cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of the Molecular Organization of Lipoprotein-Associated Apolipoprotein E, an Anti-Atherogenic Protein

Human apolipoprotein E3 (apoE3) is a 299 residue exchangeable apolipoprotein that has the ability to exist in lipid-free and lipoprotein-bound states. It is composed of an N-terminal domain bearing LDL-receptor binding sites and a C-terminal (CT) domain bearing high-affinity lipid-binding sites; the latter is also responsible for mediating cellular cholesterol efflux. ApoE plays a crucial role as an anti-atherogenic agent in atherosclerosis by virtue of its ability to mediate reverse cholesterol transport by promoting cholesterol efflux from macrophages, a process that leads to the initial formation of nascent discoidal high-density lipoproteins (nHDL). The objective of this study is to understand the molecular organization and conformation of apoE3 (1-299) and isolated CT domain (201-299) on reconstituted HDL (rHDL) and nHDL generated by macrophages. To accomplish this, we over-expressed and purified recombinant apoE3 and the CT domain bearing single Cys at selected sites. rHDL was prepared using unlabeled or pyrene-labeled single Cys variants and phospholipids, while nHDL was generated by exposing cholesterol-loaded J774 macrophages to unlabeled or labeled apoE bearing probes at defined sites. Lipid-associated apoE was obtained by density gradient ultracentrifugation. The relative organization of apoE molecules on rHDL and nHDL was followed by monitoring pyrene excimer fluorescence and by site-specific cross-linking studies, both complementary validators of spatial proximity at ∼10 A distance. The appearance of excimer emission and cross-linked dimers regardless of the location of the single Cys is indicative of pairs of apoE3 molecules oriented parallel to each other on the HDL to form a dimer. Based on our results, we propose that apoE molecules circumscribe a bilayer of lipids adopting a belt-like conformation. Our study offers mechanistic details of apoE interaction with lipids, which aids in understanding its role in cardiovascular disease.
Development of a defined medium supporting rapid growth for Deinococcus radiodurans and analysis of metabolic capacities

A morpholinepropanesulfonic acid (MOPS)-buffered rich defined medium (RDM) was optimized to support a reproducible 2.6-h doubling time at 35 °C for Deinococcus radiodurans R1 and used to gain insight into vitamin and carbon metabolism. D. radiodurans was shown to require biotin and niacin for growth in this medium. A glutamine–serine simple defined medium (SDM) was developed that supported a 4-h doubling time, and this medium was used to probe sulfur and methionine metabolism. Vitamin B12 was shown to alleviate methionine auxotrophy, and under these conditions, sulfate was used as the sole sulfur source. Phenotypic characterization of a methionine synthase deletion mutant demonstrated that the B12 alleviation of methionine auxotrophy was due to the necessity of the B12-dependent methionine synthase in methionine biosynthesis. Growth on ammonium as the sole nitrogen source in the presence of vitamin B12 was demonstrated, but it was not possible to achieve reproducibly good growth in the absence of at least one amino acid as a nitrogen source. Growth on sulfate, cysteine, and methionine as sulfur sources demonstrated the function of a complete sulfur recycling pathway in this strain. These studies have demonstrated that rapid growth of D. radiodurans R1 can be achieved in a MOPS-based medium solely containing a carbon source, salts, four vitamins, and two amino acids.
Kinetics of the decomposition of hydrated oxalates of calcium and magnesium in air

Combined thermal analysis was used to establish the dissociation steps for the hydrated oxalates of calcium and magnesium. While dehydration of calcium oxalate monohydrate is governed by three-dimensional phase boundary movement, dehydration of magnesium oxalate is governed by Avrami—Erofeev nuclei growth. Both dehydration reactions demonstrated that the activation energy and the pre-exponential factor vary with temperature over wide ranges. Accordingly, the methods of Reich and Kissinger (based on the maximum rate temperature) or Carroll and Manche are not suitable. Moreover they could not distinguish between the overlapping reactions or mechanisms. They can be only used as a guide in differentiating between the possible mechanisms obtained using the methods of Coats and Redfern or Satava and Skvara. The latter method is recommended since it gives a smaller number of possible operating mechanisms. When possible mechanisms have close activation energies both techniques are needed. Both anhydrous oxalates dissociated to the carbonates according to the Avrami—Erofeev nuclei growth, A2. For the magnesium salt, at low heating rates, this step was accompanied by dissociation of MgCO3 to MgO. Both carbonates dissociate according to a three-dimensional phase boundary migration mechanism.
Changes in pituitary and plasma levels of LH and FSH after cessation of chronic androgen treatment.

Specific bioassays of plasma and pituitary FSH and LH levels show that the changes produced in castrated rats by 5–7 weeks of strong androgen treatment are not all reversed when treatment is discontinued. Plasma FSH levels rise sooner and more than plasma LH levels. Pituitary LH stores also rise, indicatingincreased LH synthesis. Pituitary FSH levels fail to fall, suggesting a) that the need for increased FSH release may be being met by de novo synthesis and b) that the high level of FSH activity in the pituitary of the androgen treated rat may represent non-mobilizable stores. (Endocrinology 81:930,1967)
Ultra-fast Dynamic Imaging of Matter

Modern science attempts to obtain a better understanding of our world by disassembling it into its constituents and studying their interactions. Today, much about the constituents of matter and the...
The NICU Graduate: Implications for Pediatric Primary Care

Abstract Mortality rates of extremely preterm infants continue to decline as neonatal technology and care improve. Following graduation from the Neonatal Intensive Care Unit, preterm infants will transition to pediatric primary care offices for continued care and treatment. These infants often have complex health care needs that present inherent challenges to the pediatric health care providers who will provide that ongoing care. Implications for primary care providers include knowledge and treatment modalities of the common complications of the preterm infant. These complications typically include chronic lung disease; catch up growth and additional nutritional needs, neurodevelopmental monitoring, feeding challenges, retinopathy of prematurity and apnea of prematurity. Each patient–parent dyad will need a customized approach to primary care, coordinating care with physical, occupational, and speech therapy as well as other specialist in order to accomplish the best long term outcomes. Strategies for success in meeting the health care needs of infants and families following transition from the Neonatal Intensive Care Unit to primary care are provided.
Parameter estimation for 3-parameter generalized pareto distribution by the principle of maximum entropy (POME)

The principle of maximum entropy (POME) is employed to derive a new method of parameter estimation for the 3-parameter generalized Pareto (GP) distribution. Monte Carlo simulated data are used to evaluate this method and compare it with the methods of moments (MOM), probability weighted moments (PWM), and maximum likelihood estimation (MLE). The parameter estimates yielded by the POME are either superior or comparable for high skewness.
The mixed postman problem

Abstract The mixed postman problem is formulated as an integer linear program. A one to one correspondence is established between the extreme points of the linear programming polyhedron and prime assigned Euler networks. A prime assigned Euler network gives rise to a set of length equivalent prime postman tours. Some prime postman tour is optimal. Thus, it is sufficient to search the extreme points of the polyhedron to find an optimal postman tour.
Surface and collective effects in preequilibrium reactions

Surface localization of the initial target-projectile interaction has been investigated for incident protons and neutrons at bombarding energies of 14\char21{}100 MeV within the framework of the exciton preequilibrium model. Incident neutrons, at least at energies up to around 30 MeV, show a greater amount of surface peaking than do incident protons as judged by the effective well depth available to the hole degree of freedom created. With this difference included, exciton model calculations can describe the energy spectra in all four $(N,N)$ reaction channels with a consistent set of model input. To aid in this study, the excitation of strong spectroscopic collective states was included in the calculations. The addition of giant resonance state excitation has a small but helpful effect. There is a need for additional data, especially for incident neutrons above 26 MeV.
The cell cycle time of CD8+ T cells responding in vivo is controlled by the type of antigenic stimulus.

A hallmark of cells comprising the mammalian adaptive immune system is the requirement for these rare naive T (and B) lymphocytes directed to a specific microorganism to undergo proliferative expansion upon first encounter with this antigen. In the case of naive CD8+ T cells the ability of these rare quiescent lymphocytes to rapidly activate and expand into effector T cells in numbers sufficient to control viral and certain bacterial infections can be essential for survival. In this report we examined the activation, cell cycle time and initial proliferative response of naive murine CD8+ T cells responding in vivo to Influenza and Vaccinia virus infection or vaccination with viral antigens. Remarkably, we observed that CD8+ T cells could divide and proliferate with an initial cell division time of as short as 2 hours. The initial cell cycle time of responding CD8+ T cells is not fixed but is controlled by the antigenic stimulus provided by the APC in vivo. Initial cell cycle time influences the rate of T cell expansion and the numbers of effector T cells subsequently accumulating at the site of infection. The T cell cycle time varies with duration of the G1 phase of the cell cycle. The duration of G1 is inversely correlated with the phosphorylation state of the retinoblastoma (Rb) protein in the responding T cells. The implication of these findings for the development of adaptive immune responses and the regulation of cell cycle in higher eukaryotic cells is discussed.
Evaluating philanthropic foundations according to their social values

Philanthropic foundations are seen as enterprises committed to building what they view as a better world. Their visions of a better world are described in terms of social values that represent preferred end states for society or means of achieving such states. This article describes a procedure in which a foundation's espoused social values, made explicit, may serve as a referent to evaluate the foundation's performance. The process by which social values are determined is offered as a means to promote critical and reflective discourse not only within the foundation but with the public, especially those affected by the foundation's work.
Antifungals in Systemic Neonatal Candidiasis

Fungal infections are common in the newborn period, especially among premature neonates, and are responsible for considerable morbidity and mortality. Currently, three classes of antifungals are commonly used in the treatment of systemic fungal infections in neonates: the polyene macrolides (e.g. amphotericin B [deoxycholate and lipid preparations]); the azoles (e.g. fluconazole); and the fluorinated pyrimidines (e.g. flucytosine). The echinocandins (e.g. caspofungin and micafungin) are a newer class of antifungals which shows promise in this population. The available kinetic data on amphotericin B deoxycholate in neonates are derived from very small studies and exhibit considerable variability. There are no kinetic data available for the use of lipid preparations in this population and, again, much has been inferred from adult studies. The information available for flucytosine is also limited but appears similar to what is observed in adults. Fluconazole has the most neonatal pharmacokinetic data, which show slightly less variability than the other antifungals. Genomic factors which affect the metabolism of amphotericin B and fluconazole may explain some of the observed variability. Most of the data for the efficacy of antifungal drugs in neonates are derived from retrospective studies and case reports. The data for amphotericin B deoxycholate and flucytosine are limited. There are more data for the liposomal and lipid complex preparations of amphotericin B and for fluconazole in this population. These support the use of these drugs in neonates, but because of their largely noncomparative nature they can not define the optimal dosage or duration of therapy. Amphotericin B deoxycholate is primarily nephrotoxic. It also induces electrolyte abnormalities and is to a lesser degree cardiotoxic. This toxicity in neonates appears similar to published data in older children and adults. While the lipid preparations of amphotericin B owe their existence to a presumed decrease in toxicity, the observed toxicity in neonates appears to be equal to that seen with the deoxycholate, although it should be noted that the lipid preparations are usually given at much higher dosages. Fluconazole toxicity appears to be milder and less frequent in this population than is seen with amphotericin B. In the final analysis, we do not have sufficient data to define the pharmacokinetic profiles, optimal dose or duration of therapy, or toxicity for any of these compounds in neonates. Further studies are necessary if the optimisation of antifungal therapy in this population is to continue.
Body Fat Content and 25-Hydroxyvitamin D Levels in Healthy Women

Obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be secondary to an alteration in tissue distribution resulting from an increase in adipose mass. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. To study the relationship between 25-OHD levels and percentage body fat content in healthy women, we studied 410 healthy women between 20 and 80 yr of age with body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between serum 25-OHD level and percentage body fat measured by dual energy x-ray absorptiometry. We also analyzed the influence of season, dietary vitamin D intake, age, and race on this relationship. The levels of serum 25-OHD inversely correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after adjusting for race, age, season, and dietary vitamin D intake. In a multiple stepwise regression, race and season were found to have a major influence on serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest (additional R2 = 0.02), also had an independent statistically significant influence on serum 25-OHD levels. We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women.
Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate

Axial patterning in the nervous system of vertebrate embryos depends on inductive signals that derive from the organizer region (the dorsal lip in amphibians and the node in birds and mammals) and leter from the notochord and floor plate. Previous studies have shown that Pintallavis, a member of the HNF-3/fork head transcription factor family, is expressed selectively by these cell groups in frog embryos and may be involved in regulating neural development. We report here that in early rat and mouse embryos, the embryonic endoderm, the node, the notochord and the floor plate express two related transcription factors, HNF-3 alpha and HNF-3 beta, which also function in the control of liver cell differentiation. Early embryonic tissues express variant forms of HNF-3 beta which derive from the use of 5' alternative exons. Within the organizer region and notochord, HNF-3 beta and HNF-3 alpha have distinct temporal patterns of expression and appear in partially overlapping domains. The early expression pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate cells is similar to that of Pintallavis in frog embryos. There does not appear to be a Pintallavis homologue in mice. This prompted us to isolate and analyze the expression of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expressed in the dorsal lip, pharyngeal endoderm and floor plate. In contrast to mammalian HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after neural tube closure. Thus, the combined expression patterns of Pintallavis and HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within neural tissue, the onset of expression of these regulatory genes define successive stages in the differentiation of floor plate cells. The results reported here show that closely related members of the HNF-3/fork head gene family are expressed by axial midline cell groups involved in neural induction and patterning and suggest the involvement of these genes in the development of the vertebrate neuraxis.
Zinc-Dependent tRNA Binding by a Peptide Element within a tRNA Synthetase†

The class I aminoacyl-tRNA synthetases are defined by an N-terminal nucleotide binding fold that contains the active site for adenylate synthesis. Insertions and additions of idiosyncratic RNA binding elements that facilitate docking of the L-shaped tRNA structure are superimposed onto this basic fold. These RNA binding elements are imagined to have been acquired during the evolution and development of the modern genetic code. The monomeric Escherichia coli isoleucyl-tRNA synthetase has a zinc-containing peptide at its C terminus. Removal of the zinc-containing peptide was shown previously to create a shortened enzyme with activity for adenylate synthesis but no detectable binding to tRNAIle. We show here that the isolated zinc-containing peptide binds to tRNA with relatively low affinity. This binding is not tRNA-specific but shows a strict requirement for zinc. In contrast, the zinc-containing peptide conferred specific and high-affinity binding when combined with the shortened enzyme. Thus, when combin...
Age differences in lightness perception

Adults and children made lightness judgments of targets in light and in shadow when the targets were presented singly and mounted together on a chart. The adults showed greater constancy than the children when the targets were presented simultaneously on a chart. Presented singly, however, the differences between the adults and the children were not statistically reliable. These results indicate the importance of the cues in the perceptual situation in relation to developmental differences in lightness perception.
The effect of phase continuity on the fatigue and crack closure behavior of a dual-phase steel

The effect of phase continuity on the low cycle fatigue and fatigue crack growth behavior of a Fe-C-Mn dual-phase steel has been investigated. Two microstructures, one consisting of continuous ferrite and the other continuous martensite, were examined. Although there was no difference in the low cycle fatigue lives between the two microstructures, the continuous martensite structure exhibited an extremely high fatigue threshold value of 20 MPa m1/2, compared to 16 MPa m1/2 for the continuous ferrite microstructure. A major effect of phase continuity has also been found in the crack closure levels during fatigue crack propagation studied over three decades of crack growth rates. The continuous martensite microstructure exhibited much higher closure levels due to the martensite constraining the plastic deformation in the ferrite and bearing a larger portion of the applied cyclic load. This effect is similar to the extrinsic toughening phenomenon cited in the literature. After accounting for the closure levels the intrinsic or effective fatigue crack growth rates are similar for the two microstructures. These intrinsic thresholds are predicted by employing experimentally obtained low cycle fatigue parameters and the ferrite grain size.
ULTRASONOGRAPHIC ANATOMY OF THE CANINE BRAIN

Midline or lateral craniotomies were made in the skull of six normal dogs to allow ultrasound examination of the brain. The purposes of the study were (1) to describe the normal sonographic anatomy of the canine brain and (2) to develop the use of burr hole as research tool to allow sonographic examination of the canine brain. The sonographic appearance of the falx cerebri, splenial sulci, cingulate gyrus, callosal sulci, lateral ventricles, third ventricle, caudate nuclei, thalamus, hippocampus, cerebellum, and osseous tento-rium were described. Results of this study suggest that the surgical creation of cranial defect is safe, reliable, and effective in providing window for ultrasound observation. The anatomic description should also allow recognition of sonographic abnormalities in the brain of dogs with persistent fontanelles.
A health index to evaluate clinically a ß‐hemolytic streptococcal infectious disease model in the horse

Quantification of the clinical manifestations of a disease has been a serious problem particularly as related to clinical trials or drug efficacy studies. Historically, this quantification has been limited to categorizing each patient into one of three or four groups, e.g. worse, no improvement, improved. This problem becomes serious when an investigation utilizes an experimentally induced animal disease model. A health index, which quantifies the clinical state of horses which have an experimentally induced s-hemolytic streptococcal infection, is described. Aspects of experimental design and statistical analysis are also discussed in relationship to the use of the index for drug efficacy studies.
Anisotropic 11B and 13C NMR Interaction Tensors in Decamethylcyclopentadienyl Boron Complexes

Solid-state double-resonance and triple-resonance 13C, 11B, and 1H NMR experiments are used to investigate two main group metallocene complexes: the decamethylcyclopentadienylborinium cation, [Cp*2B]+, and bis(pentamethylcyclopentadienyl)methylborane, Cp*2BMe. The crystal structure for the latter complex is reported herein. A combination of magic-angle-spinning and static 11B{1H} NMR experiments are used to measure 11B nuclear quadrupole coupling constants (CQ) and rare instances of anisotropic boron chemical shielding tensors. Boron-11 nuclear quadrupole coupling constants reflect the higher spherical symmetry of [Cp*2B]+ compared to Cp*2BMe, with CQ(11B) = 1.14 MHz in the former and CQ(11B) = 4.52 MHz in the latter. Chemical shielding tensor spans are measured for [Cp*2B]+ and Cp*2BMe as Ω = 73.0 and 146.0 ppm, respectively. Hartree−Fock and hybrid density functional theory (B3LYP) calculations of electric field gradient and chemical shielding tensors are in quantitative agreement with experiment, and ...
Weighted versus uniform dose of tranexamic acid in patients undergoing primary, elective knee arthroplasty: a prospective randomized controlled trial.

In a prospective, randomized, double-blinded, controlled study (25 controls), TA was infused parenterally before tourniquet release in two study groups. Group 1 (n = 20) received a 1 g dose, and group 2 (n = 20) received a 20 mg/kg dose. There was no significant difference between groups 1 and 2 with intra-operative, post-operative and total blood loss. Both groups 1 and 2 exhibited significant improvements in intra-operative, post-operative, and total blood loss compared to the control group (P < 0.05). Two blood transfusions were given to one patient in the weighted group, compared to 19 transfusions (10 patients) in the control group. This study suggests that a single 1-g dose can be used with the same efficacy as a weighted 20 mg/kg dose.
Videotape modeling: A method of parent education

Abstract Within the area of parent training automated methods are coming into vogue. Many therapists are trying to make their training replicable by producing packaged visual aids. This paper summarizes the components of a parent‐training program based on videotape modeling for which empirical support is available. The aspects discussed here include a rationale for the use of a videotape program as a method of parent training, the content of the videotape program, and guidelines for developing and using videotape modeling programs. In the face of continuing shortages of therapeutic personnel, techniques to increase the efficiency of training parents promises to be a valuable way to meet more of the community's therapeutic needs.
Internet Use and Self-Injurious Behaviors Among Adolescents and Young Adults: An Interdisciplinary Literature Review and Implications for Health Professionals

The ease and accessibility of the Internet has created an environment where individuals can both remain anonymous and interact with others who share their interests. Electronic discussion boards and social-networking sites allow individuals to communicate with others, via public postings, regarding specific topics of interest. These interactions have taken a therapeutic form for adolescents and young adults seeking practical and emotional support on the Internet. Support sites exist for many issues and illnesses, but sites focusing on self-injurious behaviors (SIB) have garnered recent attention because of their potential to either aid in recovery or exacerbate symptoms. SIB are those behaviors in which an individual purposely inflicts harm to his or her body. Based on an interdisciplinary literature review, self-injurious Web sites have been shown to provide anonymous support for individuals experiencing SIB from others who have experienced similar emotions. However, the literature also reveals that some peers who are providing the support are accepting of SIB and guilty of glossing over potentially serious posts. The emotional support received on these sites differs from services those individuals would receive from professionals, such as coping strategies to deal with stressors and a more detailed examination of ominous signs. The use of these Web sites as a help or a hindrance to an individual's recovery from SIB remains highly contested; health professionals should be aware of the pros and cons associated with this phenomenon and should be able to identify safe means of communication for clients suffering from SIB.
Multiple hypothesis testing on composite nulls using constrained p-values

Multiple hypothesis testing often encounters composite nulls and intractable alternative distributions. In this case, using p-values that are defined as maximum significance levels over all null distributions (“pmax”) often leads to very conservative testing. We propose constructing p-values via maximization under linear constraints imposed by data’s empirical distribution, and show that these p-values allow the false discovery rate (FDR) to be controlled with substantially more power than pmax.
Measurement of Bioelectric Current with a Vibrating Probe

Electric fields, generated by active transport of ions, are present in many biological systems and often serve important functions in tissues and organs. For example, they play an important role in directing cell migration during wound healing. Here we describe the manufacture and use of ultrasensitive vibrating probes for measuring extracellular electric currents. The probe is an insulated, sharpened metal wire with a small platinum-black tip (30-35 μm), which can detect ionic currents in the μA/cm2 range in physiological saline. The probe is vibrated at about 200 Hz by a piezoelectric bender. In the presence of an ionic current, the probe detects a voltage difference between the extremes of its movement. A lock-in amplifier filters out extraneous noise by locking on to the probe's frequency of vibration. Data are recorded onto computer. The probe is calibrated at the start and end of experiments in appropriate saline, using a chamber which applies a current of exactly 1.5 μA/cm2. We describe how to make the probes, set up the system and calibrate. We also demonstrate the technique of cornea measurement, and show some representative results from different specimens (cornea, skin, brain).
Improving immigrants' access to public services in the United States: language access policy and policy implementation1

Language access mandates in the USA, which require that governmental services be provided in any needed language, have been largely ignored since their first enacting. However, the past decade has seen an increase in the number of national, state, and local efforts to accommodate limited English-proficient individuals. This article provides an overview of methods used to provide oral communication in multiple languages and reviews technologies used in interpreting practices. More broadly, this article calls attention to language access in the USA as an increasingly noticed area of minority rights and shows how technologies have become a vital component in implementing language access policies.
Prognostic indicators from electrodiagnostic studies for ulnar neuropathy at the elbow.

Introduction: We examined the prognostic value of electrodiagnostic (EDX) studies for ulnar neuropathy at the elbow (UNE). Methods: In this retrospective study, EDX results were compared with subjective recovery (resolution of symptoms) and surgery in patients diagnosed with UNE. Results: Of the 193 patients, 59 with “definite” UNE were included in the analysis. The combination of conduction block across the elbow to the first dorsal interosseous (FDI) and normal distal compound muscle action potential (CMAP) amplitude from the abductor digiti minimi (ADM) was strongly associated with recovery: 86% of these subjects achieved full subjective recovery compared to only 7% without conduction block and with an abnormal CMAP. There were no EDX predictors of surgery. Conclusion: EDX results contain useful prognostic information in UNE. Muscle Nerve, 2011
Analysis of the inhibition of mammalian carboxylesterases by novel fluorobenzoins and fluorobenzils.

We have synthesized and assessed the ability of symmetrical fluorobenzoins and fluorobenzils to inhibit mammalian carboxylesterases (CE). The majority of the latter were excellent inhibitors of CEs however unexpectedly, the fluorobenzoins were very good enzyme inhibitors. Positive correlations were seen with the charge on the hydroxyl carbon atom, the carbonyl oxygen, and the Hammett constants for the derived Ki values with the fluorobenzoins.
Some aspects of the scientific significance of high energy gamma ray astrophysics

The attraction of high energy gamma-ray astronomy lies in this radiation relating directly to those processes in astrophysical situations which deviate most from thermo-dynamic equilibrium. Some examples of these phenomena which are known to or expected to emit gamma rays are cosmic rays as they interact in intergalactic space, the high energy particles in the magnetic fields of neutron stars, the death of a black hole, the explosion and residual of a supernova, lumps of Weakly Interacting Massive Particles, energetic solar particles interacting near the sun, and very high energy particles in the extreme conditions associated with active galaxies. Although the intensities are known to be low as seen near the earth, a partially compensating characteristic is that the very penetrating nature of high energy gamma rays increases the probability that they can escape from their origin and reach the solar system.
Abnormal Lipogenesis in Thyroid Hormone-Deficient Epidermis

Striking skin changes can accompany hypothyroidism, among them a scaly ichthyosis. The pathogenesis of these disorders is unknown. Since altered sterol metabolism has been associated with other scaling dermatoses, we tested the hypothesis that altered epidermal lipogenesis may accompany hypothyroidism and induce the observed scaling. Thyroidectomized (TX) rats were sacrificed 53 days postthyroidectomy, and the rate of incorporation of the radiolabeled precursor, [14C]acetate, into epidermal lipids was determined. Approximately 2-fold decreases in incorporation of precursor into both polar and neutral lipids were observed in the TX epidermis; the most significant decreases, however, were in the neutral lipids, particularly the sterol and sterol-ester moieties. Total cholesterol pool size was also reduced in the TX epidermis. Similar decreases in sterol biosynthesis were noted in human keratinocytes cultivated in medium devoid of thyroid hormone. These findings demonstrate that lipid metabolism, and notably sterol synthesis, is altered in epidermal keratinocytes deprived of thyroid hormone and suggest that, as in other scaling disorders, this abnormal sterologenesis may lead to the clinically observed ichthyosis that can accompany hypothyroidism.
Parallel Observation Matching System for crafting overlaid science for the Hubble Space Telescope

Once primary science observations have been placed on the timeline for the Hubble Space Telescope (HST) we schedule additional (parallel) science observations that use the other science instruments. This is possible because the instruments use different places in the focal plane, because multiple instruments may be operated at once and because of improvements in the software that processes the science proposals. The Parallel Observation Matching System (POMS) forms the heart of these improvements. It identifies suitable places on the timeline for the parallel science and crafts science visits to fit them. The new version of POMS, which has been in use for 2 years, was designed to significantly reduce the special processing for parallel proposals. Parallel proposals are now described in a similar fashion to primary science proposals, so the standard software processing can be applied. The result is template visits with some flexible parameters. POMS considers each proposal in a prioritized sequence and uses the current operational version of the proposal transformation program (TRANS) to produce the detailed observation description. Currently the entire process takes under 1.5 hours to craft and schedule seven days worth of science parallel observations for the two active parallel instruments. The addition of new parallel proposals for future instruments is now a simple procedure.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
The role of CD4+ and CD8+ T cells in controlling HIV infection

Presently, it is thought that virus-specific T cells play a major role in restricting lentiviral replication and determining the rate of disease progression in humans. However, it remains unclear why this restriction fails in the majority of infected individuals. The major exception is a rare subgroup of HIV-infected long-term nonprogressors (LTNPs) who have been infected for approximately 20 years yet maintain normal CD4+ T-cell counts and less than 50 copies of viral RNA/mL of plasma. Although virus-specific cellular (CD4+ and CD8+ T lymphocytes) immune responses have been shown to exert some degree of in vivo control of HIV replication, the precise correlates of protective immunity differentiating LTNPs from patients with progressive disease remain unknown. A greater understanding of the components and magnitude of an effective immune response to HIV is an important step toward the development of effective vaccines and immunotherapies.
Real-time analysis of clathrin-mediated endocytosis during cell migration

Simultaneous dual-color total-internal-reflection fluorescence microscopy (TIR-FM) was performed to analyze the internalization and distribution of markers for clathrin-mediated endocytosis (clathrin, dynamin1, dynamin2 and transferrin) in migrating cells. In MDCK cells, which endogenously express dynamin2, the dynamin2-EGFP fluorescence demonstrated identical spatial and temporal behavior as clathrin both prior to and during internalization. By contrast, in the same cells, the neuronal dynamin1 only localized with clathrin just prior to endocytosis. In migrating cells, each endocytic marker was polarized towards the leading edge, away from the lagging edge. These observations suggest a re-evaluation of the functional differences between dynamin1 and dynamin2, and of the role of clathrin-mediated endocytosis in cell migration.
Interferon gamma and T cells inhibit osteogenesis induced by allogeneic mesenchymal stromal cells

The mesenchymal stromal cells (MSCs) are reported to be immunoprivileged and osteogenic. We hypothesized that the use of allogeneic MSCs for bone repair was possible if they displayed an ability to induce similar osteogenesis in syngeneic as well as in allogeneic hosts. To test this hypothesis we used a cloned bone marrow derived cell, termed D1, isolated from Balb/c mice. The D1 cells were subcutaneously injected in syngeneic Balb/c, allogeneic immunocompetent B6, allogeneic T-cell deficient NCr nude, and allogeneic B6 Pfp-/- Rag2-/- mice that lack matured T and B cells as well as NK-cell cytolytic functions. D1 cells formed ectopic bones only in syngeneic or allogeneic immunocompromised hosts but not in allogeneic B6 hosts. The lack of T cells alone in allogeneic NCr mice was sufficient to promote osteogenesis in allogeneic environment. We observed a significantly higher number of T cells, B cells, macrophages and significantly higher expression of interferon gamma (IFN-γ) in B6 allogeneic implants as compared to the syngeneic implants. These factors correlated with severe inhibition of expression of alkaline phosphatase, osteocalcin, and runx2 genes in the implants from B6 mice. Our data suggest that strategies to inhibit T cells and IFN-γ functions will be useful for bone repair mediated by allogeneic MSCs.
Exploring the Limitations for Cotton Growth and Yield

Abstract Most crops do not achieve their genetic potential, even under the best crop husbandry, because of environmental constraints. Improvements in crop adaptation to environmental stresses can be better assessed if the maximum potential is known. Here, we report the results from cotton plants grown in naturally lit growth chambers in which temperature and atmospheric carbon dioxide concentration [CO2] were controlled and varied systematically under optimum water and nutrient conditions. Photosynthesis of cotton canopies was measured continuously along with other related vegetative growth parameters and abiotic variables. Cotton canopies growing under potential growth conditions intercept most of the radiation available in the US Midsouth after beginning flowering and are not light-saturated. Present-day cotton cropping practices schedule the maximum crop demand for photosynthates to occur during declining solar radiation. Growing plants in high CO2 results in augmented vegetative growth during fruiting...
Parameter estimation and GLRT detection in colored non-Gaussian autoregressive processes

The problem of estimating signal and noise parameters from a mixture of nonGaussian autoregressive noise with partially known deterministic signal is discussed. Two models are considered in order to examine different kinds of additive mixing. The Cramer-Rao bounds to the joint estimation of the signal amplitude and the noise parameters are presented. A computationally simple estimator, which was previously proposed for estimation in the absence of signal, is extended for the two models under consideration. The proposed method essentially consists of two stages of least squares estimation which is motivated by the maximum likelihood estimation. The technique is applied to the problem of detecting a signal known except for amplitude in colored nonGaussian noise Two slightly different mixing models are used, and a generalized likelihood ratio test (GLRT), coupled with the proposed estimation scheme, is used to solve the problems. The results of computer simulations are presented as evidence of the validity of the theoretical productions of performance. >
METAL ABUNDANCES OF KISS GALAXIES. II. NEBULAR ABUNDANCES OF 12 LOW-LUMINOSITY EMISSION-LINE GALAXIES

We present follow-up spectra of 39 emission-line galaxies (ELGs) from the KPNO International Spectroscopic Survey (KISS). Many targets were selected as potentially low-metallicity systems based on their absolute B magnitudes and the metallicity-luminosity relation. The spectra, obtained with the Lick 3 m telescope, cover the full optical region from [O II] λλ3726, 3729 to beyond [S II] λλ6717, 6731 and include measurement of [O III] λ4363 in 12 objects. The spectra are presented and tables of the strong line ratios are given. For 12 high signal-to-noise ratio spectra, we determine abundance ratios of oxygen, nitrogen, neon, sulfur, and argon. We find these galaxies to be metal deficient with three systems approaching O/H of 1/25th solar. We compare the abundance results from the temperature-based Te method to the results from the strong-line p3 method of Pilyguin.
Flavor changing neutral currents and ΔS = 2 transitions in the hypercolor scenario☆

Abstract We consider the problem of flavor changing neutral currents (FCNC's) in a hypercolor-based scenario for dynamical symmetry breaking. Within the framework of a simplified model we focus on a part of the ΔS = 2 amplitudes hitherto considered dangerous, and show that it is subject to a measure of natural suppression, via a GIM-like mechanism herein called pseudo-GIM. Furthermore, this part depends on angles which cannot be determined, directly, from low energy experiments and which may — in the present state of the art — be regarded as adjustable parameters. The FCNC problem, of hypercolor, thus largely reduces to a non-problem. We also note that the failure of two groups at PETRA to observe very light pseudo-Goldstone bosons is a non-problem as well. Present phenomenology therefore fails to provide any credible evidence that may be used in reaching a verdict on hypercolor; until higher energy machines go into operation one must either reserve judgement or appeal to aesthetic criteria.
Binding studies of a large antiviral polyamide to a natural HPV sequence.

Abstract PA1 is a large hairpin polyamide (dImPyPy-β-PyPyPy-γ-PyPy-β-PyPyPyPy-β-Ta; Py = pyrrole, Im = imidazole, β = beta alanine) that targets the sequence 5′-WWGWWWWWWW-3′ (W = A or T) and is effective in eliminating HPV16 in cell culture (Edwards, T. G., Koeller, K. J., Slomczynska, U., Fok, K., Helmus, M., Bashkin, J. K., Fisher, C., Antiviral Res . 91 (2011) 177–186). Described here are its DNA binding properties toward a natural DNA, a 523 bp portion of HPV16 (2150–2672) containing three predicted perfect match sites. Strategies for obtaining binding data on large fragments using capillary electrophoresis are also described. Using an Fe EDTA conjugate of PA1, 19 affinity cleavage (AC) patterns were detected for this fragment. In many cases, there are multiple possible binding sequences (perfect, single and double mismatch sites) consistent with the AC data. Quantitative DNase I footprinting analysis indicates that perfect and most single mismatch sites bind PA1 with K d s between 0.7 and 4 nM, indicating excellent tolerance for the latter. Double mismatch sites exhibit K d s between 12 and 62 nM. A large fraction of the accessible sequence is susceptible to PA1 binding, much larger than predicted based on the literature of polyamide-DNA recognition rules.
Creating a psychosocial measurement model from stressful life events

Some have argued that failure to find evidence of a link between psychosocial stress factors and birth outcomes in humans may be attributed to a restriction in the range of measures used to characterize stress severity. This study describes the process of building and testing a measurement model from real life stressful experiences. To create a conceptual model, seven life events identified as stressful by successive samples of 3205 and 2090 Hartford inner city women between 1987 and 1992 and ten other experiences identified as potentially stressful were submitted to 10 academic colleagues and 4 health professionals associated with a preterm birth prevention project. Each rater attempted to identify a meaningful conceptual structure for clustering these psychosocial stressors. Seven of the thirteen proposed models were suitable for testing by means of structural equation modeling. Three models emerged as conceptually close and statistically acceptable with the number of information laden stressors dropping from 17 to 11 and clustering to form three latent variables representing economic, social support, and family stressors. The root mean square error of approximation was 0.03, where a value as low as 0.08 represents an adequate fit, and the generalized fit index was 0.99. The final model was cross-validated on the second sample where these and other fit indices were similar, indicating that a structurally meaningful measurement model fit the data well and could be used to investigate further the relationship of these theoretical variables to birth outcomes.
The Erk MAP Kinase Pathway Is Activated at Muscle Spindles and Is Required for Induction of the Muscle Spindle-Specific Gene Egr3 by Neuregulin1

Muscle spindles are sensory receptors composed of specialized muscle fibers, known as intrafusal muscle fibers, along with the endings of sensory neuron axons that innervate these muscle fibers. Formation of muscle spindles requires neuregulin1 (NRG1), which is released by sensory axons, activating ErbB receptors in muscle cells that are contacted. The transcription factor Egr3 is transcriptionally induced by NRG1, which in turn activates various target genes involved in forming intrafusal fibers. We have previously shown that, in cultured muscle cells, NRG1 signaling activates the Egr3 gene through SRF and CREB, which bind to a composite regulatory element, and that NRG1 signaling targets SRF by stimulating nuclear translocation of SRF coactivators myocardin-related transcription factor (MRTF)-A and MRTF-B and targets CREB by phosphorylation. The current studies examined signaling relays that might function in the NRG1 pathway upstream of SRF and CREB. We found that transcriptional induction of Egr3 in response to NRG1 requires the MAP kinase Erk1/2, which acts upstream of CREB to induce its phosphorylation. MRTFs are targeted by the Rho-actin pathway, yet in the absence of Rho-actin signaling, even though MRTFs fail to be translocated to the nucleus, NRG1 induces Egr3 transcription. In mouse muscle in vivo, activation of Erk1/2 is enhanced selectively where muscle spindles are located. These results suggest that Erk1/2 acts in intrafusal fibers of muscle spindles to induce transcription of Egr3 and that Egr3 induction occurs independently of MRTFs and involves Erk1/2 acting on other transcriptional regulatory targets that interact with the SRF-CREB regulatory element.
The Flynn Effect and Its Critics: Rusty Linchpins and "Lookin' for g and Gf in Some of the Wrong Places"

The consensus of most intelligence scholars is that the Flynn effect (FE) is real, IQ test batteries are now routinely restandardized on a regular basis. A cornerstone in Flynn’s explanation of the FE is his analysis of select Wechsler subtest scores across time. The featured articles by Kaufman and Zhou, Zhu, and Weiss question whether Flynn’s arguments are grounded in the unproven assumption that similarly named Wechsler scores measure the same constructs across editions. Kaufman raises the issue by means of a detailed task analysis of changes in test administration and scoring directions for similarly named tests across different Wechsler editions. The author applauds Zhou et al. for bringing methodological rigor to the comparison of similarly named Wechsler Performance composite scores across time. Unfortunately, both Kaufman and Zhou et al. inadvertently perpetuate some of Flynn’s incorrect interpretations of select Wechsler measures (Similarities and Performance tests) as measures of the novel