitude‐gated CT scans and treatment can be actively controlled by patient herself.
An examination of geologic carbon sequestration policies in the context of leakage potential

Abstract Carbon dioxide (CO2) injected into geologic reservoirs for long-term sequestration, or the brine it displaces, may leak through natural or manmade pathways. Using a leakage estimation model, we simulated fluid leakage from a storage reservoir and its migration into overlying formations. The results are discussed in the context of policies that seek to assure long-term sequestration and protect groundwater. This work is based on a case study of CO2 injection into the Mt. Simon sandstone in the Michigan sedimentary basin, for which we constructed a simplified hydrologic representation of the geologic formations. The simulation results show that (1) CO2 leakage can reach an aquifer containing potable water, but numerous intervening stratigraphic traps limit the rate to be orders of magnitude less than the rate of leakage from the storage reservoir; (2) U.S. Department of Energy guidelines for storage permanence allow for more leakage from larger injection projects than for smaller ones; (3) well leakage permeability is the most important variable in determining leakage processes and substantial leakage requires that numerous wells leaking with the anomalously high permeability of 10−10 m2; and (4) leakage can reduce the U.S. Environmental Protection Agency’s Area of Review.
Superconductivity of Hydrides and Deuterides of Thorium

Superconductivity has been observed in the hydrides and deuterides of thorium with H-or D-to-metal atom ratios of 3.6 to 3.65. Transition temperatures fall in the range from 8.05 to 8.35 K. These materials are apparently type-II superconductors with ${H}_{c2}$ of the order of 25-30 kG at 1.1 K. There is no evidence for an isotope effect within the limits of experimental uncertainty.
Treatment of Juvenile Recurrent Parotitis of Childhood: An Analysis of Effectiveness

Importance Juvenile recurrent parotitis (JRP) is characterized by recurrent painful swelling of the parotid gland that occurs in the pediatric population. Sialendoscopy with and without ductal corticosteroid infusion (DCI) has been found to be effective in the treatment of JRP and autoimmune parotitis. Objective To determine the utility of instrumentation vs pharmacotherapy alone for juvenile recurrent parotitis. Design, Setting, and Participants A retrospective medical record review of pediatric patients undergoing DCI without sialendoscopy at a tertiary pediatric hospital was conducted. The medical records were reviewed to determine the frequency of parotitis events before and after treatment. A multiquestion telephone survey of patients and their parents who underwent the procedure was then conducted to determine patient satisfaction. Interventions Ductal corticosteroid infusion with hydrocortisone through catheter inserted in the parotid duct. Main Outcomes and Measures Frequency of symptoms before and after treatment and parental satisfaction with the treatment. Results Twelve patients with a mean age of 6.7 years were identified. The mean duration and frequency of symptoms before the procedure were 22 months and every 2 months, respectively. Five patients had a recurrence, on average 4 months after the procedure. Four patients underwent repeated surgical procedures. All had a longer duration between episodes compared with before DCI. Eight parents participated in the survey on satisfaction with the procedure, and 75% reported improvement in their child’s life postprocedure. Conclusions and Relevance Current literature shows sialendoscopy with corticosteroid application is successful in treating JRP, but it is unclear whether corticosteroid application alone would treat JRP equally. This study shows that DCI alone has similar results as sialendoscopy with corticosteroid application, indicating that it is the corticosteroid application and not the sialendoscopy causing improvement in symptoms. Because JRP must be differentiated from sialolithiasis, we recommend ultrasonography of the involved parotid(s) prior to using DCI alone to ensure no stone is present. Sialendoscopy should be reserved to rule out other parotid ductal pathologic conditions.
Transfer of discrimination from solid objects to pictures by pigeons: A test of theoretical models of pictorial perception

Various authors have suggested that learning associations between objects and pictures is a necessary condition for the perception of pictures. If so, then animals, never exposed to situations in which those associations might be learned, should not show transfer between objects and pictures. In this investigation, pigeons trained to discriminate between two solid objects were retrained with reinforcement reversal on either the objects themselves or photographs, line drawings, or silhouettes of the objects. Significant negative transfer indicated object-photograph and object-silhouette equivalence, but no transfer was found to line drawings. Positive transfer to photographs was also demonstrated. Transfer did not appear to be a function of object-picture confusability.
Temperature tolerance and water balance in feral and domestic honey bees, Apis mellifera L

Abstract Feral and domestic honey bees were compared to determine relative levels of adaptation to the Arizona desert. Feral honey bees were more tolerant to high temperatures than domestic honey bees. Monthly critical thermal maxima (CTMs) of feral bees were significantly different from those of domestic bees (P
Four-particle perimetric coordinates

An attempt was made to find perimetric coordinates for a 4-particle system. It is conjectured that such coordinates do not exist.
Facing Up to Aging: Mid-Life Women's Attitudes toward Cosmetic Procedures

Despite the fact that mid-life and older women are a major consumer group for cosmetic procedures (e.g., botox, face lifts), few studies have been done on their attitudes toward these procedures and their willingness to undergo them. The purpose of the present study was to gather information about the popularity of these procedures among a group of 57 mid-life American women, examine whether some personality and attitudinal measures might predict attitudes toward these procedures, and consider the ramifications of the data for the treatment of women in feminist therapy. About one third (38.5%) of our sample had had one or more cosmetic procedures, and 81% said that they would have a procedure if cost were not an issue. Positive attitudes toward cosmetic surgery and preoccupation with being over-weight best predicted women's interest in cosmetic procedures. The popularity of these procedures is discussed in light of the double standard of aging and age discrimination, weight as a “normative discontent,” an...
Random walk to and interaction with an impurity

A random walker tagged with a spin may conveniently be studied by small amounts of paramagnetic impurities which significantly affect the spin relaxation at concentrations as low as a few parts per million. Examples are found in nuclear magnetic resonance (NMR) and muon spin rotation (μSR). At low temperature relaxation is determined by the time for the walker to reach an impurity, and thus the impurity acts like a simple trap. Details of the interaction with the impurity are important at higher temperatures, and the relaxation rate is shown to go through a maximum because of this. Special features associated with many returns to the origin, particularly important in one-dimensional walks, and the difference between incoherent (rapidly fluctuating paramagnetic spin) and coherent (stationary paramagnetic spin) returns are discussed.
Ethics in bioengineering.

Bioengineering, as the decisive extension of engineering action to human life itself, constitutes a fundamental enlargement of the technical realm, and calls for a commensurate expansion of ethical reflection. In fact, the engineering profession has been actively pursuing the development of new ethical codes, and the promotion of ethics by bioengineers both in the United States and on the international level deserves philosophical recognition and support.
Quantized electronic states in nanostructures

Abstract This brief introduction explores the electronic structure and synthesis of surfaces that are structured at the nanometer level. Magnetic multilayers serve as examples of two-dimensional structures, decorated steps represent one-dimensional systems. Synchrotron radiation spectroscopy can play a leading role in the investigation of electronic states and magnetism of these systems if it can be combined with structural characterization by scanning tunneling microscopy.
A srial ASCII keyboard-printer.

Abstract The construction of a simple keyboard—printer is described. It is intended for use with single-board microcomputers such as the KIM and SYM which have a 20-mA loop ASCII interface.
Analysis of three-dimensional grids: the eight-point cube

It is widely believed that quadratic coefficients cannot be estimated from eight data in cubical array. This paper illustrates the estimation of those coefficients by means of by operational equations. The coefficients are compared to the quadratic coefficients obtained by Taylor expansion of the functions generating the data. The agreement may be sufficient to interest experimentalists.
The Endoplasmic Reticulum–associated Degradation of the Epithelial Sodium Channel Requires a Unique Complement of Molecular Chaperones

The epithelial sodium channel (ENaC) is composed of a single copy of an alpha-, beta-, and gamma-subunit and plays an essential role in water and salt balance. Because ENaC assembles inefficiently after its insertion into the ER, a substantial percentage of each subunit is targeted for ER-associated degradation (ERAD). To define how the ENaC subunits are selected for degradation, we developed novel yeast expression systems for each ENaC subunit. Data from this analysis suggested that ENaC subunits display folding defects in more than one compartment and that subunit turnover might require a unique group of factors. Consistent with this hypothesis, yeast lacking the lumenal Hsp40s, Jem1 and Scj1, exhibited defects in ENaC degradation, whereas BiP function was dispensable. We also discovered that Jem1 and Scj1 assist in ENaC ubiquitination, and overexpression of ERdj3 and ERdj4, two lumenal mammalian Hsp40s, increased the proteasome-mediated degradation of ENaC in vertebrate cells. Our data indicate that Hsp40s can act independently of Hsp70 to select substrates for ERAD.
Heavy ion backscattering spectrometry for high sensitivity

Abstract Heavy ion backscattering spectrometry (HIBS) using moderate energy (a few hundred keV) heavy ions has demonstrated sensitivity for medium-to-heavy surface impurities on Si more than 1000 × greater than conventional Rutherford backscattering spectrometry (RBS). Problems with pileup are eliminated by a thin, self-supporting foil in front of the surface barrier detector (SBD), ranging out ions scattered from the substrate and allowing only ions scattered from impurities heavier than the substrate to reach the detector. Limitations to a SBD approach arise from relatively poor energy resolution at low energies, leading to the inability to resolve closely spaced impurity masses (such as Fe and Cu), as well as requiring an analysis beam of 250 keV or higher. In order to bypass these limitations and explore means of increasing sensitivity and mass resolution, we have built a time-of-flight (TOF) HIBS prototype, optimized for large solid angle.
Linear extrapolation method of analyzing solvent denaturation curves

The two most common methods of measuring the conformational stability of a protein are differential scanning calorimetry and an analysis of solvent denaturation curves by using the linear extrapolation method. In this article, we trace the history of the linear extrapolation method, review how the method is used to measure protein stability, and then discuss some of the other important uses.
Context-specific parasitism in Tubifex tubifex in geothermally influenced stream reaches in Yellowstone National Park

AbstractParasites can regulate host abundance and influence the composition and structure of communities. However, host–parasite interactions might be context-specific if environmental conditions can alter the outcome of parasitism and disease. An understanding of how host–parasite interactions might change in different contexts will be useful for predicting and managing disease against a background of anthropogenic environmental change. We examined the ecology of Myxobolus cerebralis, the parasite that causes whirling disease in salmonids, and its obligate host, Tubifex tubifex, in geothermally variable stream reaches in Yellowstone National Park. We identified reaches in 4 categories of geothermal influence, which were characterized by variable substrates, temperatures, specific conductivities, and pH. In each reach, we measured aspects of host ecology (abundance, relative abundance, size, and genotype of T. tubifex), parasite ecology (infection prevalence in T. tubifex and abundance of M. cerebralis-in...
Group-based parent training programmes demonstrate positive effects on the psychosocial well-being of both mothers and fathers.

A previous meta-analysis by the same first author focused on parent training using data on mothers found that parent training programmes improved mothers’ psychosocial well-being, including depression, anxiety/stress, self-esteem and spouse/marital adjustment.1
Superoxide Fluxes Limit Nitric Oxide-induced Signaling

Independently, superoxide (O2-) and nitric oxide (NO) are biologically important signaling molecules. When co-generated, these radicals react rapidly to form powerful oxidizing and nitrating intermediates. Although this reaction was once thought to be solely cytotoxic, herein we demonstrate using MCF7, macrophage, and endothelial cells that when nanomolar levels of NO and O2- were produced concomitantly, the effective NO concentration was established by the relative fluxes of these two radicals. Differential regulation of sGC, pERK, HIF-1alpha, and p53 were used as biological dosimeters for NO concentration. Introduction of intracellular- or extracellular-generated O2- during NO generation resulted in a concomitant increase in oxidative intermediates with a decrease in steady-state NO concentrations and a proportional reduction in the levels of sGC, ERK, HIF-1alpha, and p53 regulation. NO responses were restored by addition of SOD. The intermediates formed from the reactions of NO with O2- were non-toxic, did not form 3-nitrotyrosine, nor did they elicit any signal transduction responses. H2O2 in bolus or generated from the dismutation of O2- by SOD, was cytotoxic at high concentrations and activated p53 independent of NO. This effect was completely inhibited by catalase, suppressed by NO, and exacerbated by intracellular catalase inhibition. We conclude that the reaction of O2- with NO is an important regulatory mechanism, which modulates signaling pathways by limiting steady-state levels of NO and preventing H2O2 formation from O2-.
Molecular analysis of familial human growth hormone disorders.

There is a diverse group of human genetic disorders affecting growth hormone action that lead to short stature. Insights into their pathophysiology can be gained by a combination of classical and molecular genetic studies.
Validating a 3-point prediction rule for surgical site infection after coronary artery bypass surgery.

BACKGROUND. Surgical site infection (SSI) after coronary artery bypass graft (CABG) surgery is an increasing healthcare problem. Investigators from Australia proposed a new, 3-point scale that assesses SSI risk on the basis of diagnosis of diabetes mellitus and body mass index. OBJECTIVE. To validate the Australian Clinical Risk Index among patients undergoing CABG surgery in the United States. DESIGN AND SETTING. Nested case-control study involving patients undergoing CABG surgery at 9 hospitals during 1991-2002. PATIENTS. Case patients were those who developed SSIs after CABG surgery. Control subjects were matched to case patients on the basis of hospital, age, and procedure date. METHODS. Odds ratios (ORs) for SSIs were calculated for the comparison of case patients with control subjects for all risk categories determined using the Australian Clinical Risk Index and National Nosocomial Infections Surveillance System (NNIS) risk index. An adjusted area under the curve was used to compare predictive values among risk indices. RESULTS. Four hundred sixty patients were studied, including 269 patients with SSI and 191 control subjects. NNIS risk group 2 was associated with increased rate of SSI (OR, 1.79; 95% confidence interval [CI], 1.19-2.67). No patient had an NNIS risk index of 3. The remaining NNIS categories were not predictive of infection. In contrast, an increase in Australian Clinical Risk Index was associated with an increase in risk of SSI (category 2: OR, 2.39 [95% CI, 1.33―4.29]; category 3: OR, 4.46 [95% CI, 1.83-10.85]). CONCLUSIONS. The NNIS risk index predicts the risk of SSI associated with many procedures, but it has limited use in predicting the risk of SSI after CABG surgery. The new Australian Clinical Risk Index stratified patients into discrete groups associated with increased risk of SSI. Data from our study support the use of this new risk index in the US population.
Synergy among Nuclear Receptor Coactivators: Selective Requirement for Protein Methyltransferase and Acetyltransferase Activities

Hormone-activated nuclear receptors (NR) bind to specific regulatory DNA elements associated with their target genes and recruit coactivator proteins to remodel chromatin structure, recruit RNA polymerase, and activate transcription. The p160 coactivators (e.g., SRC-1, GRIP1, and ACTR) bind directly to activated NR and can recruit a variety of secondary coactivators. We have established a transient-transfection assay system under which the activity of various NR is highly or completely dependent on synergistic cooperation among three classes of coactivators: a p160 coactivator, the protein methyltransferase CARM1, and any of the three protein acetyltransferases, p300, CBP, or p/CAF. The three-coactivator functional synergy was only observed when low levels of NR were expressed and was highly or completely dependent on the methyltransferase activity of CARM1 and the acetyltransferase activity of p/CAF, but not the acetyltransferase activity of p300. Other members of the protein arginine methyltransferase family, which methylate different protein substrates than CARM1, could not substitute for CARM1 to act synergistically with p300 or p/CAF. A ternary complex of GRIP1, CARM1, and p300 or CBP was demonstrated in cultured mammalian cells, supporting a physiological role for the observed synergy. The transfection assay described here is a valuable new tool for investigating the mechanism of coactivator function and demonstrates the importance of multiple coactivators, including CARM1 and its specific protein methyltransferase activity, in transcriptional activation.
Re-visiting the Endogenous Capacity for Recombinant Glycoprotein Sialylation by Baculovirus-Infected Tn-4h and DpN1 Cells

It was previously reported that Tn-4h and DpN1 cells have the endogenous capacity to efficiently sialylate secreted alkaline phosphatase (SEAP) when infected with a baculovirus expression vector. In contrast, it has been found that lepidopteran insect cell lines that are more widely used as hosts for baculovirus vectors typically fail to sialylate SEAP and other recombinant glycoproteins. Thus, the N-glycan processing capabilities of Tn-4h and DpN1 cells are of potential interest to investigators using the baculovirus expression system for recombinant glycoprotein production. In this study, we experimentally re-assessed the ability of Tn-4h and DpN1 cells to sialylate SEAP with Sf9 and glyco-engineered Sf9 cells (SfSWT-1) as negative and positive controls, respectively. Our results showed that the SEAP purified from SfSWT-1 cells was strongly sialylated and initially indicated that the SEAP purified from Tn-4h cells was weakly sialylated. However, further analyses suggested that the SEAP produced by Tn-4h cells only appeared to be sialylated because it was contaminated with an electrophoretically indistinguishable sialoglycoprotein derived from fetal bovine serum. We subsequently expressed, purified, and analyzed a second recombinant glycoprotein (GST-SfManI) from all four cell lines and found that only the SfSWT-1 cells were able to detectably sialylate this product. Together, these results showed that neither Tn-4h nor DpN1 cells efficiently sialylated SEAP or GST-SfManI when infected by baculovirus expression vectors. Furthermore, they suggested that previous reports of efficient SEAP sialylation by Tn-4h and DpN1 cells probably reflect contamination with a sialylated, co-migrating glycoprotein, perhaps bovine fetuin, derived from the serum used in the insect cell growth medium.
Evaluation of the influence of a thioether substituent on the solid state and solution properties of N3S-ligated copper(II) complexes

Admixture of a N3S(thioether) ligand having two internal hydrogen bond donors (pbnpa: N-2-(phenylthio)ethyl-N,N-bis-((6-neopentylamino-2-pyridyl)methyl)amine; ebnpa: N-2-(ethylthio)ethyl-N,N-bis-((6-neopentylamino-2-pyridyl)methyl)amine) with equimolar amounts of Cu(ClO4)2·6H2O and NaX (X = Cl−, NCO−, or N3−) in CH3OH/H2O yielded the mononuclear Cu(II) derivatives [(pbnpa)Cu–Cl]ClO4 (1), [(ebnpa)Cu–Cl]ClO4 (2), [(pbnpa)Cu–NCO]ClO4 (3), [(ebnpa)Cu–NCO]ClO4 (4), [(pbnpa)Cu–N3]ClO4 (5), and [(ebnpa)Cu–N3]ClO4 (6). Each complex was characterized by FTIR, UV-VIS, EPR, and elemental analysis. Complexes 1, 2, 3 and 6 were characterized by X-ray crystallography. The structural studies revealed that [(pbnpa)Cu–X]ClO4 derivatives (1, 3) exhibit a distorted square pyramidal type geometry, whereas [(ebnpa)Cu–X]ClO4 complexes (2, 6) may be classified as distorted trigonal bipyramidal. EPR studies in CH3OH/CH3CN solution revealed that 1–6 exhibit an axial type spectrum with g∥ > g⊥ > 2.0 and A∥ = 15–17 mT, consistent with a square pyramidal based geometry for the Cu(II) center in each complex. A second species detected in the EPR spectra of 2 and 6 has a smaller A∥ value, consistent with greater spin delocalization on to sulfur, and likely results from geometric distortion of the [(ebnpa)Cu(II)–X]+ ions present in 2 and 6.
Within- and among-tree variation of the induced response of loblolly pine to a fungus associated with Dendroctonus frontalis Zimmermann (Coleoptera: Scolytidae) and sterile wounding

The variation in response to fungal inoculation and sterile wounding within and among Pinus taeda L. was evaluated. The mean fungal-induced lesion size among the 20 trees sampled was 105.8 mm (coefficient of variation of 49.19), compared with a mean lesion size of 19.4 mm (coefficient of variation of 36.40) for the sterile control treatment. Mean lesion size for the fungal inoculation of individual trees ranged from 61 to 192 mm with a range in variances from 10 368.48 to 166.64, and the mean lesion size produced in response to sterile wounding varied from 16 to 26 mm with a range in variances from 254.28 to 0.35. The variance in response to the fungal treatment was on average 16.39-fold greater than the mean compared with only 1.97-fold greater than the mean for the control. There was no relationship between size of responses to either treatment and the position of the sample site on the tree. We suggest that intra-tree variation of the kind demonstrated in earlier studies for the chemical constituents and for physical size of the tree response to invasion may make it very difficult for arriving beetles to assess actual tree susceptibility or suitability for colonization. This may be critical as a component of tree defense in this system where successful reproduction by the insect is dependent on death of the host tree.
Spatial mapping of structural and connectional imaging data for the developing human brain with diffusion tensor imaging

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain.
Novel β-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy

Novel phage-displayed random linear dodecapeptide (X(12)) and cysteine-constrained decapeptide (CX(10)C) libraries constructed in fusion to the amino-terminus of P99 beta-lactamase molecules were used for identifying beta-lactamase-linked cancer cell-specific ligands. The size and quality of both libraries were comparable to the standards of other reported phage display systems. Using the single-round panning method based on phage DNA recovery, we identified several beta-lactamase fusion peptides that specifically bind to live human breast cancer MDA-MB-361 cells. The beta-lactamase fusion to the peptides helped in conducting the enzyme activity-based clone normalization and cell-binding screening in a very time- and cost-efficient manner. The methods were suitable for 96-well readout as well as microscopic imaging. The success of the biopanning was indicated by the presence of approximately 40% cancer cell-specific clones among recovered phages. One of the binding clones appeared multiple times. The cancer cell-binding fusion peptides also shared several significant motifs. This opens a new way of preparing and selecting phage display libraries. The cancer cell-specific beta-lactamase-linked affinity reagents selected from these libraries can be used for any application that requires a reporter for tracking the ligand molecules. Furthermore, these affinity reagents have also a potential for their direct use in the targeted enzyme prodrug therapy of cancer.