SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
This article concludes this symposium on potential agents of warfare and terrorism with discussion of 3 topics. First, influenza A virus is discussed as a potential biological weapon. Although it does not receive much attention in this role, the potential for mass casualties and public panic certainly exist if an epidemic of a virulent influenza A virus were initiated. Second, agroterrorism, terrorism directed at livestock or poultry or crops, is briefly discussed. Finally, the potential role of techniques of modern molecular biology to create new agents for bioterrorism or enhance the terrorist potential of available agents, and the known roles of these techniques in defense against biological warfare or terrorism are discussed.
OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.
In this paper we have made a draft of a physical fractal essence of the universe, a sketch of a new cosmology, which we believe to lay at the root of our new holistic biological paradigm. We present the fractal roomy spiraled structures and the energy-rich dancing "infinite strings" or lines of the universe that our hypothesis is based upon. The geometric language of this cosmology is symbolic and both pre-mathematical and pre-philosophical. The symbols are both text and figures, and using these we step by step explain the new model that at least to some extent is able to explain the complex informational system behind morphogenesis, ontogenesis, regeneration and healing. We suggest that it is from this highly dynamic spiraled structure that organization of cells, organs, and the wholeness of the human being including consciousness emerge. The model of "dancing fractal spirals" carries many similarities to premodern cultures descriptions of the energy of the life and universe. Examples are the Native American shamanistic descriptions of their perception of energy and the old Indian Yogis descriptions of the life-energy within the body and outside. Similar ideas of energy and matter are found in the modern superstring theories. The model of the informational system of the organism gives new meaning to Bateson's definition of information: "A difference that makes a difference", and indicates how information-directed self-organization can exist on high structural levels in living organisms, giving birth to their subjectivity and consciousness.
Explore the source record for details and available documents.
The rise of applied biology was one of the most striking feature of the biological sciences in the early 20th century. Strongly oriented toward agriculture, this was closely associated with the growth of a number of disciplines, notably, entomology and mycology. This period also saw a market expansion of the English University system, and biology departments in the newly inaugurated civic universities took an early and leading role in the development of applied biology through their support of Economic Biology. This sought explicitly to promote the application of biological knowledge to economically important problems and especially to agriculture. The impact of Economic Biology was felt most strongly within Zoology, where it became synonymous with entomology. The transience of Economic Biology belies its significance, for example, in providing a means for the expansion of biology at the civic universities. More broadly, it opened up new research and employment opportunities within the life sciences. In late Edwardian Britain, newly available state funds for agriculturally relevant biological disciplines transformed the life sciences. This paper examines the impact of these funds - mobilized either under the 1909 Development Act, or under the auspices of colonial interests - on Economic Biology and the institutionalization of applied biology. The rise and fall of Economic Biology casts new light on the way in which institutional and political alignments profoundly shaped the development of British biology.
Research in the biological sciences has undergone a fundamental and dramatic change during the last decades. Whereas biology was more phenomenologically oriented for a long time, today many biological processes are investigated and understood in molecular detail. It has become evident that all biological phenomena have a chemical basis: Biology is based on chemical principles. In the past, this insight had led to the development of biochemistry, molecular biology, and modern pharmacology. Today it increasingly determines the manner in which various biological phenomena are studied. The tools provided by classical biological techniques often are not sufficient to address the prevailing issues in precise molecular detail. Instead, the strengths of both chemical and biological methodology have to be used. Several recent research projects have proven that combining the power of organic synthesis with cell biology may open up entirely new and alternative opportunities for the study of biological problems. In this review we summarize the successful interplay between three disciplines-organic synthesis, biophysics, and cell biology-in the study of protein lipidation and its relevance to targeting of proteins to the plasma membrane of cells in precise molecular detail. This interplay is highlighted by using the Ras protein as a representative example. The development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of their biophysical properties, in particular the ability to bind to model membranes, and finally the use of synthetic Ras peptides and Ras proteins in cell biological experiments are addressed. The successful combination of these three disciplines has led to a better understanding of the factors governing the selective targeting of Ras and related lipid-modified proteins to the plasma membrane.
OBJECTIVE: Flash sterilization is most commonly used for emergency sterilization of unwrapped items in a gravity displacement sterilizer for three minutes. Sterilization quality assurance is monitored by biological indicators that require a 24-hour incubation prior to reading. In this study, we compared a new biological indicator that provides results within 60 minutes with three conventional, 24-hour biological indicators for monitoring flash sterilization and three chemical indicators. DESIGN: Conventional biological indicators tested included the conventional Attest 1261, Proof Flash and Assert, while the rapid readout indicator tested was Attest 1291. Attest Rapid Readout detects the presence of a Bacillus stearothermophilus enzyme by reading a fluorescent product that is produced by the enzymatic break-down of a nonfluorescent substrate. Chemical indicators tested included Comply, Incheque, and Thermalog S. Survival at 132 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 hours at 56 degrees C for the three conventional biological indicators, fluorescence at 60 minutes for the Attest Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated four times with 10 of each biological and chemical indicator per run. RESULTS: The conventional biological indicators (Attest, Proof Flash, and Assert) had 90%, 48%, and 40% spore survival at two minutes exposure; 23%, 3%, and 0% at three minutes exposure; and 3%, 0%, and 0% at four minutes exposure respectively. The Attest Rapid Readout biological indicator had 88%, 33%, and 0% enzyme activity detectable at 2, 3, and 4 minutes exposure. The chemical indicators Comply, Incheque, and Thermalog S revealed sterilization failure rates of 100%, 100%, and 100% at 0 minutes exposure; 100%, 100%, and 45% at one minute; 0%, 0%, and 28% at two minutes exposure; 0%, 0%, and 18% at three minutes exposure; and 0%, 0%, and 0% at four minutes exposure, respectively. CONCLUSION: The sensitivity of the Attest Rapid Readout parallels the conventional biological indicators. These data suggest that a 60-minute rapid readout biological indicator is equivalent to the 24-hour biological indicators. If further studies demonstrate that a four-minute flash sterilization cycle provides a needed safety margin to ensure sterilization, then consideration should be given to requiring a four-minute flash sterilization cycle. Chemical indicators were too sensitive to the processing conditions (eg, steam) and are inadequate to ensure adequate sterilization.
OBJECTIVE: In this study, we compare a new biological indicator that provides results within 3 hours with four conventional, 48-hour biological indicators and five chemical indicators. DESIGN: Biological indicators tested included the conventional Attest 1262, Proof Plus, Assert, and Biosign, and the new Attest 1292 Rapid Readout biological indicator. Chemical indicators tested included Comply, Propper, Chemdi, Sterigage, and Thermalog S. Spore survival following 121 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 and 48 hours at 56 degrees C for the conventional biological indicators, fluorescence at 3 hours for the Attest 1292 Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated 12 times with 5 samples of each indicator per run (ie, 60 replicates per indicator). RESULTS: At 48 hours, the conventional biological indicators Attest 1262, Proof Plus, Assert, and Biosign showed 100%, 95%, 88%, and 93% spore survival at 5 minutes' exposure 0%, 0%, 0% and 8% at 10 minutes; and all showed 0% survival at 15 minutes' exposure. Following a 3-hour incubation, the Attest 1292 Rapid Readout biological indicator showed fluorescence at 100%, 72%, and 0% at 5, 10, and 15 minutes, respectively. The chemical indicators Comply, Propper, Chemdi, Sterigage, and Thermalog S revealed sterilization failure rates of 100%, 100%, 100%, 100%, and 100% at 5 minutes' exposure; 0%, 0%, 0%, 92%, and 100% at 10 minutes; and 0%, 0%, 0%, 3%, and 27% at 15 minutes' exposure, respectively. CONCLUSIONS: The sensitivity of the Attest 1292 Rapid Readout biological indicator parallels that of conventional biological indicators. These data suggest that a 3-hour rapid readout biological indicator is equivalent to a standard 48-hour biological indicator. Some chemical indicators (eg, Thermalog S) failed to indicate adequate sterilization at 15 minutes' exposure. These chemical indicators have the potential of causing unnecessary recall of adequately sterilized items.
Some advantages of biological compared with environmental monitoring and some preparatory steps and difficulties to be overcome during the planning of a biological monitoring program are firstly discussed. Then the biological compartments, their peculiarities and their use in the field of biological monitoring are described. The problem concerning the biological thresholds of the reference normal values and the biological limits corresponding to environmental limits (biological equivalent limits, BEL) is the next topic, followed by the description of the methods for measuring the BELs (in case of linear regression between biological and environmental values) and of the methods for the upper and lower confidence limits (UCL, LCL) of a biological value. They are to be used for a decision of compliance or noncompliance biological exposure. Finally some ways of using biological UCL-LCL and variation coefficients during cross-sectional and longitudinal studies (biological monitoring strategies) are shown.
A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers would be of vital importance for physiological processes, and disturbance of these networks and balances would be a critical factor of pathological processes. Therefore, the investigators who want to get a deep and full understanding of the mechanism of a biological process should pay attention to the roles of both free radical and bioactive molecule species, and the free radical scavengers, which are used for health protection, such a vitamin E and carotenoid, should be taken in a suitable dosage.
It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT) incorporates patient-specific biological information and provides an outstanding opportunity for us to truly individualize radiation treatment. The proposed formalism lays a technical foundation for BCRT and allows us to maximally exploit the technical capacity of IMRT to more intelligently escalate the radiation dose.
As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood.
The mission of the American Society of Naturalists is "to advance and diffuse knowledge of organic evolution and other broad biological principles so as to enhance the conceptual unification of the biological sciences." In this article, I argue that the area of biology least integrated with knowledge of organic evolution is the field of ecosystem ecology, as evidenced by a semiquantitative literature survey of use of terms in the scientific literature. I present an overview of recent theoretical developments and empirical findings in the emerging field of biological stoichiometry (the study of the balance of energy and multiple chemical elements in living systems). These developments hold some promise as a means to conceptually integrate ecosystem ecology, with its emphasis on flows and pools of energy and chemical elements, with evolutionary biology, with its emphasis on genetic fitness and the biochemical products of the genome. For example, recent evidence indicates that organismal C : P and N : P ratios have a major impact on biologically mediated flows of energy and phosphorus; in turn, variations among taxa in these ratios are connected to evolved differences in organismal growth rate because of the connection between growth rate and the need for increased allocation to P-rich ribosomal RNA. In this way, evolutionary change in growth-related traits, by altering organismal P requirements, has direct biogeochemical implications, while ecosystem conditions can constrain evolutionary acceleration of growth rates by imposing a direct P limitation on production of the needed biochemical machinery of growth. Thus, stoichiometric theory provides a broad biological principle that can interconvert the currencies and concerns of ecosystem ecology and evolutionary biology, facilitating integration of diverse fields of study and contributing to conceptual unification of the biological sciences.
A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.