cssi/SciSciGPT-SciSciNet huggingface dataset:
IDENTIFICATION OF INTERPROTEIN INTERACTIONS BETWEEN THE SUBUNITS OF EUKARYOTIC INITIATION FACTORS EIF2 AND EIF2B

Modulation of protein/protein interaction is an important mechanism involved in regulation of translation initiation. Specifically, regulation of the interaction of eIF2 with the guanine nucleotide exchange factor, eIF2B, is a key mechanism for controlling translation under a variety of conditions. Phosphorylation of the α-subunit of eIF2 converts the protein into a competitive inhibitor of eIF2B by causing an increase in the binding affinity of eIF2B for eIF2. Consequently, it has been assumed that the α-subunit of eIF2 is directly involved in binding to eIF2B. In the present study, eIF2 was found to bind only to the δ- and e-subunits of eIF2B, and eIF2B was shown to bind only to the β-subunit of eIF2 by far-Western blot analysis. The binding site on eIF2β for either the eIF2B holoprotein, or the isolated δ- or e-subunits of eIF2B was shown to be located within approximately 70 amino acids of the C terminus of the protein. Phosphorylation of the α-subunit of eIF2 did not promote binding of eIF2B to the isolated subunit. However, it did cause an increase in the affinity of eIF2B for eIF2. Finally, phosphorylation by protein kinase A of the β-subunit of eIF2 in the C-terminal portion of the protein increased the guanine nucleotide exchange activity of eIF2B, whereas phosphorylation by casein kinase II or protein kinase C was without effect.
Narcissism as a moderator of the relationship between job characteristics and job reactions

A growing body of research has begun to examine the relationship between narcissism and human behavior in organizations. The research to date, however, has been anecdotal and impressionistic. The present research represents the first attempt to use a questionnaire methodology to examine systematically narcissism as an individual difference variable within an organizational context. Using an interactionist perspective, it is posited that narcissism will moderate the relationship between perceived role and job characteristics and work satisfaction. Data are analyzed from a convenience sample of 272 persons who worked full time and who attended college, using subgroup analysis and moderated multiple regression. Only modest evidence of the predicted moderator effects was found. Explanations for the weak results are offered and three possible modifications for future research are recommended.
In vivo synthesis and properties of uracil-containing DNA

All known living cells contain thymine in their DNA, but it is not clear why uracil, which base pairs adenine as does thymine, would not suffice. A considerable expenditure of energy is required to synthesize dTTP from dUTP, and the pathway shown in Fig. 1 suggests that dUTP is an obligate precursor of dTTP in wild type Escherichia coli, and probably most other organisms. An alternate route could be the salvage of thymine or thymidine, but it is not known how much dTTP is synthesized by this pathway in various organisms. In wild type E.coli probably very little, if any, dTTP is synthesized in this manner (1).
Analysis of damage due to moist heat treatment of spores of Bacillus subtilis

Aims: To determine conditions for generation and recovery of Bacillus subtilis spore populations heavily damaged by moist heat treatment. Methods and Results: Bacillus subtilis spores were treated with moist heat and spore viability was assessed on different media. A rich medium and several minimal media gave similar spore recoveries after moist heat treatment, but lack of glucose in minimal media greatly decreased spore recovery. High NaCl levels also greatly decreased the recovery of moist heat-treated spores on minimal media, and addition of good osmoprotectants reversed this effect. Moist heat treatment did not decrease spore recovery on minimal media with high salt through DNA damage or by eliminating spore germination, but by affecting spore outgrowth. Conclusions: Conditions for generating B. subtilis spore populations with high levels of conditional moist heat damage have been determined. The major conditional damage appears to be in spore outgrowth, perhaps because of damage to one or more important metabolic enzymes. Significance and Impact of the Study: This work has provided new insight into the mechanism of B. subtilis spore killing by moist heat.
A comparison of two methods of estimating the intensity of a noisy complex process

Two methods of estimating the squared modulus or intensity of a noisy complex observation process are considered. Both use a serial combination of a linear optimal filter and a memoryless nonlinear operator; the difference between the two methods is in the order of application of the two devices. Mean-squared-error expressions are obtained for arbitrary signal and noise spectra and are evaluated numerically for the case of a first-order autoregressive signal process in white noise. A simulation study is undertaken for the same case, the results of which indicate that preceding the nonlinear device with the optimal filter yields lower mean-squared error, but the difference between the two schemes is not significant in most cases of interest. >
Understanding users’ perceptions of trail resource impacts and how they affect experiences: An integrated approach

Abstract This exploratory study employed an integrated methodological approach to examine the relationships among trail resource impacts, users’ perceptions of such impacts, and how those perceptions affected users’ recreation experiences. The study was conducted using a convenience sample of 75 undergraduate students on a 1-km hiking trail that contained a variety of recreation-related resource impacts. The extent of impacts was objectively measured before study participants walked the trail. Participants then completed a questionnaire focusing on what impacts they noticed and the effects those impacts might have had on their experiences. The top 3 measured impacts, in terms of lineal extent of the study trail segment impacted, were exposed roots, parallel trails, and soil erosion. Users’ reports of which trail impacts they perceived varied according to the form of the questions in the questionnaire. Initial open-ended responses indicated that trail erosion, litter, and mud were noticed most often, while mud, exposed roots, and standing water were most apparent based on subsequent closed-ended responses which prompted respondents about particular impacts. All but 1 impact type had an overall negative effect on user experience, with mud, standing water, and litter having the most detrimental effects on hikers’ experiences. The results suggest the value of an integrated research design in understanding impact perceptions and effects. These findings have potential implications for trail design and maintenance priorities as well as for designing and guiding future studies. Other implications for research and management are discussed.
Theoretical Study of the Adsorption of Acetylene on the Si(001) Surface

Recent STM measurements and electronic structure calculations have revealed that the Si(001)/acetylene surface is far more complex than previously assumed, with there being at least three different binding arrangements of an acetylene molecule on the surface. In the present study density functional theory with slab models and periodic boundary conditions are used to study the adsorption of acetylene on the Si(001) surface. Nine different local potential energy minima, including three not previously described, are characterized. The relative stability of the two lowest energy structures is found to reverse with increasing surface coverage. The minimum energy pathways between selected pairs of local minima are calculated.
The effect of complex modifiers on large enzyme systems

Abstract Cellular function results from the cumulative function of many cellular enzyme systems. A large number of the enzymatic activators and inhibitors such as cyclic AMP, calcium and magnesium ion, and various hormones are known to exercise their overall effects by modification at many of the sublevels of total function. Analysis of the overall effect of complex modifiers on the function of large enzyme systems is approached using concepts evolved naturally from the basic precepts of simple and allosteric enzyme kinetics. Random walk theory serves as the theoretical framework for the analysis.
Reactivity of superoxide radical anion with cyclic nitrones: role of intramolecular H-bond and electrostatic effects.

Limitations exist among the commonly used cyclic nitrone spin traps for biological free radical detection using electron paramagnetic resonance (EPR) spectroscopy. The design of new spin traps for biological free radical detection and identification using EPR spectroscopy has been a major challenge due to the lack of systematic and rational approaches to their design. In this work, density functional theory (DFT) calculations and stopped-flow kinetics were employed to predict the reactivity of functionalized spin traps with superoxide radical anion (O2•-). Functional groups provide versatility and can potentially improve spin-trap reactivity, adduct stability, and target specificity. The effect of functional group substitution at the C-5 position of pyrroline N-oxides on spin-trap reactivity toward O2•- was computationally rationalized at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) and PCM/mPW1K/6-31+G(d,p) levels of theory. Calculated free energies and rate constants for the reactivity of O2•- with model n...
MicroRNA-153 physiologically inhibits expression of amyloid-β precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients

Regulation of amyloid-β (Aβ) precursor protein (APP) expression is complex. MicroRNAs (miRNAs) are expected to participate in the molecular network that controls this process. The composition of this network is, however, still undefined. Elucidating the complement of miRNAs that regulate APP expression should reveal novel drug targets capable of modulating Aβ production in AD. Here, we investigated the contribution of miR-153 to this regulatory network. A miR-153 target site within the APP 3′-untranslated region (3′-UTR) was predicted by several bioinformatic algorithms. We found that miR-153 significantly reduced reporter expression when co-transfected with an APP 3′-UTR reporter construct. Mutation of the predicted miR-153 target site eliminated this reporter response. miR-153 delivery in both HeLa cells and primary human fetal brain cultures significantly reduced APP expression. Delivery of a miR-153 antisense inhibitor to human fetal brain cultures significantly elevated APP expression. miR-153 delivery also reduced expression of the APP paralog APLP2. High functional redundancy between APP and APLP2 suggests that miR-153 may target biological pathways in which they both function. Interestingly, in a subset of human AD brain specimens with moderate AD pathology, miR-153 levels were reduced. This same subset also exhibited elevated APP levels relative to control specimens. Therefore, endogenous miR-153 inhibits expression of APP in human neurons by specifically interacting with the APP 3′-UTR. This regulatory interaction may have relevance to AD etiology, where low miR-153 levels may drive increased APP expression in a subset of AD patients.
Bayesian adaptive model selection for optimizing group sequential clinical trials

This article presents a new approach to the problem of deriving an optimal design for a randomized group sequential clinical trial based on right-censored event times. We are motivated by the fact that, if the proportional hazards assumption is not met, then a conventional design's actual power can differ substantially from its nominal value. We combine Bayesian decision theory, Bayesian model selection and forward simulation (FS) to obtain a group sequential procedure that maintains targeted false-positive rate and power, under a wide range of true event time distributions. At each interim analysis, the method adaptively chooses the most likely model and then applies the decision bounds that are optimal under the chosen model. A simulation study comparing this design with three conventional designs shows that, over a wide range of distributions, our proposed method performs at least as well as each conventional design, and in many cases it provides a much smaller trial.
Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity

Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired.
Live Subgroup B Respiratory Syncytial Virus Vaccines that Are Attenuated, Genetically Stable, and Immunogenic in Rodents and Nonhuman Primates

Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vaccine containing viruses of both subgroups A and B. Live subgroup B RSV mutants were generated containing multiple attenuating mutations, ts (temperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis. The cold-passaged (cp)-52 mutant was restricted in replication compared to wild type virus in rodents and nonhuman primates. In addition, the attenuation phenotype of cp-52 was stable after prolonged replication in immunosuppressed rodents. One or two ts mutations were then introduced into the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus. Tests in humans are being done to determine if one or more of the RSV B-1 mutants exhibit a satisfactory balance between attenuation and immunogenicity.
Effect of Particle Size on the Performance of an N95 Filtering Facepiece Respirator and a Surgical Mask at Various Breathing Conditions

The effect of aerosol particle size on the performance of an N95 filtering facepiece respirator (FFR) and a surgical mask (SM) was evaluated under different breathing conditions, including breathing frequency and mean inspiratory flow (MIF) rate. The FFR and SM were sealed on a manikin headform and challenged with charge-equilibrated NaCl aerosol. Filter penetration (Pfilter) was determined as the ratio of aerosol concentrations inside and outside the FFR/SM size-selectively (28 channels) within a range of 20 to 500 nm. In addition, the same models of the FFR and SM were donned, but not sealed, on an advanced manikin headform covered with skin-like material. Total inward leakage (TIL), which represents the total particle penetration, was measured under conditions identical to the filter penetration experiment. Testing was conducted at four mean MIFs (15, 30, 55 and 85 L/min) combined with five breathing frequencies (10, 15, 20, 25 and 30 breaths/min). The results show that SM produced much higher Pfilter and TIL values, and thus provide little protection against aerosols in the size range tested. Pfilter was significantly affected by particle size and breathing flow rate (p <0.05) for the tested FFR and SM. Surprisingly, for both devices, Pfilter as a function of the particle size exhibited more than one peak under all tested breathing conditions. The effect of breathing frequency on Pfilter was generally less pronounced, especially for lower MIFs. For the FFR and SM, TIL increased with increasing particle size up to about 50 nm; for particles above 50 nm, the total penetration was not significantly affected by particle size and breathing frequency; however, the effect of MIF remained significant.
A multi-body modeling and design of experiment investigation of a motorcyclist impact on roadside barriers at upright and sliding configurations

Roadside guard systems such as concrete and wire barriers and steel guard rails are mainly developed to protect occupants of the errant cars or trucks. Yet motorcycle riders are vulnerable to these barriers and guard systems, and impact on these barriers may result in major injuries. The objective of this study is to examine the major factors causing injuries in motorcycle-barriers accidents. A mathematical multi-body motorcycle model with a motorcycle anthropometric test device, MATD, is developed in the MADYMO 7.2 for this purpose. The motorcycle model as well as the motorcycle and rider model are validated using full-scale crash test data available in the literature. The simulations results are found to be in a reasonable agreement with the experimental data. A parametric study using the design of experiment (DOE) is then conducted to investigate the nature of crash injuries for various impact speeds, impact angles, different bike and rider positions to assess the rider kinematics and potential injuries. The results from this study can help in designing road barriers and guard systems in order to protect the motorcycle riders.Copyright © 2011 by ASME
The control of elongation by the yeast Ccr4–Not complex

The Ccr4–Not complex is a highly conserved nine-subunit protein complex that has been implicated in virtually all aspects of gene control, including transcription, mRNA decay and quality control, RNA export, translational repression and protein ubiquitylation. Understanding its mechanisms of action has been difficult due to the size of the complex and the fact that it regulates mRNAs and proteins at many levels in both the cytoplasm and the nucleus. Recently, biochemical and genetic studies on the yeast Ccr4–Not complex have revealed insights into its role in promoting elongation by RNA polymerase II. This review will describe what is known about the Ccr4–Not complex in regulating transcription elongation and its possible collaboration with other factors traveling with RNAPII across genes. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.
The Human Antibody Response to Dengue Virus Infection

Dengue viruses (DENV) are the causative agents of dengue fever (DF) and dengue hemorrhagic fever (DHF). Here we review the current state of knowledge about the human antibody response to dengue and identify important knowledge gaps. A large body of work has demonstrated that antibodies can neutralize or enhance DENV infection. Investigators have mainly used mouse monoclonal antibodies (MAbs) to study interactions between DENV and antibodies. These studies indicate that antibody neutralization of DENVs is a “multi-hit” phenomenon that requires the binding of multiple antibodies to neutralize a virion. The most potently neutralizing mouse MAbs bind to surface exposed epitopes on domain III of the dengue envelope (E) protein. One challenge facing the dengue field now is to extend these studies with mouse MAbs to better understand the human antibody response. The human antibody response is complex as it involves a polyclonal response to primary and secondary infections with 4 different DENV serotypes. Here we review studies conducted with immune sera and MAbs isolated from people exposed to dengue infections. Most dengue-specific antibodies in human immune sera are weakly neutralizing and bind to multiple DENV serotypes. The human antibodies that potently and type specifically neutralize DENV represent a small fraction of the total DENV-specific antibody response. Moreover, these neutralizing antibodies appear to bind to novel epitopes including complex, quaternary epitopes that are only preserved on the intact virion. These studies establish that human and mouse antibodies recognize distinct epitopes on the dengue virion. The leading theory proposed to explain the increased risk of severe disease in secondary cases is antibody dependent enhancement (ADE), which postulates that weakly neutralizing antibodies from the first infection bind to the second serotype and enhance infection of FcγR bearing myeloid cells such as monocytes and macrophages. Here we review results from human, animal and cell culture studies relevant to the ADE hypothesis. By understanding how human antibodies neutralize or enhance DENV, it will be possible to better evaluate existing vaccines and develop the next generation of novel vaccines.
Railton’s Moral Properties and Sinclair’s Critique of Them

The field of Ethics in philosophy is confusing for many, even those having worked in the field a few years. Thus, the field of Meta-ethics may be even more confusing. Meta-ethics, in a nutshell, is arguing about how to argue about Ethics. A question to ask in this field is what are moral properties? That is, what makes claims about morality true or false? Peter Railton takes them to be naturalistic properties (facts in the natural and social sciences) that play an explanatory role in empirical theories. Railton’s ethical naturalism is one such theory of morality. Here I will focus on an objection to Railton’s theory. Neil Sinclair claims that instrumentally rational people might sometimes not agree with Railton’s definition of moral rightness; moral rightness being identical with satisfying the objective interests of a group of people. Based on this, Sinclair argues, one should reject Railton’s claim that moral properties are identical with facts in the natural and social sciences. My argument allows for exceptions in Railton’s theory such that it preserves his definition of moral rightness and allows for instrumentally rational agents to sometimes disagree with his definition of moral rightness. Editor's Note: Honorable Mention Paper, 17th Annual Pacific University Undergraduate Philosophy Conference (2013)
Molecular weight distribution predictions for heterogeneous Ziegler-Natta polymerization using a two-site model

Abstract In the past there have been important improvements in several areas of Ziegler-Natta polymerizations, such as activity and selectivity enhancement. However, there still remains disagreement on the origins of the broad molecular weight distribution (MWD) characteristic of these polymers. Researchers have taken sides on either of the two groups explaining this phenomenon. These are (a) multiplicity of sites, and (b) diffusional limitations. Both theories have some points in their favour. To the knowledge of the authors, no work has been done combining the two. It is the purpose of this work to try to fill the gap. A model is developed and used to predict degree of polymerization and polydispersity, using concepts from monomer mass transfer and multiplicity of sites. For the cases evaluated it is shown that the broad MWD is not due to restrictions in monomer availability but is a consequence of the presence of different types of sites.
Partitioning chi-squape in contingency tables: A teaching approach

A representation of sums and differences of the form 2n log n, the lnn function, is introduced to express likelihood-ratio chi-square test statistics in contingency table analysis. This is a concise explicit form to display when partitioning chi-square statistics in accordance with hierarchical models. The lnn representation gives students insights into the construction of test statistics, and assists in relating identical forms under differing model sets. Hierarchies are presented for independence and equi-probability in two-way tables, for symmetry in correlated square tables, for independence-and-homogeneity of two-way responses across levels of a factor, and for mutual independence in three-way tables, along with relevant partitions of chi-square.
Modeling of the dynamics of jointed beam structures

Mechanical joints can have significant effects on the dynamics of assembled structures. The goal of our work is to develop physics based, reduced-order, finite element models that are capable of replicating the effects of joints on vibrating structures. Various studies have shown that micro and macro-slip along the joint interface cause the interface stiffness to change and introduce energy dissipation, leading to the observed hysteresis. The authors recently developed the so-called adjusted Iwan beam element (AIBE) for finite element analysis of jointed beam structures. The element consists of two adjusted Iwan models that are arranged to give two-dimensional beam behavior. The adjusted Iwan model is a combination of springs and frictional sliders that exhibits hysteretic behavior due to the stick-slip behavior of the sliders. In this paper, the sensitivity of the performance of an adjusted Iwan model, particularly its capacity to dissipate energy, to variations in its parameters is studied. Parametric analysis is also carried out on the adjusted Iwan beam element to investigate the effects of joint parameters on dynamic responses of jointed beams. Hammer tests are conducted on a jointed beam and its monolithic counterpart. The decay envelopes of impulsive responses for the two systems exhibit distinctly different dynamic properties. To verify that the adjusted Iwan beam element is capable of actually modeling the effects of joints on a vibrating structure, numerical simulations are performed of two hammer tests with different forcing levels. The joint parameters of the jointed beam are identified from the experimentally-obtained acceleration response from one hammer test by using a multi-layer feed-forward neural network (MLFF). Then, using the identified joint parameters, acceleration responses of the jointed beam in the other hammer test are predicted. The capability of the AIBE to capture the effects of bolted joints on the dynamic responses of beam structures is demonstrated through good agreement between simulated and experimental results.Copyright © 2003 by ASME
Medication adherence in HIV-positive patients with diabetes or hypertension: a focus group study

Background People with HIV are living longer with potent antiretroviral therapy (ART), and HIV is increasingly complicated by other chronic medical comorbidities. The objective of this study was to explore HIV-positive patients’ perspectives on living with HIV and diabetes mellitus (DM) or hypertension (HTN) and factors affecting medication adherence.
The Surface Morphology and Fine Structure of CHO (Chinese Hamster Ovary) Cells Following Enucleation

Chinese hamster ovary cells grown in monolayer culture and exposed to cytochalasin B were enucleated by centrifugation. Thereafter, the karyoplasts (the nucleated parts obtained from the bottoms of the centrifuge tubes) and the cytoplasts (the enucleated cytoplasmic parts attached to the coverslips) were allowed to recover and subsequently were examined by scanning and transmission electron microscopy. Microscopy of thin sections revealed that the karyoplasts, limited by an intact plasma membrane, contain an intact nucleus surrounded by a layer of cytoplasm that includes ribosomes, mitochondria, and fragments of the endoplasmic reticulum, but no centrioles or microtubules. The cytoplasts, similarly examined, appear to contain all cytoplasmic organelles and systems, including centrioles and microtubules. The karyoplasts, when replated in fresh medium adhere to the substrate but remain essentially spherical and are incapable of motility. They disintegrate in about 72 hr. The cytoplasts, under identical conditions, recover a shape similar to that of the whole Chinese hamster ovary cell and display some motility. They generally survive not more than 48 hr. It appears that this enucleation procedure consistently separates the nucleus and limited cytoplasm from the centrosphere and microtubule-containing cytoplasts and, furthermore, that the formdetermining and motility mechanisms reside in the cytoplast and function without nuclear participation for the short period of viability.
Cell death during development.

Abstract There are many ways to measure apoptosis and other forms of programmed cell death in development. Once nonmammalian embryos have passed the midblastula transition, or much earlier in mammalian embryos, apoptosis is similar to that seen in adult organisms, and is used to sculpt the animal, fuse bilateral tissues, and establish the structure of the nervous system and the immune system. Embryos present unique problems in that, in naturally occurring cell deaths, few cells are involved and they are frequently in very restricted regions. Thus, identification of apoptotic or other dying cells is more effectively achieved by microscopy-based techniques than by electrophoretic or cell-sorting techniques. Since embryos have many mitotic cells and are frequently more difficult to fix than adult tissues, it is best to confirm interpretations by the use of two or more independent techniques. Although natural embryonic deaths are frequently programmed and require protein synthesis, activation of a cell death pathway is often post-translational and assays for transcriptional or translational changes—as opposed to changes in aggregation of death-related molecules or proteolytic activation of enzymes—is likely to be uninformative. Also, embryos can frequently exploit partially redundant pathways, such that the phenotype of a knockout or upregulated death-related gene is often rather modest, even though the adult may develop response or regulation problems. For these reasons, the study of cell death in embryos is fascinating but researchers should be cautious in their analyses.
Complicated version of a robust control scheme

A new robust control design is introduced. The worst cases of controlled system performance and control magnitude are both investigated. Their comparison with early counterparts is also made.
Benefits of NSF work

This fall I will leave my rotatorship as Associate Director for Chemical Oceanography at the National Science Foundation. I have very much enjoyed my duty and want to outline for those who may become “rotators” some of the job's benefits, since NSF is now seeking applicants to replace me. Batiza, Rea and Rumble [Eos, 69, 801, 1988] have discussed the rotator's experience; my comments supplement their points. The most important benefit in working at NSF is the breadth of vision you acquire. This is important for researchers, because it pulls you away from your narrowly focused subfield and forces you to review again, as you did as a graduate student, your entire field. For teachers, this benefit is equally important, because you will keep up with current research even while away from teaching your up-to-date balanced courses. During my stay here I have reviewed proposals to study trace metals scavenging, gas exchange, sediment traps, biochemical cycling, stable and unstable isotopes, lipid biomarkers, sediment diagenesis, anoxic redox processes, and many other exciting topics. Some research areas, such as the vent and seep studies, had not been conceived when I was a graduate student in the sixties, so my experience here has been, in fact, a real sabbatical.
Effects of coiling on the micromechanics of the mammalian cochlea

The cochlea transduces sound-induced vibrations in the inner ear into electrical signals in the auditory nerve via complex fluid–structure interactions. The mammalian cochlea is a spiralshaped organ, which is often uncoiled for cochlear modelling. In those few studies where coiling has been considered, the cochlear partition was often reduced to the basilar membrane only. Here, we extend our recently developed hybrid analytical/numerical micromechanics model to include curvature effects, which were previously ignored. We also use a realistic cross-section geometry, including the tectorial membrane and cellular structures of the organ of Corti, to model the apical and basal regions of a guinea-pig cochlea. We formulate the governing equations of the fluid and solid domains in a curvilinear coordinate system. The WKB perturbation method is used to treat the propagation of travelling waves along the coiled cochlear duct, and the O(1) system of the governing equations is solved in the transverse plane using finite-element analysis. We find that the curvature of the cochlear geometry has an important functional significance; at the apex, it greatly increases the shear gain of the cochlear partition, which is a measure of the bending efficiency of the outer hair cell stereocilia.
Direct identification of a novel disulfide bond linkage system of new isolated isomer (isomer V) in recombinantly produced h-IGF-I.

Insulin-like growth factor I (IGF-I or somatomedin C) is a serum polypeptide with three intramolecular disulfide bond. In the course of synthesis by the recombinant DNA method, three disulfide bond isomers, all of which have Cys18-Cys61 with three combinations of two disulfide bonds formed by Cys6, Cys47, Cys48 and Cys52, were identified. Natural type, isomer II, was proved to have a Cys6-Cys48, Cys18-Cys61, Cys47-Cys52 disulfide bond system. Now, the fourth isomer, isomer V which doesn't have Cys18-Cys61 disulfide, has been isolated, and its novel disulfide bond linkage system was identified by a chemical synthetic method. The supposed conformation constrained in 3D structure for isomer V would be discussed for its biological activity.
Three conserved members of the RNase D family have unique and overlapping functions in the processing of 5S, 5.8S, U4, U5, RNase MRP and RNase P RNAs in yeast.

The biogenesis of a number of RNA species in eukaryotic cells requires 3′ processing. To determine the enzymes responsible for these trimming events, we created yeast strains lacking specific 3′ to 5′ exonucleases. In this work, we describe the analysis of three members of the RNase D family of exonucleases (Rex1p, Rex2p and Rex3p). This work led to three important conclusions. First, each of these exonucleases is required for the processing of distinct RNAs. Specifically, Rex1p, Rex2p and Rex3p are required for 5S rRNA, U4 snRNA and MRP RNA trimming, respectively. Secondly, some 3′ exonucleases are redundant with other exonucleases. Specifically, Rex1p and Rex2p function redundantly in 5.8S rRNA maturation, Rex1p, Rex2p and Rex3p are redundant for the processing of U5 snRNA and RNase P RNA, and Rex1p and the exonuclease Rrp6p have an unknown redundant essential function. Thirdly, the demonstration that the Rex proteins can affect reactions that have been attributed previously to the exosome complex indicates that an apparently simple processing step can be surprisingly complex with multiple exonucleases working sequentially in the same pathway.
Two-dimensional thin-layer chromatographic separation of phospholipid molecular species using plates with both reversed-phase and argentation zones

Utilisation de la chromatographie couche mince bidimensionnelle pour separer les types moleculaires de l'acide phosphatidique dimethyl marque au phosphore 32, forme par la phosphorylation du glycerol (diacyl-1,2) provenant de l'hydrolyse de la phosphatidylcholine du foie de porc par la phospholipase C de Clostridium welchii
Experimental determination of the activity of chromite in multicomponent spinels

We determined activity–composition relationships in Pt-Cr and Pt-Fe-Cr alloys at 1300°C experimentally and used the results to constrain the thermodynamic properties of chromite–picrochromite spinels. The Pt-Cr binary is characterized by strong negative deviations from ideality throughout the investigated composition range and the activity–composition relationship can be fit by a four-suffix asymmetric regular solution with three binary interaction parameters. The ternary alloy was modeled as a four-suffix asymmetric regular solution; the three ternary interaction parameters in this model were constrained by combining interaction parameters for the three bounding binaries taken from this and previous work with results for a set of experiments in which the activity of Cr in Pt-Fe-Cr-alloys was fixed by coexisting Cr_(2)O_3 at known fO_2. The free energy of formation of FeCr_(2)O_4 at 1300°C was determined using the activities of Fe and Cr in Pt-alloys in equilibrium with oxide mixes of FeCr_(2)O_4 and Cr_(2)O_3. The free energy of formation of chromite from Fe+Cr_(2)O_3+O_2 is −202.7 ± 0.4 kJ/mol (1σ), indistinguishable from literature values. The corresponding free energy of formation of FeCr_(2)O_4 from the elements is −923.5 ± 2.1 kJ/mol (1σ), and the enthalpy of formation at 298 K is −1438 kJ/mol. The activity–composition relationship for the chromite component in (Fe,Mg)Cr_(2)O_4 solid solutions was determined from a set of experiments in which Pt-alloys were equilibrated with spinel + Cr_(2)O_3. (Fe,Mg)Cr_(2)O_4 spinels are nearly ideal at 1300°C; modeling our data with a one-site symmetric regular solution yields an interaction parameter of +2.14 ± 0.62 kJ/mol (1σ), similar to values based on data from the literature.
Augmentation of umbilical cord blood (UCB) transplantation with ex vivo–expanded UCB cells: results of a phase 1 trial using the AastromReplicell System

Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo-expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin-) cells. CD3+ cells did not expand under these conditions. Clinical-scale ex vivo expansion of UCB is feasible, and the administration of ex vivo-expanded cells is well tolerated. Augmentation of UCB transplants with ex vivo-expanded cells did not alter the time to myeloid, erythroid, or platelet engraftment in 21 evaluable patients. Recipients of ex vivo-expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo-expanded UCB cells is beneficial.
THE EFFECT OF TESTOSTERONE-PROPIONATE ON THE X-ZONE OF THE MOUSE ADRENAL

Masui and Tamura (1) described the zona reticularis of the mouse adrenal as being well-developed and showing peculiar characteristics. Howard-Miller (2) renamed this inner zone of the cortex the ‘X-zone’ and described the differences between the adrenals of male and female mice. She traced the changes taking place here during the life history of the animals, and proved the transitory character of the X-zone. Deansley (3) confirmed this age-sex dimorphism of the X-zone. The possible analogy of the mouse X-zone to the inner zone of the human adrenal reticularis at birth (4) has stimulated interest in this structure. The fact that the X-zone in the mouse exhibits an age-sex relationship suggests its dependence upon male and female hormones. It is thought to be andromimetic in function (5). The male and female X-zone both begin development at 9 to 12 days of age and continue to develop until maturity (30 to 32 days). At this time the X-zone of the male rapidly disappears by a process described as a cytolysis ...
The Review of the Economic Legislation in May 2015

In May, the following amendments were introduced in the legislation: from September 2013 amendments to Cl.4 and Cl.5 of Section I of Part I and Article 1153 of Part III of the Civil Code of the Russian Federation will be in effect; the specifics of carrying out of labor activities by high-skilled experts-foreign nationals was updated; procedure for identification of a foreign national who has no valid document was specified and definition of “the state support of innovation activities” was provided.
A graph cut based active contour for multiphase image segmentation

In this paper, we introduce a novel hierarchical approach for multiphase image segmentation. The approach presents a unified framework that unifies two basic segmentation approaches; level set methods and graph cut algorithms. In the work of El-Zehiry et al. (2007), we have presented a bimodal image segmentation approach that have the advantages of the level set methods such as robustness to noise, blurred edges and topology changes and the advantages of graph cuts vis-a-vis global optimization and speed. Our main objective in this paper is to extend our previous approach to segment n classes. The results section will show that our algorithm outperforms the multiphase image segmentation approach introduced in the work of Vese and Chan (2002).
Bacterial agents used for bioterrorism.

Background: Bacterial pathogens and their products are potential agents of biological terrorism and biological warfare. These agents can be deployed through simple aerosol delivery systems and thereby cause widespread disease and death. Methods: This report is a review of bacterial species that have been employed for development of biological terrorism, relying on a system for classification of their threat developed by the Centers for Disease Control. Results: Physicians must understand how to recognize early signs and symptoms caused by bacterial agents. Clinical findings often seen on presentation are emphasized along with a summary of therapeutic approaches. Conclusions: Initiation of immediate therapy and supportive care provides the best chance for survival from these potentially lethal and devastating infections. A high index of suspicion must be maintained, especially in the setting of a sudden influx of cases with what are often relatively nonspecific symptoms.
How personality, coping styles, and perceived closeness influence help-seeking attitudes in suicide-bereaved adults

This study examined the impact of personality, coping, and perceived closeness on help-seeking attitudes in suicide bereaved adults. Participants (n = 418; mean age = 49.50; 90% women, 89.7% Caucasian) completed measures of personality (neuroticism, extraversion, openness, conscientiousness, and agreeableness), coping, and attitudes toward seeking mental health services. Regression analyses revealed neuroticism as the strongest predictor of help-seeking attitudes. Relatively neurotic adult women bereaved by suicide may be at-risk for developing unhealthy coping styles, low stigma indifference, and more negative help-seeking attitudes.
Improving approximate value iteration with complex returns by bounding

Approximate value iteration (AVI) is a widely used technique in reinforcement learning. Most AVI methods do not take full advantage of the sequential relationship between samples within a trajectory in deriving value estimates, due to the challenges in dealing with the inherent bias and variance in the n-step returns. We propose a bounding method which uses a negatively biased but relatively low variance estimator generated from a complex return to provide a lower bound on the observed value of a traditional one-step return estimator. In addition, we develop a new Bounded FQI algorithm, which efficiently incorporates the bounding method into an AVI framework. Experiments show that our method produces more accurate value estimates than existing approaches, resulting in improved policies.
The Classical Foundations of the American Constitution: Constitution-Making and Ancient History

A s is abundantly clear from their voices quoted in chap ter 2, the Founders were preoccupied with endowing substantial competence to the new general government of the United States. At the same time, the Framers of the structural Constitution were positively obsessed with cabining and controlling the exercise of governmental authority. This meant preventing the accumulation of power in any one branch of the federal government, protecting the prerogatives of the individual states, and (most difficult of all) ensuring that no particular social segment or cohort gained at the expense of the common weal. Government, as Alexander Hamilton observed, had to be poised on a knife-edge by having “[p]ower [be made] always the rival of power.” The control of power was thus regarded by the Framing generation as being intimately related to the preservation of individual liberty. At this level of inquiry, there was a fundamental unity between the “structural Constitution” of the first seven articles of the national Charter and the “rights Constitution” of the Bill of Rights' ten amendments. Indeed, the distinction between these two aspects of American constitutionalism may be an utter fiction. After all, the Tenth Amendment provides a central tenet of federalism in its reservation of state powers. Moreover, the main body of the Constitution not only explicitly provides the affirmative legislative powers of Congress (and, by implication, of the national government), but specifically prohibits the general government from legislating against the “Privilege of the Writ of Habeas Corpus,” commands that “No Bill of Attainder or ex post facto Law shall be passed,” and ensures that no “religious Test shall ever be required as a Qualification for any Office or public Trust under the United States.”
Application of Constant Absorptivity Ring (Car) to Improve Polysilicon Thickness Uniformity In A Rapid Thermal Chemical Vapor Deposition Reactor

Rapid Thermal Chemical Vapor Deposition (RTCVD) is a promising technology for thin film deposition in advanced cluster tool systems. It is well known that, if left uncompensated, excessive heat losses that occur around the wafer edge can lead to temperature and deposition non-uniformities. Using polysilicon deposition on SiO 2 as an example we have shown that deposition non-uniformity can be aggravated by absorptivity variations across the wafer. In this paper, we propose a novel approach to alleviate this problem. In this technique, the edge cooling effect is compensated by increasing the absorptivity of the substrate around its perimeter. This is achieved by etching a thin (width≈200μm) ring from the isolation oxide around the wafer perimeter prior to polysilicon deposition. During polysilicon deposition, the absorptivity of the silicon-oxide-polysilicon structure continually changes resulting in positive and negative feedback mechanisms in certain polysilicon thickness ranges determined by both modeling and experiments. However, this absorptivity always remains less than the constant absorptivity of the silicon-polysilicon ring along the perimeter which is referred to here as the Constant Absorptivity Ring (CAR). The higher absorptivity of CAR shields edge cooling effects from the rest of the wafer. In this paper, we present the results of our experiments conducted to demonstrate the effectiveness of CAR in improving uniformity of polysilicon. We show that by using CAR uniform films can be obtained in a reactor which otherwise delivers a polysilicon non-uniformity of 30-40%.