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The use of preliminary injunctions in patent infringement cases is examined. It is contended that preliminary injunctions can serve an economic purpose for a plaintiff by imposing significant costs on the defendant. This increases the potential rewards for the plaintiff and can disadvantage smaller companies.

Researchers conducted a study to investigate the biological risk factors in older hospital patients with venous thromboembolism. Participants included 79 geriatric patients, 60 women and 19 men, with a mean age of 83 years who had at least one proven episode of venous thromboembolism. The study confirmed that hereditary deficiencies in coagulation inhibitors are seldom involved in the pathogenesis of venous thromboembolism in older subjects.

The Republican Party's political hold on Orange County, CA, has declined due to the changing nature of politics, changing demographics and several embarrassing controversies. The single most important cause of this decline was the voter passage of term limits in 1992 which limited the term of congressmen to six-years and that of senators to eight years. Other causes include the passage of a campaign finance law that put a cap on campaign financing and the passage of an open primary system that lessens the chance of ideological domination by a portion of the voter population.

The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization.

AbstractThe transmission line (TL) subsystem associated with the ITER electron cyclotron heating and current drive system has reached the conceptual design maturity. At this stage the responsibility of finalizing the design has been transferred from the ITER Organization to the U.S. Domestic Agency. The purpose of the TL is to transmit the microwaves generated by the 170-GHz gyrotrons installed in the radio-frequency building to the launchers located in one equatorial and four upper tokamak ports. Each TL consists of evacuated HE11waveguides, direct-current breaks, power monitors, mitre bends, polarizers, switches, loads, and pumping sections and will have a typical length that ranges from 100 to 160 m. Overall transmission efficiency could be as high as 92% depending on the specific path between a given gyrotron and launcher. All components are required to be 2-MW compatible, and their layout and organization have been optimized for simplifying the maintenance accessibility and monitoring the primary tritium barrier integrity. Two different TL layouts are at the moment under study, to accommodate the two alternative options for the European sources: four 2-MW units or eight 1-MW units. In this paper the actual design is presented and the technical requirements are discussed.

Candida dubliniensis is a recently described species that shares many phenotypic and morphological features with Candida albicans. The clinical significance of isolating C. dubliniensis from the pediatric population is not clear, as most clinical isolates have been recovered from the oral cavities or bloodstreams of adults infected with human immunodeficiency virus. In order to understand further the epidemiology of C. dubliniensis in our pediatric population, we identified C. dubliniensis isolates from clinical isolates previously identified in the laboratory as C. albicans and conducted a retrospective chart review of cases of C. dubliniensis infections. A total of 205 isolates from 183 patients were tested, and only 14 (6.8%) were identified as C. dubliniensis. In 5 of the 14 positive cultures, C. dubliniensis was the sole organism isolated (two respiratory tract specimens, one tongue specimen, one vaginal specimen, and one skin specimen). A case review showed that there were no adverse outcomes for any of the patients, and only one of the patients with cultures positive for C. dubliniensis was immunocompromised. In our pediatric population, the distinction of C. dubliniensis from C. albicans did not prove to have significant clinical relevance. Data from further investigations may help to define better the role of C. dubliniensis as a potential pathogen in children.

ABSTRACTCandida dubliniensisis a recently described species that shares many phenotypic and morphological features with Candida albicans. The clinical significance of isolating C. dubliniensisfrom the pediatric population is not clear, as most clinical isolates have been recovered from the oral cavities or bloodstreams of adults infected with human immunodeficiency virus. In order to understand further the epidemiology of C. dubliniensisin our pediatric population, we identified C. dubliniensisisolates from clinical isolates previously identified in the laboratory as C. albicansand conducted a retrospective chart review of cases of C. dubliniensisinfections. A total of 205 isolates from 183 patients were tested, and only 14 (6.8%) were identified as C. dubliniensis. In 5 of the 14 positive cultures, C. dubliniensiswas the sole organism isolated (two respiratory tract specimens, one tongue specimen, one vaginal specimen, and one skin specimen). A case review showed that there were no adverse outcomes for any of the patients, and only one of the patients with cultures positive for C. dubliniensiswas immunocompromised. In our pediatric population, the distinction of C. dubliniensisfrom C. albicansdid not prove to have significant clinical relevance. Data from further investigations may help to define better the role of C. dubliniensisas a potential pathogen in children.

Explores various principles involved in the patent system. Changes in the U.S. patent law and policy; Effect of enforcement costs on the value of patent protection; Overview of the global patent system for pharmaceuticals.

We investigated the relationship between prostate volume and cancer detection by needle biopsy, and determined the effect of an increased number of cores on the sampling error of needle biopsy on large prostate glands.

The three‐dimensional diurnal atmospheric angular momentum (AAM) budget is investigated, and its geographical features and meteorological dynamics are explored. It is shown that the diurnal atmospheric torques are associated with mass effect (ellipsoidal torque for the equatorial component and mountain torque for the axial component). It is shown that there is an important difference between the torque and angular momentum approaches on diurnal timescales, with the AAM time derivative generally exceeding the calculated torques. For the retrograde diurnal band, however, which is of interest for Earth nutation, the torque approach predicts much larger AAM changes than those observed. The AAM budget equation is also investigated theoretically, in order to give condition on the torques and AAM in order to verify the equation. Alternatively to the condition proposed by Bell, [1994], a condition on the local torque is shown sufficient to verify the AAM budget equation in the retrograde band, that is, the local torque have to balance the ellipsoidal effect. This condition is shown to be verified qualitatively. However, when separating the AAM budget equation into prograde and retrograde part, this last part become very sensitive to the error on the computation of the local torque. This explains why the torque approach always give one order of magnitude larger than the AAM approach at the retrograde diurnal frequencies.

The rural non‐farm sector has traditionally been viewed as a low‐productivity sector which produces low quality goods. It is often expected to wither away as a country develops. Recent years have seen a shift away from this position towards recognition that the rural non‐farm sector can, and often does, contribute to economic growth, rural employment, poverty reduction, and a more spatially balanced population distribution. This paper reviews the literature on the conceptual and empirical underpinnings of this more recent perspective, focussing on the experience in developing countries. The paper documents the size and heterogeneity of the sector, pointing to evidence that in many countries the sector is expanding rather than declining. The issues associated with measuring the sector's economic contribution are discussed, followed by empirical assessments for several countries and regions. The distributional impact of non‐farm earnings is examined and it is found that a pro‐poor impact, while by no means inevitable, can be considerable. The sector's trajectory over time, in different settings, is reviewed and the scope for, and experience of, various policy interventions is discussed.

DNA minicircles, where the length of DNA is below the persistence length, are highly effective, preferred, ligands for HMG-box proteins. The proteins bind to them “structure-specifically” with affinities in the nanomolar range, presumably to an exposed widened minor groove. To understand better the basis of this preference, we have studied the binding of HMG1 (which has two tandem HMG boxes linked by a basic extension to a long acidic tail) and Drosophila HMG-D (one HMG box linked by a basic region to a short and less acidic tail), and their HMG-box domains, to 88 bp and 75 bp DNA minicircles. In some cases we see cooperative binding of two molecules to the circles. The requirements for strong cooperativity are two HMG boxes and the basic extension; the latter also appears to stabilize and constrain the complex, preventing binding of further protein molecules. HMG-D, with a single HMG box, does not bind cooperatively. In the case of HMG1, the acidic tail is not required for cooperativity and does not affect binding significantly, in contrast to a much greater effect with linear DNA, or even four-way junctions (another distorted DNA substrate). Such effects could be relevant in the hierarchy of binding of HMG-box proteins to DNA distortions in vivo, where both single-box and two-box proteins might co-exist, with or without basic extensions and acidic tails.

The high-mobility group (HMG) proteins HMG1, HMG2 and HMG2a are relatively abundant vertebrate DNA-binding and bending proteins that bind with structure specificity, rather than sequence specificity, and appear to play an architectural role in the assembly of nucleoprotein complexes. They have two homologous “HMG-box” DNA-binding domains (which show about 80 % homology) connected by a short basic linker to an acidic carboxy-terminal tail that differs in length between HMG1 and 2. To gain insights into the role of the acidic tail, we examined the DNA-binding properties of HMG1, HMG2b and HMG2a from chicken erythrocytes (corresponding to HMG1, HMG2 and HMG2a in other vertebrates). HMG1, with the longest acidic tail, is less effective than HMG2a and 2b (at a given molar input ratio) in supercoiling relaxed, closed circular DNA, in inducing ligase-mediated circularisation of an 88 bp DNA fragment, and in binding to four-way DNA junctions in a gel-shift assay. Removal of the acidic tail increases the affinity of the HMG boxes for DNA and largely abolishes the differences between the three species. Switching the acidic tail of HMG1 for that of HMG2a or 2b gives hybrid proteins with essentially the same DNA-binding properties as HMG2a, 2b. The length (and possibly sequence) of the acidic tail thus appears to be the dominant factor in mediating the differences in properties between HMG1, 2a and 2b and finely tunes the rather similar DNA-binding properties of the tandem HMG boxes, presumably to fulfill different cellular roles. The tail is essential for structure-selective DNA-binding of the HMG boxes to DNA minicircles in the presence of equimolar linear DNA, and has little effect on the affinity for this already highly distorted DNA ligand, in contrast to binding to linear and four-way junction DNA.

We have previously shown the existence of two DNA-binding sites on the globular domain of H5 (termed GH5), both of which are required for nucleosome organisation, as judged by the protection of a 166 bp chromatosome intermediate during micrococcal nuclease digestion of chromatin. This supports a model in which GH5 contacts two duplexes on the nucleosome. However, studies of a nucleosome assembled on the 5 S rRNA gene have argued against the requirement for two DNA-binding sites for chromatosome protection, which has implications for the role of linker histones. We have used this proposed difference in the requirement for a second site on the globular domain in the two models as a means of investigating whether bulk and reconstituted 5 S nucleosomes are indeed fundamentally different. GH5 protects a 166 bp chromatosome in both “bulk” and 5 S systems, and in both cases protection is abolished when all four basic residues in site II are replaced by alanine. Binding to four-way DNA junctions, which present a pair of juxtaposed duplexes, is also abolished. Single mutations of the basic residues did not abolish chromatosome protection in either system, or binding to four-way junctions, suggesting that the residues function as a cluster. Both bulk and 5 S nucleosomes thus require a functional second DNA-binding site on GH5 in order to bind properly to the nucleosome. This is likely to reflect a similar mode of binding in each case, in which two DNA duplexes are contacted in the nucleosome. There is no indication from these experiments that linker histones bind fundamentally differently to 5 S and bulk nucleosomes.

In order to assess the potential of hydropsychid capture net anomalies as a bioindicator of chronic toxicity in streams and rivers, the effects of 2,4-dichlorophenol (2,4-DCP) exposure on the net-spinning behavior of Hydropsyche slossonaewere examined for anomalies after 0, 5, 10, 15, and 20 exposure days to gradient concentration of 2,4-dichlorophenol. The net-spinning behavior was significantly affected when larvae were exposed to 1.0, 10, 25, and 50 μg·L−1, as expressed by the occurrence of two distinct abnormalities. The first one was a distortion of the midline meshes, where the normal diamond-shape structure is disrupted and the meshes are separated by extra strands (called “midline” anomaly). The second aberration observed was called “chaotic” net, where the nets are highly irregular without any real structure or well-defined areas. A good correlation was found between the chaotic net frequencies and the reduction of ATP concentrations in the larvae, indicating possible uncoupling effects of 2,4-DCP on the oxidative phosphorylation process. Toxicity curves demonstrate that the sensitivity threshold of chaotic net frequencies ranged from 3.5 to 7 μg·L−1, which is highly sensitive compared with other sublethal effects of 2,4-DCP on other aquatic species.

AbstractSatellite gravity measurements expected in the next few years will provide unprecedented views of the Earth's gravity field and, given sufficient duration, its changes with time. Gravity changes directly reflect changes in the masses of the ocean (thus allowing the separation of steric (heat induced) and non-steric contributions to sea-level rise), the Greenland and Antarctic ice sheets, and the water stored in the continents. Not only can measurements of those changes provide a truly global integrated view of the Earth, they have, at the same time, sufficient spatial resolution to aid in the study of individual regions of the Earth. These data should yield information on water cycling previously unobtainable and be useful to both fundamental studies of the hydrologic cycle and practical assessments of water availability and distribution. Together with complementary geophysical data, satellite gravity data represent a new frontier in studies of the Earth and its fluid envelope.

ABSTRACTStreptococcus pneumoniaeundergoes spontaneous phase variation between a transparent and an opaque colony phenotype, the latter being more virulent in a murine model of sepsis. Opaque pneumococci have previously been shown to express lower amounts of C polysaccharide (cell wall teichoic acid) and in this study were shown to have a higher content of capsular polysaccharide by immunoelectron microscopy. This report then examined the relationship between expression of these two cell surface carbohydrate structures and their relative contribution to the increased virulence of opaque variants. Comparison of genetically related strains showed that the differential content of capsular polysaccharide did not affect the amount of teichoic acid as measured by a capture enzyme-linked immunosorbent assay (ELISA). In contrast, when the teichoic acid structure was altered by replacing choline in the growth medium with structural analogs, the quantity of capsular polysaccharide as measured by a capture ELISA was decreased, demonstrating a linkage in the expression of the two surface carbohydrate structures. A standardized assay was used to assess the relative contribution of cell surface carbohydrates to opsonophagocytosis. The opaque variants required 1.2- to 30-fold more immune human serum to achieve 50% opsonophagocytic killing than did related transparent variants (types 6B and 9V). The opsonophagocytic titer was proportional to the quantity of capsular polysaccharide rather than teichoic acid. The major factor in binding of the opsonin, C-reactive protein (CRP), was also the amount of capsular polysaccharide rather than the teichoic acid ligand. Only for the transparent variant (type 6B), which bound more CRP, was there enhanced opsonophagocytic killing in the presence of this serum protein. Increased expression of capsular polysaccharide, therefore, appeared to be the major factor in the decreased opsonophagocytic killing of opaque pneumococci.

We have investigated the nature of the “structure-specific” binding of the tandem A and B HMG boxes of high mobility group protein 1 (HMG1) to four-way junction DNA. AB didomain binding favours the open, planar form of the junction, as shown by reaction with potassium permanganate. Site-directed cleavage of the DNA by a 1,10-phenanthroline-copper moiety attached to unique natural or engineered cysteine residues in the A or B domain shows that the two linked HMG boxes are not functionally equivalent in four-way junction binding. The A domain of the didomain binds to the centre of the junction, mediating structure-specific binding; the concave surface of the domain interacts with the widened minor groove at the centre, contacting one of the four strands of the junction, and the short arm comprising helices I and II and the connecting loop protrudes into the central hole. The B domain makes contacts along one of the arms, presumably stabilising the binding of the didomain through additional non-sequence-specific interactions. The isolated B domain can, however, bind to the centre of the junction. The preferential binding of the A domain of the AB didomain to the centre correlates with our previous finding of a higher preference of the isolated A domain than of the B domain for this structurally distinct DNA ligand. It is probably at least partly due to the higher positive surface potential in the DNA-binding region of the A domain (in particular to an array of positively charged side-chains suitably positioned to interact with the negatively charged phosphates surrounding the central hole of the junction) and partly to differences in residues corresponding to those that intercalate between bases in other HMG box/DNA complexes.

A monoclonal antibody was raised against Drosophila melanogaster histone H1. Immunoscreening of proteolytic cleavage fragments of H1 and of a set of all possible overlapping synthetic octapeptides corresponding to the amino acid sequence of H1, revealed that the antibody recognizes an epitope within the sequence 207VTAAKPKA214 near the centre of the carboxy-terminal tail. This antibody gives positive immunofluorescence over the entire length of native D. melanogaster polytene chromosomes isolated from salivary glands by microdissection at physiological pH and ionic strength. Bands, interbands and puffs are all seen to contain H1. The immunofluorescence over puffs, albeit lower than that over bands and interbands, indicates that chromatin decondensation can occur without complete loss of H1 in these structures. The reaction of the antibody with bands suggests that the segment of the C-terminal tail containing the epitope may be exposed in the condensed 30 nm chromatin filament.

Les sujets très âgés représentent une part croissante des patients hospitalisés dans les unités de court séjour. Leurs filières de soins, leur morbidité et les facteurs explicatifs de la durée de séjour demeurent mal connus. Ce travail prospectif porte sur 150 séjours de patients de 90 ans et plus dans une unité de médecine interne et gériatrie. La morbidité est dominée par la multiplicité des diagnostics qui font presque tous l'objet d'une prise en charge durant l'hospitalisation (en moyenne: 2,8 ± 1,3). Les démences dégénératives, les troubles du rythme cardiaque, les accidents iatrogènes sont les catégories diagnostiques les plus fréquemment observées, articulées en modèles de morbidité spécifique. Le mode d'admission principal est l'admission non programmée. On note un taux élevé de décès durant l'hospitalisation (17%). Chez les patients non décédés le taux de retour à l'habitat antérieur (domicile personnel le plus souvent avec des aides sociales et/ou sanitaires) est de 88%. La durée de séjour chez les patients non décédés est significativement corrélée (P< 0,001) au nombre de diagnostics pris en charge durant le séjour, à la nécessité d'une modification du lieu de vie et au sexe. Ce modèle explique plus de 20% de la variance de la durée de séjour. Ces données confirment la spécificité de la prise en charge hospitalières des sujets très âgés et laissent penser que le programme de médicalisation des systèmes d'information (PMSI) doit être adapté pour garder une pertinence en médecine interne gériatrique.

During the first 12 years of operation the perinatal mortality rate in Paisley Maternity Hospital fell steadily from 27 per 1,000 in 1970 to 10 per 1,000 in 1981. During this period the nulliparous birth rate remained constant, but the parous birth rate fell. Improved survival of premature babies, falling numbers of babies with neural tube defects and reduction in intrapartum asphyxia are identified as responsible for this fall. Unexplained intra-uterine death remains an unsolved problem.

The asymmetric catalyzed metallo-ene reaction was studied. Enantioselectivities up to 47% were observed using the Pd-ene reaction applied on the substrate 4. © 1997 Elsevier Science Ltd.

Antibody responses against nucleosome core histones in systemic lupus erythematosus have been shown, by immunoblotting, to be directed largely against the trypsin‐sensitive regions of the histones. These occur at the N‐terminal regions of all 4 core histones and at the C‐terminal ends of H2A and H3. Since these regions are often not the most antigenic when individual histones are used as immunogens, and appear to be exposed in the nucleosome, the active immunogens in systemic lupus erythematosus seem likely to be chromatin‐bound, rather than free, histones.

The hepatitis B virus (HBV) P gene which encodes the reverse transcriptase and other proteins required for replication is expressed on the bicistronic mRNA pregenome which also encodes the capsid protein in its first cistron. Recent results have suggested that the hepadnaviral P gene is translated by internal entry of ribosomes upstream from the P gene, in the overlapping C gene. Using a reporter gene fused to the HBV C or P gene, we demonstrate that the C sequence does not allow internal initiation of translation. Alternatively, our results support a model in which the HBV P gene is translated by ribosomes which scan from the capped extremity of the bicistronic mRNA pregenome. The mechanism by which the ribosomes scan past four AUGs before they initiate translation at the P AUG was analyzed. Our results show that these AUGs are skipped via two mechanisms: leaky scanning on AUGs in a weak or suboptimal initiation context and translation of an out-of-C-frame minicistron followed by reinitiation at P AUG. The minicistron translation allows ribosomes to bypass an AUG in a favorable context that would otherwise be used as a start codon for translation of a truncated capsid protein. Our results suggest that this elaborated scanning mechanism permits the coordinate expression of the HBV C and P genes on the viral bicistronic mRNA pregenome.

• A series of highly specific inhibitors and substrates were used to specifically characterize the esterases present in the five vestibular end organs (the three semicircular canal cristae, the utriclar, and the saccular macula) from four young adult cats. No butyrylcholinesterase or nonspecific acetylcholinesterase activity was found. The results indicate a dense localization of acetylcholinesterase activity beneath and between the hair cells, at the sensory epithelial and subepithelial junction, and within vascular elements. This reaction product extends along the entire length of the sensory epithelium. Activity also extends proximally to the areas of the nerves' entrance into the subepithelial tissue. It should be noted that most of the activity is likely to be located in the extracellular matrix, as well as in the endoneurium. This extracellular distribution may represent an enzymatic barrier to the diffusion of acetylcholine that may be essential for the normal function of the end organ and possibly similar to the blood-brain barrier in some respects.(Arch Otolaryngol Head Neck Surg 1987;105:543-546)

Les canalisations en acier galvanisé et en cuivre sont largement utilisées dans les réseaux de distributions privés. Or le maintien d'une bonne protection contre la corrosion est lié à une dissolution très lente, mais permanente, de ces matériaux, dissolution nécessaire à la stabilité des produits protecteurs. Les teneurs en cuivre et/ou en zinc qui en résultent peuvent être plus ou moins élevées et atteindre, en extrémité de réseau, les valeurs autorisées par les normes actuellement en vigueur, soit 1 mg. l-1pour le cuivre et 5 mg. l-1pour le zinc.Le présent travail met en évidence que l'effet inhibiteur de ces métaux vis-à-vis de l'entartrage est extrêmement important, même à des teneurs inférieures aux valeurs maximales admissibles. L'étude a été conduite en utilisant un essai d'entartrage rapide sur un support en polyéthylène, ceci pour s'affranchir des méthodes électrochimiques d'entartrage accéléré. En effet, ces dernières conduisent à une réduction du cuivre et du zinc, ce qui n 'est pas admissible pour démontrer un effet sur l'entartrage.Ces résultats ont pu être corroborés par une autre méthode de " Précipitation Contrôlée Rapide " (PCR) où l'eau est portée durant l'essai, à un degré de sursaturation de l'ordre de 30 fois le produit de solubilité de CaCO3.On montre, ainsi, que la germination de CaCO3est fortement inhibée à partir de 200 µg. l-1de Cu2+et 20 µg. l-1de Zn2+et qu 'elle est pratiquement bloquée pour des teneurs de cuivre et de zinc supérieures, respectivement, à 600 µg. l-1et 50 µg. l-1.

Nucleosome dimers from chicken erythrocytes show an ionic strength dependence of sedimentation coefficient similar to that of trimers, and indicative of a degree of compaction over a range of low ionic strengths. This is not easily reconciled with straight linkers but is consistent with bending or kinking of the linker DNA.

An earlier study by Dickey et al.[1992] established the existence of globally coherent interannual fluctuations in atmospheric angular momentum (AAM), associated with the El Niño-Southern Oscillation (ENSO) cycle. In this paper, we pursue the origin and the structure of these fluctuations using an ensemble of experiments generated by the National Centers for Environmental Prediction, medium range forecast model version 9. In the control experiments, where the observed sea surface temperatures (SSTs) were used as the lower boundary conditions, the model captures the characteristic V-like structure in time-latitude plots of zonally averaged AAM found by Dickey et al., while experiments with climatological SSTs and those with either perpetual warm or cold ENSO conditions superimposed on the climatological SSTs failed to reproduce this structure. The numerical results indicate that these AAM structures are related to SST variations associated with transitions between different phases of the ENSO cycle and have both propagating and standing components. The largest zonal wind contribution from the levels studied (850, 500, and 200 hPa) is at 200 hPa, where the tropical convective outflow is the strongest. Composites of zonal wind and geopotential height show a clear relationship between the stages of the global AAM oscillation and the ENSO cycle. The strong similarity between the simulated and observed AAM series attests to the model's ability to realistically simulate the interannual response of the atmosphere to ENSO SST anomalies.

Two eukaryotic proteins involved in translation termination have recently been characterized in in vitro experiments. Eukaryotic release factor 1 (eRF1) catalyzes the release of the polypeptide chain without any stop codon specificity. The GTP-binding protein eRF3 confers GTP dependence to the termination process and stimulates eRF1 activity. We used tRNA-mediated nonsense suppression at different stop codons in a cat reporter gene to analyze the polypeptide chain release factor activities of the human eRF1 and eRF3 proteins overexpressed in human cells. In a chloramphenicol acetyltransferase assay, we measured the competition between the suppressor tRNA and the human release factors when a stop codon was present in the ribosomal A site. Whatever the stop codon (UAA, UAG, or UGA) present in the cat open reading frame, the overexpression of human eRF1 alone markedly decreased translational readthrough by suppressor tRNA. Thus, like the procaryotic release factors RF1 and RF2 in Escherichia coli, eRF1 seems to have an intrinsic antisuppressor activity in human cells. Levels of antisuppression of overexpression of both eRF3 and eRF1 were almost the same as those of overexpression of eRF1 alone, suggesting that eRF1-eRF3 complex-mediated termination may be controlled by the expression level of eRF1. Surprisingly, when overexpressed alone, eRF3 had an inhibitory effect on cat gene expression. The results of cat mRNA stability studies suggest that eRF3 inhibits gene expression at the transcriptional level. This indicates that in vivo, eRF3 may perform other functions, including the stimulation of eRF1 activity.

The C gene products of all mammalian hepadnaviruses contain a region with sequence similarities to the catalytic center of the aspartyl proteases. This region could have the capacity to cleave precore proteins, leading to the synthesis of e antigen. By site-directed mutagenesis on a plasmid containing the hepatitis B virus C gene, we have replaced either the Asp residue of the putative aspartyl protease catalytic center or an Asp residue located 3 amino acids upstream. Transient expression of the mutated hepatitis B virus C gene in human and mouse cells showed that none of these mutations prevented the secretion of an accurately processed HBe antigen. Thus, we demonstrated that the aspartyl protease responsible for e antigen precursor processing is not C gene encoded but is more likely to be a cellular enzyme. From these results, we suggest a model for the mechanism of e antigen synthesis.

The recent demonstration that the synthesis of duck hepatitis B virus (HBV) reverse transcriptase does not require translational frameshifting and the finding that poliovirus mRNA translation occurs in a cap-independent manner by internal binding of ribosomes in the 5' noncoding region led us to design experiments to test the hypothesis of internal entry of ribosomes on C gene mRNA for HBV P gene expression. We show that in human cells, translation can be initiated at the first AUG of the HBV P gene by entry of ribosomes in a region located upstream of the P gene. Moreover, the leaky scanning of ribosomes observed on the first AUG of the HBV P gene could be responsible for the synthesis of the two forms of reverse transcriptase described for HBV particles.

Background: Rhinoviruses have long been associated with mild upper respiratory illness in both adults and children. However, the role of rhinoviruses as lower respiratory tract pathogens has not been fully characterized. Previous data suggests that rhinoviruses may cause severe lower respiratory illness in young children or infants. Objectives: The present study describes the clinical presentations, severity of illness and outcomes for a large cohort of pediatric patients with documented rhinovirus infections. Subjects and methods: A retrospective chart review was done on 93 pediatric patients from whom 101 nasopharyngeal or endotracheal specimens were positive by viral culture for a rhinovirus. All patients were hospitalized or seen in the pediatric emergency department at The Children's Hospital of Philadelphia between 1 January, 1990 and 31 May, 1996. Results: Of the 93 patients, 52 were male and 41 female. The age range was 0 days to 18 years with 25 (27%) less than 3 months, 42 (45%) between 3 and 12 months and 26 (28%) over the age of 12 months. Clinical presentations on evaluation in the emergency department or admission included 78 (84%) patients with acute respiratory illness, 13 (17%) with fever and suspected sepsis and 11 (12%) with other complaints. Reported physical findings on examination included one or more lower respiratory symptoms or signs of acute distress and fever greater than or equal to 38.1°C. A total of 64 (69%) children were noted to have significant past medical histories, including 28 (44%) with prematurity or complicated neonatal courses, 11 (17%) with prior reactive airways, 8 (12%) with congenital cardiac disease and 7 (11%) with neurologic disorders. Of the patients, 29 (31%) were considered to be otherwise healthy children with no underlying dysfunctions. The mean duration of hospitalization for 69 patients admitted with respiratory illness who did not develop subsequent unrelated complications was 3.7 days. No significant bacterial or fungal pathogens were identified in 91% of the cases. Conclusions: This study shows that rhinoviruses were associated with severe lower respiratory illness and hospitalization in a large pediatric population and that rhinovirus infection was a complicating factor in those patients with underlying or predisposing conditions.

The purpose of this article is to selectively offer insights from the discipline of sociology which rehabilitation counselors could find useful in improving the practice of their profession. Among the dominant topics discussed are the role of society in shaping and defining man's behavior, the role of society in rehabilitation, the concept and conferment of deviance, and Merton's self-fulfilling prophecy construct. Implications for rehabilitation counseling practice are presented.

The basic chromatin fibre (the 10 nm diameter fibre) is a linear repeating array of nucleosomes, or nucleosome filament. The core of each disk-like nucleosome is a wedge-shaped protein octamer containing two molecules of each of the four core histones (H3, H4, H2A and H2B) around which two turns of DNA are wound in a left-handed superhelix with about 80 base-pairs per turn. The two turns are sealed by a molecule of the fifth histone H1 (or H5 in nucleated erythrocytes). The linker DNA that connects one two-turn particle to the next varies from essentially zero to about 80 base-pairs in chromatins from different sources. The exact significance of this variation is unclear. Interphase chromatin exists largely in the form of 30 nm fibres. Folding of the nucleosome filament into very similar 30 nm fibres, which is Hl-dependent, occurs in vitro in the presence of monovalent cations or much lower concentrations of divalent cations. These higher-order structures probably arise by helical coiling of the nucleosome filament into a solenoid. Systematic studies of chromatin folding in solution, for a range of chromatin fragment sizes and ionic strengths, reveal two discontinuities in behaviour that reflect two structural transitions. One is interpreted as the formation of a turn of a solenoid with about six nucleosomes, at ionic strength 25 HIM, and is a common feature of chromatin from three different sources, which differ in DNA repeat length, and type and amount of Hl. The other transition is interpreted in terms of hydrodynamic shearing of long solenoids at low ionic strengths (below ∼45mM). It suggests a more stable higher-order structure for chicken erythrocyte chromatin than for rat liver chromatin (attributed largely to the presence of H5), and may prove to be a useful general assay for the relative stabilities of different chromatins, which might be relevant to their ease of unravelling for transcription. A study of short (165 base-pair) repeat chromatin from cerebral cortex neurons has led to the suggestion that in the general case the linker DNA might be located, perhaps with Hl, in the central hole in the solenoid. H1 molecules in both extended and condensed chromatin (although not when dissociated from it) are close enough to be chemically cross-linked with reagents of span 2-12Å. This suggests an H1 polymer in chromatin, which might have a role in chromatin condensation. Chemical cross-linking studies using cleavable, bifunctional amino-group reagents have permitted the domains of H1 molecules that are in proximity in the extended and condensed states to be determined, and changes occurring on folding to be identified. In another approach towards understanding the role and behaviour of H1 we have studied further the ability of H1 molecules to migrate between sites on different chromatin fragments. H1 and H5 (an extreme H1 variant) also exchange, but show differences in behaviour that may reflect their different abilities to stabilize higher-order structures, revealed in the sedimentation studies outlined above. In particular, H5 shows a greater preference than H1 for sites in higher-order structures.

The effect of age on the peripheral nervous system was investigated by clinical examination and neurophysiological studies in 59 subjects aged 60–103 years and 23 young subjects. A full laboratory screen for factors which, though clinically silent, may constitute risk factors (RFs) for peripheral neuropathy was also performed in the elderly subjects. Our findings show that the presence of RFs affects exceptionally the electrophysiological parameters in a statistically significant way. The age-dependent changes in nerve conduction parameters were well predicted by non-linear models. The simultaneous electromyographical study demonstrates the re-innervation capacity of the motor system