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PubMed2002

Youth social action: building a global latticework through information and communication technologies.

New technologies and a growing global consciousness have created innovative opportunities for young people to connect locally, nationally and internationally for social action. This paper describes the dynamics of collective action in this new environment. Particular attention is given to how youth social action initiatives use information and communication technologies (ICT) to foster connection, action and sustainability. In-depth interviews were performed with five youths (aged 18-24 years) and two youth workers at two international non-government organizations (NGOs) focusing on social justice and human rights: Global Youth Connect and Amnesty International Canada. Qualitative methods were used to code and analyze the interview tapes and notes. Three main results are discussed: (i) the role of connection in building a youth action movement; (ii) the differential use of various communication technologies; and (iii) access barriers to connection opportunities. ICT enables new and expanded ways of connecting youth to express and share their experiences, which is a key success factor for social action initiatives.

Adolescent↗
PubMed2000

Derivation of indoor gamma dose rate from high resolution in situ gamma ray spectra.

The dose build up factor B related to the ratio of primary to scattered gamma radiation in indoor environment was calculated with Monte Carlo simulations using the MCNP code for different indoor geometries and gamma source distributions. The main conclusion is that the B factor does not depend strongly on parameters such as dimensions of the rooms, the thickness of walls, the density of the building materials, and the gamma source geometry. The calculated dose build up factors were used within the framework of the full absorption peak analysis method in order to deduce the dose rates in air from about 100 indoor in situ gamma spectrometry measurements performed at the town of Thessaloniki, Greece. A spectral "stripping method," which has been recently developed, was applied to the same 100 spectrometry measurements. The results of the dose rates obtained by the two methods are compared and discussed.

Gamma Rays↗
PubMed2001

Spatial coding of visual and somatic sensory information in body-centred coordinates.

Because sensory systems use different spatial coordinate frames, cross-modal sensory integration and sensory-motor coordinate transformations must occur to build integrated spatial representations. Multimodal neurons using non-retinal body-centred reference frames are found in the posterior parietal and frontal cortices of monkeys. We used functional magnetic resonance imaging to reveal regions of the human brain using body-centred coordinates to code the spatial position of both visual and somatic sensory stimuli. Participants determined whether a visible vertical bar (visual modality) or a location touched by the right index finger (somatic sensory modality) lay to the left or to the right of their body mid-sagittal plane. This task was compared to a spatial control task having the same stimuli and motor responses and comparable difficulty, but not requiring body-centred coding of stimulus position. In both sensory modalities, the body-centred coding task activated a bilateral fronto-parietal network, though more extensively in the right hemisphere, to include posterior parietal regions around the intraparietal sulcus and frontal regions around the precentral and superior frontal sulci, the inferior frontal gyrus and the superior frontal gyrus on the medial wall. The occipito-temporal junction and other extrastriate regions exhibited bilateral activation enhancement related to body-centred coding when driven by visual stimuli. We conclude that posterior parietal and frontal regions of humans, as in monkeys, appear to provide multimodal integrated spatial representations in body-centred coordinates, and these data furnish the first indication of such processing networks in the human brain.

Adult↗
PubMed1999

Fetal dose assessment from invasive special procedures by Monte Carlo methods.

The assessment of fetal dose from a special procedure in the clinical environment is difficult as patient size, fluoroscopic beam motion, and imaging sequences vary significantly from study to study. Fetal dose is particularly difficult to estimate when the fetus is exposed partially or totally to scatter radiation from images taken in other locations of the mother's body. A method to reliably estimate fetal dose has been developed by using template based input files for the Monte Carlo radiation transport code MCNP. Female patient phantoms at 0, 3, 6, and 9 months of pregnancy and source terms for common diagnostic tube potentials are used to rapidly build an input file for MCNP. The phantoms can be easily modified to fit patient shape. The geometry and beam location for each type of image acquired (i.e. fluoroscopy, spot filming, etc.) is verified by the use of a 3D visualization code (Sabrina). MCNP is then run to estimate the dose to the embryo/fetus and the exposure to skin entrance (ESE) for the beam being modeled. The actual ESE for the beam is then measured with ion chambers and the fetal dose is determined from the MCNP supplied ratio of ESE to fetal dose. Runs are made for each type of imaging and the doses are summed for the total fetal dose. For most procedures, the method can provide an estimate of the fetal dose within one day of the study. The method can also be used to prospectively model a study in order to choose imaging sequences that will minimize fetal dose.

Biophysical Phenomena↗
PubMed1990

Molecular volumes and surfaces of biomacromolecules via GEPOL: a fast and efficient algorithm.

A triangular tesselation approach to build up surfaces has been adapted to the study of biomolecules. By using a data-coded generic pentakisdodecahedron each atom is assigned a particular sphere whose radii are chosen according to any suitable property. Different types of surfaces have been adapted to this method: van der Waals, surface accessible, and Richard's molecular surface. A simple method is used to eliminate all triangles found at the intersection volume of the atomic spheres and a fast algorithm is employed to calculate the area of the envelope surface and the volume therein. The data about the surface are given by the coordinates of the center of each triangle, elementary surface value, and vector coordinates of the normal to the surface. Color coding of standard properties such as charge densities, potential energy, or any scalar property can be easily done with standard graphics libraries. Fairly detailed information on vector properties, such as electric field and atom velocity, can also be graphically represented by using projections along the normals with adequate color coding.

Algorithms↗
PubMed1999

Uridine insertion/deletion RNA editing in trypanosome mitochondria--a review.

The uridine insertion/deletion RNA editing in trypanosome mitochondria is a unique posttranscriptional RNA maturation process that involves the addition or removal of uridine residues at precise sites usually within the coding regions of mitochondrial transcripts. This process creates initiation and termination codons, corrects frameshifts and even builds entire open-reading frames from nonsense sequences. The development of several in-vitro editing assays has provided much insight into the molecular mechanism of RNA editing, which appears to involve cleavage, U addition, exonuclease trimming and ligation, essentially as proposed in the original 'enzyme cascade' model (Blum, B., Bakalara, N., Simpson, L., 1990. A model for RNA editing in kinetoplastid mitochondria: 'Guide' RNA molecules transcribed from maxicircle DNA provide the edited information. Cell 60, 189-198). However, little is known about the biochemical properties of the proteins involved and the significance and role of this process. This article is a review of recent findings on uridine-insertion/deletion editing in trypanosome mitochondria, with an emphasis on the proteins isolated and characterized that may have a role in this process.

Animals↗
PubMed2001

Efficient elimination of selectable marker genes from the plastid genome by the CRE-lox site-specific recombination system.

Incorporation of a selectable marker gene during transformation is essential to obtain transformed plastids. However, once transformation is accomplished, having the marker gene becomes undesirable. Here we report on adapting the P1 bacteriophage CRE-lox site-specific recombination system for the elimination of marker genes from the plastid genome. The system was tested by the elimination of a negative selectable marker, codA, which is flanked by two directly oriented lox sites (>codA>). Highly efficient elimination of >codA> was triggered by introduction of a nuclear-encoded plastid-targeted CRE by Agrobacterium transformation or via pollen. Excision of >codA> in tissue culture cells was frequently accompanied by a large deletion of a plastid genome segment which includes the tRNA-ValUAC gene. However, the large deletions were absent when cre was introduced by pollination. Thus pollination is our preferred protocol for the introduction of cre. Removal of the >codA> coding region occurred at a dramatic speed, in striking contrast to the slow and gradual build-up of transgenic copies during plastid transformation. The nuclear cre gene could subsequently be removed by segregation in the seed progeny. The modified CRE-lox system described here will be a highly efficient tool to obtain marker-free transplastomic plants.

Base Sequence↗
PubMedDate not supplied

The evolution of the millennium bug.

How could mankind, knowing the year 2000 would inevitably arrive, manoeuvre into worldwide technical problems because of a little computer bug? Two major parallels can be drawn to biological systems, and both are based on evolutionary principles. First, any new steps in development are founded on building blocks invented earlier. Basic building blocks are hardly changed anymore because further developments depend on their function. Second, imperfections of such building blocks are irrelevant as long as no corresponding selection pressure exists. If a time-coded computer bug occurs sufficiently early during technological development it can become part of innumerous hard-wired or soft-coded programs and devices without ever attracting attention. However, the arrival of a certain data can instantly put a high selection pressure upon it. This behaviour can be understood as a direct consequence of the autonomous dynamics that the development of complex systems implicates.

Animals↗
PubMed1988

[Immunology of transplantation].

Immunologic events leading to the acute rejection of a grafted organ follow three sequential stages: 1) recognition of the antigens fully specific expressed by the allograft; 2) proliferation and differentiation of the T lymphocytes; 3) destruction of the graft mediated by various cellular types: sensitized cytotoxic T lymphocytes, lymphokine activated lymphocytes or macrophage cells, and, more hypothetically, by the so-called "killer" cells. The T lymphocytes infiltrating the grafts during rejection include functionally distinct subsets: inducer T cells (CD4+ cells) and suppressor/cytotoxic cells, T cells (CD8+ cells). In reversible acute rejections the role of activated cytotoxic cells (CD3+ CD8+) seems to be predominant. The functional nature of the lymphoblasts infiltrating the allograft is heterogeneous. It includes cell-mediated cytotoxicity, the proliferative response to alloantigens and the production of lymphokines. Finally, the role of the T cell receptor for the recognition of the antigen appears to be essential. The necessity for the immune system to build up a large repertoire of different T receptors is dependent on a mechanism of genetic coding similar to the one used by immunoglobulins. In the near future, one may hope to alter specifically the repertory of the T receptors used by the lymphocytes responsible for rejection. This would represent the dawn of a new era in transplantation immunity with the beginning or specific immunosuppression.

Child↗
PubMed2024

On the Hunt for the Histone Code.

Our genome is not made of naked DNA but a fiber (chromatin) composed of DNA and proteins packaged into our chromosomes. The basic building block of chromatin is the nucleosome, which has two copies of each of the proteins called histones (H2A, H2B, H3, and H4) wrapped by 146 base pairs of DNA. Regions of our genetic material are found between the more open (euchromatin) and more compact (heterochromatin) regions of the genome that can be variably accessible to the underlying genes. Furthermore, post-translational modifications (PTMs) on histones, such as on H3, are critical for regulating chromatin accessibility and gene expression. While site-specific antibodies were the tool of choice for histone PTM analysis in the early days (pre-2000s), enter Don Hunt changing the histone PTM field forever. Don's clever thinking brought new innovative mass spectrometry-based approaches to the epigenetics field. His lab's effort led to the discovery of many new histone modifications and methods to facilitate the detection and quantification of histone PTMs, which are still considered state of the art in the proteomics field today. Due to Don's pioneering work in this area, many labs have been able to jump into the epigenetics field and "Hunt" down their own histone targets. A walkthrough of those early histone years in the Hunt Lab is described by three of us who were fortunate enough to be at the right place, at the right time.

Animals↗
PubMed1998

Person-centered code of practice/code of ethics: configuring an ethical commitment to the care provider and care receiver.

Transformation in Care Delivery (TCD), a program at Piedmont Medical Center in Atlanta, Georgia, emphasizes building connections and achieving new and different relationships between all persons in the health care system: those who receive services as well as those who give services. A process called opportunity management mandates involvement of all affected people and provides the mechanism for TCD decisions and actions. The desired environment for TCD is a practiced philosophy of person-centeredness, lived through a new Code of Practice/Code of Ethics. The philosophy and Code are built on respect for the diverse beliefs, values, and practices of all people receiving and providing service. This article highlights the way these processes result in improved value for all stakeholders through a new personal and organizational ethical commitment to excellence.

Ethics, Nursing↗
PubMed1990

Metabolic complexity in the RNA world and implications for the origin of protein synthesis.

A model is presented for the evolution of metabolism and protein synthesis in a primitive, acellular RNA world. It has been argued previously that the ability to perform metabolic functions logically must have preceded the evolution of a message-dependent protein synthetic machinery and that considerable metabolic complexity was achieved by ribo-organisms (i.e., organisms in which both genome and enzymes are comprised of RNA). The model proposed here offers a mechanism to account for the gradual development of sophisticated metabolic activities by ribo-organisms and explains how such metabolic complexity would lead subsequently to the synthesis of genetically encoded polypeptides. RNA structures ancestral to modern ribosomes, here termed metabolosomes, are proposed to have functioned as organizing centers that coordinated, using base-pairing interactions, the order and nature of adaptor-mounted substrate/catalyst interactions in primitive metabolic pathways. In this way an ancient genetic code for metabolism is envisaged to have predated the specialized modern genetic code for protein synthesis. Thus, encoded amino acids initially would have been used, in conjunction with other encoded metabolites, as building blocks for biosynthetic pathways, a role that they retain in the metabolism of contemporary organisms. At a later stage the encoded amino acids would have been condensed together on similar RNA metabolosome structures to form the first genetically determined, and therefore biologically meaningful, polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Code↗
PubMed2005

Anticipatory activity in primary motor cortex codes memorized movement sequences.

Movement sequences, defined both by the component movements and by the serial order in which they are produced, are fundamental building blocks of motor behavior. The serial order of sequence production is strongly encoded in medial motor areas. It is not known to what extent sequences are further elaborated or encoded in primary motor cortex. Here, we describe cells in the primary motor cortex of the monkey that show anticipatory activity exclusively related to a specific memorized sequence of upcoming movements. In addition, the injection of muscimol, a GABA agonist, into motor cortex resulted in an increase in the error rate during sequence production, without concomitant effects on nonsequenced motor performance. Our results challenge the role of medial motor areas in the control of well-practiced movement sequences and suggest that motor cortex contains a complete apparatus for the planning and production of this complex behavior.

Action Potentials↗
PubMed1999

Dynamics of intrinsic electrophysiological properties in spinal cord neurones.

The spinal cord is engaged in a wide variety of functions including generation of motor acts, coding of sensory information and autonomic control. The intrinsic electrophysiological properties of spinal neurones represent a fundamental building block of the spinal circuits executing these tasks. The intrinsic response properties of spinal neurones--determined by the particular set and distribution of voltage sensitive channels and their dynamic non-linear interactions--show a high degree of functional specialisation as reflected by the differences of intrinsic response patterns in different cell types. Specialised, cell specific electrophysiological phenotypes gradually differentiate during development and are continuously adjusted in the adult animal by metabotropic synaptic interactions and activity-dependent plasticity to meet a broad range of functional demands.

Adult↗
PubMed1996

A predictive index of axillary nodal involvement in operable breast cancer.

We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis.

Adult↗
PubMed2025

CancerTrialMatch: a computational resource for the management of biomarker-based clinical trials at a community cancer center.

MOTIVATION: The widespread implementation of next-generation sequencing in cancer care has enabled routine use of molecular and biomarker profiling. At our cancer center, as with many others, biomarker-based clinical trials are increasingly available to oncologists as potential treatment options via molecular tumor boards. To better support this effort, we developed CancerTrialMatch, a systematic approach to capture structured clinical trial data and match patients to trials based on their disease characteristics and sequencing profiles. RESULTS: CancerTrialMatch is an open-source application designed to streamline clinical trial curation and patient trial matching, while also enabling an institution's curated trial portfolio to be distributed across the institution for easy access to providers, care teams and researchers. It facilitates curating, updating, and searching for trials through a semi-automated interface built using R Shiny, MongoDB, and Docker. While much of the trial data is retrieved via the clinicaltrials.gov Application Programming Interface, certain items like biomarkers and disease subtypes are entered manually. The user inputs disease type using the OncoTree classification, and provides relevant biomarker details, such as mutations, copy numbers, fusions, and other disease-specific markers. This resource reduces the time required for institutional trial management and helps to identify potential clinical trials for patients, ultimately supporting larger clinical trial enrollment and enhancing the clinical application of precision oncology. AVAILABILITY AND IMPLEMENTATION: CancerTrialMatch was implemented and tested on Windows 11 (64-bit, 32 GB RAM) using WSL2 with Ubuntu 22.04. Docker 27.0.3 and Docker Compose 2.28.1 were used to build images and containers. Users can build it by cloning the repo and following the README instructions and supplemental file (cancertrialmatchsupplemental.pdf) . The source code and example data are available in GitHub and Figshare at https://github.com/AveraSD/CancerTrialMatch and 10.6084/m9.figshare.28447367 respectively.

Humans↗
PubMed2005

Dose build up correction for radiation monitors in high-energy bremsstrahlung photon radiation fields.

Conventional radiation monitors have been found to underestimate the personal dose equivalent in the high-energy bremsstrahlung photon radiation fields encountered near electron storage rings. Depth-dose measurements in a water phantom were carried out with a radiation survey meter in the bremsstrahlung photon radiation fields from a 450 MeV electron storage ring to find out the magnitude of the underestimation. Dose equivalent indicated by the survey meter was found to build up with increase in thickness of water placed in front of the meter up to certain depth and then reduce with further increase in thickness. A dose equivalent build up factor was estimated from the measurements. An absorbed dose build up factor in a water phantom was also estimated from calculations performed using the Monte Carlo codes, EGS-4 and EGSnrc. The calculations are found to be in very good agreement with the measurements. The studies indicate inadequacy of commercially available radiation monitors for radiation monitoring within shielded enclosures and in streaming high-energy photon radiation fields from electron storage rings, and the need for proper correction for use in such radiation fields.

Algorithms↗
PubMed2000

CART classification of human 5' UTR sequences.

A nonredundant database of 2312 full-length human 5'-untranslated regions (UTRs) was carefully prepared using state-of-the-art experimental and computational technologies. A comprehensive computational analysis of this data was conducted for characterizing the 5' UTR features. Classification and regression tree (CART) analysis was used to classify the data into three distinct classes. Class I consists of mRNAs that are believed to be poorly translated with long 5' UTRs filled with potential inhibitory features. Class II consists of terminal oligopyrimidine tract (TOP) mRNAs that are regulated in a growth-dependent manner, and class III consists of mRNAs with favorable 5' UTR features that may help efficient translation. The most accurate tree we found has 92.5% classification accuracy as estimated by cross validation. The classification model included the presence of TOP, a secondary structure, 5' UTR length, and the presence of upstream AUGs (uAUGs) as the most relevant variables. The present classification and characterization of the 5' UTRs provide precious information for better understanding the translational regulation of human mRNAs. Furthermore, this database and classification can help people build better computational models for predicting the 5'-terminal exon and separating the 5' UTR from the coding region.

5' Untranslated Regions↗