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PubMedDate not supplied

A new description of the photon beam peak-depth profile as a function of field size.

The dose profile at peak depth in water is described as the product of an apparatus function and a source function. In principle, the source function is the circularly symmetric profile which would be measured at peak depth without any collimation. In practice, the peak-depth profile in the diagonal plane, measured for the largest collimator setting, is used for this purpose. The apparatus function represents the collimator acting upon the source function, and is referred to as the collimator function. The collimator function for any field size can be developed from the ratio of the peak-depth profile for a single medium-sized field and the source function. The method has been tested for a set of irregularly flattened 4-MV x-ray beams as well as for practically flat 15-MV x-ray beams. The model requires as basic data only three peak-depth profiles: one in each principal plane of a medium-sized square field and the peak-depth profile in the diagonal plane for the largest field. It replaces the peak-depth transformation in the projective beam model.

Humans↗
PubMed2026

Imaging-Guided Omics Technologies for Resolving Rare Cancer States and Advancing Nanomedicine.

The ability to resolve rare and transient cellular states is critical for understanding metastasis, immune evasion, and therapy resistance in cancer, yet these dynamic processes often escape detection by conventional sequencing and imaging approaches. Recent advances at the interface of nanotechnology, high-resolution live-cell imaging, and single-cell/spatial multiomics methods have enabled functional profiling of cells with unprecedented precision within their native microenvironment. In this Mini-Review, we highlight emerging nanoscale platforms that couple real-time phenotypic imaging with molecular readouts, such as FUNseq and CIN-seq, to directly link functional heterogeneity to transcriptomic, proteomic, and epigenomic information. By integrating nanoscale optical imaging, microengineered perturbation tools, and AI-driven computational analysis, these technologies open up new avenues for dissecting rare metastatic, therapy-resistant, or immune-evasive subpopulations. We further discuss how these next-generation imaging-guided single-cell and spatial omics platforms not only advance fundamental cancer biology but also create opportunities to accelerate the development of nanomedicine applications.

Humans↗
PubMed1988

Genetic profile of the transcriptional signals from the adenovirus major late promoter.

Identical functional profiles were obtained for in vivo and in vitro transcription assays of more than 30 site-directed point mutants within the adenovirus major late promoter. The functional limits of the functional regions encompassing upstream promoter element are defined (-51 to -61), as well as a region around the transcription start site (-1 to +1), flanked by regions insensitive to sequence alterations.

Adenoviridae↗
PubMed1990

The role of pharmacological profiling in safety assessment.

The profiling of new drug candidates for general pharmacological properties requires a systematic examination of the functional effects of agents in a variety of in vitro and in vivo assays. Both the behavioral and physiological consequences of drug treatment are monitored in models of central nervous system, cardiovascular, autonomic, gastrointestinal, and renal functions. Broad functional profiling provides valuable information to the preclinical pharmacologist with respect to the selectivity of new agents and may serve to identify new and useful therapeutic indications of investigational drugs. At the same time, knowledge of the effects on these physiological systems can also play an important role in safety assessment. Pharmacological activity of a new agent that is both unintended and undesirable can be referred to as "pharmacological toxicity." In general, the spectrum of toxicities disclosed in pharmacological profiling includes a variety of acute functional or physiological effects which are not life-threatening and are readily reversible. On rare occasions, unanticipated and life-threatening pharmacological effects (e.g., convulsions, arrhythmias) are detected which can seriously detract from the usefulness of a new agent and may therefore deter the drug development process. It should also be noted that repeated exposure to acute pharmacological effects may lead to less obvious chronic findings, such as target organ effects or tumor formation in animals. The interpretation of pharmacological toxicity with respect to the safety profile of a new drug candidate is dependent not only upon the types of reactions observed and the doses at which they occur but also upon the nature of the effects elicited as to whether they represent expected extensions of the primary mechanism of action of a compound or constitute reactions unrelated to the primary pharmacological activity. The ultimate impact of pharmacological toxicity, as with all adverse findings in preclinical assessment, is dependent upon the projected therapeutic margin of safety as well as the risk-to-benefit ratio for new drug entities. In addition to supplementing the existing armamentarium of preclinical safety studies, pharmacological profiling can also play an important role in (1) the selection of new drug candidates with reduced toxic potential, (2) the design and conduct of preclinical toxicology studies, (3) the investigation of preclinical and clinical safety issues, and (4) the identification of potential functional effects to be monitored most closely in clinical trials of new drug entities.

Animals↗
PubMedDate not supplied

Return to work after rehabilitation following traumatic brain injury.

The relationship of medical variables and discharge functional status to vocational and educational outcomes was examined in 79 closed head-injured patients who were consecutively admitted to an inpatient rehabilitation hospital during a two-year period. A follow-up study, conducted after hospital discharge (median, 16.5 months), found that 66% (n = 52) of the patients had returned to work or school, while 34% (n = 27) did not. Patients were divided into return and non-return to work groups. Traditional variables included age, severity of brain-damage as characterized by CT head scan, duration of post-traumatic amnesia, duration of coma, length of stay and acute inpatient rehabilitation program. Discharge functional scores were analysed by t-tests and chi-square analysis. Results suggest that traditional factors of younger age, shorter length of coma, minimal CT head scan findings and shorter length of stay were significant contributors to educational/vocational outcome. Their significance was enhanced by discharge functional profile measurement of medical, physical and psychological/neuropsychological integrity. Those functional measures not significant were in social, vocational, recreational and communication areas. These factors may continue to improve over a longer period of time and should be tracked in the post-acute rehabilitation phase for their significance in return to work/school.

Activities of Daily Living↗
PubMed1989

Functional and neutralization profile of seven overlapping antigenic sites on the HN glycoprotein of Newcastle disease virus: monoclonal antibodies to some sites prevent viral attachment.

We have previously identified five antigenic sites on the hemagglutinin-neuraminidase (HN) glycoprotein of the Australia-Victoria isolate of Newcastle disease virus (Iorio and Bratt, J. Virol. 48, 440-450; Iorio et al., J. Gen. Virol. 67, 1393-1403). Two additional sites (designated 12 and 23) are now described, bringing to a total of seven the number of antigenic sites defined by our panel of neutralizing anti-HN antibodies. Competition antibody binding and additive neutralization assays reveal that each of these newly-identified sites overlaps two previously-defined ones. The seven HN antigenic sites thus form a continuum in the three-dimensional conformation of the molecule. Studies on the inhibition of hemagglutination (HA), neuraminidase (NA) and the attachment of virus to chick cell monolayers have been used to construct a functional profile of each antigenic site. Monoclonal antibodies (mAbs) to three overlapping sites (12, 2 and 23) inhibit HA and NA and prevent viral attachment to chick cell monolayers. These findings are consistent with the domains recognized by these mAbs being close to the NA and receptor-binding sites. MAbs to two other overlapping sites, 14 and 1 (which in turn, overlap site 12), inhibit HA quite effectively, and attachment to a lesser extent. Sites 14 and 1 probably identify a second domain involved in receptor recognition. MAbs to the two remaining sites (3 and 4), though neutralizing, are negative in all three assays, thus recognizing domains not involved in HA or NA or attachment to chick cells.

Animals↗
PubMed1991

Selectivity profile of the novel muscarinic antagonist UH-AH 37 determined by the use of cloned receptors and isolated tissue preparations.

1. Functional in vitro experiments were carried out to determine the antimuscarinic potencies of the pirenzepine derivative UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-dibenzo- [b,e] [1,4] diazepine-11-one hydrochloride) at M1 muscarinic receptors of rabbit vas deferens, M2 receptors of rat left atria and M3 receptors of rat ileum. Furthermore, N-[3H]-methylscopolamine competition binding experiments were performed to obtain its affinities for the five cloned human muscarinic receptors (m1-m5) stably expressed in CHO-K1 cells. Pirenzepine served as a reference drug throughout all experiments. 2. In all preparations used, UH-AH 37 interacted with muscarinic receptors in a fashion characteristic of a simple competitive antagonist. 3. In the functional studies, UH-AH 37, like pirenzepine, showed high affinity for M1 (pA2 8.49) and low affinity for M2 muscarinic receptors (pA2 6.63). In contrast to pirenzepine, UH-AH 37 also displayed high affinity for M3 receptors (pA2 8.04). 4. In agreement with its functional profile, UH-AH 37 bound with highest affinity to m1 (pKi 8.74) and with lowest affinity to m2 receptors (pKi 7.35). Moreover, it showed a 7 fold higher affinity for m3 (pKi 8.19) than for m2 receptors, whereas pirenzepine bound to both receptors with low affinities. 5. The binding affinity of UH-AH 37 for m4 and m5 receptors (pKi 8.32 for both receptors) was only ca. 2.5 fold lower than that for m1 receptors, while the corresponding affinity differences were 6 and 13 fold in case of pirenzepine. 6. In conclusion, the receptor selectivity profile of UH-AH 37 differs clearly from that of its parent compound, pirenzepine, in both functional and radioligand binding studies, the major characteristics being its pronounced M2 (m2)/M3 (m3) selectivity. UH-AH 37 thus represents a useful tool for the further pharmacological characterization of muscarinic receptor subtypes.

Animals↗
PubMed1975

Quantitative assays of human monocyte-macrophage function.

Monocyte-macrophages are required for the development of cell mediated immunity to a variety of microorganisms and tumors. Quantitative assays of human monocyte-macrophage function would be most useful in the evaluation of cell mediated immune function in man. Five quantitative assays are described that provide a human monocyte-macrophage function profile. These assays parallel the physiologic steps necessary for monocyte-macrophages to function as phagocytes: 1) chemotaxis, 2) opsonization, 3) phagocytosis, 4) phagocytosis-induced metabolic stimulation and 5) destruction of foreign material. Application of these quantitative assays will allow detection and dissection of disorders of monocyte-macrophage function in man.

Adult↗
PubMed1986

Simultaneous measurement of pressure profile and pull-through force in the urethra of 25 female patients.

Simultaneous registration of urethral pressure profile and pull-through force was performed to study the dynamics of sphincteric function in 25 female patients. Three separate types of catheters of six different sizes were used. A 6-French smooth catheter was used to measure maximal urethral closure pressure, functional profile length and length to maximal urethral pressure. The results were divided into three groups (A, B and C) with significantly different closure pressure values, only correlated to the age of the patient. In all three groups (A, B and C), the mean maximal urethral closure pressure increased in linear correlation to the catheter diameter and did not bear any relation to the shape of the catheter tip, either of the bulb or the ball type. A significant exponential correlation was demonstrated between pull-through force and catheter diameter. Also the correlation between force and length of the pull-through force curve was exponential, while only the mean values of closure pressure and force correlated exponentially. No further correlations were found, even after force values were ranked to form three other groups (I, II and III). In contrast to the groups A, B and C, no distinct differences in clinical diagnosis was noticed between groups I, II and III. The pressure and force curves can be explained on a physical basis, despite the variety in pathology. On the basis of this evidence it appears that a more accurate measurement of sphincter function in the female can be obtained by measuring pressure and force simultaneously with different sizes of catheters, especially with a diameter of 15 French or more.

Adolescent↗
PubMed1988

Blood-monocyte functions in acute bacterial meningitis.

The blood-monocyte chemotactic, phagocytic and microbicidal activities were studied in 20 patients with acute bacterial meningitis. The cell functions were measured on admission, during treatment and after clinical recovery. In general, monocyte functions were within normal range on admission. However, in 2/2 patients with Neisseria meningitidis meningitis, complicated by disseminated intravascular coagulation, defective chemotaxis was observed. Other patients had normal or enhanced monocyte chemotaxis. Two patients died: one had normal monocyte functions, one had initially defective chemotaxis and microbicidal activity. During treatment, cell functions normalized and after recovery all but one patient had a normal blood-monocyte function profile. In conclusion, acute bacterial meningitis is not due to, or followed by, abnormal nonspecific functions of blood monocytes. However, development of disseminated intravascular coagulation is associated with depressed chemotactic responsiveness.

Acute Disease↗
PubMed1985

Criteria for referral of CVA patients for rehabilitation.

A multi-stage follow-up project is in progress at the Loewenstein Rehabilitation Hospital. In the first stage, a group of 153 patients was examined while in the acute phase of CVA (1 to 5 days from stroke), and again 6 months later, by a physician, a physiotherapist and an occupational therapist. Medical, demographical and functional profiles were determined. The most severe cases were admitted for rehabilitation and those with apparently good functioning ability were discharged to their homes. Six months later, the group referred for rehabilitation remained at a very low functional level (35% of them were still at the rehabilitation hospital); on the other hand, those sent home were lacking in general function (37%), in spite of their good ADL and hand performance. Most strikingly, 72% were not engaged in any meaningful activity. Age proved to be a strongly limiting factor. A more selective criterion for referral is required, while allowing patients with medium-grade cognitive and locomotor disturbances the chance of admission to rehabilitation.

Activities of Daily Living↗
PubMed1991

Assessing the functional status during an asthma attack with Dartmouth COOP charts. Validity with respect to the change in asthma.

The functional status of patients was determined during an acute attack of asthma requiring medical intervention. Patients were recruited during two months from general practice: all 28 patients consulting for an acute asthma attack were invited to take part: four refused or were withdrawn from follow up. Matched control patients with asthma, not suffering from an acute attack were selected from the practice file. Patients were investigated directly after the initial intervention and exactly 14 days later: respiratory symptoms, peak expiratory flow rates and functional status were recorded. In all cases the intervention resulted in the relief of symptoms and a return of peak expiratory flow to the normal predicted range for age, sex and height. After the 14 days, patients had no longer evidence of an exacerbation of their asthma. During the attack, there were indications of reduced physical and psychological functions, and reduced daily and social activities. A difference was found in the functional profile of asthmatics with an asthma attack and asthmatics without an asthma attack. After 14 days, the functional status of all the dimensions had improved. There was no evident correlation to the change in functional status and peak expiratory flow rates. An asthma attack hampers the patient in his daily functioning--not only physically, but also in social functioning and feelings. There are indications that the recuperation in terms of functioning takes longer than the symptoms to disappear or the peak expiratory flow to return to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗
PubMed2026

Host-independent metagenomics reveal gut bacteria contribution to Delia antiqua growth by vitamin B6 provision.

Insect guts host a diverse and abundant array of microorganisms. These microbes improve host fitness by extensively involving in a range of crucial physiological processes, which have mainly been revealed by high-throughput sequencing, particularly metagenomics. However, it is almost impossible to make an accurate and complete distinction between the genetic functions of microbial symbionts and insect hosts without host genome data. By comparing metagenomic data from gut germ-free and nonaxenic larvae, we accurately identified the data belonging to the gut microbiome of the onion maggot Delia antiqua (Diptera: Anthomyiidae). Besides, a correlation between bacteria of the genus Wohlfahrtiimonas (Gammaproteobacteria: Pseudomonadaceae) and vitamin B6 metabolism was detected through collinearity analysis. Furthermore, in vitro tests confirmed that the gut bacterium Wohlfahrtiimonas larvae contributed to the growth of D. antiqua larvae via the independent synthesis of vitamin B6. This study provides a comprehensive view of the gut bacterial diversity in D. antiqua and reveals a functional profile that is strictly specific to the gut microbiota of this species. It has preliminarily revealed the functional differentiation between insect hosts and their symbiotic microorganisms. This study also offers a technical reference for the study of microbial symbiotic functions in other insect-microbe symbioses without host genomic data.

Animals↗
PubMed1989

Urethral pressure profilometry in the anaesthetised bitch: a comparison between double and single sensor recording.

A comparison was made between urethral pressure profiles obtained using a single sensor and 'subtracted' urethral pressure profiles resulting from double sensor recordings in 50 bitches. There were small but significant differences in the functional profile lengths and maximum urethral closure pressures between the two types of recording. The differences were partially explained by a significant fall in the intravesical pressure recorded during profilometry and variations due to respiration. The profiles from single and double sensor recording were of equal significance in the diagnosis of sphincter mechanism incompetence.

Animals↗
PubMed2026

Comparative characterization of six teleost piscidins reveals distinct antimicrobial, antibiofilm and stability profiles.

Piscidins are cationic α-helical antimicrobial peptides (AMPs) that constitute a key component of the innate immune defense of teleost fish, yet the relationship between their genomic organization, structural properties, and functional specialization remains incompletely understood. In this study, six piscidin peptides from Epinephelus akaara, Seriola dumerili, Thunnus maccoyii, Argyrosomus regius, Dicentrarchus labrax, and Epinephelus coioides were characterized through an integrated sequence-to-function approach combining comparative genomics, structural modeling, physicochemical analysis, and in vitro validation, with the aim of identifying candidates with potential for biomedical and biotechnological applications. All genes studied exhibited the conserved four-exon, three-intron architecture characteristic of teleost piscidins. Structural modeling and circular dichroism confirmed α-helical conformations under membrane-mimetic conditions, despite measurable differences in hydrophobicity, charge distribution, and predicted membrane insertion parameters. Antimicrobial assays revealed distinct functional profiles: Sd_FI25 and Epinecidin_1 displayed broad antibacterial activity against Gram-positive and Gram-negative pathogens, whereas Dl_FI22 showed selective activity with reduced temporal persistence associated with lower peptide stability. Ea_FF25 exhibited comparatively weak antibacterial potency. Antibiofilm activity varied among peptides and did not uniformly parallel planktonic MIC values. Computational predictions further suggested antiviral and antitumoral potential for several sequences, extending their prospective relevance beyond classical antibacterial roles. Conserved genomic architecture and α-helical structure coexist with pronounced functional diversification among teleost piscidins. These findings demonstrate that integrating structural prediction with experimental validation is an effective strategy for identifying fish-derived innate immune peptides as candidates for biomedical applications.

Antimicrobial activity↗
PubMed1978

Evaluation of linear profile scans; mathematical treatment of line-spread functions.

The profile measurement capability of a scanning multidetector whole-body counter is described using line spread functions. Measurements in air and water phantoms, as a function of energy, are discussed in relationship to the relevant physical processes. A computer program for evaluating bodyprofile scans and an attempt to improve the resolution are reported.

Evaluation Studies as Topic↗
PubMed2025

Genome-wide identification and expression profiling of the MADS-box gene family in Lavandula angustifolia.

BACKGROUND: MADS-box genes encode transcription factors critical for plant development, particularly floral organogenesis, flowering time regulation, and adaptation to environmental stresses. Among these, the MIKCC-type genes are pivotal regulators in floral developmental processes. Although the evolutionary diversification and functional dynamics of MADS-box genes have been extensively characterized in model plants such as Arabidopsis thaliana and Oryza sativa, their evolutionary relationships and functional profiles in Lavandula angustifolia, an economically significant aromatic plant, remain poorly understood. RESULTS: Genome-wide analysis identified 173 MADS-box genes in L. angustifolia, categorized into type I (Mα: 26; Mβ: 0; Mγ: 10) and type II (MIKCC: 125; MIKC*: 12) based on phylogenetic comparisons with A. thaliana. The MIKCC subgroup was further subdivided into 12 subclasses, including genes central to the ABCDE model of floral organ specification. Structural analyses revealed distinct conserved motifs and exon-intron configurations specific to each subgroup, indicative of functional divergence. Synteny analysis demonstrated Whole Genome Duplication (WGD) and segmental duplications as major contributors to MIKCC gene family expansion, notably among genes linked to floral organ development. Expression profiling via RNA-seq and quantitative real-time PCR (qPCR) showed type II MADS-box genes exhibited higher expression levels with pronounced tissue-specific and developmental stage-specific expression patterns compared to type I genes. Many type II genes displayed significant associations with floral organogenesis, floral transition, and abiotic stress responses, underscoring their essential roles in reproductive development and environmental adaptability in L. angustifolia. CONCLUSIONS: The identification and comprehensive characterization of 173 MADS-box genes in L. angustifolia highlight the significant expansion of the MIKCC subgroup driven primarily by WGD and segmental duplications. The distinct structural features and specific expression patterns observed provide insights into the functional divergence and complexity of these genes, particularly regarding floral organogenesis and adaptation to environmental stress. This study establishes a robust molecular basis for further functional analysis and genetic improvement of aromatic plants.

MADS Domain Proteins↗