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Evidence of two major genotypes of hepatitis C virus in France and close relatedness of the predominant one with the prototype virus.

Hepatitis C virus (HCV) cDNA sequence in the nonstructural region NS3 was amplified from the serum of 66% French non-A, non-B hepatitis patients by the nested polymerase chain reaction. A 407 base-pair sequence was determined from four such cases, which revealed the presence of two different virus genotypes F1 (three cases) and F2 (one case) with 19-20% sequence divergence. F1 showed close homology (97.5%) to the prototype US isolate, but only limited (79%) homology to the reported Japanese isolates. In contrast, F2 had 91.6% homology to the Japanese isolate, but only 81% homology to the prototype US virus. Hybridization of the amplified products from 50 French samples with labeled F1 and F2 fragments suggested the F1-related strain(s) as the major hepatitis C virus genotype. Further studies involving a greater variety of samples will confirm whether the F1-related strain is the predominant hepatitis C virus strain circulating in France. Such data will have important implications for the PCR detection of HCV infection and production of HCV vaccines.

Antisense Elements (Genetics)

A knowledge-based support system for mechanical ventilation of the lungs. The KUSIVAR concept and prototype.

The KUSIVAR is an expert system for mechanical ventilation of adult patients suffering from respiratory insufficiency. Its main objective is to provide guidance in respirator management. The knowledge base includes both qualitative, rule-based knowledge and quantitative knowledge expressed in the form of mathematical models (expert control) which is used for prediction of arterial gas tensions and optimization purposes. The system is data driven and uses a forward chaining mechanism for rule invocation. The interaction with the user will be performed in advisory, critiquing, semi-automatic and automatic modes. The system is at present in an advanced prototype stage. Prototyping is performed using KEE (Knowledge Engineering Environment) on a Sperry Explorer workstation. For further development and clinical use the expert system will be downloaded to an advanced PC. The system is intended to support therapy with a Siemens-Elema Servoventilator 900 C.

Adult

Two French genotypes of hepatitis C virus: homology of the predominant genotype with the prototype American strain.

A hepatitis C virus (HCV) cDNA covering part of the nonstructural region, NS3, was amplified from the serum of 50 out of 76 French non-A, non-B hepatitis patients by the nested polymerase chain reaction (PCR). Determination of a 407-bp sequence from four such cases revealed the presence of two different virus genotypes, F1 and F2, which exhibited 19-20% sequence divergence. F1 was represented by three of the four isolates and showed a sequence homology of about 97.5% to the prototype American HCV isolate, but of only 79% to a reported Japanese isolate. In contrast, F2 had 91.6% homology to the Japanese isolate, but only 81% homology to the prototype American HCV. PCR products from the 50 samples were hybridized with labeled F1 and F2 fragments under stringent conditions; results indicated the F1-related strain(s) as the major HCV genotype. Furthermore, a total of 1477 bp of sequence has been determined for one of the isolates belonging to the F1 category. These results will have implications for the PCR detection of HCV infection and production of HCV vaccines, especially for European countries.

Americas

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans

Development of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy activity.

Structural modification of 3,4-dihydro-4-oxoquinazoline-2-carboxylic acid leading to ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy activity of the disodium cromoglycate type, is described. This prototype is 10 times more potent than disodium cromoglycate in the rat passive cutaneous anaphylaxis test. Structure-activity studies indicate that a carboxylic acid moiety directly attached to the 2 position of the pyrimidine ring is most favorable for intravenous activity while esters of this acid are preferred for oral activity. The oral activity of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate (ED50 = 3 mg/kg) places this ester among the more potent orally active antiallergy agents reported to date.

Animals

Specific exemplar retention and prototype abstraction in young and old adults.

The effects of age differences in retention of information about specific concept members on the ability to abstract central tendency information were examined. Young and older adults were presented with a series of visual patterns that were organized around a prototype. They were then presented with these same patterns plus a set of new patterns varying in prototype similarity in a recognition test. It was found that young adults retained more information about specific acquisition set exemplars, which resulted in slightly different recognition responses for new patterns. However, the recognition behavior of both young and older adults appeared to be governed by the same rules. It is suggested that the organization of conceptual information does not change with age, but the poorer retention of specific item information in older adults may result in a less complete representation.

Adolescent

Categories and particulars: prototype effects in estimating spatial location.

A model of category effects on reports from memory is presented. The model holds that stimuli are represented at 2 levels of detail: a fine-grain value and a category. When memory is inexact but people must report an exact value, they use estimation processes that combine the remembered stimulus value with category information. The proposed estimation processes include truncation at category boundaries and weighting with a central (prototypic) category value. These processes introduce bias in reporting even when memory is unbiased, but nevertheless may improve overall accuracy (by decreasing the variability of reports). Four experiments are presented in which people report the location of a dot in a circle. Subjects spontaneously impose horizontal and vertical boundaries that divide the circle into quadrants. They misplace dots toward a central (prototypic) location in each quadrant, as predicted by the model. The proposed model has broad implications; notably, it has the potential to explain biases of the sort described in psychophysics (contraction bias and the bias captured by Weber's law) as well as symmetries in similarity judgments, without positing distorted representations of physical scales.

Adolescent

Comparison of a human T-cell lymphotropic virus type I strain from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis with a prototype human T-cell lymphotropic virus type I.

The isolation and characterization of a human T-cell lymphotropic retrovirus related to human T-cell lymphotropic virus type I (HTLV-I) from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis is described. The virus isolate is a typical type C retrovirus as seen by electron microscopy and is related to prototype HTLV-I isolated from patients with adult T-cell leukemia but is not identical to this prototype HTLV-I as seen by restriction enzyme mapping.

Aged

A prototype microcomputer-based decision support system for industrial hygienists.

A prototype Industrial Hygiene Decision Support System (IH-DSS) was designed and implemented in a microcomputer environment using an integrated knowledge management system as the implementation vehicle. The heart of the system is a relational data base designed to minimize redundant data entry and to support flexible retrieval. An industrial hygienist's routine and ad hoc requirements for information retrieval and analysis support are met by screen displays, printed reports, and graphical summaries which may be presented on the screen, in a printed form, or as multicolored plots. A petroleum refinery was selected as the application environment for the prototype system because of the variety of processes, agents, and sampling methodologies involved in industrial hygiene support in that environment.

Computers

Prototype volume-controlled neonatal/infant resuscitator.

Face mask or bag endotracheal tube manual ventilation of neonates and infants has relied primarily on the use of self-inflating resuscitation devices (SIRs). While SIRs have the advantage of being simple to use and, therefore, require minimal training, recent research has demonstrated significant drawbacks to these devices. These drawbacks have included their large physical size, the tendency of such devices to cause significant hyperventilation, and the extreme variability of pressures necessary to activate the pop-off valve safety feature. This latter problem is especially serious in the infant where large pressure variations may increase the potential for pulmonary barotrauma. In an attempt to minimize the disadvantages of SIRs, we developed a prototype volume-controlled resuscitation device (VCD). We then compared the VCD to the SIRs in a cat model using blinded volunteer health care personnel previously familiar with SIRs only. Ventilation of the cat with the VCD yielded arterial and end-tidal CO2 values more closely resembling the physiologic state at a lower mean airway pressure. The data suggest that a human trial of manual ventilation with the prototype VCD is warranted.

Animals

Detection of reassortant orbiviruses (Wallal serogroup) in a prototype strain isolated from a pool of biting midges (Culicoides dycei).

Genetic variation between clones selected from early passage pools of Wallal virus (Reoviridae, Orbivirus) was investigated. The virus had been isolated in 1970 from a pool of 100 insects (Culicoides dycei), caught in the wild, by laboratory passage in suckling mice. Gel electrophoresis and oligonucleotide fingerprint analysis of clones indicated that multiple reassortant genotypes were present in early passages of the original isolate. The virus, previously described as the prototype strain of Wallal virus, was one of the reassortant clones. A virus recovered during reisolation from the same insect pool was genotypically and serologically distinct from the prototype strain and represents a second Wallal serotype. We have concluded that the clonal variation was due to the presence of two orbivirus serotypes in the original insect pool and that a range of reassortant viruses were generated during early passages of the material in mice.

Animals

A prototype for integrative review and meta-analysis of nursing research.

Meta-analysis has gained international recognition as a statistical approach to research synthesis. What is missing in research reviews, however, is the systematic compilation of results from non-experimentally designed studies. An approach is described which extends the rigours of integrative research review and meta-analysis to descriptive studies. A model for conceptualizing a systematically derived research synthesis is presented with selected accompanying generic elements. The model serves as a prototype for application to a variety of topical areas of interest. Generic elements contained in the prototype may be tailored to specific topics with relative ease. Resources and time required for topic development from conceptualization through to dissemination can be considerably reduced by adaptation of the generic elements.

Clinical Nursing Research

V and C gene contribution in creating anti-alpha-1,3 dextran antibodies in mice. I. Characteristics of Ig-lal prototype responses.

The light (L) and heavy (H) chain and the antigenic, idiotypic (Id) composition of the antibody (Ab) plaque-forming cells (PFC) and serum Ab specific for alpha-1,3 dextran have been characterized in Ig-lal BALB/c prototype mice, in Ig-la- [30] mice, and in BALB/c congenic and recombinant strains. Four distinct Ab Id specificities were identified by using criteria of Id relatedness to three Id-distinct, alpha-1,3 dextran-binding BALB/c myeloma proteins (MP), all associated, in the Ig-lal mice with the lambda (lambda) chains: a major, common IdX in 40--90% of the molecules; three minor, individual IdI in 1--49% of the molecules; and a fifth, Id-undefined one. These specificities were expressed at the PFC and serum level in the mu and gamma isotypes. A minor, kappa (kappa), Id-negative Ab was discerned only at the PFC level. The Ig-la- CBA and C3H mice responded with anti-alpha-1,3 dextran, kappa Id-negative Ab. The BALB/c, congenic strain CB20 (BALB/c Ig-lb, carrying the C57Bl/Ka, Ig-lb variable H (VH) gene complement and CH phenotype, made anti-alpha-1,3 dextran kappaId-negative Ab of the Ig-lb prototype. The recombinant BAB/14, carrying in the C57Bl/Ka CH-Ig-lb phenotype the BALB/c Ig-lal VH gene(s) controlling anti-alpha-1,3 dextran lambda Ab responsiveness and Id specificity (VH-DEX+), express the BALB/c lambdaId repertoire.

Animals

A prototype epithermal neutron beam for boron neutron capture therapy.

An epithermal neutron beam has been designed and tested at the Georgia Institute of Technology's 5-MW Research Reactor. The prototype facility consists of aluminum and sulfur disks in a tangential beam port for fast neutron filtration. A cadmium sheet at the port exit removes the thermal neutrons from the transmitted beam, leaving an intensely epithermal neutron beam spanning five energy decades, each contributing to the flux demanded by boron neutron capture therapy. The thermal neutron flux generated by the incident epithermal neutrons in a polyethylene head phantom peaks at a depth of 3 cm and remains above the incident thermal flux to a 7-cm depth. The beam thus provides the penetration required for treating deep-seated gliomas. Photon contamination in the prototype facility is high, and a number of basic modifications are proposed for reducing it to safer levels.

Boron

Strain gauge transduction of lip and jaw motion in the midsagittal plane: refinement of a prototype system.

This paper describes the design refinements made in an earlier prototype system for transducing lip and jaw movements in the midsagittal plane. Major improvements over the prototype system included: reduced transducer loading, improved two-dimensional separation and resolution, elimination of possible artifacts due to lateral-medial or rotational movement, electrical isolation of the subject from the transducer, increased capability to transduce movements of children as well as adults, and an accessory instrument for orienting the transducers with reference to defined anatomical planes.

Humans

Three adenovirus type 8 genome types defined by restriction enzyme analysis: prototype stability in geographically separated populations.

Adenovirus type 8 strains were collected over a 19-year period from eye specimens from patients with keratoconjunctivitis. These strains were divided by restriction enzyme analysis with the endonucleases SalI, HindIII, SacI, KpnI, and SmaI into three genotypic subgroups. The prototype strain (Trim) was found throughout the United States from 1966 through 1985 and also in Taiwan and Greece in the early 1980s. Genotype 8C was identified in an arc from Maryland to Missouri to Alabama from 1971 through 1974. Genotype 8D was found only in an epidemic of eye disease among Vietnamese refugees being resettled in northwest Florida in 1975. Genotypes 8C and D were distinct from genotypes 8A and B described from Japan in 1975 through 1981. Hemagglutination tests with a battery of avian and mammalian erythrocytes did not distinguish between the genotypic subgroups. Similarly, the genotypes could not be differentiated by hemagglutination inhibition or serum neutralization tests with reference prototype antisera. The long-term prevalence of the Trim strain suggests that adenovirus type 8 has greater genetic stability than the other adenovirus types studied to date.

Adenoviridae Infections

Evaluation of a prototype DNA probe test for the noncultural diagnosis of gonorrhea.

A prototype, nonisotopic, chemiluminescent DNA probe test called the Gen-Probe PACE (Probe Assay-Chemiluminescence Enhanced) system for Neisseria gonorrhoeae (Gen-Probe, San Diego, Calif.) was compared with conventional Martin-Lewis culture medium in JEMBEC plates for the laboratory diagnosis of gonorrhea. This 2-h noncultural assay is based upon the use of an acridinium ester-labeled DNA probe. The rRNA-directed DNA probe hybridizes with the target rRNA, and the hybridized probe is separated from the unhybridized probe through the use of magnetic microparticles. The esterified acridinium is hydrolyzed from the hybridized probe by the addition of an alkaline hydrogen peroxide solution, resulting in the production of visible light which is measured in a luminometer. The amount of light generated is directly proportional to the amount of gonococcal target rRNA present in the sample. A total of 407 clinical specimens (203 urethral and 204 endocervical) were collected from high-risk walk-in patients attending a sexually transmitted disease clinic. Separate patient specimens were collected for culture on Martin-Lewis medium in JEMBEC plates and for DNA probe assay. Statistical analysis of the overall comparative results showed that the DNA probe assay had a sensitivity, specificity, and positive and negative predictive values of 93, 99, 97, and 99%, respectively, in a patient population with a gonococcal disease prevalence of 21%. The results of this comparative study showed that the prototype chemiluminescent DNA probe assay is a rapid and reliable noncultural alternative for the laboratory diagnosis of gonorrhea.

DNA Probes

Heterogeneity of capsid proteins of echovirus type 25 wild-type strain and prototype strain, studied by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were used to compare the capsid proteins of 19 antigenic variants of echovirus type 25 wild-type strains isolated in France between 1976 and 1987 with those of the prototype JV-4 reference strain isolated in 1957. Immunoblots were developed by using polyclonal sera from rabbits and mice immunized with the reference strain. Immunoblotting patterns revealed reactivity only against viral protein VP1 for sera from both animals. Comparative immunoblotting patterns showed differences in the electrophoretic mobilities of viral protein VP1, especially for the Montpellier 76.1262 wild-type strain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methioinine-labeled viral polypeptides revealed that the two variant strains, Montpellier 76.1262 and Thionville 86.222, exhibited significant and reproducible shifts in the relative mobilities of VP1 and VP3 and, to a lesser extent, in those of VP0 and VP2. The relative mobility of VP4 seemed very similar for the JV-4 reference strain and the two variants. Interestingly, the structural differences in VP1 and VP3 of Montpellier 76.1262 were not correlated with the pattern of neutralization by monoclonal antibodies, unlike in our previous study, in which this strain differed from the prototype strain in only two epitopes. We concluded that, in addition to the heterogeneity of their biological and antigenic properties that we observed previously, echovirus type 25 wild-type strains may exhibit differences in their structural proteins.

Animals