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PubMed1978

[Consideration of modern demographic questions (author's transl)].

It is assumed that the decrease in the birth rate can be checked or that an increase in births can be stimulated by models or value judgements. On the basis of articles reflecting the official demographic opinion published by the Federal Office for Statistics, an attempt was made to reflect the intellectual foundation for such views. With the help of population statistics and model computations as well as vaguely intimated ideologies, changes in procreative activity considered necessary could be induced. The investigation concluded with the question of whether the detachment of procreative activity in highly industrialized, capitalistic countries with their specialized instruments, technologies, and institutions can be attributed to economic factors.

Birth Rate↗
PubMed2003

Effect of hydrogen peroxide on titanium surfaces: in situ imaging and step-polarization impedance spectroscopy of commercially pure titanium and titanium, 6-aluminum, 4-vanadium.

To analyze titanium's response to representative surgical wound environments, a study was conducted on commercially pure titanium (CPTi) and titanium, 6-aluminum, 4-vanadium (Ti-6Al-4V) exposed to phosphate-buffered saline (PBS) with 30 mM of hydrogen peroxide (H(2)O(2)) added. The study was characterized by simultaneous electrochemical atomic force microscopy (EC AFM) and step-polarization impedance spectroscopy (SPIS). Surfaces were covered with protective oxide domes that indicated topography changes with potential and time of immersion. Less oxide dome coarsening was noted on surfaces treated with PBS containing H(2)O(2) than on surfaces exposed to pure PBS. Electrical data deduced from current transients collected while stepping voltage between 0 V and 1 V indicated that charge transfer in hydrogen peroxide solutions was an order of magnitude larger than it was in pure PBS. Oxide (early) resistances of CPTi samples were higher than were Ti-6Al-4V oxide resistances in both types of solutions, but CPTi oxide resistance was lower in the hydrogen peroxide solution compared to pure PBS. Capacitance data suggest that CPTi oxide films thicken in hydrogen peroxide solution more than they do in pure PBS. Differences in electrical properties between CPTi and Ti-6Al-4V surfaces suggest that CPTi, but not Ti-6Al-4V, has catalytic activity on H(2)O(2) and that the catalytic activity of CPTi oxide affects its ability to grow TiO(2). Differences in electrical properties are related to catalytic and oxidative mechanisms that take place directly on the titanium oxide surface and in wound environments. The study provides a foundation and theoretic basis for the porous oxide model on commercially pure titanium exposed to hydrogen peroxide.

Aluminum↗
PubMed2004

Development of the mouse retina: emerging morphological diversity of the ganglion cells.

The time course and regulatory mechanisms of dendritic development are subjects of intense interest. We approached these problems by investigating dendritic morphology of retinal ganglion cells (RGCs) at four early postnatal stages. The RGCs develop from a diffusely stratified and poorly differentiated group at birth (P0), to 16 distinct, morphologically well-defined subtypes before eye opening (P13). Even before bipolar cells make synaptic contacts with the RGCs (P8), most adultlike RGC subtypes are already present. Similar to previous studies in other mammalian species, our results indicate that the initiation of the RGC morphological maturation is independent of light stimulation and of formation of glutamatergic synapses. This study narrowed down the window of RGCs morphological maturation and highlighted a few early postnatal events as potential factors controlling the developmental process. Because mouse is the most popular mammalian model for genetic manipulation, this study provided a foundation for further exploring regulatory mechanisms of RGC dendritic development.

Animals↗
PubMed1998

Direct Determination of the Dependence of the Surface Shear and Dilatational Viscosities on the Thermodynamic State of the Interface: Theoretical Foundations.

Recent developments in nonlinear optical techniques for noninvasive probing of a surfactant influenced gas/liquid interface allow for the measurement of the surfactant surface concentration, c, and thus provide new opportunities for the direct determination of its intrinsic viscosities. Here, we present the theoretical foundations, based on the Boussinesq-Scriven surface model without the usual simplification of constant viscosities, for an experimental technique to directly measure the surface shear (µs) and dilatational (kappas) viscosities of a Newtonian interface as functions of the surfactant surface concentration. This ability to directly measure the surfactant concentration permits the use of a simple surface flow for the measurement of the surface viscosities. The requirements are that the interface must be nearly flat, and the flow steady, axisymmetric, and swirling; these flow conditions can be achieved in the deep-channel viscometer driven at relatively fast rates. The tangential stress balance on such an interface leads to two equations; the balance in the azimuthal direction involves only µs and its gradients, and the balance in the radial direction involves both µs and kappas and their gradients. By further exploiting recent developments in laser-based flow measuring techniques, the surface velocities and their gradients which appear in the two equations can be measured directly. The surface tension gradient, which appears in the radial balance equation, is incorporated from the equation of state for the surfactant system and direct measurements of the surfactant surface concentration distribution. The stress balance equations are then ordinary differential equations in the surface viscosities as functions of radial position, which can be readily integrated. Since c is measured as a function of radial position, we then have a direct measurement of µs and kappas as functions of c. Numerical computations of the Navier-Stokes equations are performed to determine the appropriate conditions to achieve the requisite secondary flow. Copyright 1998 Academic Press.

Journal Article↗
PubMed2004

The developmental psychopathology of self-injurious behavior: compensatory regulation in posttraumatic adaptation.

This article utilizes a developmental psychopathology framework to explicate one pathway, originating in childhood traumatic experience, toward the development of self-injurious behavior (SIB). The descriptive psychopathology of SIB is summarized first, followed by an overview of theoretical interpretations of SIB within psychoanalytic, neo-analytic, behavioral, and biological paradigms. Building on these empirical and theoretical foundations, a developmental psychopathology framework is used to model the development of SIB in the aftermath of childhood traumatic experience, particularly maltreatment. In this model, maltreatment undermines positive adaptation at motivational, attitudinal, instrumental, emotional, and/or relational levels of competence. In turn, vulnerabilities in the child's adaptive resources necessitate the application of alternative regulatory and relational strategies, such as self-injury, to the negotiation of contemporaneous and prospective developmental issues. The article concludes with a discussion of the empirical and clinical implications of a developmental understanding of SIB as a compensatory regulatory strategy in posttraumatic adaptation.

Adaptation, Psychological↗
PubMed1975

On the theory of ionic solutions.

One of the purposes of this paper is to assess the degree of applicability of the nonlinear Poisson-Boltzmann equation. In order to do this we compare the thermodynamic properties calculated through this equation with Monte Carlo data on 1-1 and 2-2 electrolytes described by the restricted primitive model, in which the ions are modeled by hard spheres with a coulombic potential and the solvent is modeled as a continuum dielectric medium of uniform dielectric constant epsilon. We choose Monte Carlo data rather than real experimental data since all parameters are completely specified and there is no liberty for "adjustment." Thus this serves as a definitive test. In addition, we present a simple but numerically accurate alternative approximation scheme which is not only numerically superior to the Poisson-Boltzmann equation but avoids the necessity of solving a nonlinear partial differential equation which is approximate in the first place. The new approximation scheme that is presented here is suggested by recent developments in the statistical mechanical theories of ionic solutions which are reviewed in the Introduction. Although these theories themselves yield exceedingly good comparison with experimental (Monte Carlo) data, they involve fairly advanced theoretical and mathematical techniques and do not appear to be readily solvable for other than very simple geometries. The two approximations suggested here require only the solution of the linear Debye-Hückel equation, which has been solved for a variety of systems. These two approximations are simple to apply and yield good thermodynamic properties up to concentrations of 2 M for the restricted primitive model. In addition, they have a sound theoretical foundation and are offered as a substitute for the difficult-to-solve nonlinear Poisson-Boltzmann equation.

Ions↗
PubMed1998

Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein.

We previously established a novel mouse model for human aging and identified the genetic foundation responsible for it. A defect in expression of a novel gene, termed klotho (kl), leads to a syndrome resembling human aging in mice. The kl gene encodes a single-pass membrane protein whose extracellular domain carries homology to beta-glucosidases. In this report, we present the entire mouse kl gene organization. The mouse kl gene spans about 50 kilobases and consists of five exons. The promoter region lacks a TATA-box and contains four potential binding sites for SP1. We further show that two kl gene transcripts encoding membrane or secreted protein are generated through alternative transcriptional termination. These findings provide fundamental information for further study of the kl gene which may regulate aging in vivo.

Alternative Splicing↗
PubMed2007

A circadian timing mechanism in the cyanobacteria.

Cyanobacteria such as Synechococcus elongatus PCC 7942, Thermosynechococcus elongatus BP-1, and Synechocystis species strain PCC 6803 have an endogenous timing mechanism that can generate and maintain a 24 h (circadian) periodicity to global (whole genome) gene expression patterns. This rhythmicity extends to many other physiological functions, including chromosome compaction. These rhythmic patterns seem to reflect the periodicity of availability of the primary energy source for these photoautotrophic organisms, the Sun. Presumably, eons of environmentally derived rhythmicity--light/dark cycles--have simply been mechanistically incorporated into the regulatory networks of these cyanobacteria. Genetic and biochemical experimentation over the last 15 years has identified many key components of the primary timing mechanism that generates rhythmicity, the input pathways that synchronize endogenous rhythms to exogenous rhythms, and the output pathways that transduce temporal information from the timekeeper to the regulators of gene expression and function. Amazingly, the primary timing mechanism has evidently been extracted from S. elongatus PCC 7942 and can also keep time in vitro. Mixing the circadian clock proteins KaiA, KaiB, and KaiC from S. elongatus PCC 7942 in vitro and adding ATP results in a circadian rhythm in the KaiC protein phosphorylation state. Nonetheless, many questions still loom regarding how this circadian clock mechanism works, how it communicates with the environment and how it regulates temporal patterns of gene expression. Many details regarding structure and function of the individual clock-related proteins are provided here as a basis to discuss these questions. A strong, data-intensive foundation has been developed to support the working model for the cyanobacterial circadian regulatory system. The eventual addition to that model of the metabolic parameters participating in the command and control of this circadian global regulatory system will ultimately allow a fascinating look into whole-cell physiology and metabolism and the consequential organization of global gene expression patterns.

Amino Acid Sequence↗
PubMedDate not supplied

Establishing the most appropriate databases for addressing source level propositions.

Previous papers in Science & Justice have described the work of the Case Assessment and Interpretation (CAI) project that has been running for several years within the Forensic Science Service (FSS). The principles of the CAI model, which have developed through casework, are the foundation of a balanced, robust and logical approach to interpretation. The question arises frequently as to what is the most appropriate database that should be available to assist in assigning a value to a given probability. In this paper we present a set of guidelines in the form of flowcharts and explore them within the context of a range of case examples.

Databases, Factual↗
PubMed2002

The structure and dynamics of the U4/U6 snRNP: implications for pre-mRNA splicing and use as a model system to investigate the RNA-mediated effects of (5F)Ura.

Pre-mRNA splicing is one of the most complex and intricate processes in eukaryotic cell biology. Over the past decade, my laboratory has been interested in determining the structures of RNA components of the spliceosome, and in investigating how the structure, stability and dynamics of these RNA components are perturbed by nucleoside analog substitution. In particular, we have investigated the U4/U6 snRNA complex as a model system for understanding the biophysical basis for the RNA-mediated effects of the widely-used anticancer drug 5-fluorouracil ((5F)Ura). In this review, our studies that have provided novel information concerning the structure of U4 snRNA and its interactions with U6 snRNA and the Sm (or common) snRNA binding proteins are summarized. These studies have also quantified the structural and thermodynamic consequences of (5F)Ura in this model system. Our work to date provides the foundation on which future studies investigating the biophysical basis for spliceosomal assembly and for clarifying the mechanisms of anticancer drugs targeted at nucleic acid-mediated processes will be developed.

Base Sequence↗
PubMed1995

Chemopreventive activity of Oltipraz against N-nitrosobis(2-oxopropyl)amine (BOP)-induced ductal pancreatic carcinoma development and effects on survival of Syrian golden hamsters.

The synthetic dithiolethione Oltipraz has marked cancer chemopreventive and phase II enzyme inducing activity in various animal carcinogenesis models, but has not been examined in any animal models of ductal pancreatic cancer relevant to the human disease. The chemopreventive potential of Oltipraz on pancreatic tumor incidence and multiplicity was examined in the N-nitrosobis(2-oxopropyl)-amine (BOP)-induced ductal pancreatic adenocarcinoma model in Syrian hamsters. Animals were maintained on control semipurified diets or semipurified diets containing 300 and 600 mg/kg Oltipraz beginning 2 weeks prior to BOP initiation and throughout the 26 week study. Oltipraz at 300 mg/kg had no effect on the incidence or multiplicity of preneoplastic, neoplastic or metastatic lesions, while at 600 mg/kg dietary Oltipraz the incidence of pancreatic adenocarcinomas was reduced significantly (P < or = 0.05) compared to BOP-treated controls. Dietary Oltipraz at both doses had a significant influence on reducing mortality and morbidity in tumor-bearing animals with metastatic disease. At 26 weeks, total hepatic glutathione-S transferase (GST) activity and GST mu activity were elevated significantly in Oltipraz-treated animals, while total pancreatic GST activity was reduced, albeit not significantly. Serum lipase activity, a marker for pancreatic damage, exhibited a progressive decline in BOP-treated animals administered Oltipraz compared to BOP-treated controls at 12 weeks of the study; by week 26, lipase activity was comparable in all groups and reduced compared to activity at week 12. Positive nuclear immunostaining for the p53 tumor suppressor protein, a hallmark of human pancreatic cancer and a transient response to DNA damage, was observed in only a small percentage of BOP-induced pancreatic lesions and was not influenced Oltipraz administration. Further chemoprevention and pharmacologic studies of Oltipraz in relevant animal models of ductal pancreatic cancer could provide a foundation for future studies in human populations at potential risk for pancreatic cancer.

Animals↗
PubMed2000

UK CropNet: a collection of databases and bioinformatics resources for crop plant genomics.

The UK Crop Plant Bioinformatics Network (UK CropNet) was established in 1996 in order to harness the extensive work in genome mapping in crop plants in the UK. Since this date we have published five databases from our central UK CropNet WWW site (http://synteny.nott.ac.uk/) with a further three to follow shortly. Our resource facilitates the identification and manipulation of agronomically important genes by laying a foundation for comparative analysis among crop plants and model species. In addition, we have developed a number of software tools that facilitate the visualisation and analysis of our data. Many of our tools are made freely available for use with both crop plant data and with data from other species.

Crops, Agricultural↗
PubMed1999

Developing recombinant and synthetic vaccines for the treatment of melanoma.

To develop new vaccines for the treatment of patients with cancer, target antigens presented on tumor cell surfaces have been cloned. Many of these antigens are non-mutated differentiation antigens and are expressed by virtually all melanomas, making them attractive components for a widely efficacious melanoma vaccine. These antigens are also expressed by melanocytes, however, and are likely to be subject to immune tolerance. A central challenge for tumor immunologists has thus been the breaking of tolerance to cancer antigens. We review recent clinical trials using experimental cancer vaccines, including recent evidence that therapeutic vaccines can induce objective responses in patients with metastatic malignant melanoma. We focus on the foundations of these approaches in new experimental animal models designed to test novel vaccines and report on what these new models predict for the future development of therapeutic vaccines for cancer.

Adjuvants, Immunologic↗
PubMedDate not supplied

Designing and building new local public health agencies in Nebraska.

Prior to 2001, the local public health system in Nebraska was weak, fragmented, and severely under funded. Local public health departments covered only 22 of the state's 93 counties. The Turning Point project provided the impetus for change by allowing a diverse group of public health stakeholders to develop a strategic plan for strengthening and transforming the public health system. The plan acted as a catalyst to use some of the Nebraska Tobacco Settlement Funds to provide dedicated state funding to build the local public health system. By June 2002, 16 new local public health departments had been organized, ultimately covering all of the 93 counties in the state. Some of the keys to long-term sustainability are creating a network of community health partners that support collaborative decision making, continually seeking input from the community, developing and implementing an education and training plan for public health professionals and local board of health members, and demonstrating accountability by documenting results and communicating them to policy makers and the general public.

Community Health Planning↗
PubMed2025

mamp-ml: A deep learning approach to epitope immunogenicity in plants.

Eukaryotes detect biomolecules through surface-localized receptors, key signaling components. A subset of receptors survey for pathogens, induce immunity, and restrict pathogen growth. Comparative genomics of both hosts and pathogens has unveiled vast sequence variation in receptors and potential ligands, creating an experimental bottleneck. We have developed mamp-ml, a machine learning framework for predicting plant receptor-ligand interactions. We leveraged existing functional data from over two decades of foundational research, together with the large protein language model ESM-2, to build a pipeline and model that predicts immunogenic outcomes using a combination of receptor-ligand features. Our model achieves 73% prediction accuracy on a held-out test set, even when an experimental structure is lacking. Our approach enables high-throughput screening of LRR receptor-ligand combinations and provides a computational framework for engineering plant immune systems.

Journal Article↗
PubMed2005

Hybridization theory between localized mode and free propagating modes for light scattering from a dielectric sphere.

Light scattering from a homogeneous dielectric sphere is discussed in terms of hybridization between a localized mode excited inside the dielectric sphere and free propagating modes in vacuum. This theory is a photonic counterpart of the Anderson model in electron systems, yielding a rigorous theoretical foundation of the heavy photon concept, which was numerically proposed for almost flat photonic bands. The magnitude of the hybridization is analytically expressed. The localized mode is identified with the photon virtual bound state. In order to confirm the validity of the present theory, a comparison is made between the present theory and conventional numerical calculation for results of the photonic density of states.

Journal Article↗
PubMed2005

Global topology analysis of the Escherichia coli inner membrane proteome.

The protein complement of cellular membranes is notoriously resistant to standard proteomic analysis and structural studies. As a result, membrane proteomes remain ill-defined. Here, we report a global topology analysis of the Escherichia coli inner membrane proteome. Using C-terminal tagging with the alkaline phosphatase and green fluorescent protein, we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins. By constraining a topology prediction algorithm with this data, we derived high-quality topology models for the 601 proteins, providing a firm foundation for future functional studies of this and other membrane proteomes. We also estimated the overexpression potential for 397 green fluorescent protein fusions; the results suggest that a large fraction of all inner membrane proteins can be produced in sufficient quantities for biochemical and structural work.

Alkaline Phosphatase↗